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a method of performing a medical procedure on a patient comprises forming a burr hole through the cranium of the patient , mounting a permanently integrated plug electrode within the burr hole , and electrically coupling the plug electrode to an electronics device . another method of performing a medical procedure on a patient comprises forming a burr hole through the cranium of the patient , mounting an electrode within the burr hole , such that the electrode does not extend within the brain of the patient , and electrically coupling the electrode to an electronics device . a hybrid plug / electrode comprises a plug body configured for being anchored within a burr hole formed within a cranium of a patient , at least one electrode disposed on a distal - facing surface of the plug body , and at least one electrode lead affixed within the plug body in electrical communication with the at least one electrode .

turning first to fig1 , an exemplary cortical brain stimulation system 10 constructed and arranged in accordance with one embodiment of the present inventions is shown implanted within a patient for the treatment of a debilitating disease such as , parkinson &# 39 ; s disease , dystonia , essential tremor , seizure disorders , obesity , depression , etc . the system 10 comprises a hybrid plug / electrode array 12 and a plurality of minimally invasive plug electrodes 14 implanted within the head 2 of a patient 1 for both stimulating and recording electrical signals from the cortical brain tissue ( not shown in fig1 ). both of the hybrid plug / electrode array 12 and plug electrodes 14 can be considered plug electrodes , with the main difference being that the hybrid plug / electrode array 12 comprises a plurality of electrodes , whereas the plug electrodes 14 comprise a single electrode . as will be described in further detail below , the hybrid plug / electrode array 12 and plug electrodes 14 are mounted within the cranium of the patient in order to stimulate or record signals of the cortical brain tissue . as illustrated in fig2 , the hybrid plug / electrode array 12 , in one embodiment , is used to stimulate a portion of the cortical brain tissue at a stimulation site , and the plug electrodes 14 are used to record electrical signals at first and second recording sites of the cortical brain tissue . thus , electrical stimulation energy can be conveyed from the hybrid plug / electrode array 12 into the cortical brain tissue to treat the disease , and electrical signals can be sensed at the plug electrodes 14 to monitor the disease . alternatively , the hybrid plug / electrode array 12 can be used to record electrical signals from one of the two recording sites of the cortical brain tissue , and the plug electrodes 14 may be used to convey stimulation energy to the stimulation site of the cortical brain tissue . in another alternative embodiment , some of the plug electrodes 14 may be used to convey stimulation energy to the stimulation site of the cortical brain tissue , and others of the plug electrodes 14 may be used to record electrical signals from one or both of the recording sites of the cortical brain tissue . in an optional embodiment , the electrical signals sensed at the first and second recording sites can be used to modify or adjust stimulation parameters in accordance with which the stimulation energy is delivered from the plug / electrode array 12 to the stimulation site . further details discussing this closed - loop manner of delivery stimulation energy to a patient are described in u . s . patent application ser . no . ______ ( attorney docket no . 06 - 00363 - 01 ), which is expressly incorporated herein by reference . the cortical brain stimulation system 10 further comprises an implantable electronics device 16 . in the illustrated embodiment , the electronics device 16 takes the form of a electronics device 16 , such as an implantable pulse generator ( ipg ), radio frequency ( rf ) receiver - stimulator , or any other device coupled to and capable of delivering electrical stimulation energy to the hybrid plug / electrode array 12 in a controlled and therapeutic manner . in the illustrated embodiment , the electronics device 16 may also include recording circuitry capable of processing electrical signals sensed at the plug electrodes 14 . in this manner , the electronics device 16 can be considered both a neurostimulator and a recorder . alternatively , separate neurostimulator and recording devices can be utilized . in any event , the cortical brain stimulation system 10 further comprises a plurality of individual electrical leads 18 respectively coupled to the hybrid plug / electrode array 12 and plug electrodes 14 , a connector hub 20 that receives the ends of the electrical leads 18 , and a lead extension 22 coupled between the connector hub 20 and the electronics device 16 . as will be described , the electrical leads 18 , in certain cases , may carry electrodes that form portions of the plug electrodes 14 . the connector hub 20 may be implanted underneath the scalp of the patient , and the individual electrical leads 18 may be subcutaneously routed from the hybrid plug / electrode array 12 and plug electrodes 14 underneath the scalp , along external surface of the cranium of the patient , to the connector hub 20 . in this manner , the individual electrical leads 18 can be wired through the single lead extension 22 . the lead extension 22 may be subcutaneously advanced underneath the scalp of the patient 1 to the electronics device implantation site , thereby facilitating the location of the electronics device 16 away from the cranium of the patient . the electronics device 16 may be generally implanted in a surgically - made pocket in the torso of the patient ( e . g ., the chest or shoulder region ). the electronics device 16 may , of course , also be implanted in other locations of the patient &# 39 ; s body . in alternative embodiments , the electronics device 16 may be directly implanted on or within the cranium of the patient 1 , as described in u . s . pat . no . 6 , 920 , 359 , which is expressly incorporated herein by reference . in this case , the lead extension 22 may not be needed . the system 10 may include external components , such as a patient handheld programmer , a clinician programming station , and an external charger ( all not shown ), the details of which will not be described herein for purposes of brevity . turning now to fig3 , the hybrid plug / electrode array 12 will now be described . as there shown , the hybrid plug / electrode array 12 is mounted within a burr hole 4 conventionally formed through the cranium 3 of the patient 1 . the hybrid plug / electrode array 12 comprises a plug body 24 that is sized to firmly fit within the burr hole 4 , thereby firmly anchoring the hybrid plug / electrode array 12 to the cranium 3 and preventing leakage of cerebral spinal fluid between the outer surface of the plug body 24 and the burr hole 4 . to this end , the plug body 24 has a cylindrical outer wall 26 having an outer diameter substantially the same as the diameter of the burr hole 4 . the burr hole 4 may have a conventional size ; for example , over 10 mm in diameter , and typically between 14 - 15 mm in diameter . the plug body 24 comprises a fastener , and in particular , a thread 28 disposed on the outer surface of the cylindrical wall 26 , for engaging the inner surface of the burr hole 4 , and thereby , anchoring the hybrid plug / electrode array 12 within the burr hole 4 . in this manner , the hybrid plug / electrode array 12 may be conveniently screwed into the burr hole 4 . alternatively , other types of fastening means , such as sutures or bone screws , can be used to anchor the hybrid plug / electrode array 12 to the cranium 3 . the plug body 24 further comprises a distal surface 30 that faces the cortical brain tissue 5 of the patient 1 when the hybrid plug / electrode array 12 is anchored within the burr hole 4 . in the illustrated embodiment , the distal surface 30 of the plug body 24 is flat , although in alternative embodiments , may be concave or convex . the height of the plug body 24 has a relatively small profile , such that the distal surface 30 does not protrude into the cranial cavity of the patient ( i . e ., does not extend past the inner surface of the cranium 3 ) when the hybrid plug / electrode array 12 is anchored within the burr hole 4 . for example , as shown in fig3 , the distal surface 30 is recessed relative to the inner surface of the cranium 3 . in some cases , it may be desirable for the hybrid plug / electrode array 12 to extend into the cranial cavity and sit or push gently on the dura mater , thus placing the active portion of the hybrid plug / electrode array 12 closer to the target neural tissue . the plug body 24 may be composed of a suitable hard biocompatible material , such as titanium , stainless steel ( e . g ., mp35n ), alloys , or hard polymers ( e . g ., a high durometer silicone , polyurethane , or polyethertheterketone ( peek )). if the plug body 24 is composed of an electrically conductive material , the hybrid plug / electrode array 12 may comprise an electrically insulative coating ( not shown ) disposed on the outer surface of the plug body 24 to ensure that the cranium 3 is electrically insulated from the hybrid plug / electrode array 12 and to minimize noise from electromyograms ( emgs ) during recording . the hybrid plug / electrode array 12 further comprises a plurality of electrodes 32 suitably mounted to the distal surface 30 of the plug body 24 , such that the electrodes 32 face the cortical brain tissue 5 . as shown , because the distal surface 30 of the plug body 24 is recessed within the burr hole 4 , the electrodes 32 are likewise recessed within the burr hole 4 . although the electrodes 32 are not in direct contact with the cortical brain tissue 5 , they are still electrically coupled to the cortical brain tissue 5 via the dura mater 6 and cerebrospinal fluid 7 . thus , the electrodes 32 may potentially convey electrical stimulation energy ( originating from the electronics device 16 ) to the cortical brain tissue 5 or receive electrical signals from the cortical brain tissue 5 for subsequent processing in the electronics device 16 . the electrodes 32 may be disposed on the distal surface 30 of the plug body 24 in any conventional manner ( e . g ., electroplating , sputtering , or bonding ), and may be composed of any suitable biocompatible , electrically conductive material , such as stainless steel or a platinum alloy . the hybrid plug / electrode array 12 further comprises an electrical connector 34 and a plurality of electrode leads 36 ( shown in phantom ) extending between the electrical connector 34 and the respective electrodes 32 . in the illustrated embodiment , the electrical connector 34 takes the form of a connector header that is affixed to the top of the plug body 24 using suitable means , such as welding . alternatively , the electrical connector 34 may be formed as a portion of the plug body 24 . the electrical connector 34 includes electrical terminals ( not shown ) that are external accessible when the hybrid plug / electrode array 12 is anchored within the burr hole 4 . in this manner , the respective electrical lead 18 may be mated with the electrical connector 34 , such that electrical contacts ( not shown ) located on the proximal end of the electrical lead contact the electrical terminals of the electrical connector 34 . the electrical lead 18 that is coupled to the hybrid plug / electrode array 12 comprises a plurality of insulated wires ( not shown )— one for each electrical contact . the electrode leads 36 extend through the plug body 24 between the respective electrodes 32 to the electrical connector 34 in contact with the electrical terminals . the electrode leads 36 may be suitably coupled to the electrodes 32 and connector 34 , e . g ., using soldering . if the plug body 24 is composed of an electrically conductive material , each of the electrode leads 36 may have an electrically insulative coating ( not shown ) to prevent electrical shorting between the electrode leads 36 and the plug body 24 . in the illustrated embodiment , the number of electrode leads 36 equals the number of electrodes 32 , such that each electrode lead 36 is connected to a respective one of the electrodes 32 . in an alternative embodiment , the number of electrode leads 36 may be less or more than the number of electrodes 32 . for example , there may be many electrode leads 36 and a single electrode 32 , or there may be many electrodes 32 and a single electrode lead 36 . referring now to fig4 - 9 , various embodiments of the minimally invasive plug electrodes 14 will now be described . each of the plug electrodes 14 may be configured for being anchored within a very small burr hole 8 formed within the cranium 3 , thereby minimizing the trauma caused to the patient 1 . the diameter of the burr hole 8 is preferably less than 10 mm , and more preferably less than 5 mm . like the hybrid plug / electrode array 12 , each plug electrode 14 is sized to be firmly secured within the respective burr hole 8 , without extending into the brain of the patient , and in these illustrated cases , without extending within the cranial cavity of the patient . referring specifically to fig4 , one embodiment of a minimally invasive plug electrode 14 ( 1 ) will now be described . the plug electrode 14 ( 1 ) comprises a plug body 40 that includes comprises a shaft 42 configured for being mounted within the burr hole 8 and a head 44 that is externally accessible when the plug body 40 is anchored within the burr hole 8 . the plug body 24 comprises a fastener , and in particular , a thread 46 disposed on the outer surface of the shaft 42 for engaging the inner surface of the burr hole 8 , and thereby , anchoring the plug electrode 14 ( 1 ) within the burr hole 8 . the distal end of the shaft 42 is preferably blunt to ensure that the cortical brain tissue 5 is not pierced or otherwise damaged . the plug body 40 includes a tool engagement element 48 for engaging a tool ( not shown ) that can provide a mechanical advantage for rotation of the plug electrode 14 ( 1 ). in the illustrated embodiment , the tool engagement element 48 is a slotted recess for receiving a flathead screwdriver . other types of tool engagement elements , such as a hex recess for receiving a hex wrench , a crossed recess for receiving a phillips screwdriver , or a bolt head for receiving an open - ended wrench , box - end wrench , or socket wrench can also be used . thus , it can be appreciated from the foregoing that the plug body 24 takes the form of a screw , which allows the plug electrode 14 ( 1 ) to be conveniently screwed into the burr hole 4 , which may be formed prior to screwing the plug electrode 14 ( 1 ) therein , or may be formed by screwing the plug electrode 14 ( 1 ) directed into the cranium 3 . the plug body 40 is composed of a suitable hard and electrically conductive biocompatible material , such as titanium , stainless steel ( e . g ., mp35n ), or alloy . to ensure that the cranium 3 is electrically insulated from the electrically conductive plug body 40 and to minimize noise from electromyograms ( emgs ) during recording , the plug electrode 14 ( 1 ) comprises a durable electrically insulative coating 50 ( such as , e . g ., epoxy or parylene ) disposed on the outer surface of the plug body 24 ( including the shaft 42 and head 44 ). significantly , the distal end of the shaft 42 is left exposed to form an electrode 52 that faces the cortical brain tissue 5 . the plug electrode 14 ( 1 ) can be considered permanently integrated in that the plug body 40 and electrode 52 are either formed as a unibody design or are otherwise integrated in a manner ( e . g ., bonding ) that would prevent them from being separated from each other without destroying or otherwise damaging the plug electrode 14 ( 1 ). as shown , the exposed electrode 52 is recessed within the burr hole 8 , and therefore , does not extend into the cranial cavity . although the exposed electrode 52 is not in direct contact with the cortical brain tissue 5 , like the aforementioned electrode array 32 ( shown in fig3 ), it is indirectly electrically coupled to the cortical brain tissue 5 via the dura mater 6 and cerebrospinal fluid 7 . thus , the electrode 52 may potentially convey electrical stimulation energy ( originating from the electronics device 16 ) to the cortical brain tissue 5 or receive electrical signals from the cortical brain tissue 5 for subsequent processing in the electronics device 16 . the electrical lead 18 may be connected to the head 42 of the plug body 40 using suitable means , such as soldering , tightening screws , or sutures . thus , it can be appreciated that the electrical lead 18 is electrically coupled to the exposed electrode 52 via the shaft 42 of the plug body 40 . referring to fig5 , another embodiment of a minimally invasive plug electrode 14 ( 2 ) will now be described . the plug electrode 14 ( 2 ) is similar to the plug electrode 14 ( 1 ) illustrated in fig4 in that it is permanently integrated . in particular , the plug electrode 14 ( 2 ) comprises a plug body 60 that includes a shaft 62 configured for being mounted within the burr hole 8 and a head 64 that is externally accessible when the plug body 40 is anchored within the burr hole 8 . the plug body 24 comprises a fastener , and in particular , a thread 66 disposed on the outer surface of the shaft 62 for engaging the inner surface of the burr hole 8 , and thereby , anchoring the plug electrode 14 ( 2 ) within the burr hole 8 . in this manner , the plug electrode 14 ( 2 ) may be conveniently screwed into the burr hole 4 much like the plug electrode 14 ( 1 ) described above . the distal end of the shaft 62 is preferably blunt to ensure that the cortical brain tissue 5 is not pierced or otherwise damaged . the plug body 40 includes a tool engagement element 68 for engaging a tool ( not shown ) that can provide a mechanical advantage for rotation of the plug electrode 14 ( 2 ). in the illustrated embodiment , the tool engagement element 68 a pair of slotted recesses for a special tool . other types of tool engagement elements , such as those described above , can also be used . the plug electrode 14 ( 2 ) mainly differs from the plug electrode 14 ( 1 ) in that a portion of the plug body 60 is composed of an electrically insulative material . in particular , the plug electrode 14 ( 2 ) has a top portion 74 ( including the head 64 and the proximal end of the shaft 62 ) that is composed of an electrically insulative material , such as peek , and a bottom portion 76 ( the distal portion of the shaft 62 ) that is composed of a suitable hard and electrically conductive biocompatible material , such as titanium , stainless steel ( e . g ., mp35n ), or alloy . the top portion 74 of the plug body 40 comprises a blind lumen 78 that houses an inner electrical conductor 80 . the distal end of the blind lumen 78 is open , such that the bottom portion 76 of the plug body 40 ( i . e ., the electrode ) is in electrical communication with the inner conductor 80 , and the proximal end of the blind lumen 78 is closed . in the illustrated embodiment , the blind lumen 78 , and thus , the inner conductor 80 , are t - shaped . to ensure that the cranium 3 is electrically insulated from the electrically conductive top portion 74 of the plug body 40 and to minimize noise from electromyograms ( emgs ) during recording , the plug electrode 14 ( 2 ) comprises a durable electrically insulative coating 70 ( such as , e . g ., epoxy or parylene ) disposed on outer surface of the shaft 62 . significantly , the distal end of the shaft 62 is left exposed to form an electrode 72 that faces the cortical brain tissue 5 . as shown , the exposed electrode 72 is recessed within the burr hole 8 , and therefore , does not extend into the cranial cavity . although the exposed electrode 72 is not in direct contact with the cortical brain tissue 5 , like the aforementioned electrode array 32 , it is indirectly electrically coupled to the cortical brain tissue 5 via the dura mater 6 and cerebrospinal fluid 7 . thus , the electrode 72 may potentially convey electrical stimulation energy ( originating from the electronics device 16 ) to the cortical brain tissue 5 or receive electrical signals from the cortical brain tissue 5 for subsequent processing in the electronics device 16 . the electrical lead 18 may be connected to the inner conductor 80 within the plug body 60 , and in particular , the horizontal portion of the inner conductor 80 , via a solder or other suitable connection . thus , it can be appreciated that the electrical lead 18 is electrically coupled to the exposed electrode 72 via the inner conductor 80 and the bottom portion 76 of the plug body 40 . referring to fig6 , yet another embodiment of a minimally invasive plug electrode 14 ( 3 ) will now be described . the plug electrode 14 ( 3 ) is similar to the plug electrode 14 ( 1 ) illustrated in fig4 in that it comprises a plug body 90 that includes a shaft 92 configured for being mounted within the burr hole 8 and a head 94 that is externally accessible when the plug body 90 is anchored within the burr hole 8 . the plug body 90 comprises a fastener , and in particular , a thread 96 disposed on the outer surface of the shaft 92 for engaging the inner surface of the burr hole 8 , and thereby , anchoring the plug electrode 14 ( 3 ) within the burr hole 8 . in this manner , the plug electrode 14 ( 3 ) may be conveniently screwed into the burr hole 4 . the plug body 90 includes a tool engagement element 98 for engaging a tool ( not shown ) that can provide a mechanical advantage for rotation of the plug electrode 14 ( 3 ). in the illustrated embodiment , the tool engagement element is a slotted recess for receiving a flathead screwdriver , although other types of tool engagement elements , such as those described above , can also be used . the plug electrode 14 ( 3 ) mainly differs from the plug electrode 14 ( 1 ) in that it is not permanently integrated . in particular , the plug electrode 14 ( 3 ) includes an inner electrical conductor 104 concentrically and removably disposed within the plug body 90 . in particular , the plug body 90 comprises a lumen 106 extending vertically up the shaft 92 and then out the top of the head 94 . the inner conductor 104 takes the form of a screw that includes a shaft 108 , which is received within the lumen 106 of the plug body 90 , and a head 110 received within the tool engagement element 98 of the plug body 90 . the exterior surface of the shaft 104 of the inner conductor 104 and the inner surface of the lumen 106 include threads 112 , such that the inner conductor 104 can be screwed into the plug body 40 until the distal end of the shaft 108 of the inner conductor 104 , which forms an electrode 102 , distally protrudes from the distal end of the plug body 40 . the distal ends of the shaft 92 of the plug body 90 and shaft 108 of the inner conductor 104 are preferably blunt to ensure that the cortical brain tissue 5 is not pierced or otherwise damaged . the inner conductor 104 includes a tool engagement element 114 for engaging a tool ( not shown ) that can provide a mechanical advantage for rotation of the inner conductor 104 within plug body 90 . in the illustrated embodiment , the tool engagement element 114 is a slotted recess for receiving a flathead screwdriver , although other types of tool engagement elements , such as those described above , can also be used . the plug body 90 is composed of a suitable hard and electrically conductive biocompatible material , such as titanium , stainless steel ( e . g ., mp35n ), or alloy . to ensure that the cranium 3 is electrically insulated from the electrically conductive plug body 90 and to minimize noise from electromyograms ( emgs ) during recording , the plug electrode 14 ( 3 ) comprises a durable electrically insulative coating 100 ( such as , e . g ., epoxy or parylene ) disposed on the outer surface of the plug body 90 . while only the head 94 of the plug body 90 is shown with the insulative coating 100 , the shaft 92 of the plug body 90 may have the insulative coating 100 as well . alternatively , the plug body 90 may be composed of an electrically insulative material , in which case , the electrically insulative coating 100 may not be needed . as shown , the electrode 102 is recessed within the burr hole 8 , and therefore , does not extend into the cranial cavity . although the electrode 102 is not in direct contact with the cortical brain tissue 5 , like the aforementioned electrode array 32 , it is indirectly electrically coupled to the cortical brain tissue 5 via the dura mater 6 and cerebrospinal fluid 7 . thus , the electrode 102 may potentially convey electrical stimulation energy ( originating from the electronics device 16 ) to the cortical brain tissue 5 or receive electrical signals from the cortical brain tissue 5 for subsequent processing in the electronics device 16 . in the case where the plug body 90 is composed of an electrically conductive material , the electrical lead 18 may be connected to the head 94 of the plug body 90 using suitable means , such as soldering , tightening screws , or suturing . in the case where the plug body 90 is composed of an electrically insulative material , the distal end of the electrical lead 18 may be inserted through a lumen ( not shown ) within the head 94 of the plug body 90 and connected to the inner conductor 104 using suitable means , such as soldering . thus , it can be appreciated that the electrical lead 18 , when connected to the inner conductor 104 ( either directly or indirectly through the plug body 90 ), will be electrically coupled to the exposed electrode 102 . it can be appreciated that the plug electrode 14 ( 3 ) is particularly advantageous in that the position of the electrode 102 within the burr hole 8 may be adjusted simply by rotating the inner conductor 104 ( using the tool ). thus , the electrode 102 can be properly positioned regardless of the thickness of the cranium 3 . referring to fig7 , yet another embodiment of a minimally invasive plug electrode 14 ( 4 ) will now be described . the plug electrode 14 ( 4 ) is similar to the plug electrode 14 ( 3 ) illustrated in fig6 in that it comprises a plug body 120 that includes a shaft 122 configured for being mounted within the burr hole 8 and a head 124 that is externally accessible when the plug body 120 is anchored within the burr hole 8 . the plug body 120 comprises a fastener , and in particular , a thread 126 disposed on the outer surface of the shaft 122 for engaging the inner surface of the burr hole 8 , and thereby , anchoring the plug electrode 14 ( 4 ) within the burr hole 8 . in this manner , the plug electrode 14 ( 4 ) may be conveniently screwed into the burr hole 4 . the plug body 120 includes a tool engagement element 128 for engaging a tool ( not shown ) that can provide a mechanical advantage for rotation of the plug electrode 14 ( 4 ). in the illustrated embodiment , the tool engagement element is a slotted recess for receiving a flathead screwdriver , although other types of tool engagement elements , such as those described above , can also be used . the plug electrode 14 ( 4 ) mainly differs from the plug electrode 14 ( 3 ) in that , instead of having a screw - like inner electrical conductor , the electrical lead 18 , itself , is removably disposed within the plug body 120 . in particular , the plug body 120 comprises a lumen 136 extending vertically up the shaft 62 and then horizontally out of the head 124 . the electrical lead 18 , which carries an electrode 132 at its distal end , is configured to firmly slide within the lumen 136 , such that the electrical lead 18 can be threaded into an opening 134 at the head 124 until the electrode 132 distally protrudes from the distal end of the plug body 120 . to this end , the diameter of the lumen 136 is substantially equal to the outer diameter of the electrical lead 18 . the distal end of the shaft 122 of the plug body 120 and the distal end of the electrical lead 18 are preferably blunt to ensure that the cortical brain tissue 5 is not pierced or otherwise damaged . the plug electrode 14 ( 4 ) further comprises a tightening screw 138 that can be screwed into the top of the head 124 to firmly secure the electrical lead 18 once it is confirmed that the electrode 132 is in its proper place . to ensure that the cranium 3 is electrically insulated from the plug electrode 14 ( 4 ) and to minimize noise from electromyograms ( emgs ) during recording , the plug body 120 may be composed of an electrically insulative material , and the electrical lead 18 , with the exception of its distal end , can be coated within an electrically insulative material . as shown , the exposed electrode 132 is recessed within the burr hole 8 , and therefore , does not extend into the cranial cavity . although the exposed electrode 132 is not in direct contact with the cortical brain tissue 5 , like the aforementioned electrode array 32 , it is indirectly electrically coupled to the cortical brain tissue 5 via the dura mater 6 and cerebrospinal fluid 7 . thus , the electrode 132 may potentially convey electrical stimulation energy ( originating from the electronics device 16 ) to the cortical brain tissue 5 or receive electrical signals from the cortical brain tissue 5 for subsequent processing in the electronics device 16 . it should be appreciated that the plug electrode 14 ( 4 ) is particularly advantageous in that the position of the electrode 132 within the burr hole 8 may be adjusted simply by sliding the electrical lead 18 within the lumen 136 of the plug body 120 when the tightening screw 138 is loosened . thus , the electrode 132 can be properly positioned regardless of the thickness of the cranium 3 . referring to fig8 , yet another embodiment of a minimally invasive plug electrode 14 ( 5 ) will now be described . the plug electrode 14 ( 5 ) is similar to the plug electrode 14 ( 4 ) illustrated in fig7 in that it comprises a plug body 140 capable of sliding receiving the electrical lead 18 . thus , the plug body 140 comprises a shaft 142 configured for being mounted within the burr hole 8 and a head 144 that is externally accessible when the plug body 140 is anchored within the burr hole 8 . the plug body 140 comprises a lumen 156 extending vertically up the shaft 142 . the electrical lead 18 , which carries an electrode 152 at its distal end , is configured to firmly slide within the lumen 156 , such that the electrical lead 18 can be threaded into an opening 154 at the head 144 until the electrode 152 distally protrudes from the distal end of the plug body 140 . to this end , the diameter of the lumen 156 is substantially equal to the outer diameter of the electrical lead 18 . the distal ends of the plug base shaft 62 and electrical lead 18 are preferably blunt to ensure that the cortical brain tissue 5 is not pierced or otherwise damaged . the plug electrode 14 ( 5 ) also comprises a tightening screw 158 that can be screwed into the top of the head 144 to firmly secure the electrical lead 18 once it is confirmed that the electrode 152 is in its proper place . to ensure that the cranium 3 is electrically insulated from the electrically conductive plug body 140 and to minimize noise from electromyograms ( emgs ) during recording , the plug body 140 may be composed of an electrically insulative material , and the electrical lead 18 , with the exception of its distal end , can be coated within an electrically insulative material . as shown , the exposed electrode 152 is recessed within the burr hole 8 , and therefore , does not extend into the cranial cavity . although the exposed electrode 152 is not in direct contact with the cortical brain tissue 5 , like the aforementioned electrode array 32 , it is indirectly electrically coupled to the cortical brain tissue 5 via the dura mater 6 and cerebrospinal fluid 7 . thus , the electrode 152 may potentially convey electrical stimulation energy ( originating from the electronics device 16 ) to the cortical brain tissue 5 or receive electrical signals from the cortical brain tissue 5 for subsequent processing in the electronics device 16 . it should be appreciated that the plug electrode 14 ( 5 ) is particularly advantageous in that the position of the electrode 52 within the burr hole 8 may be adjusted simply be sliding the electrical lead 18 within the lumen 156 of the plug body 140 when the tightening screw 158 is loosened . thus , the electrode 152 can be properly positioned regardless of the thickness of the cranium 5 . the plug electrode 14 ( 5 ) mainly differs from the plug electrode 14 ( 4 ) in that it uses a different fastening means for anchoring the plug body 140 within the burr hole 8 . in particular , the plug electrode 14 ( 5 ) comprises a series of annular ribs 146 formed on the external surface of the plug body 140 , such that when the plug electrode 14 ( 5 ) is inserted within the burr hole 8 , the annular ribs 146 grasp the burr hole 8 , thereby firmly securing the plug electrode 14 ( 5 ) within the burr hole 8 . unlike the plug electrode 14 ( 4 ), no tool is needed to anchor the plug electrode 14 ( 5 ) into the burr hole 8 . the electrical lead 18 also comprises a plurality of vertical ribs 158 ( as best illustrated in fig9 ) that facilitate engagement within the lumen 156 of the plug body 140 . although particular embodiments of the present inventions have been shown and described , it will be understood that it is not intended to limit the present inventions to the preferred embodiments , and it will be obvious to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the present inventions . thus , the present inventions are intended to cover alternatives , modifications , and equivalents , which may be included within the spirit and scope of the present inventions as defined by the claims .

US-93536807-A

package for elongated sharp - edged objects , in particular for tools useful for surgical applications , which are secured in a fixed position in a package consisting at least partially of plastic , wherein the package comprises an a first enlarged package part which defines an interior into which the object that is to be protected and secured protrudes with its sharp edges in a noncontact manner and a second package part in which the shaft of the object is accommodated and held in a fixed position by holding elements .

fig1 and 2 as well as fig3 and 4 show a first embodiment of a package that includes a top part 5 , which may be pivotably connected to a bottom part 6 by a lateral pivot axis 2 and a film hinge 3 arranged therein . the pivot axis 2 is shown with dashed lines in fig1 , where it can be seen that the top part 5 may be designed to be pivotable with respect to the bottom part 6 in the direction of the arrow 31 . a snap lock 4 may be arranged opposite the pivot axis 2 between the top part and the bottom part ( 5 , 6 ), so that the two package parts ( 5 , 6 ) can be releasably locked together by means of the snap lock 4 . fig5 shows as an exemplary embodiment of a snap lock an opening strap 25 , which may be attached in a flexible , elastic manner to the one side of the top part 5 and may engage in the locked condition through a latch 27 situated on the bottom part 6 . the opening strap 25 may be operated in the direction of the arrow 26 , so that the top part 5 can be pivoted upward in the direction of the arrow 28 away from the bottom part 6 in the pivot axis 2 . instead of a snap lock 4 , all other releasable closures may of course also be used such as , for example , pushbuttons , hook - and - loop closures , magnetic closures or closures , in which tooth elements in the form of rows of teeth oriented in the longitudinal direction engage with a protrusion engaging in the rows of teeth . such a snap lock with intermeshing rows of teeth is illustrated in the exemplary embodiment according to fig4 a . furthermore , fig4 a shows that in comparison with fig4 , a pivot bearing 24 may be formed by the fact that the top part 5 engages with a protruding journal in a respective slot - shaped receptacle in the bottom part 6 , thereby forming a pivot bearing . fig4 shows a means of securing the film hinge 3 , such that a securing strap 22 which engages with its free lower end in a recess 23 provided in the bottom part 6 may be arranged on the top part . thus , there is an additional securing device for the film hinge 3 . likewise the load on the film hinge 3 can be relieved by this securing strap 22 . the presently disclosed invention is of course not limited to the arrangement of a securing strap 22 on the top part and conversely in the arrangement of a recess 23 in the bottom part . all the aforementioned embodiments , as well as the embodiments to be mentioned later , also function in a kinematic inversion . consequently , the terms “ top part 5 ” and “ bottom part 6 ” as well as all the mutually supplementing parts mentioned in this context are to be understood as interchangeable and having equivalent meanings . the package 1 may consist essentially of two regions in the direction of the longitudinal extent of an object 8 to be secured : a front part 20 with an interior 11 having a larger volume in comparison with the volume of the object protruding therein , and a smaller holding part 12 which is smaller by comparison and is suitable for accommodating the shaft 9 of the object 8 that is to be secured in a frictionally engaged manner . in addition to this friction - locking method of securing the shaft 9 of the object 8 to be secured , additional form - fitting connections may also be provided , holding the object 8 in a form - fitting manner at additional locations , such as the recesses according to fig1 to 19 , for example . in the exemplary embodiment shown herein according to fig1 and 2 , the holding elements 7 , which are opposite one another on the inside of the top part 5 and on the inside of the bottom part 6 , and are shown as elastomerically deformable plastic ribs or sheets , may be in one piece with the material and may be connected to the plastic of the top part 5 and the bottom part 6 of the package . in embodiments , this is a two - component material formed from different soft plastic components . consequently , the retaining elements may consist of a tpe ( thermoplastic elastomer ), for example , while the other parts of the package 1 may consist of a polypropylene suitable for a film hinge . fig4 and 4 a show that the object 8 may be exposed when the two package parts ( 5 , 6 ) are flipped open and the object can thus be gripped by its shaft , for example , and removed . however , this type of packaging prevents any contact of the sharp - edged blade with the surfaces of the interior 11 . the object can be gripped only by the shaft . it is important that the dimensions of the interior 11 have been selected to be so large in comparison with the dimensions of the object protruding into it that the blade 10 of the object 8 to be secured is kept free of any contact with the surfaces of the interior 11 . thus , the blade 10 protrudes into the interior 11 in a free - standing accommodation without there being any risk that it will come into contact with any surface of the interior 11 , even if the package is displaced sharply , such as if the package falls to the ground . fig3 shows as another exemplary embodiment that the package 1 may be formed by two regions and consist of a bottom part 6 which is connected to a top part 5 by a pivot axis 2 . the package may also consist of more than two regions or two parts . in the exemplary embodiment shown according to fig3 , the two parts ( 5 , 6 ) are pivotably joined together and the holding part 12 of the package is additionally designed in two parts and consist of a shaft part 13 and rear flap part 14 connected to it by a bending edge 15 . the elastomerically deformable holders 7 are arranged in the shaft part 13 , and the flap part 14 consists of two parts that can be flipped oppositely from one another in the direction of the arrow 16 by means of bending edges 15 , which can be folded up according to fig3 to thereby expose the shaft 9 of the object 8 being secured , so that the slot 18 of a tool receptacle 17 may be inserted through the coupling opening 36 in the direction of arrow 21 and can be locked in place there . in order to prevent the blade 10 from coming in contact with plastic parts in the securing part 12 , it is provided that the two package parts ( 5 , 6 ) are connected to one another so they can be pivoted in the pivot axis 2 . on opening the package by pivoting it in the pivot axis 2 , the object 8 to be protected may be completely exposed and can be removed without coming in contact with a package surface . the protective package is thus removed from the object to be protected without coming in contact with it , which is gripped by its shaft . in all embodiments , it is important that the blade 10 of the object 8 is protected from contact with parts of the package 1 . there is no risk of injury to the blade or shape edge of the object or to the person removing the object from the package . this is true in particular of the embodiment according to fig3 and fig8 because the shaft 9 of the object 8 to be secured is already freely accessible therein and can be easily removed without any risk of contact between the sensitive blade 10 of the object 8 and the package material . in these embodiments , the additional flap part 14 is omitted because the shaft 9 may be longer than the length of the package . the package 1 , with its snap lock 4 , may be designed so that it can also be operated easily with surgical gloves . fig4 a also shows another embodiment of a snap look which consists of intermeshing sawtooth - like protrusions that can be locked together in any position in height ( or a closing position ). in this case the film hinge 3 may extend in the direction of the transverse extent of the package 1 . this is illustrated in fig6 . fig5 a shows as another embodiment that snap locks 4 a may also be arranged on both sides to design the interior volume of the package and thus also the pressing force in the holding part 12 to be adjustable with respect to the holding elements 7 arranged there . in other words , if the top part 5 is moved in the opposite direction from the direction of the arrow 31 shown here with respect to the bottom part 6 , then the snap lock 4 a arranged on the left side and on the right side may be adjusted accordingly , so that the package volume is increased or decreased . accordingly , the pressing force of the holding elements 7 on the shaft 9 of the object 8 to be held is designed to be adjustable — see the position 6 ′ of the bottom part . fig5 shows as another embodiment that the pressing force of the holding elements 7 can also be achieved by a convex shape and a resulting prestress on the two package parts ( 5 , 6 ). the two parts ( 5 , 6 ) can be produced by the injection molding process , so that they naturally have a convex shape , which results in the holding elements 7 being provided with a bias in the top part 5 and the bottom part 6 ( more precisely in the holding part 12 ). the bias force on the holding elements 7 can thus be prestressed through the shaping of the plastics comprising the top part and the bottom part . in addition , fig5 — in combination with fig8 — shows that a stop edge 35 running in the longitudinal direction and orienting the object 8 to be secured is provided on one or both ends , each in the region of the shaft 9 of the object 8 to be secured , namely in the region of the holding part 12 . such a stop edge 35 may also be arranged on the opposite end . this is also discernible in the section of view according to fig5 . it is also indicated there that the two package parts may be pre - stressed against one another in the direction opposite the direction of the arrow 30 . it is also possible that the curved shape 29 is provided only in the holding part 12 of the package 1 and that the other package parts , in particular the package parts which form the interior 11 , do not have such a curved shape . fig2 also shows that the two package parts may furthermore have a locking hook 32 instead of a snap lock , so that the two package parts according to fig2 are releasably connected to one another in the hold part 12 by the locking hooks 32 . fig5 a shows that the snap lock 4 a , which consists of the saw - tooth intermeshing protrusions , can be opened in the direction of the arrow 33 , so that suitable gripping are also arranged on the bottom side of the snap locks 4 , 4 a . all the figures also show a plane of separation 34 between the top part 5 and the bottom part 6 . the embodiment according to fig6 to 8 shows another implementation of the presently disclosed invention in which the package length is shorter than the length of the object to be secured . the object 8 to be secured protrudes out of the holding part 12 of the package 1 with its shaft 9 in the packaged state according to fig7 . the two package parts ( 5 , 6 ) may be pivotable or can be connected to one another in a releasable manner in general to remove one part , for example , to remove the top part 5 from the bottom part 6 . fig8 shows an embodiment in which the two package parts ( 5 , 6 ) are pivotably connected to one another by means of the film hinge 3 along a longitudinal edge and are assigned to this pivot axis 2 opposite the snap lock 4 . fig9 and 10 show a variety of instruments and objects 8 a , 8 b , indicating that the blades 10 of the objects 8 a , 8 b to be protected can lie in different positions and it is still always ensured that the sensitive blades 10 protrude into the front part 20 of the package 1 without coming into contact with any surfaces . the two package parts ( 5 , 6 ) may be opened in the direction of the arrow 19 and are closed in the opposite direction ( see fig4 and 4 a ). fig1 to 15 illustrate different surface profiles 37 , 38 , 39 , 41 of holding elements 7 , which may be arranged in the holding part 12 of the package 1 , shown in views from above and from the front . fig1 shows a surface profile 37 consisting of individual waves forming upwardly directed tips , so that the shaft 9 of the object to be secured can yield and deform elastically and comes to lie in contact with both sides of the shaft 9 under elastic deforming force . fig1 shows instead of the wavy surface profile 37 a rib - shaped surface profile 38 which is rounded in the direction of the shaft to be secured , so that only the small radii of the surface profile pointing upward are in contact with the bottom side or the top side of the shaft 9 of the object 8 . fig1 shows a modification of a surface profile 39 which consists of individual holding tips which are profiled to be approximately triangular or half - round . fig1 shows a surface profile of a holding element which is also illustrated in fig1 through 5 . fig1 shows as another embodiment a surface profile 41 consisting of rectangular holding tips . instead of the embodiments shown here , other elastomerically deformable holding elements with different surface profiles 37 - 39 and 41 may also be used . the surface profiles shown in the drawings in fig1 through 15 may also be combined . as another exemplary embodiment , fig1 through 19 show an additional form - fitting means of securing the object to be held . in the package , for example , in the top part 5 and / or in the bottom part 6 , additional holding nubs 43 , which engage in recesses 42 on the object 8 are provided . the shape of the holding nubs 43 may be adapted to the shape of the recesses 42 , such that different shapes of recesses 42 are illustrated in fig1 and 19 . the recesses 42 need not necessarily be located in the shaft area of the object to be secured but may also be arranged in other areas of the object 8 to be secured . therefore , a form - fitting receptacle in the holding nubs 43 may additionally be combined with the elastomerically deformable holding elements 7 in the holding part 12 by engagement in the recesses 42 . in another embodiment , the elastomeric holding elements 7 in the holding part 12 may also be omitted entirely and instead only the form - fitting holding elements which are shown in fig1 to 19 and hold in a form - fitting manner the object that is to be secured at any location outside of the sensitive blade 10 in the package and only these are present here . such a form - fitting holder is used in particular when the length of the object to be secured is greater than the package length , for example , as illustrated in fig6 and 7 . in this exemplary embodiment , the shaft 9 protrudes through a slot 44 on the rear side of the holding part 12 of the package 1 . instead of the holding elements 7 shown there , the form - fitting holding elements may also be used with the holding nubs 43 according to fig1 to 19 . it is thus important that the holding nubs 43 are in form - fitting contact with the inside walls of the recesses 42 and that a form - fitting contact is ensured . it is not necessary for the holding nubs 43 to lock in the recesses 42 although this is also possible .

US-201414202344-A

a storage container system comprising an arrangement for adjustable ventilation intended for storing at least one article that is thermally sensitive and / or requires ventilation to the ambient atmosphere . the device includes at least one door and at least one aperture ventilation assembly . the aperture ventilation assembly includes a planar wall aperture array and a corresponding planar shutter aperture array , wherein the sliding relationship between the two arrays results in a plurality of ventilation levels , including a fully open state , and a closed state capable of substantially sealing off the contents of the container from the ambient atmosphere . certain preferred embodiments include a plurality of storage compartments configured within the container &# 39 ; s inner volume wherein each compartment is sealed from one another and possesses its own aperture ventilation assembly for ventilation adjustments .

with reference to the drawings of the present invention , several embodiments pertaining to the communication system and method of use thereof will be described . in describing the embodiments illustrated in the drawings , specific terminology will be used for the sake of clarity . however , the invention is not intended to be limited to the specific terms so selected , and it is to be understood that each specific term includes all technical equivalents that operate in a similar manner to accomplish a similar purpose . terminology of similar import other than the words specifically mentioned above likewise is to be considered as being used for purposes of convenience rather than in any limiting sense . in this context , the portable storage container having a means for manually adjustable ventilation may be constructed from a variety of durable materials . preferred embodiments , are substantially fabricated from thermally insulative , rigid type materials so that the portable storage container &# 39 ; s inner storage volume is thermally isolated from the ambient atmosphere when the container &# 39 ; s ventilation level is in the closed state . exemplary preferred class of materials is available from coastal enterprises located at 1925 west collins ave ., orange , calif ., 92863 - 4875 . the materials are available in sheet form and classes include low temp polyurethane precision boards as well as precision board plus pblt — made with green “ eco - friendly ” urethane components . these durable materials possess a closed cell structure to prevent absorption , possess excellent thermal insulation properties , and are easily cut or machined with standard cutting tools . plastic materials suitable for use in the construction of the device are those normally solid , organic polymers that are readily shaped or molded or otherwise fabricated into the desired container form and possess sufficient rigidity . preferably , the polymers are thermoplastic and are relatively inert to those materials which are to be stored or contained within the unit . because of their low cost and superior structural properties , polymers used in structural applications , so - called engineering plastics , present a logical material choice . preferred polymers include : polystyrene , styrene / acrylonitrile copolymers , styrene / butadiene copolymers , styrene / butadiene / acrylonitrile copolymers , rubber modified styrene polymers , and other polymers of monovinylidene aromatic carbocyclic monomers are generally preferred . other polymers which may be suitably employed are acetal plastics such as polyformaldehyde resin , polyolefins such as polyformaldehyde resin , polyolefins such as amides , such as nylon , rigid polyvinyl chloride , polyesters such as poly ( ethylene terephthalate ) acrylic resins such as poly ( methyl methacrylate ), and the like . the polymers , among others , can be formed into the desired shape by conventional forming techniques , e . g ., blow molding , extrusion , rotational molding , and injection molding . it is understood that material selection considerations are dependent on a variety of factors , including : compatibility with the items to be stored , attributes of user ( s ), method of transportation ( e . g . manual transport , hand - cart , automobile ), compatibility expected environmental conditions , device cost considerations , and the like . fig1 illustrates a front orthogonal view of an exemplary portable storage container 100 with the hingedly connected door 102 in the closed state . lock / handle assembly 104 is located on the top center portion of door 102 , and includes lock 106 , and handle 108 for opening door 102 . lock 106 is controlled by key 1702 ( depicted in fig1 ) and controls locking arm 206 ( depicted in fig2 ) which impermanently engages strike plate 208 at the discretion of the user ( s ) providing locked and unlocked states for door 102 . the bottom edge portion of door 102 is fastened to the upper portion of continuous hinge ( piano hinge ) 114 by fasteners ( screws ) 116 ; whereas the lower portion of continuous hinge ( piano hinge ) 114 is fastened to the front edge of bottom wall 216 in like manner . holding magnet ( left side ) 110 and holding magnet ( right side ) 112 both function as convenience accessories for temporarily holding steel key 1702 ( as depicted in fig1 ), or the like magnetic material . feet 120 are positioned about the four corners of bottom wall 216 to provide a compliant interface between bottom wall 216 and a receiving surface . fig2 illustrates open door configuration 200 , depicting a perspective front view of exemplary portable storage container 100 with hingedly connected door 102 in the open state . inner storage volume 210 is configured from the following edgedly connected planar surfaces : door ( front wall ) 102 , top wall 212 , back wall 214 , bottom wall 216 , left side wall 218 ( overlaid with left shutter member 226 ), and right side wall 220 ( overlaid with right shutter member 224 ). retractor cable assembly 204 includes retractor cable 205 , wherein one end of cable 205 is retractably secured to top wall 212 via cable assembly 204 , while the opposing end of cable 205 is fastened to door 102 via door fastener 222 . the retracting system provides a means for a controlled opening and / or assisted closing of hingedly connected door 102 . more specifically , controlled opening will prevent door 102 from dropping open or slamming , by dampening the opening motion . the pulling force associated with retractor cable 205 on door 102 additionally provides a user with an assisted closing feature . door travel limiters 202 are two fixed length cords with one of the ends fastened to door 102 via fasteners 222 and opposing ends fastened to the upper - front portion of both left side wall 218 and right side wall 220 . door travel limiters 202 limit the range of motion of door 102 to approximately ninety degrees , which enables door 102 to function as a temporary storage surface or shelf when extended to the open position . fig3 illustrates storage volume detail 300 , depicting a perspective view of the right side wall 220 portion of inner storage volume 210 . by way of example , but not limitation , features and functions of right side wall 220 are mirrored on the left side wall 218 . right side wall 220 and right shutter member 224 are component members comprising right wall aperture ventilation assembly 500 ( depicted in fig5 ). right side wall 220 possesses wall aperture array 304 comprised of a plurality of wall apertures 302 . wall apertures 302 each possess a wall aperture shape and a wall aperture size . by way of example , but not limitation , the wall aperture shape is configured as an oval slot , wherein the wall aperture size dictates slot parameters such as length , width , open area , and the like . in preferred embodiments , wall apertures 302 are symmetrically disposed about right side wall 220 , thereby providing an aesthetically pleasing , functional wall aperture array 304 . fastened onto right side wall 220 are wall magnetic fastening material ( rear member ) 306 and wall magnetic fastening material ( front member ) 308 , both fastening materials shall be referred to as second magnetic fastening materials . fig4 illustrates a front view of right shutter member 400 . right shutter member 400 possesses a right shutter aperture array 404 comprised of a plurality of right shutter apertures 402 . shutter apertures 402 each possess a shutter aperture shape and a shutter aperture size . by way of example , but not limitation , the shutter aperture shape is configured as oval slots , wherein the shutter aperture size dictates slot parameters such as length , width , open area , and the like . in preferred embodiments shutter apertures 402 are symmetrically disposed about right shutter member 224 , thereby providing an aesthetically pleasing , functional shutter aperture array 404 . fastened onto right shutter member 224 , are shutter magnetic fastening materials 406 a , 406 b , 408 a , and 408 b ; these four fastening materials shall be referred to as first magnetic fastening materials . fig5 illustrates right wall aperture ventilation assembly 500 , depicting a detailed perspective view of right shutter member 224 superjacently engaging right side wall 220 . right shutter member 224 and right side wall 220 possess a coordinated sliding relationship with each other . right shutter member 224 is held onto right side wall 220 by the interactive magnetic forces between the first and second magnetic fastening materials . these magnetic forces ( attracting ) additionally generate a biasing force urging right shutter member 224 onto right side wall 220 creating frictional engagement that encourages sealing between the two surfaces . shutter aperture array 404 is substantially identical to wall aperture array 304 , both possessing oval slots having the same aperture size , coordinate locations , and so forth , to enable all shutter apertures 402 to align with corresponding wall apertures 302 when shutter aperture array 404 is slid to the open position . with shutter aperture array 404 in the open position , inner storage volume 210 can intake and / or exhaust air to the outside environment or ambient atmosphere . sliding shutter aperture array 404 to the closed position will misalign all shutter apertures 402 with respect to corresponding wall apertures 302 , thereby sealing off inner storage volume 210 from the ambient atmosphere preventing or greatly reducing air intake and / or exhaust . depicted is user 502 slidingly positioning shutter member 224 from inner storage volume 210 . the biasing force urging right shutter member 224 onto right side wall 220 is a continuous fastening force , present when right side wall 220 is experiencing sliding motion , in addition to static positions . this dynamic fastening system provides an effective means for slidingly holding said shutter member 224 against said wall aperture array 304 located on right side wall 220 . additonally , the dynamic fastening system does not require a slot or rail system to slidingly hold shutter member 224 in place . therefore shutter member 224 can be easily detached and removed by a user by merely overcoming the magnetic holding forces . such a configuration enables quick , simple disassembly / assembly to facilitate device cleaning . fig6 illustrates left wall aperture ventilation assembly 600 , depicting an external view of left side wall 218 . note that the depicted left wall aperture ventilation assembly 600 is a substantial mirror image of the aforementioned right wall aperture ventilation assembly 500 and associated drawings and explanations , with the exception of the added external shutter control assembly 604 feature . otherwise , all components comprising right wall aperture ventilation assembly 500 have equivalent left wall aperture ventilation assembly 600 components , which function in like manner ; the component relationships , dimensions , and the like , are to be regarded as comparable for the present discussion . external shutter control assembly 604 provides a means for adjusting left shutter member 226 from the outside of the container . the left shutter member 226 can be adjusted with the container in any state ( i . e . door 102 in the open , closed , or closed and locked states ). external shutter control assembly 604 includes control knob 606 , and control knob slot 608 having an open position located at the far left and an opposing closed position located at the far right . control knob 606 is securely fastened to left shutter member 226 ; knob 606 can be positioned by a user along any point between and including the open and closed positions depicted on control knob slot 608 . the positioning of control knob 606 along slot 608 determines the amount of airflow 610 permitted through every wall aperture 602 ( comprising array of wall apertures 602 ) simultaneously . left wall aperture ventilation assembly 600 depicts control knob 606 in the open position , resulting in maximum airflow 610 through array of wall apertures 602 . a detailed drawing further elaborating on the maximum airflow 610 configuration is depicted in fig9 . fig6 additionally depicts shoulder strap assembly 612 , which provides a user a convenient means for carrying the container . shoulder strap assembly 612 is particularly useful when the container is storing heavy items , e . g . liquids . shoulder strap assembly 612 is configured to be user removable . fig7 illustrates left wall aperture ventilation assembly 700 , depicting an external view of left side wall 218 . depicted is control knob 606 positioned mid - way between the open position and a closed positions disposed on control knob slot 608 , resulting in a reduced airflow 702 condition . a detailed drawing further elaborating on the reduced airflow 702 configuration is depicted in fig1 . fig8 illustrates left wall aperture ventilation assembly 800 , depicting an external view of left side wall 218 . depicted is control knob 606 positioned in the closed position located on the far left portion of control knob slot 608 , resulting in a zero or no airflow 802 condition where the inner storage volume is substantially sealed off from the ambient atmosphere . a detailed drawing further elaborating on the no airflow 802 configuration is depicted in fig1 . fig9 illustrates a fully open ventilation level 900 . fig9 depicts the ventilation details associated with left wall aperture ventilation assembly 600 , depicting control knob 606 in the open position , resulting in maximum airflow 610 . wall aperture 602 is in full alignment with left shutter aperture ( analogous to right shutter aperture 402 of fig4 ). fig1 illustrates a partially open ventilation level 1000 . fig1 depicts the ventilation details associated with left wall aperture ventilation assembly 700 , depicting control knob 606 positioned mid - way between the open position and a closed positions located on control knob slot 608 , resulting in a reduced airflow 702 condition . wall aperture 602 is in partial alignment with left shutter aperture ( analogous to right shutter aperture 402 of fig4 ). depicted is a portion of left shutter member 226 material blocking wall aperture 602 resulting in reduced airflow . fig1 illustrates a no ( zero ) ventilation level 1000 condition . fig1 depicts the ventilation details associated with left wall aperture ventilation assembly 800 , depicting control knob 606 positioned to the closed position located on control knob slot 608 , resulting in a no ( zero ) airflow 802 condition . wall aperture 602 is in complete misalignment with left shutter aperture ( analogous to right shutter aperture 402 of fig4 ). depicted is a left shutter member 226 material completely blocking wall aperture 602 resulting in a no ( zero ) airflow 802 condition . fig1 illustrates storage volume detail 1200 , depicting a perspective view of left side wall 218 . this container embodiment includes side wall shelf support member 1204 and back wall shelf support member 1202 for supporting a removable shelf so to provide a means for efficiently utilizing the container &# 39 ; s inner storage volume . fig1 illustrates inner storage volume double shelf support system 1300 , depicting a means for supporting a lower and an upper self . this container embodiment includes side wall shelf support member 1204 and back wall shelf support member 1202 for removably supporting an upper shelf ; and side wall shelf support member 1304 and back wall shelf support member 1302 supporting removable lower shelf 1306 . fig1 illustrates a multi - compartment portable storage container 1400 , comprising a lid 1402 hingedly connected to body 1404 , where lid 1402 is in the closed state . lock assembly 1406 , includes latching arm 1406 a , which is pivotally attached to lid 1402 , mating strike plate 1406 b further comprising latching arm release 1406 c and key hole 1406 d . lock assembly 1406 provides a means for locking lid 1402 to body 1404 to prevent unauthorized access to storage container 1400 . external shutter control assembly 1410 corresponds to left compartment wall aperture array 1408 further depicting a sealed or a no ( zero ) ventilation level comparably depicted in fig1 . external shutter control assembly 1414 corresponds to right compartment wall aperture array 1412 further depicting a sealed or a partially open ventilation level comparably depicted in fig1 . fig1 illustrates a multi - compartment portable storage container 1500 , depicting a perspective front view of an exemplary container with lid 1402 hingedly connected to body 1404 ; where lid 1402 is in the open state . left compartment inner storage volume 1514 and right compartment inner storage volume 1516 are partitioned by separation wall 1504 ; in preferred embodiments , separation wall 1504 is configured from a thermally insulative material . left compartment inner storage volume 1514 possesses an aperture ventilation assembly that includes a left shutter member 1506 that cooperates with left compartment wall aperture array 1408 to provide a means for adjustable ventilation . left shutter member 1506 is externally controllable using external shutter control assembly 1410 via control knob 1610 . likewise , right compartment inner storage volume 1516 possesses an aperture ventilation assembly that includes a right shutter member 1508 that cooperates with right compartment wall aperture array 1412 to provide a means for adjustable ventilation . right shutter member 1508 is externally controllable using external shutter control assembly 1414 via control knob 1620 . in this particular embodiment , lid 1402 includes a lid inner storage volume 1510 ; for exemplary purposes , thermos 1512 is shown housed in lid inner storage volume 1510 . it is understood that other embodiments containing a lid inner storage volume 1510 can include one or more aperture ventilation assemblies . removable lid bottom wall 1502 functions as a thermal barrier such that inner storage volumes 1514 , 1516 , and lid inner storage volume 1510 are thermally isolated from each other when the multi - compartment portable storage container 1500 is in the closed or assembled state as shown in fig1 . fig1 illustrates a pair of shutter members 1600 ; comprising left shutter member 1506 , right shutter member 1508 , used in left compartment inner storage volume 1514 and right compartment inner storage volume 1516 , respectively . left shutter member 1506 includes a plurality of left shutter apertures 1606 that forms a left shutter aperture array 1608 configured to cooperate and function as a shutter with left compartment wall aperture array 1408 . functioning in like manner to aforementioned embodiments , aperture ventilation assemblies include attached magnetic fastening materials 1602 , 1604 that are magnetically attracted to corresponding magnetic materials located and fastened within the respective storage compartment ; and control knob 1610 provides a means for externally controlling left shutter member 1506 . likewise , right shutter member 1508 includes a plurality of right shutter apertures 1616 that forms a right shutter aperture array 1618 configured to cooperate and function as a shutter with right compartment wall aperture array 1412 . functioning in like manner to aforementioned embodiments , aperture ventilation assemblies include attached magnetic fastening materials 1612 , 1614 that are magnetically attracted to corresponding magnetic materials located and fastened within the respective storage compartment ; and control knob 1620 provides a means for externally controlling right shutter member 1508 . fig1 illustrates a refrigerator appliance 1700 , depicting a portable storage container 100 stored within . shown is key 1702 ( cooperates with lock / handle assembly 104 ), removably stored on holding magnet 112 for convenience . refrigerator appliance 1700 provides an example of a controlled ambient atmosphere 1704 . portable storage container 100 containing items that are to be kept cold , e . g . certain medicines , foods , and the like ; would have all aperture ventilation assemblies set to the fully open ventilation level ( as shown in fig6 and 9 ) to permit the cool ambient atmosphere 1704 produced by refrigerator appliance 1700 to freely enter container 100 . when portable storage container 100 is removed from refrigerator appliance 1700 , the aperture ventilation assemblies on the container should be set to the fully closed ventilation level 1100 ( as shown in fig8 and 11 ) to maintain the cool ambient atmosphere within , and reduce / prevent stored items from interacting with warm air temperatures found outside of the refrigerator appliance 1700 . the process is reversed when container 100 is returned to an appropriate cool ambient atmosphere .

US-201213533767-A

it is an object of the present invention to provide a hand - held radiation device for treating bacterial , viral , fungal and parasitic infections found on the skin of a patient and in various of the body &# 39 ; s anatomical orifices . the device of the invention is particularly effective in treating methicillin resistant staphlococcus aureus colonies in the nose and on the skin surface of a patient . the device includes a reusable uv light source and a uv - transparent disposable cover for covering the probe portion of the reusable uv light source . the device further includes a combination probe cover ejector and disabling assembly for safely ejecting the probe cover after use without the necessity of the operator touching the contaminated probe cover and for disabling the device if the cover is not in place over the probe .

referring to the drawings and particularly to fig1 through 5 , one form of the novel irradiation device of the invention for treating bacterial colonies on the skin of the patient and in various body orifices , such as the mouth , the urethra , the vagina , the rectum and the external ear canal is there shown and generally designated by the numeral 14 . this form of the device here comprises a housing 16 having a hollow , generally cylindrical - shaped body portion 18 and an elongated probe portion 20 that is connected to housing portion 18 and extends outwardly therefrom . probe portion 20 , which has a forward irradiating portion 20 a and rearward portion 20 b , is connected to the forward hub portion 18 b of body portion 18 in the manner shown in fig1 and 5 . operably associated with probe 20 is a conventional radiation source 22 for emitting uv radiation in a direction toward the elongated probe portion 20 a . disposed within housing 16 is a timer 24 , the function of which will presently be described ( fig5 ). removably connected to the forward irradiating portion of the elongated probe is a uniquely constructed , substantially uv radiation - transparent probe cover 26 . as best seen in fig3 , 7 and 8 , probe cover 26 includes a generally tubular - shaped forward portion 28 that covers the forward portion of the probe and a generally tubular - shaped , slotted connector portion 30 that is telescopically receivable over the forward hub portion 18 b of housing portion 18 . forward portion 28 can be constructed from polypropylene , certain varieties of teflon that are transparent to uv light in the uv - c range ( 200 - 280 nm ) and other amorphous fluropolymers . disposed intermediate forward portion 28 and connector portion 30 is an enlarged diameter radiation shield 32 that functions to shield the user &# 39 ; s hand from radiation ( see also fig8 and 9 ). as indicated in fig8 , shield 32 is constructed from a uv radiation - opaque material , such as polycarbonate , polystyrene and like materials that will effectively shield the surrounding tissue so that only the target areas of the patient will receive the germicidal uv energy . it is to be understood that the unique design of the probe cover as shown in the drawings not only provides protection for the uv light probe 20 and a method of preventing probe contamination , the probe also sets the proper distance from the light source to the tissue being exposed to the uv radiation . this factor is especially important because the energy transmitted to the tissue decreases exponentially with the distance between the light source and the tissue surface . in this regard , it should be appreciated that in carrying out the method of the invention for treating bacterial , viral , fungal , and parasitic infections in the patient &# 39 ; s tissue , pre - setting the distance between light source and tissue in this manner is quite different than simply holding a uv light over the tissue as this approach does not stretch the tissue as does the uv light probe 20 . in accordance with one form of the method of the invention , the tissue is uniformly stretched so that the tissue is uniformly exposed to the light energy which is critical to the successful germicidal use of uv light as it is a ‘ line of sight ’ process . creases or folds can hide bacteria from exposure to the light energy , preventing them from receiving a lethal dose of irradiation . additionally , the probe covers of the apparatus are designed so that they slightly dilate the lumen of the orifice into which they are inserted , such as the vagina and rectum . in accordance with the method of the invention , this dilation sets the distance from light source to tissue surface very accurately as the dilated tissue conforms to the probe cover , giving uniform coverage of the uv light energy to the tissue to be treated . carried by housing 16 is switching means for controllably energizing the source of uv radiation 22 , which here comprises a conventional , readily commercially available uv - generating lamp . in the present form of the invention this switching means , which comprises a part of the electrical circuitry of the invention ( see fig5 ), is provided in the form of a conventional , readily commercially available , one - touch activator switch 34 . switch 34 is mounted on the exterior wall 16 c of the housing 16 ( fig1 ) and , as shown in fig4 and 5 , is operably interconnected in a conventional manner with a source of electrical power 36 and with the uv radiation source 22 via a conventional transformer 33 , a conventional relay 35 , the timer 24 and the novel disabling means of the invention , the character of which will presently be described . timer 24 , which ensures that the tissue is irradiated for a predetermined period of time , is here provided in the form of a conventional , readily commercially available , adjustable timer that can be pre - set to control the length of time that the uv radiation source remains energized after the circuit is closed . radiation source 22 , timer 24 , switch 34 , relay 35 and transformer 36 are interconnected within the electrical circuitry in a manner well understood by those skilled in the art . an important feature of the present invention is the provision of a novel combination cover - ejecting means and safety - disabling means . the cover - ejecting means permits the operator to safely eject the cover after it becomes contaminated without touching the cover . the novel safety - disabling means here functions to prevent energizing the uv radiation source by the switching means of the invention unless the probe cover 26 is correctly in position over the probe 20 . in the present form of the invention this novel combination cover - ejecting means and safety - disabling means comprises an assembly generally designated by the numeral 40 that is carried by housing 16 in the manner best seen in fig2 and 5 . in this embodiment of the invention , assembly 40 comprises an ejector member 42 that is movable by portion 30 of the cover 20 from a first extended position shown in fig2 to a second retracted position shown in fig5 . with the ejector member having been moved by the rim portion 30 a of the cover ( see fig3 , 4 and 5 ) into the second retracted position shown in fig5 , the electrical circuit between points 44 and 46 is completed so that the source of radiation can be energized by the operation of switch 34 . once energized , the uv radiation source will remain in its energized state for the period of time set on the timer 24 . at the expiration of this time , the uv energy source will be automatically de - energized and the probe cover can be safely ejected from the hub portion 18 b of the housing . it is to be noted that as the probe cover is ejected from the hub portion 18 b of the housing , the ejector member is urged by the biasing means , or spring 48 , into the extended position shown in fig2 , thereby breaking the electrical circuit between points 44 and 46 so that the source of radiation 22 cannot be re - energized by the operation of switch 34 . on the other hand , as can be seen by referring to fig2 and 5 , movement of the ejector member toward its retracted position by positioning the cover 26 over the probe 20 in the manner shown in fig4 and 5 , will once again complete the electrical circuit between points 44 and 46 . movement of the ejector member into the retracted position shown in fig5 will also move a finger - engaging ejector slide assembly 49 , which is slidably connected to housing 16 , rearwardly of the housing against the urging of spring 48 . finger - engaging ejector slide assembly 49 , which comprises a part of the cover - ejecting means of the invention , includes a finger - engaging ejector slide 52 and an integrally formed ejector frame 54 . portion 54 a of ejector frame 54 is in operable engagement with spring 48 , while portion 54 b of the frame is in operable engagement with ejector member 42 . with this construction , after the irradiation treatment has been completed , the contaminated cover can be readily ejected from the hub portion 18 b by merely sliding the finger - engaging ejector slide 52 forwardly of the housing . in this regard , as the finger - engaging ejector slide 52 moves forwardly , the ejector member 42 will be caused to move toward its extended position and , in so doing , will safely eject the contaminated cover from the hub portion 18 b of the housing . in this way , the operator can safely and conveniently eject the contaminated cover into an appropriate disposal container without touching it . in using the device of the invention to carry out the method of the invention , the user first positions a clean probe cover 26 over the probe in the manner shown in fig4 and 5 . this done , timer 24 is set and the tip portion of the cover is inserted into the body orifice , such as the patient &# 39 ; s nostril , in the manner illustrated in fig1 for a timed application to the nose of germicidal uv energy . turning to fig6 , an alternate form of the apparatus of the invention is there shown and generally designated as 56 . this alternate form of the invention is identical in construction and operation to the embodiment of fig1 through 5 , save for the use of a different source of electrical power . as depicted in fig6 , where like numerals have been used to identify like components , the source of electrical power here comprises a plurality of conventional , appropriately interconnected batteries 58 . batteries 58 are interconnected with the electrical circuitry in the manner shown in fig6 and provide power to the uv energy source 22 . for treatment of skin lesions , the user replaces the probe cover 26 of the apparatus with an appropriately sized and shaped skin contact cover 60 of the character shown in fig1 and 12 . substantially uv radiation - transparent probe cover 60 , which is similar in construction and operation to cover 26 , here comprises a generally tubular - shaped forward portion 62 that covers the forward portion of the probe and a generally tubular - shaped , slotted connector portion 64 that is telescopically receivable over the forward hub portion 18 b hub of housing portion 18 . forward portion 62 , which includes a tip cover portion 62 a , can be constructed from polypropylene , certain varieties of teflon that are transparent to uv light in the uv - c range ( 200 - 280 nm ) and other amorphous fluropolymers . disposed proximate tip portion 62 a is an enlarged diameter radiation shield 66 that functions to shield the user &# 39 ; s hand from radiation ( see fig1 and 12 ). as before , shield 66 is constructed from a uv radiation - opaque material , such as polycarbonate , polyethylene and like materials that will effectively shield the surround tissue so that only the target areas of the patient will receive the germicidal uv energy . the alternate form of the invention shown in fig1 is identical in construction and operation to the embodiment of fig1 through 5 , save for the use of the differently configured probe cover 60 . in certain instances , germicidal uv energy may be selectively applied both to various body orifices , such as the nostril , as well as to the skin of the patient using the probe cover 70 illustrated in fig1 of the drawings . probe cover 70 , which is also similar in construction and operation to cover 26 , here comprises a generally tubular - shaped forward portion 72 that covers the forward portion of the probe and a generally tubular - shaped , slotted connector portion 74 that is telescopically receivable over the forward hub portion 18 b hub of housing portion 18 . forward portion 72 , can be constructed from polypropylene , certain varieties of teflon that are transparent to uv light in the uv - c range ( 200 - 280 nm ) and other amorphous fluropolymers . disposed intermediate forward portion 72 and slotted connector portion 74 is an enlarged diameter radiation shield 76 that functions to shield the user &# 39 ; s hand from radiation . as before , shield 76 is constructed from a uv radiation - opaque material such as polycarbonate , polyethylene and like materials that will effectively shield the surrounding tissue so that only the target areas of the patient will receive the germicidal uv energy . having now described the invention in detail in accordance with the requirements of the patent statutes , those skilled in this art will have no difficulty in making changes and modifications in the individual parts or their relative assembly in order to meet specific requirements or conditions . such changes and modifications may be made without departing from the scope and spirit of the invention , as set forth in the following claims .

US-51796306-A

a pair of cooperating catheters are used together to provide rapid access to the left heart for diagnostic or therapeutic interventions . the initial entry point for the catheter pair is the groin . the pair of catheters can be used to carry out an electrographic determination of the location of the fossa ovalis on the septum . features on the catheter system permit quick and reliable confirmation of the catheter location via echo or x - rays . once across the septum the inner catheter is removed from the outer catheter and a standard intervention may be carried out through the lumen of the outer catheter .

the method of using lancer with a companion device will be described . the lancer device is a device to perforate the septum of the heart and dilate that puncture . it is carried in the handle and adapted for sliding motion . it also has electrode connections and functions as a probing electrode . the lancer device has an internal lumen that can support and carry a guide wire . this permits lancer to follow over a guide wire . turning to fig1 lancer generally designated 100 . there is user interface handle 112 . a thumb operated slide 114 is carried in the handle 112 and adapted from sliding motion along the axis 116 of lancer . in operation the thumb slide 114 forces a tang 118 to compress a spring 120 located along and concentric with the axis 116 . motion of the thumb slide 114 toward the distal end of the lancer causes the electrode / needle distal assembly 125 ( fig2 ) to emerge as identified at 126 ( fig3 ) from the casing 122 , as seen in fig2 and fig3 respectively . the distal assembly has three important features . the hypo - tube 128 has series of laser - machined partially circumferential slits typified by slit 130 which cooperate together to render the distal tip assembly flexible in any direction or plane and be compliant with the shape of a companion catheter . the distal tip is cut to form a piercing tip 132 . this tip is electrically coupled via wire 134 to the connector generally designated 136 . the distal sheath casing 122 tapers to a small diameter seen near ref numeral 138 , this tapered shape serves as a dilation surface 138 . fig4 shows the lancer 100 coupled to the companion flexor 200 device . in general the lancer is carried within flexor and they are moved together as a single unit . the lancer is supported by flexor and in general the lancer stiffens the flexor and functions in part as a stylet to help the operation of flexor 200 . fig5 is a top view of the outer catheter flexor 200 showing the appearance of the top of the handle 212 . the flexor sheath 214 extends form the distal end of handle 212 while the control knob 216 is located near the proximal end of the handle . the control knob turns on a control axis 220 defined by axel 224 orthogonal to the flexor axis 218 . in use the physician turns the control knob with his left hand and uses the thumb of the left hand to activate the control button 228 . when this button is depressed as depicted at ref numeral 230 the tooth 232 disengages from lock pinion gear 234 . in the depressed or activated state the motion of the knob is unlocked and the control knob may be turned to steer or flex the distal tip of the device . when released the tooth 232 urged by spring pressure of compression spring 221 . fig8 and fig9 show a cutaway of the interior of the flexor 200 . the pinion 234 engages both rack 236 and rack 238 . rotation of the pinion 234 drives the racks , with each rack driven in the opposite direction . cable anchors 242 and cable anchor 240 are moved with respect to each other providing traction to the pulls wires ( not seen ) that deflect the deflectable distal tip 244 through an arc in a plane . fig1 a shows the deflectable distal tip 244 in its un - deflected state corresponding to the rack positions seen in fig9 . 9 . fig1 b shows the deflectable tip moving through a 180 arc driven by pull wire 246 and pull wire 248 , each connected to its respective cable anchor 240 or 242 . this curvature corresponds to the rack positions seen in fig8 . fig1 c shows an intermediate position corresponding to a deflection of approximately 90 degrees . fig1 shows a side view of the flexor depicting the recess 250 in the handle to educe the profile of the control knob 216 . the construction details of the invention as shown in the preceding figures are that the useable length of the distal tubular section shall be sufficient to reach from a patient &# 39 ; s vascular insertion site , in the groin area , to the left atrium of their heart , typically 50 to 75 centimeters , but may be longer in taller patients . as is well known only the proximal and distal section of the catheters illustrated to facilitate disclosure of the invention and the inventive features in the most proximal and distal areas of the catheters . the inner diameter of the distal tubular section shall be sufficient to accommodate various catheter devices , typically 5 french ( 1 . 65 mm ) to 12 french ( 3 . 96 mm ). the distal tubular section shall be made of a medical grade polymer and may include wire braiding within its wall . the distal tubular section 210 shall have coatings or a biomimetic surface on its patient - contacting surfaces to provide lubricity and / or deter the formation of blood clots . the side port tube shall be made of a medical grade polymer and have an external length of approximately 5 to 20 - centimeters . the mechanical deflection actuator may be configured as a rotatable wheel , rotatable coaxial collar , slide , or lever . the figures depict the control knob actuator 214 as a rotatable wheel , other actuation mechanism may be employed . fig1 shows guider 300 coupled to lancer 100 . fig1 shows that guider 300 provides a faired shaped section providing a torque handle 301 which forms a directional indication . the side port 310 does not cross the torque handle 301 and therefore does not interfere with the use of the torque handle 301 . this arrangement eliminates interference and entanglement with adjacent devices , and mitigates the risks of clot formation on the blood - contacting surfaces of the introducer . also seen in this figure is the most proximal section of a guide wire 101 . referring now to the invention in more detail , in fig1 there is shown the entire guiding vascular introducer device 300 comprised of a distal tubular section 310 that traverses through a proximal handle 314 . in further detail , still referring to the invention of fig1 , distal tubular section 310 has a curved tip section 312 . the handle 314 is further comprised of a side port tube 316 . the external part of the side port tube 316 is located at the distal end of the handle 312 . in the fig1 there is shown a strain relief 320 at the junction of the distal tubular section 310 and handle 314 as well as a canted pass - through aperture 318 for the side port tube 316 to enter the handle 314 . the construction details of the invention are selected such that the useable length of the distal tubular section 310 ; including its curved tip section 312 , shall be sufficient to reach from a patient &# 39 ; s vascular insertion site , in the groin area , to the left atrium of their heart , typically 50 to 75 centimeters , but may be longer in taller patients . the inner diameter of the distal tubular section 310 , including its curved tip section 312 , shall be sufficient to accommodate various catheter devices , typically 5 french ( 1 . 65 mm ) to 12 french 3 . 96 mm ). the distal tubular section 310 , including its curved tip section 312 , shall be made of a medical grade polymer and may include wire braiding within its wall . the distal tubular section 310 , including its curved tip section 312 , shall have coatings on its patient - contacting surfaces to provide lubricity and / or deter the formation of blood clots . the side port tube 316 shall be made of a medical graced polymer and have an external length of approximately 5 to 20 centimeters . the handle 314 shall be a length sufficient to efficiently manipulate the introducer with the thumb and 3 - 5 fingers , typically between 3 - 5 centimeters . furthermore , the handle 314 shall be of shape that provides an intuitive directional indicator that is in plane with the curved tip section 312 . one such shape is an inverted teardrop , as depicted in fig1 . the handle 314 , including the canted pass - through aperture 318 , shall be made of a medical grade thermoplastic such as polycarbonate , polyethylene , or nylon . referring now to fig1 there is shown the handle 314 , distal tubular section 310 , side port tube 316 , strain relief 320 , canted pass - through aperture 318 , and catheter access port 322 . of note , the side port tube 316 and distal tubular section 310 exit from the handle 314 in a parallel orientation . the construction details of the side port tube 116 , distal tubular section 110 , hemostasis valve housing 124 and mounting stem 118 shown in fig1 are now described . the hemostasis valve housing 324 and integral mounting stem 325 are made of a medical grade thermoplastic such as polycarbonate , polyethylene , or nylon . the distal tubular section 310 is connected to the hemostasis valve housing 324 via injection molding or medical grade adhesive . the entire valve housing 324 shall be contained internally within the handle 314 . the side port tube 316 is connected to the mounting stem 318 via medical grade adhesive . the advantages of the present invention include , without limitation , is that it allows the operator to efficiently torque the introducer during a procedure . typically , the operator only has a small hemostasis valve housing to serve as a torque handle . furthermore , by removing the side port tube from the primary area of device manipulation eliminates the risks of interfering with operation and entangling with , and possibly dislodging , an adjacent device . finally , the addition of a biomimetic coating on the patient - contacting surfaces with mitigate the risks of thrombogenesis , or the production of blood clots , which may lead to such adverse effects as stroke , myocardial infarction , or pulmonary embolus , all of which may be fatal . in broad embodiment , the present invention is a guiding vascular introducer designed with an ergonomic torque handle with features that promote efficient and an improved safety profile . 1 . the physician uses the seldinger procedure to gain access to the femoral vein with a conventional needle puncture . 2 . a long guidewire is inserted through the needle and advanced under fluoroscopic guidance to the svc . 3 . withdraw the needle over the wire leaving the wire in place . 4 . the lancer - flexor or lancer - guilder is advanced into the wound and over the wire to the svc . 5 . pull the gw into the lancer . 6 . rotate the lancer - flexor or lancer - guider to point medial as to be perpendicular to the plane of the interarterial septum . 7 . connect the extension lead form lancer to an emg recording system to display unipolar signal from the distal tip of lancer 8 . while maintaining system alignment via monitoring fluoroscopic imaging , electro gram and optional ultrasound imaging to locate the fossa ovalis . 9 . once the fossa ovalis location has been confirmed hold the system securely and actuate the thumb lever to advance the puncture element through the fossa ovalis , 10 . optionally confirm presence in the left atrium via contrast injection of pressure recording , and advance the gw into the left atrium . 11 . release the thumb lever automatically retracting the puncture element under the force supplied by spring . 12 . advance system into the left atrium while monitoring the electro gram . 13 . holding the system securely release and uncouple lancer and push sheath toward tip of lancer . 14 . with the sheath near the wall of the atrium the lancer is withdrawn form the sheath , and the sheath is aspirated and flushed with heparinized saline . the sheath is now placed for the desired intervention such as ablation or device placement . fig1 shows a state during the method . in the figure the lancer 100 extends beyond d the distal tip of the guiding sheath 214 in this instance of a flexor device . the flexor outer sheath 214 and lancer 100 and the guidewire 101 move together to correspond to steps 1 and 2 of fig2 . fig1 shows a state in the method . in the figure the gw is retracted into the lancer 100 . the system , lancer 100 and flexor 200 are moved to gather and the distal tip of lancer is dragged along the svc to the high septal surface while recording a displaying the electro gram . a typical electro gram in this position is seen in fig1 , where the injury current is a response to the contact with the lancer electrode . this corresponds to steps 5 , 6 and 7 of fig2 . fig1 shows continued motion of the catheter pair an electrographic at fig1 , and visual confirmation of the lancer 100 at the fossa ovalis . fig1 represents real time recording associated with the path depicted in fig1 . it is typical 1 for the time scale of the emg recorder to preserve several seconds of emg so that comparisons can be made over time by the physician . fig2 shows the characteristic electro grams that will be sensed by lancer - flexor or lancer - guider as it navigates the left heart atrium . fig2 and fig2 show the time domain representation of exploratory motions in side of the left atrium . fig2 and fig2 show a flow chart of illustrative steps in the method .

US-201514715788-A

a computed tomography - fluoroscopy method is invented for interventions comprising the steps of combining a floating patient table with a cross - sectional imaging modality for interventions under visual computed tomography control . a handle is installed on the patient table , which is mechanically decoupled from the central control system . during an intervention , the table is brought to a random position , and a single - scan or scan - series is triggered . a light - beam localizer is used for orientation and positioning the single - scan or scan - series .

the invention is based on the object to develop a method and an apparatus by which , for computed tomography - radioscopy for interventions , exact positioning of the patient can be achieved and the number of scans for seeking the needle can be reduced . this object was solved by combining a floating table for the patient with a sectional drawing modality for biopsies under a visual ct check . the apparatus according to the invention comprises a table for the patient , which is included in a scannograph and which is provided with a handle serving for mechanically setting a random position of the table after decoupling from the central control system , and foot switches for triggering a light - beam localiser on the one hand and a single scan on the other hand . the handle newly mounted to the table for the patient enables random positioning of the table after mechanical decoupling from central control . the foot switches are installed in the examination room . they can trigger both the light - beam localiser and a single scan . the term &# 34 ; floating table for the patient &# 34 ; designates a day - bed for the patient , which , with but small mechanical effort , can freely be moved by the examining person along an axis at any time during examination . by &# 34 ; sectional drawing modality &# 34 ; an examination technique is meant which , for visualising an examined object , generates sectional drawings in a plane with a defined lamination thickness . the sectional drawing modalities include computed tomography , ultrasonics or nuclear spin resonance tomography . installation of the handle on the table for the patient enables setting of any table position by hand during surgical treatment . the digitally indicated table position always corresponds to the real position . the light - beam localiser is triggered via an additionally installed foot switch in the examination room just like -- via a further foot switch a single scan ( one lamination ). in order to check the position of the needle , the table is -- without any control from the console -- rapidly moved out of the gantry and into the gantry again so that a fresh single scan can be triggered . surprisingly , it was found that the way of proceeding according to the invention provides , considering all the modifications -- light , single scan following a pressure exerted by the foot , manually movable table with position indicator , and immediate tomogram monitoring , an examination modality by which biopsies can be conducted in more reliable a manner and which will lead to shortened examination periods . since the patient can , by hand , be rapidly moved out of the gantry and into the gantry again -- without having to leave the examination program --, the required amount of time will be considerably reduced . in order that the physician may stay in the room for inspecting the tomogram --, the latter as taken becomes visible to the examining person on a monitor standing in the gantry room . another advantage resides in that the patient is less exposed to radiation since , due to the exact table position achieved in accordance with the invention , superfluous scans for seeking the needle will be avoided . during surgical treatment , the medical personnel will remain in the examination room so as to affect the psyche of the patient in positive manner , if need be . apart from saving time , application of the method and apparatus according to the invention brings about multiplication of the technical possibilities and shows another new way in the field of computed tomography - radioscopy for interventions . further advantages reside in minor exposition to radiation due to reduction of superfluous scans , in higher sensitivity , and , indirectly , in less complications as well -- primarily due to the fact that the frequent manipulation , in case of needle correction , is not required any more under computed tomography - radioscopy . with conventional radioscopy , continuous projection roentgenograms are produced , not permitting any spatial allocation . when doing so , a needle is guided to its destination under constant irradiation insofar as said destination can be made out at all in the projection . the hand of the examining person is mainly situated in the direct optical path . however , movement of the table for the patient -- which , on principle , is possible with most x - ray apparatuses -- will not be brought about since puncturing is carried out under x - ray vision and the represented roentgenogram depicts areas of from 5 by 5 to 35 by 35 cm . insofar , the invention is based on a principle which is different from single - scan triggering and moving the table by hand . a manually operated scannograph has not become known since such a scannograph , because of the usually required lamination examination at defined lamination distances , cannot be realised and is of no clinical relevance . the combination of a floating table with a sectional drawing modality is new . moreover , it would make sense only for biopsies under a visual ct check . the invention shall be explained in detail on the basis of one embodiment . the table 1 for the patient p is equipped with a handle 2 enabling the table to be taken to a random position after mechanical decoupling from central control 3 . the digital indication of the table position is not affected thereby . after the patient p has been prepared in the usual way , the physician , subsequently to switching on of the light - beam localiser 4 via an additionally installed foot switch , 5 can now exactly position the table 1 within the sectional drawing modality 9 . then , a single scan ( one lamination ) will be triggered in the examination room via a second foot switch 6 . four seconds later , the tomogram will appear on a monitor 7 ; it will appear after one second , provided that all additional filters and subsequent tomogram processings are done without . the tonogram as taken becomes visible to the examining person on a monitor 7 standing in the gantry room . the physician will remain in the examination room and , during surgical treatment , can affect the psyche of the patient p in positive manner . when the position of the needle has to be checked , the table 1 can rapidly be moved out of the gantry 8 and into the gantry 8 again without any control from the console . thereafter , a fresh single scan can be triggered . the invention being thus described , it will be obvious that the same may be varied in many ways . such variations are not to be regarded as a departure from the spirit and scope of the invention , and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims .

US-77621297-A

an orthodontic bracket wherein an opened channel receiving an orthodontic wire , includes covering element to cover the opened channel , the covering element can be opened to allow a fast and easy insertion of the orthodontic wire into the channel and can be closed and blocked to avoid that the wire goes out from the channel .

the orthodontic bracket of the present invention , will be described in accordance with a preferred embodiment thereof , making reference to the accompanying drawings wherein the same signs and numbers refer to the same parts of the shown drawings , wherein the bracket of the present invention , comprising : a cross - shaped lower base member , comprising a first arm 2 , a second arm 3 , a third arm 4 and a four arm 5 , each having rounded ends and edges evenly distributed ; each having an upper surface 6 and a lower surface 7 having a plurality of undulated slots 8 to receive an adhesive in order to be adhered to a tooth surface ; a tubular member 9 integrally and centrally mounted on the upper surface of the lower base member , having an upper surface to receive a bracket ; a first 11 , a second 12 , a third 13 and a four cut corner 14 , a first 15 and a second lateral side 16 , a first 17 and a second longitudinal side 18 and an upper face 19 ; a lower base 20 , joined to the upper surface of the tubular member ; a main channel 21 opened to the upper face 19 of the bracket and crossing it longitudinally , immediately after of the first 11 and second cut corner 12 , to receive a first orthodontic wire ( not shown ), wherein said main channel 21 has an opened quadrangular - shaped cross section ; a passage 22 longitudinally crossing the bracket , beginning from the third cut corner 13 , and leading at the four cut corner 14 , through which a second orthodontic wire ( not shown ) passes , wherein said passage has a quadrangular cross section ; a first housing 23 longitudinally placed between the first 11 and second cut corner 12 of the bracket and between the lateral side 17 and the main channel 21 in which it leads , having a first 24 and a second lateral wall 25 and a longitudinal wall 26 ; a second quadrangular - shaped housing 27 longitudinally placed between the third 13 and four cut corner 14 of the bracket and between the second longitudinal side 18 and the main channel 21 , wherein it leads , and over the passage 22 , said housing having a first and a second lateral wall , a rear surface and a lower surface , wherein each lateral wall includes a guide channel 28 in an upper portion along of all its length : covering means to cover the main channel 21 , comprising : a main lid 29 to cover the main channel 21 , pivoting on two hinge elements 30 , 30 ′ which form an integral part of the lateral walls 24 and 25 of the first housing and in which it is retained , said lid having an upper surface 31 and a lower surface 32 , a tong 33 at a front portion , opposed where the lid is joined with the hinges 30 , 30 ′, located at the same plane as the lower surface 32 and a quadrangular aperture 34 located in a central portion thereof , said lid 29 completely crossing the main channel 21 but covering it only partially , and wherein the whole of the tongue 33 rest in an end of the lower surface of the second housing 27 when it is at a closed portion ; gripping means for the lid , comprising : a wedge - shaped sliding lid 35 , slide retained on the second housing 27 , and which covers it as a whole , including an upper surface 36 , a lower surface 36 ′, a quadrangular housing “ c ” in its upper surface 36 and a rectangular element 37 directly depending from the lower surface , located at a front portion of the lid 35 , having a lower surface 38 , two lateral walls 39 , 39 ′, a rear surface “ p ” including a housing “ r ” and a front surface 40 , wherein : the front surface 40 includes a rectangular groove 41 and each lateral surface 39 , 39 ′ including a lateral gripping element 42 , 42 ′ each depending directly from a respective lateral surface 39 , 39 ′, and each of which is slide retained in a guide channel 28 of the second housing 27 . each lateral gripping element 42 , 42 ′ presents a rear surface 43 , 43 ′ which are in the same plane as the rear surface “ p ” of the rectangular element , which , together with the lower surface 36 of the sliding lid 35 , form a longitudinal lying “ l ”- shaped lower stop edge . wherein said lid can slide behind of the second housing 27 , until the guide channels 28 allows it and wherein said lid 35 may return sliding forward until the guide channels 28 allows it , to an original closed position wherein the second housing 27 is completely covered . the wedge shape of the slide lid 35 allows that it be adapted to the curved shape of the upper face 19 of the bracket , so that it can maintain an upper face completely smooth when the sliding lid 35 is closed ; pushing means comprising a spring element 44 placed in the second housing 27 , to push said longitudinal lying “ l ”- shaped lower stop edge of the sliding lid 35 , so as to constantly push forward all the sliding lid 35 to the front face 17 of the bracket , this is , forwardly , maintaining it in a closed position , wherein said sliding lid 35 can be slide behind compressing the spring element 44 between the longitudinal lying “ l ”- shaped lower stop edge of the sliding lid 35 and the upper surface of the lower stop wall ; wherein the main lid 29 remains gripped in a closed position because its tong 33 is placed and gripped in the rectangular housing 41 of the sliding lid and wherein , to open the main lid 29 , the sliding lid 35 must be slide behind to discover the tong 33 of the main lid 29 and could be lifted upwardly to place an orthodontic wire in the main channel 21 . the quadrangular aperture 34 of the main lid 29 located in its central portion , facilitates the insertion of a tool to open and close said lid 29 and the housing “ c ” of the sliding lid 35 facilitates the insertion of a tool to slide said lid 35 forward and backward to release or grip the main lid 29 in a closed position . the main lid 29 opens to allow a fast and easy insertion of an orthodontic wire and , when closed and gripped with the sliding lid 35 , avoids completely that the orthodontic wire could go out from the bracket . additionally , the main channel 21 can include means to reduce the friction between the wire and the channel , such as a depression in the lower wall of the channel to reduce the contact area between the wire and the channel 21 . although it was described that the bracket of the present invention includes a passage 22 for a second orthodontic wire , in other embodiments of the invention this cannot be included or else , to include one or more passages . also , in other embodiments of the invention , the gripping means for the main lid 29 could comprise any other type of suitable gripping means , as for example , elements in the lid which fits under pressure in the corresponding gripping means . finally , it should be understood that the orthodontic bracket of the present invention is not limited to the above described embodiment and that those skilled in the art will be able , with the teachings herein established , to make changes in the orthodontic bracket of the present invention , which scope will be established exclusively by the following claims .

US-201113185051-A

in a method of producing a protective helmet the steps include applying a first layer of hardenable synthetic resin and fibrous tissue on a predetermined surface of a positive - type mold , thereafter tensioning the fibrous tissue , and subsequently repeating the layer - applying and tensioning steps a prearranged number of times , so as to obtain successive layers forming the protective helmet .

the invention will be further described with the aid of an example of a preferred embodiment . although the implementation example describes the manufacture of a so - called integral helmet , the invention is of course , equally applicable to the manufacture of half - shell type helmets , or so - called jet - helmets . in order to fabricate the protective helmet , according to the present invention , it is first necessary to obtain a preliminary massive positive - type , or male , basic mold 10 of the helmet , formed in the present example as an integral helmet . the positive - type mold is preferably made in two parts , 10a and 10b , and with its aid and that of a support plate 19 , there is fabricated a split - or two - part negative - type , or female , shell or mold 11 , for example from fiber - reinforced synthetic resin , the inner space of which is filled thereafter preferably with a pu ( polyurethane ) type hardenable foam , for example , by spraying , so as to produce an intermediate two - part polyutherane positive - type or male mold 12 . the dimensions of the so - produced intermediate two - part positive - type or male mold 12 are then reduced by an amount which corresponds to the thickness of the padding to be added later to the interior of the helmet . the space remaining between the reduced dimensions of the positive - type mold 12 , and the previously fabricated negative - type shell 11 is then filled with foam , preferably , for example , by spraying pu type hardenable foam , into that space . following hardening of the pu type hardenable foam , a final two - part positive - type mold or shell 13 , composed of parts 13a and 13b , is obtained , by joining together , for example by gluing , the two half - shells , 13a and 13b , which have resulted from the hardened foam which had filled the space between the reduced two - part positive - type mold 12 , and the negative - type shell 11 . after cutting away appropriate portions from the resulting compound shell 13 , so as to form a facial cut - out 15 , the resulting shell 13 forms a base for the fabrication of the helmet proper . the resultant compound shell 13 forms a base , on which the helmet 14 to be produced is built up . for this purpose a first thin layer of resin , preferably epoxy resin , is applied to the surface of the final positive - type mold or shell 13 . a first fibrous tissue is then applied to the still moist layer of resin , for example , by extending a tissue or web 16 having dimensions approximately 100 cm by 45 cm across the final positive - type mold 13 , until the final positive - type mold 13 is covered up to the upper edge of a facial cut - out 15 thereof . the tissue 16 is then gripped on the laterally overhanging ends and pulled down or tensioned without exerting any significant force , until it entirely covers the surface of the final positive - type mold 13 uniformly up to a longitudinal chin - protecting region 18 of the helmet to be built up , without forming any folds . finally the ends of the tissue 16 are laterally folded over the longitudinal portion , which eventually forms the chin - protection region 18 , so that this relatively weak region 18 is covered by two tiers of tissue 16 . after the first tissue 16 has been applied over the entire surface of the final positive - type mold or shell 13 , and appropriately tensioned , it is carefully impregnated with artificial resin , and in turn covered by a second tissue 16 in the aforedescribed manner . in practice it has been shown that in general a total of five such types of tissues or webs 16 applied over the mold or shell 13 are adequate , so that the helmet produced therefrom satisfies even the most rigorous safety requirements . the fibrous tissue preferably consists of fully aromatic polyamides , known by the trademark &# 34 ; aramide &# 34 ;. it is , of course , possible , to utilize other chemical fibers , for example fibers consisting of inorganic raw materials , such as glass -, metal -, or carbon - fibers , for the fabrication of the helmet 14 . so as to obtain a partial reinforcement of the helmet 14 in any endangered regions , particularly in the regions set aside for testing resistance to penetration , these regions , or portions , may be covered by an additional fibrous tissue 16 and tensioned thereafter over at least these regions or portions . as a result of applying such an additional tissue 16 to the final positive - type shell 13 , it is possible to dispense with at least one of the tissues 16 covering the entire surface of the shell 13 , so that the weight of the helmet to be produced is not increased by this measure . so as to increase the frontal and lateral stability of the protective helmet , the helmet may be additionally reinforced , for example , by means of a belt 17 preferably composed of carbon fibers . such a belt 17 may , for example , extend on the inner surface of a helmet , fabricated in an integral manner , at the level of the chin - protection region 18 . a fibrous belt 17 of this type is therefore advantageously wrapped around and tensioned over the final positive - type mold or shell 13 , before the first fibrous tissue 16 is applied over the entire surface of the positive - type mold or shell 13 . it is alternately possible to extend such a belt 17 over any additional tissue 16 just below the first tissue 16 to be applied , and / or between any one of two successive tissues 16 . after all tissues 16 have been applied to the final positive - type mold or shell 13 , the positive - type shell 13 is left below all layers 16 , so as to serve as a support therefor . following hardening of the resin - impregnated tissues 16 , the final positive - type shell 13 acts as a shock - absorbing padding in the completed protective helmet . an integral type helmet 14 produced according to the inventive method weighs about 800 grams , inclusive of the shock - absorbing padding , but exclusive of a visor , while the lightest of the known helmets weighs at least 1100 grams . it will be apparent that numerous variations and modifications can be made to the method of the present invention , without the exercise of any inventive ingenuity , by one skilled in the art .

US-10507679-A

electrosurgery method and apparatus . in the method , tissue is cut or coagulated , with an electrically low conductive liquid providing cooling . in another method , skin is cut by electrosurgery in a dry field using a low duty cycle signal energizing the cutting electrode , minimizing tissue charring . a combination coagulation and cutting electrode performs both functions . the cutting is performed by a blade edge generating a local plasma adapted for cutting . superimposed on the blade edge is an electrode of greater surface area electrically insulated from the cutting electrode , for coagulation . in another version , a single component cutting / coagulation blade has a cutting and a flat partially insulated portion defining through holes in the insulation for coagulation . also provided is an electrical circuit whereby each electrode is isolated by a filter from cross talk and feedback of the rf signal from the other electrode , minimizing arcing .

fig1 a , which bears some similarity to fig1 of u . s . pat . no . 7 , 238 , 185 , shows an apparatus 10 for cutting material 12 submerged in a low conductivity liquid medium 14 . fig1 b shows detail of fig1 a , enlarged . note that in u . s . pat . no . 7 , 238 , 185 this medium 14 is expressly described as being a conducting liquid medium and the electrode generates the plasma in the conducting liquid medium . that is a difference between present fig1 b and fig1 of u . s . pat . no . 7 , 238 , 185 since in present fig1 the plasma is generated in the tissue being operated on , and the electrode is in effect in contact with the tissue in order to generate the plasma . material 12 is biological tissues including , for instance , muscle tissue 12 a , nerve tissue 12 b , bone 12 c and connective tissue 12 d . apparatus 10 includes handpiece 19 terminating in cutting electrode 16 . suitable material for the electrode 16 for instance would be tungsten , titanium , molybdenum , stainless steel or alloys thereof . again , this is not limiting . the cutting electrode 16 is surrounded by insulating layer 20 . a return electrical path is provided by conventional patient grounding pad 22 . insulating layer 20 can be any suitable dielectric material . fluid 14 is supplied via handpiece 19 at 18 , 20 which define an outlet near electrode 16 . fluid 14 may alternatively by supplied via a separate tubing or conduit , not part of handpiece 19 , in any case from an external reservoir . also provided is a voltage control unit 24 also known as a radio frequency ( rf ) generator which provides the electrical ( radio frequency in this case ) signals which energize the apparatus via lead or leads 62 . in this case unit 24 has a pulse control for pulsing the voltage in accordance with a predetermined modulation format , see u . s . pat . no . 7 , 238 , 185 incorporated herein by reference . in this case a thin layer of a plasma 28 is formed around the cutting blade 16 . thus electrode 16 is immersed in the low conductive fluid 14 and put in contact with tissue 12 and a suitable rf signal applied to electrode 16 , such that tissue 12 is heated to produce a vapor cavity region 30 around the blade 16 adjacent to the tissue . vapor cavity region 30 is thereby filled with water vapor and other gasses 32 emanating from the tissue 12 during the vaporization . the layer of gas 32 is ionized in the strong electric field around the cutting electrode 16 to make a thin layer of plasma 28 . the actual nature of the applied electrical signals which are suitable to create the desired plasma effect is well known in the field . for instance , in one case the applied signal is an rf ( radio frequency ) signal having a frequency in the range of 100 khz to 10 mhz . typically this energy is applied in the form of bursts of pulses . each burst typically has a duration in the range of 10 microseconds to 1 millisecond . the individual pulses in each burst typically each have a duration of 0 . 1 to 10 microseconds with an interval therebetween of 0 . 1 to 10 microseconds . the actual pulses are typically square waves and bi - phasic , that is alternating positive and negative amplitudes . generally the interval between pulses must be shorter than a lifetime of the plasma vapor cavity in order to maintain the cavity and the plasma regime during each pulse burst . in one embodiment the bursts each are separated by a duration of at least one millisecond . typically the time between the pulse bursts is sufficient so that the duty - cycle is relatively low as explained above . this minimizes the undesirable heating effects . however , as indicated here the provision of the cooling fluid reduces heating problems also . typically the plasma has a temperature greater than 100 ° c . the following discloses a new electrode configuration intended for a combination cutting and coagulation and fulguration and ablation , shown also in fig1 a but not required for the method of fig1 a . an overview of the hand piece 80 ( corresponding to handpiece 19 in fig1 a ) is shown in fig2 for the present such combination device . this figure omits the pulse generator 24 and associated electrical lead or leads 62 shown in fig1 a , which are provided for the fig2 apparatus but not shown here for simplicity . the fig2 device 80 is mostly conventional in configuration except as disclosed further herein . it includes a hand grip portion 82 with hand grip ridges as shown on the lower part thereof . this portion is intended to be held in the surgeon &# 39 ; s hand . two control buttons 84 , 86 activate electric switches ( not shown ) which are provided for purposes of respectively selecting the cutting or coagulation regimes . note that the ablation function can also be carried out , in the cutting regime , by a sweeping of the cutting electrode over the region to be ablated . the rear portion 88 is for balance and for holding the electrical leads extending there from which terminate in a conventional electrical connector ( not shown ) which connects to lead ( or leads ) 62 to the generator 24 ( also not shown in fig2 ). the dimensions of the device of fig2 are such that it is comfortably held in a hand , yet small enough for surgery for the intended application . the working end of the device of fig2 includes at its distal end the electrode tip assembly 92 , described below with reference to fig3 . assembly 92 is attached to the body portion 82 by an intermediate portion ( shaft ) 96 . the intermediate portion 96 carries the electrical leads to the tip assembly 92 as described with reference to fig3 . in a typical situation , the entire assembly 80 is disposable and is disposed of after each surgery . of course , this disposable aspect is not limiting . the materials for the device of fig2 are conventional and the portions shown are typically molded from plastic with the exception of the electrical leads and electrode tip assembly 92 , whose configuration is described further below . fig3 shows in a perspective view detail of the electrode tip assembly 92 and the nearest part of the intermediate portion 96 . fig3 is a semi - exploded view as described hereinafter . in fig3 , the cutting blade subassembly ( electrode ) 102 includes the actual cutting electrode . associated therewith and fixed thereto is the left side coagulation electrode subassembly 104 and the right side coagulation electrode subassembly 106 ( mostly not visible ). electrical insulation , which is plastic heat shrink tubing 108 and 110 , is provided for electrodes 104 and 106 . also provided are lengths of heat shrink plastic tubing 112 and 114 . as indicated by the arrow associated with insulation 114 , this piece of tubing is meant to be slid forward during assembly of this device . ( it is shown in the retracted view merely for purposes of illustration .) the rf energizing signals are provided to the three electrodes 102 , 104 , 106 by respectively a length of wire 116 and a second length of wire 118 . in one embodiment , these are 30 gauge insulated wire . the three electrodes are adhered together by an epoxy adhesive layer indicated at 124 . ( a similar epoxy layer , not visible , adheres electrode 106 to electrode 102 .) a length of large diameter plastic heat shrink tubing 120 is provided and slides forward as indicated by the arrow during the assembly of the device at the factory . this is intended to be slid all the way forward to cover the other pieces of insulating tubing at location d . dimensions a and b are respectively 0 . 030 inches ( 0 . 75 mm ) and 0 . 02 inches ( 0 . 5 mm ). of course these dimensions are merely illustrative . these dimensions define the distance between the edge of the cutting electrode 102 and the coagulation electrodes 104 , 106 . note that the right hand side ( lower ) coagulation electrode subassembly 106 is mostly not visible in fig3 because it is on the bottom side of the apparatus 92 . hence in this particular embodiment , there are two coagulation electrodes , one on the top which is mostly visible at 104 , and a second only partly visible at 106 . this allows even coagulation on both sides of the cut . these same two coagulation electrodes each perform fulguration , at a different power setting than used for coagulation . not shown in fig3 is the coaxial tubing 97 for fluid delivery of fig2 , which fits around coaxially the left most ( rear ) part of tubing 120 . the terminus of tubing 97 defines the opening portion 18 , 20 of fig1 b which delivers the cooling fluid 14 to the area being operated on . in another embodiment , tubing 97 is omitted since the fig3 apparatus does not require the cooling fluid , or cooling fluid may be delivered by other means . also , tubing 97 may be used to deliver conductive fluid , such as saline solution , depending on the intended use by the surgeon . fig4 a and 4b respectively show perspective views of part of the cutting blade subassembly 102 and the left side ( upper ) coagulation electrode subassembly 104 . the right side ( lower ) coagulation electrode subassembly 106 is essentially a mirror image of the fig4 b component . the cutting blade subassembly 102 of fig3 is relatively simple . in this embodiment it includes a support piece of annealed sheet titanium 0 . 1 mm thick as shown in fig4 a , to which is spot welded a slightly wider cutting blade of approximately similar shape and made of stainless steel ( or titanium ) sheet which is 0 . 01 inch ( 0 . 25 mm ) thick . the actual edge 126 thereof is honed to a sharp edge tapered at e . g . 10 ° on one side only . a number of each of these components is typically conventionally machined , stamped , or etched out of a large sheet of metal . in one embodiment , the entire structure 102 is approximately 0 . 61 inches ( 15 mm ) long and its width is 0 . 217 inches ( 5 . 5 mm ). the rounded edge 126 here is , e . g ., a section of a circle ( not limiting ). the coagulation electrode subassembly 104 of fig4 b is more complicated since it exhibits three dimensionality as shown in the fig4 b perspective view . the active ( exposed ) portion of the electrode is the c - shaped section 128 , which as shown is slightly raised . in one embodiment , the c - shaped section has an overall thickness of 0 . 008 inches ( 0 . 2 mm ) and the raised portion is 0 . 004 inches ( 0 . 1 mm ) thick . the open part of the c - shaped section subtends approximately a 60 ° arc . the total length of the fig4 b structure in one embodiment is 0 . 681 inches ( 17 . 3 mm ). again this component is typically one of many etched or stamped or machined out of a large sheet of , e . g ., titanium , which has been annealed for hardness . the overall diameter of the c - shaped section in one embodiment is approximately 0 . 138 inches ( 3 . 5 mm ). the other coagulation electrode 106 is essentially similar but a mirror image , since it lies on the other side of the cutting electrode . with reference to fig3 , not shown is an overall glass or other electric insulating layer covering most of the structure but leaving the c - shaped section of electrode 104 ( and electrode 106 ) exposed and also leaving exposed the actual edge 126 of the cutting blade portion 102 . moreover there is similar insulation ( dielectric ) provided between each of cutting blade subassembly 102 and the two coagulation electrodes 104 , 106 . this typically again is a coating of glass or ceramic approximately 0 . 005 to 0 . 5 mm thick , preferably 0 . 01 to 0 . 2 mm thick . the insulation extends to the proximal portion of each electrode . the glass type insulation is typically applied by a conventional process of dipping each relevant component prior to assembly in liquid ( molten ) glass and then annealing the glass . in fig3 , wire 116 provides the rf signal for the coagulation function and is spot welded or otherwise attached to the proximal terminal ( and uninsulated ) portions of both coagulation electrodes 104 and 106 . the other wire 118 similarly attaches to the terminal proximal portion of cutting blade subassembly 102 . further with regard to fig3 , in general the exposed c - shaped surface area of each of the coagulation electrodes 104 , 106 is much larger than that of the exposed cutting edge 126 of electrode 102 , since most of the cutting blade assembly 102 ( except its edge ) is covered by the insulation material so that typically only the actual edge 126 is exposed and this lies more or less flush with the surrounding insulating material . the width of the exposed edge 126 is in the range of 0 . 01 to 0 . 1 mm . the larger exposed surface area of the coagulation electrodes 104 , 106 makes coagulation of large tissue surfaces or blood vessels easier due to the extended area of contact and increased application of electrical power . to prevent electrical arc between the cutting and coagulation electrodes potentially leading to electrode damage , sufficient spacing between the electrodes is provided . in general , the less the distance between electrodes , the more arcing , therefore it is desirable to maintain a certain minimum spacing between cutting and coagulation electrodes as provided by the fig3 configuration . further , the particular electrode configuration as shown in fig3 is not limiting . for instance in one embodiment , the cutting electrode instead of being a relatively large plate , mostly covered by insulation , is instead a length of wire partially embedded in an insulating body with a portion of the wire exposed . an exposed edge of a plate is equivalent in terms of plasma generation to a wire . again this wire is separated from the coagulation electrode by a suitable minimum distance along its length to prevent arcing . in these figures the return electrode is not shown since it is typically a separate grounding pad structure or equivalent of conventional type as in fig1 a , not necessarily part of the cutting / coagulation hand piece 80 . however , that is not limiting . note moreover that the apparatus of fig3 does not show how it would be used in conjunction with the introduction of the low conductivity liquid into the operating field . in one embodiment , the liquid is introduced into the surgical field by a separate length of tubing , not part of the fig2 or fig3 structures . in other embodiments a tubing or conduit is incorporated or defined in the hand piece 80 of fig2 with its distal end connected to a reservoir of suitable liquid and terminating near the working end of the fig3 structure , such as in the vicinity of the electrode assembly 92 . the surgeon conventionally controls the rate of liquid delivery ( e . g ., 10 to 200 ml / min ) through the tubing or conduit . the fluid delivery aspect is thereby illustrated in fig2 , where tubing 97 is coaxial with intermediate portion 96 . the arrows illustrate the fluid flow from tubing 97 . at the distal end of the rear portion 88 is connected tubing 99 for the fluid , connecting to valve 101 and hence to a fluid reservoir such as a bag of pure water ( not shown ). tubing 99 connects to tubing 97 via a conduit extending through hand piece 80 . typically coaxial tubing 97 terminates 10 to 20 mm from the end of intermediate portion 96 . fig4 c shows another type of combination cutting and coagulation electrode 170 , but having a single blade used for both functions . hence this is an alternative to and corresponds in terms of function to the dual electrode structure of fig3 and 4a and 4 b , but is simpler in construction . fig4 c only illustrates the blade , not the electrical leads or hand piece which would be similar to that of fig2 . note that only one electrical lead would be needed with the fig4 c electrode . fig4 c shows this electrode in a plan view . it includes a base or rear portion 172 for attachment of the electrical lead . the working portion 174 has about the same overall length , width and thickness and edge configuration as structure 102 in fig4 a , and is of a similar material , and is similarly electrically insulated , except for edge 178 , by an overlayer of e . g . glass electrical insulation 180 . electrical insulation layer 180 defines a number ( e . g ., 10 to 100 ) of openings 186 which each expose the underlying metal of the blade portion 174 . the openings 186 are more or less evenly spaced apart and are each in the range of 1 to 100 μm in diameter , preferably 10 to 50 μm . the glass insulation layer 180 is e . g . 0 . 05 to 0 . 25 mm thick . as shown in side cross sectional view in fig4 d ( not to scale ), electrode 170 has the insulating layer 180 on both its flat sides 192 , 194 both sides also defining openings 186 . note that in fig4 d the blade edge is shown as being tapered ; the tapering is somewhat exaggerated for purposes of illustration in this figure . in use , the electrode edge 178 is used for cutting , and the flat sides 192 , 194 with the penetrated insulation layer 180 , for coagulation , similar to use of the fig3 electrodes . the surgeon chooses coagulation or cutting at any one time , by activating the appropriate controls such as buttons 84 , 86 in fig2 so as to supply suitable pulsed energy to the electrode 170 . fig5 shows an electrical circuit 140 in schematic form , which typically is provided in the handle portion 82 of the hand piece 80 of fig2 on a suitable circuit board for use with the fig3 dual electrode . this circuit has two arms . the upper arm is coupled to wire ( lead ) 116 , which in turn connects to the two coagulation electrodes 104 and 106 ( not shown ). the lower arm is coupled to the second wire ( lead ) 118 , which connects to the cutting blade subassembly ( electrode ) 102 . the upper arm of fig5 includes a band pass filter 142 , including an inductance 146 and a capacitance 148 . however this is merely representative of any sort of band pass ( or band stop ) filter . the bottom portion includes a different value band pass filter 152 , including in this case inductor 154 and capacitor 156 , again not meant to be limiting but merely to illustrate a band pass ( or band stop ) filter . in this embodiment , two different electrical signals are provided as is conventional , one for coagulation and the second for cutting as controlled by hand piece 80 buttons 84 , 86 or a foot switch ( not shown ). typically coagulation uses a lower frequency rf signal than does cutting . in this case as illustrated , the coagulation rf signal applied to lead 158 is at a frequency of 0 . 46 mhz . ( the other characteristics of this signal are not indicated here since this is merely an indication of the nature of this signal .) as indicated by the arrow , this signal is intended propagate to the coagulation electrodes 104 , 106 . an rf signal of different 4 mhz frequency is applied to lead 160 which is not necessarily connected to lead 158 and this 4 mhz signal is intended to connect to the cutting blade electrode 102 . the source of both these rf signals is the rf generator unit 24 shown in fig1 . the present inventors have recognized the technical problem that the cutting electrode 102 here lies in close proximity to an arc source ( electrodes 104 , 106 ) useful for large scale coagulation which may lead to breakdown of the gap between the electrodes 102 and 104 or 106 , especially when a wet cutting head is partially exposed to air . breakdown of this gap , e . g ., shorting , may cause damage to the delicate cutting electrode and may also result in damage to the power supply unit 24 . even if the cutting electrode 102 is connected to ground to protect the rf generator 24 , an arc between the coagulation electrodes 104 , 106 and cutting electrode 102 may destroy either electrode when a high voltage bipolar waveform is used as the energizing signal . even when electrically floating , electrodes can still conduct enough current through cable ( lead ) capacitance in order to damage the cutting edge of the cutting electrode 102 , which is quite thin . therefore to reduce cross talk between the cutting and coagulation energizing signals , two different frequencies are used here for cutting and coagulation as in fig5 . the band pass filters 142 , 152 provided as shown in fig5 isolate the two signals . as illustrated this prevents the cross talk of the 4 mhz frequency signal from propagating back up into the upper arm of fig5 . similarly filter 152 prevents the coagulation signal of 0 . 46 mhz frequency , even though picked up in wire 118 , from propagating to the lower arm . band stop filters can be used instead of band pass filters if the energizing frequencies are shifted far enough from one another for complete isolation . in this way both the coagulation and cutting electrodes may be supplied with their signals from the same rf generator 24 and in some cases may even be supplied by the same output line from the generator 24 . in this case a common node 164 is provided as shown in fig5 to which both the cutting and coagulation rf signals at respectively 4 mhz and 0 . 46 mhz are applied . the filters 142 , 152 prevent the undesired signal from propagating down to the respective wires 116 and 118 in each arm of the circuit of fig5 . in other embodiments the common node 164 is not present , and separate signals are provided to lines 158 and 160 from the rf generator unit 24 . also disclosed here is a method of cutting ( resecting ) skin tissue including the epidermis ( outer layer ) and dermis ( under layer ) using an electrosurgery electrode in a dry field environment . “ dry field ” here refers to the absence of naturally occurring conductive bodily fluids and the absence of a conductive fluid applied to skin ( such as saline solution ). note that the epidermis by definition is free of blood vessels . the underlying dermis does have some blood vessels , but the blood supply is limited since the blood vessels are small . in the surgical field , it is conventional that to cut skin electrosurgically a conductive fluid is needed to prevent tissue charring . generally therefore skin is cut using a conventional scalpel . this is because the use of the added conductive fluid is difficult since the fluid tends to not remain alongside the electrode and thereby maintenance of the plasma regime along the electrode is problematic . in accordance with the present invention , dry skin or skin with only a non - conductive fluid in it or on it is cut using an electrosurgical electrode of conventional configuration or as described above . the pulsed electrical energy applied to the electrode is controlled to be of relatively low power ( much lower than is conventional in electrosurgery ), so no skin charring occurs . typically the amount of peak electrical power is at least 100 watts , and the duty cycle of the electrical signal is 15 % or less . with regard to the nature of the relatively low power also see e . g . copending and commonly owned and published u . s . application ser . no . 10 / 779 , 529 , filed feb . 13 , 2004 , inventor daniel palanker , incorporated herein by reference in its entirety , and also the above disclosure of suitable energization of the electrode . for instance , the signal applied to the electrode is in one case an rf signal having a frequency in the range of 100 khz to 10 mhz . typically this energy is applied in the form of bursts of pulses . each burst typically has a duration in the range of 10 microseconds to 1 millisecond . the individual pulses in each burst typically have a duration of 0 . 1 to 10 microseconds , with an interval therebetween of 0 . 1 to 10 microseconds , as above . typically the pulse bursts each are separated by a duration of at least 1 millisecond , thereby providing the low duty cycle . this minimizes the heating effects . this relatively low power signal maintains the desired plasma regime , and allows for tissue cooling between bursts . thus it allows for cutting the human epidermis and dermis with minimal charring . generally any resulting tissue damage is no more than that resulting from cutting skin with a conventional ( non - electrosurgery ) scalpel . the resulting wound therefore would heal as quickly as a wound created by a conventional scalpel . this approach has the advantage of allowing the surgeon to use the same electrosurgical apparatus for skin cutting as for surgery within the body . it also allows for cutting and coagulation using the same instrument . this disclosure is illustrative but not limiting ; further modifications will be apparent to those skilled in the art in light of this disclosure and are intended to fall within the scope of the appended claims .

US-201213436581-A

a pharmaceutical dosage form adapted to supply a medicament to the oral cavity for buccal , sublingual or gingival absorption of the medicament which contains an orally administrable medicament in combination with an effervescent for use in promoting absorption of the medicament in the oral cavity . the use of an additional ph adjusting substance in combination with the effervescent for promoting the absorption drugs is also disclosed .

one aspect of this invention is to use effervescent as penetration enhancers for influencing oral drug absorption . effervescent agents can be used alone or in combination with other penetration enhancers , which leads to an increase in the rate and extent of absorption of an active drug . it is believed that such increase can rise from one or all of the following mechanisms : 1 . reducing the mucosal layer thickness and / or viscosity ; 2 . tight junction alteration ; 3 . inducing a change in the cell membrane structure ; and 4 . increasing the hydrophobic environment within the cellular membrane . the present dosage forms should include an amount of an effervescent agent effective to aid in penetration of the drug across the oral mucosa . preferably , the effervescent is provided in an amount of between about 5 % and about 95 % by weight , based on the weight of the finished tablet , and more preferably in an amount of between about 30 % and about 80 % by weight . it is particularly preferred that sufficient effervescent material be provided such that the evolved gas is more than about 5 cm 3 but less than about 30 cm 3 , upon exposure of the tablet to an aqueous environment . however , the amount of effervescent agent must be optimized for each specific drug . the term “ effervescent agent ” includes compounds which evolve gas . the preferred effervescent agents evolve gas by means of a chemical reaction which takes place upon exposure of the effervescent agent ( an effervescent couple ) to water and / or to saliva in the mouth . this reaction is most often the result of the reaction of a soluble acid source and a source of carbon dioxide such as an alkaline carbonate or bicarbonate . the reaction of these two general compounds produces carbon dioxide gas upon contact with water or saliva . such water - activated materials must be kept in a generally anhydrous state and with little or no absorbed moisture or in a stable hydrated form , since exposure to water will prematurely disintegrate the tablet . the acid sources may be any which are safe for human consumption and may generally include food acids , acid and hydrite antacids such as , for example : citric , tartaric , amalic , fumeric , adipic , and succinics . carbonate sources include dry solid carbonate and bicarbonate salt such as , preferably , sodium bicarbonate , sodium carbonate , potassium bicarbonate and potassium carbonate , magnesium carbonate and the like . reactants which evolve oxygen or other gasses and which are safe for human consumption are also included . the effervescent agent ( s ) of the present invention is not always based upon a reaction which forms carbon dioxide . reactants which evolve oxygen or other gasses which are safe for human consumption are also considered within the scope . where the effervescent agent includes two mutually reactive components , such as an acid source and a carbonate source , it is preferred that both components react completely . therefore , an equivalent ratio of components which provides for equal equivalents is preferred . for example , if the acid used is diprotic , then either twice the amount of a mono - reactive carbonate base , or an equal amount of a di - reactive base should be used for complete neutralization to be realized . however , in other embodiments of the present invention , the amount of either acid or carbonate source may exceed the amount of the other component . this may be useful to enhance taste and / or performance of a tablet containing an overage of either component . in this case , it is acceptable that the additional amount of either component may remain unreacted . the present dosage forms may also include in amounts additional to that required for effervescence a ph adjusting substance . for drugs that are weakly acidic or weakly basic , the ph of the aqueous environment can influence the relative concentrations of the ionized and unionized forms of the drug present in solution according to the henderson - hasselbach equation . the ph solutions in which an effervescent couple has dissolved is slightly acidic due to the evolution of carbon dioxide . the ph of the local environment , e . g ., saliva in immediate contact with the tablet and any drug that may have dissolved from it , may be adjusted by incorporating in the tablet a ph adjusting substances which permit the relative portions of the ionized and unionized forms of the drug to be controlled . in this way , the present dosage forms can be optimized for each specific drug . if the unionized drug is known or suspected to be absorbed through the cell membrane ( transcellular absorption ) it would be preferable to alter the ph of the local environment ( within the limits tolerable to the subject ) to a level that favors the unionized form of the drug . conversely , if the ionized form is more readily dissolved the local environment should favor ionization . the aqueous solubility of the drug should preferably not be compromised by the effervescent and ph adjusting substance , such that the dosage forms permit a sufficient concentration of the drug to be present in the unionized form . the percentage of the ph adjusting substance and / or effervescent should therefore be adjusted depending on the drug . suitable ph adjusting substance for use in the present invention include any weak acid or weak base in amounts additional to that required for the effervescence or , preferably , any buffer system that is not harmful to the oral mucosa . suitable ph adjusting substance for use in the present invention include , but are not limited to , any of the acids or bases previously mentioned as effervescent compounds , disodium hydrogen phosphate , sodium dihydrogen phosphate and the equivalent potassium salt . the active ingredient suitable for use in the present dosage forms can include systematically distributable pharmaceutical ingredients , vitamins , minerals , dietary supplements , as well as non - systematically distributable drugs . preferably , the active ingredient is a systemically active pharmaceutical ingredient which is absorbable by the body through the oral mucosa . although the dosage forms can be employed with a wide range of drugs , as discussed below , it is especially suitable for drugs and other pharmaceutical ingredients which suffer significant loss of activity in the lumen of the gastrointestinal tract or in the tissues of the gastrointestinal tract during absorption process or upon passage through the liver after absorption in the intestinal tract . absorption through the oral mucosa allows the drug to enter the systemic circulation without first passing through the liver , and thus alleviates the loss of activity upon passage through the liver . pharmaceutical ingredients may include , without limitation , analgesics , anti - inflammatories , antipyretics , antibiotics , antimicrobials , laxatives , anorexics , antihistamines , antiasthmatics , antidiuretics , antiflatulents , antimigraine agents , antispasmodics , sedatives , antihyperactives , antihypertensives , tranquilizers , decongestants , beta blockers ; peptides , proteins , oligonucleotides and other substances of biological origin , and combinations thereof . also encompassed by the terms “ active ingredient ( s )”, “ pharmaceutical ingredient ( s )” and “ active agents ” are the drugs and pharmaceutically active ingredients described in mantelle , u . s . pat . no . 5 , 234 , 957 , in columns 18 through 21 . that text of mantelle is hereby incorporated by reference . alternatively or additionally , the active ingredient can include drugs and other pharmaceutical ingredients , vitamins , minerals and dietary supplements as the same are defined in u . s . pat . no . 5 , 178 , 878 , the disclosure of which is also incorporated by reference herein . the dosage form preferably includes an effervescent couple , in combination with the other ingredients to enhance the absorption of the pharmaceutical ingredient across the oral mucosa and to improve the disintegration profile and the organoleptic properties of the dosage form . for example , the area of contact between the dosage form and the oral mucosa , and the residence time of the dosage form in the oral cavity can be improved by including a bioadhesive polymer in this drug delivery system . see , e . g ., mechanistic studies on effervescent - induced permeability enhancement by jonathan eichman ( 1997 ), which is incorporated by reference herein . effervescence , due to its mucus stripping properties , would also enhance the residence time of the bioadhesive , thereby increasing the residence time for the drug absorption . non - limiting examples of bioadhesives used in the present invention include , for example , carbopol 934 p , na cmc , methocel , polycarbophil ( noveon aa - 1 ), hpmc , na alginate , na hyaluronate and other natural or synthetic bioadhesives . in addition to the effervescence - producing agents , a dosage form according to the present invention may also include suitable non - effervescent disintegration agents . non - limiting examples of non - effervescent disintegration agents include : microcrystalline , cellulose , croscarmellose sodium , crospovidone , starches , corn starch , potato starch and modified starches thereof , sweeteners , clays , such as bentonite , alginates , gums such as agar , guar , locust bean , karaya , pecitin and tragacanth . disintegrants may comprise up to about 20 weight percent and preferably between about 2 and about 10 % of the total weight of the composition . in addition to the particles in accordance with the present invention , the dosage forms may also include glidants , lubricants , binders , sweeteners , flavoring and coloring components . any conventional sweetener or flavoring component may be used . combinations of sweeteners , flavoring components , or sweeteners and flavoring components may likewise be used . examples of binders which can be used include acacia , tragacanth , gelatin , starch , cellulose materials such as methyl cellulose and sodium carboxy methyl cellulose , alginic acids and salts thereof , magnesium aluminum silicate , polyethylene glycol , guar gum , polysaccharide acids , bentonites , sugars , invert sugars and the like . binders may be used in an amount of up to 60 weight percent and preferably about 10 to about 40 weight percent of the total composition . coloring agents may include titanium dioxide , and dyes suitable for food such as those known as f . d .& amp ; c . dyes and natural coloring agents such as grape skin extract , beet red powder , beta - carotene , annato , carmine , turmeric , paprika , etc . the amount of coloring used may range from about 0 . 1 to about 3 . 5 weight percent of the total composition . flavors incorporated in the composition may be chosen from synthetic flavor oils and flavoring aromatics and / or natural oils , extracts from plants , leaves , flowers , fruits and so forth and combinations thereof . these may include cinnamon oil , oil of wintergreen , peppermint oils , clove oil , bay oil , anise oil , eucalyptus , thyme oil , cedar leave oil , oil of nutmeg , oil of sage , oil of bitter almonds and cassia oil . also useful as flavors are vanilla , citrus oil , including lemon , orange , grape , lime and grapefruit , and fruit essences , including apple , pear , peach , strawberry , raspberry , cherry , plum , pineapple , apricot and so forth . flavors which have been found to be particularly useful include commercially available orange , grape , cherry and bubble gum flavors and mixtures thereof . the amount of flavoring may depend on a number of factors , including the organoleptic effect desired . flavors may be present in an amount ranging from about 0 . 05 to about 3 percent by weight based upon the weight of the composition . particularly preferred flavors are the grape and cherry flavors and citrus flavors such as orange . one aspect of the invention provides a solid , oral tablet dosage form suitable for sublingual , buccal , and gingival administration . excipient fillers can be used to facilitate tableting . the filler desirably will also assist in the rapid dissolution of the dosage form in the mouth . non - limiting examples of suitable fillers include : mannitol , dextrose , lactose , sucrose , and calcium carbonate . tablets can either be manufactured by direct compression , wet granulation or any other tablet manufacturing technique . see , e . g ., u . s . pat . nos . 5 , 178 , 878 and 5 , 223 , 264 , which are incorporated by reference herein . the tablet may be a layered tablet consisting of a layer of the active ingredient sandwiched between a bioadhesive layer and an effervescence layer . other layered forms which include the ingredients set forth above in layers of diverse compositions . effervescence level : between 5 %- 95 % tablet size : between { fraction ( 3 / 16 )}″- ⅝ ″ tablet hardness : between 5n and 80n route of administration : sublingual , buccal , gingival the dosage form may be administered to a human or other mammalian subject by placing the dosage form in the subject &# 39 ; s mouth and holding it in the mouth , either adjacent a cheek ( for buccal administration ), beneath the tongue ( for sublingual administration ) and between the upper lip and gum ( for gingival administration ). the dosage form spontaneously begins to disintegrate due to the moisture in the mouth . the disintegration , and particularly the effervescence , stimulates additional salivation which further enhances disintegration . the dosage form should include fentanyl , an effervescent and ph adjusting substance so that the ph is adjusted to neutral ( or slightly higher ) since the pka of fentanyl is 7 . 3 . at this ph , the aqueous solubility of this poorly water - soluble drug would not be compromised unduly , and would permit a sufficient concentration of the drug to be present in the unionized form . two fentanyl formulations , each containing 36 % effervescence , were produced . these tablets were compressed using half - inch shallow concave punches . quantity formulation component ( mg ) short fentanyl , citrate , usp 1 . 57 disintegration lactose monohydrate 119 . 47 time microcrystalline 119 . 47 cellulose , silicified sodium carbonate , 46 . 99 anhydrous sodium bicarbonate 105 citric acid , anhydrous 75 polyvinylphrrolidone , 25 cross - linked magnesium stearate 5 colloidal silicon dioxide 2 . 5 total tablet mass 500 long fentanyl citrate , usp 1 . 57 disintegration lactose monohydrate 270 . 93 time sodium carbonate , 40 . 00 anhydrous sodium bicarbonate 105 citric acid , anhydrous 75 magnesium stearate 5 colloidal silicon dioxide 2 . 5 total tablet mass 500 the dosage form included prochlorperazine ( pka = 8 . 1 ), an effervescent and ph adjusting substance so that a slightly higher ph is produced to facilitate the permeation enhancement . with respect to prochlorperazine , an anti - emetic drug , two formulations , buccal and sublingual , were developed . the buccal tablets were compressed as quarter inch diameter biconvex tablets , whereas the sublingual tablets were three - eighths inch diameter biconvex tablets . these dimensions were chosen to give a comfortable fit in the respective part of the oral cavity for which they were designed . the formulae for these tablets are as follows : quantity formulation component name ( mg ) buccal prochlorperazine 5 . 00 sodium bicarbonate 15 . 52 citric acid , anhydrous 11 . 08 sodium bicarbonate 45 . 78 hpmc k4m prem 5 . 00 dicalcium phosphate 5 . 00 dihydrate mannitol 11 . 67 magnesium stearate 0 . 95 total 100 . 00 sublingual prochlorperazine 5 . 00 sodium bicarbonate 61 . 25 citric acid , anhydrous 43 . 75 sodium bicarbonate 95 sodium carbonate 91 . 25 hpmc methocel k4m prem 40 mannitol 60 magnesium stearate 3 . 75 total 400

US-97702904-A

a design methodology is provided for creating biomaterial scaffolds optimized for in vivo function with any 3d anatomic shape . the method creates all designs using voxel based design techniques . it also provides for optimization of implant and scaffold microstructure to best match functional and biofactor delivery requirements . the voxel based design techniques readily allow combination of any scaffold or implant microstructure database with any complex 3d anatomic shape created by ct or mri scanners . these designs can be readily converted to formats for layered manufacturing or casting .

the following description of the preferred embodiment is merely exemplary in nature and is in no way intended to limit the invention , its application , or uses . the present invention is generally directed towards a method approach for designing tissue engineering scaffolds , biomaterial implants , drug delivery systems , gene delivery systems and in vitro tissue testing systems that can be heterogeneously distributed to match any anatomic shape and can be fabricated using solid free form fabrication techniques . this invention incorporates image - based design techniques , homogenization theory , mathematical optimization algorithms , marching cubes and marching squares algorithms to convert image based design data to surface or wire frame geometry , and solid free form fabrication . the steps for performing the scaffold optimization of the present invention are shown in fig1 . in step 1 , the methodology creates unit cell voxel databases . that is , a set of base unit cell architectures are created in voxel format ranging over all design parameters . in step 2 , the method calculates effective physical properties . that is , the method solves homogenization equations for each unit cell to calculate effective physical property of the scaffold and the tissue that will grow in to the scaffold pores . the method can also determine functional dependence of effective stiffness , permeability , and porosity on cell design parameters . in step 3 , the method formulates and solves optimization algorithms of unit cell parameters . that is , the method solves the optimization problem that will find the best match of both scaffold and regenerate tissue properties to naturally occurring tissue properties . the solution gives the optimal design parameters for the unit cell architecture . in step 4 , the method creates an anatomic shape voxel database . that is , the method creates a voxel database of the anatomic scaffold shape with different densities representing different scaffold architectures . in step 5 , the method merges the anatomic and architecture data base . that is , the method uses image - based boolean operations to merge the anatomic data base with net erogenous density distribution with individual sets of unit cell databases . in step 6 , the method converts the voxel design to a surface or wire frame geometry . that is , the method converts the resulting complete scaffold design in voxel format to either a triangular facet representation or a wire frame representation that can be used in solid free form systems . in step 7 , the method fabricates the design scaffold from biomaterial . that is , the method fabricates the scaffold design using direct or indirect ( casting ) solid free form techniques . the methodology steps will now be individually described in greater detail . the first step in generating the optimal scaffold design is to generate a connected porous unit cell structure . this unit cell structure may be repeated periodically to create a porous architecture . the unit cell pore geometry may be characterized using a limited number of parameters . for instance , as shown in fig2 if connected cylinders are assumed as the base unit cell structure , the design may be characterized by the three cylinder diameters . the unit cell voxel database may be created in numerous ways , two of which are to 1 ) generate a geometric architecture by categorizing voxels as inside or outside a structure depending on whether the voxel location satisfies the equation for a specific geometry ( fig2 ) or 2 ) creating periodically repeating biomimetic structures created from existing tissue architecture . the next step is to compute the effective physical property of the base unit cell structure . this is done using a finite element implementation of representative volume element theory such as homogenization . the physical properties of the scaffold may include mechanical stiffness , diffusion , permeability and / or thermal conductivity . all of the formulations below are geared to mechanical stiffness . in homogenization theory , the following weak form of local equilibrium equations are solved : ∫ v unit   cell  { ɛ ^ } t  [ c ]  { ɛ } k    v unit   cell = ∫ v unit   cell  { ɛ ^ } t  { c } k   v unit   cell ( 1 ) where [ c ] is the base scaffold material stiffness , {} k is a characteristic strain distribution under the k th column of the stiffness matrix { c } k . the index k ranges from 1 - 6 to represent three normal strain states and three shear strain states . v unit cell is the unit cell structure volume and {{ circumflex over ( ε )}} is a virtual strain . solving equation 1 allows the direct calculation of the effective scaffold stiffness [ c ] scaf eff and the effective regenerate tissue stiffness [ c ] tissue eff as : [ c ] scaf eff = ∫ v unit   cell  [ c ] scaf  [ m ] scaf   v unit   cell ; [ m ] scaf =[ i ]−└{ ε } 1 { ε } 2 { ε } 3 { ε } 4 { ε } 5 { ε } 6 ┘ scaf [ 0032 ] [ c ] tissue eff = ∫ v unit   cell  [ c ] tissue  [ m ] tissue   v unit   cell ; [ m ] tissue =[ i ]−└{ ε } 1 { ε } 2 { ε } 3 { ε } 4 { ε } 5 { ε } 6 ┘ tissue ( 2 ) where [ c ] scaf eff is the effective stiffness of the scaffold alone and [ c ] tissue eff is the effective stiffness of the regenerate tissue that grows into the scaffold pores . [ c ] scaf and [ c ] tissue are the base mechanical properties of the scaffold and regenerate tissue , respectively . [ m ] scaf is a matrix that represents the effective of scaffold architecture on scaffold effective mechanical properties . likewise , [ m ] tissue represents the effective of scaffold architecture on regenerate tissue effective mechanical properties . the quantities [ m ] scaf and [ m ] tissue may both be integrated over the volume of each structure phase to give an averaged matrix as follows : [ m ] scaf = 1  v unitcell   ∫ v scaf  [ m ] scaf   v scaf ( 3 ) [ m _ ] tissue = 1  v unitcell   ∫ v tissue  [ m ] tissue   v tissue ( 4 ) if the structure has one dominantly stiff phase , the relationship between the effective scaffold stiffness , the base scaffold stiffness and the scaffold porous architecture may be approximated as : where [ c ] scaf eff is the effective scaffold stiffness , [ c ] scaf is the base scaffold stiffness , and [{ overscore ( m )}] scaf is a measure of the scaffold architecture , called the global structure matrix . similarly , the relationship between the effective regenerate tissue stiffness , the base regenerate tissue stiffness and the regenerate tissue architecture may be approximated as : where [ c ] tissue eff is the effective scaffold stiffness , [ c ] tissue is the base scaffold stiffness , and [{ overscore ( m )}] tissue is a measure in this case of the regenerate tissue architecture . equations ( 5 ) and ( 6 ) are critical to the optimization scheme based in a set of unit cell structures with similar topology because they show that it is possible to compute the entire range of values for [ m ] scaf and [ m ] tissue , and then fit these values to a known function without having to recalculate them each time the architecture is changed . specifically , [ m ] scaf and [ m ] tissue will be pre - computed and stored as a direct function of the unit cell design parameters . for example , the intersecting orthogonal cylinder design may be characterized by three design parameters being the three cylinder diameters . the relationship between [ m ] scaf and the three cylinder diameters for the unit cell design in fig2 can be fit into a third degree polynomial of the form : [{ overscore ( m )} ij ( d 1 , d 2 , d 3 )]= a 0 + a 1 d 1 + a 2 d 2 + a 3 d 3 + a 4 d 1 2 + a 5 d 1 d 2 + a 6 d 1 d 3 + a 7 d 2 2 + a 8 d 2 d 3 + a 9 d 3 2 + a 10 d 1 3 a 11 d 1 2 d 2 + a 12 d 1 2 d 3 + a 13 d 1 d 2 2 + a 13 d 1 d 2 d 3 + a 14 d 1 d 3 2 + a 15 d 2 3 + a 16 d 2 2 d 3 + a 17 d 2 d 3 2 + a 18 d 3 3 ( 7 ) note that the coefficients a 0 - a 19 are computed for each of the 36 elements of the 6 × 6 matrix { overscore ( m )} equations 5 and 6 may now be written in the following functional forms [ c ] scaf eff ≈[ c ( e 1 , e 2 , e 3 , g 12 , g 13 , g 23 , ν 12 , ν 13 , ν 23 ,)] scaf [{ overscore ( m )}( d 1 , d 2 , d 3 ,)] scaf [ c ] tissue eff ≈[ c ] tissue [{ overscore ( m )}( d 1 , d 2 , d 3 )] tissue ( 8 ) equation 8 shows that we can simultaneously design the scaffold and the regenerate tissue effective stiffness by controlling the stiffness of the base scaffold material , [ c ( e 1 , e 2 , e 3 , g 12 , g 23 , ν 12 , ν 13 , ν 23 ,)] scaf , the scaffold porous architecture [{ overscore ( m )}( d 1 , d 2 , d 3 )] scaf , and the pore structure into which the tissue grows [{ overscore ( m )}( d 1 , d 2 , d 3 )] tissue . note that if permeability and / or electrical conductivity properties are to be optimized , the relationship of permeability and conductivity to microstructure properties can be written as : [ k ] scaf eff ≈[ k ( k 1 , k 2 , k 3 )] scaf [{ overscore ( m )}( d 1 , d 2 , d 3 ,)] scaf [ k ] tissue eff ≈[ k ] tissue [{ overscore ( m )}( d 1 , d 2 , d 3 )] tissue where again [{ overscore ( m )}( d 1 , d 2 , d 3 )] scaf represents the scaffold architecture , [{ overscore ( m )}( d 1 , d 2 , d 3 )] tissue represents the regenerate tissue architecture , [ k ] scaf eff represents the effective scaffold permeability or conductivity , [ k ] tissue eff represents the effective tissue permeability or conductivity , [ k ] scaf is the base scaffold permeability or conductivity and [ k ] tissue is the base tissue permeability or conductivity . thus , the use of unit cell based periodic architecture and homogenization theory has allowed the development of an explicit functional dependence of scaffold effective stiffness and regenerate tissue effective stiffness on scaffold base material and scaffold porous architecture . note that the regenerate tissue base stiffness cannot be designed so it does not enter the equation . equation 8 provides the basis for optimizing scaffold base material properties and architecture such that both scaffold effective stiffness and regenerate tissue stiffness match desired natural tissue properties . it may also be important to place a constraint on the scaffold porosity and / or permeability . functional dependence of both porosity and permeability can be computed using homogenization theory and expressed in a functional form like equation 7 . accounting for scaffold stiffness , regenerate tissue effective stiffness , scaffold porosity and scaffold permeability allows for a very general scaffold design . the advantage of creating explicit functional representations like equation 7 is that general mathematical programming algorithms available in numerical packages like matlab ™ can be applied to solve very general optimization problems . a typical optimization formulation where the objective is to have both effective scaffold stiffness and regenerate tissue stiffness match natural tissues stiffness with a constraint on scaffold porosity is given below : e scaffold min , d 1 , d 2 , d 3  ∑ i = 1 n  ( c i natural   tissue   eff - c i regen   tissue   eff c i natural   tissue   eff ) 2 + ∑ i = 1 n  ( c i natural   tissue   eff - c i scaffold   eff c i natural   tissue   eff ) 2   where   i = 1   to   9 ( 9 ) where min stands for minimize , e scaffold is the young &# 39 ; s modulus of the scaffold base material under the assumption of isotropy , and d 1 , d 2 , d 3 are the diameters of the cylindrical pores for the unit cell shown in fig2 . e scaffold , d 1 , d 2 and d 3 are all design variables for the scaffold base material and architecture . in the objective function , c i regentissueeff is the matrix of the effective regenerate tissue elastic properties , c i scaf eff is the matrix of the effective scaffold tissue elastic properties , and c i natural tissue eff is the matrix of the desired target effective natural tissue elastic properties . the values e min and e max are the lower and upper bound constraints on the young &# 39 ; s modulus of the scaffold base material . the quantities v pore and v total are the volume of scaffold pores and total scaffold volume respectively . this optimization formulation seeks to match both the scaffold and regenerate tissue effective properties as close to the natural tissue properties while satisfying constraints on the cylinder diameters ( d 1 , d 2 , and d 3 ), the scaffold porosity and the minimum and maximum value ( e min , e max ) of the scaffold base material stiffness . note again that other physical properties like permeability and conductivity may be designed . e scaffold max , d 1 , d 2 , d 3  v pore v total ∂ 1 c i bone eff ≦ c i tissue eff ≦ α 2 c i bone eff where i = 1 to 9 ; α & gt ; α 1 β 1 c i bone eff ≦ c i scaffold eff ≦ β 2 c i bone eff where i = 1 to 9 ; β 2 & gt ; β 1 where again e scaffold is the young &# 39 ; s modulus of the scaffold base material under the assumption of isotrophy , d 1 d 2 d 3 are the diameters of the cylindrical pores for the unit cell shown in fig2 c i regentissueeff is the matrix of the effective regenerate tissue elastic properties , c i scaf eff is the matrix of the effective scaffold tissue elastic properties , c i natural tissue eff is the matrix of the desired target effective natural tissue elastic properties , e min and e max are the lower and upper bound constraints on the young &# 39 ; s modulus of the scaffold base material , and v pore and v total are the volume of scaffold pores and total scaffold volume respectively . in the equation , α 1 , α 2 , β 1 , and β 2 are scaling factors used to bound the scaffold and regenerate tissue effective stiffness . the new quantities α 1 , α 2 , β 1 and β 2 are weighting factors on the stiffness terms that modify how tightly the designed stiffness must match the target stiffness as a constraint . this optimization formulation seeks to design a scaffold with the maximum porosity possible that still matches the desired stiffness and base scaffold material properties within defined constraints . a third possible optimization formulation can include permeability of the scaffold as a constraint . permeability is important in a scaffold for two reasons . first , to load biofactors initially into the scaffolds , a high permeability is needed to ensure flow of the biofactors through the scaffold architecture . second , in vivo , high permeability is associated with the ability of cells to migrate into the scaffold . a typical optimization formulation with a constraint on scaffold permeability would have the form : e scaffold min , d 1 , d 2 , d 3  ∑ i = 1 n  ( c i natural   tissue   eff - c i regen   tissue   eff c i natural   tissue   eff ) 2 + ∑ i = 1 n  ( c i natural   tissue   eff c i natural   tissue   eff ) 2   where   n = 1   to   9 α 1  k i target ≤ k i target ≤ α 2  k i target   where   i = 1   to   3 ; α 2 & gt ; α 1   d 1 , d 2 , d 3 ≤ 900   microns   d 1 , d 2 , d 3 ≥ 300   microns  where all quantities are as defined in equation 9 with the exception of the first line of constraints with k i t arg et being the target scaffold permeability and α 1 and α 2 the weighting factors for the permeability constraint . optimization formulations presented in equations 9 - 11 may be solved using standard mathematical programming algorithms such as those available in matlab ™ or numerical recipes . this allows many different optimization formulations to be solved for any particular design . in contrast to available topology optimization methods , for which a large finite element problem must be solved at each optimization iteration , the current invention streamlines the process albeit with a more restricted set of available topologies . in other words , the current invention allows a much more rapid solution of the topology optimization problem for a scaffold ( with commercially available software ) than other topology optimization approaches at the cost of using a more restricted set of topologies . a typical implementation in matlab ™ using the f mincon option from the matlab ™ toolkit ( a sequential quadratic programming algorithm ) has the following form : where x is a vector of design variables being the scaffold architecture parameters and scaffold material properties , ‘ objective function ’ is a matlab ™ m - file containing the objective function evaluation , x0 is the initial value of the design variables , lb is the lower bound on scaffold material stiffness and scaffold wall thickness , ub is the upper bound on scaffold material stiffness and scaffold wall thickness , and ‘ nonlinear constraint ’ is the matlab ™ constraint file containing the evaluation of the volume fraction constraint or effective stiffness , both of which are nonlinear . for this study , the three orthogonal young &# 39 ; s moduli for mandibular condyle trabecular bone reported by teng and herring were chosen as the target bone properties for the optimization problem . for the stiffness design , the porosity constraint was set a 60 %. for the porosity design , the scaling factors were set to 0 . 9 and 1 . 1 for both tissue ( α 1 , α 2 ) and scaffold stiffness ( β 1 , β 2 ). this meant that both the scaffold and regenerate tissue effective properties must be between 90 % and 110 % of the original bone properties . for both design problems , e min was set to 1 . 5 gpa to represent a lower bound for degradable polymer properties and e max was set to 15 gpa to represent calcium - phosphate ceramic properties . the regenerating tissue was assumed to be isotropic using a value of 5 gpa , an upper bound from experimental results of guldberg and hollister . the fourth step in creating anatomically shaped tissue engineered scaffolds with optimized architecture is to create the anatomic shape in a voxel database of the same form as the optimized internal architecture voxel database . the most direct way to create the anatomic shape voxel database is to image the desired section of a patient &# 39 ; s anatomy using either computed tomography ( ct ) or magnetic resonance imaging ( mri ) techniques . these techniques automatically create a three - dimensional ( 3d ) voxel database representing the complex anatomic topology by a density distribution within a fixed voxel grid . the original density distribution within the anatomic database reflect attenuation of a signal through tissues . for the purpose of scaffold design , this density alteration is modified to serve as a marker for the placement of different scaffold architecture designs . density modification is accomplished either by directly indexing the anatomic array and changing the density for the given indices , or by using region of interest tools to select polygon regions on a slice and changing all pixels within the polygon region to a different density . the anatomic voxel data format is the same as the internal architecture database , allowing direct boolean substitution of a specific internal architecture database directly into a specific location of the anatomic database , using density in the anatomic database as a marker . in other words and referring to fig3 suppose that two specific optimized architectures , denoted as architecture a and architecture b , are created to fill two locations within a given anatomic shape . first , the periodic architecture unit cell database is replicated such that it covers the exact same voxel space as the anatomic voxel database at the same resolution . following this replication , the array indices for the architecture database exactly match the array indices of anatomic voxel database . due to this exact array index matching , the boolean substitution can be easily done . if the anatomic voxel database is denoted as “ anatomy ”, then the indices of the array where “ anatomy ” has a given density are substituted with the same indexed voxels from the architecture database that are linked to the specified anatomic density . this produces an optimized internal architecture in the shape of the desired anatomy . steps 1 - 6 produce a custom anatomically shaped scaffold with optimally designed interior porous architecture . the design at this point is described completely in a voxel database , with the scaffold topology represented as a density distribution within a fixed voxel grid . to fabricate these designed scaffolds using solid - free form fabrication , computer controlled machining , or other manufacturing techniques typically requires data in either a surface or wireframe geometry . specifically for solid free - form fabrication , the surface geometry is used for the . stl file format from 3d systems , inc . for surface representation , a marching cubes algorithm is used to generate an isosurface of triangular facets at a use specified density . these triangular facets are then written in a binary format according to . stl specifications . the generation of triangular facets is automatic , the user need only specify the density level at which the surface is generated from the scaffold design voxel database . for a wireframe representation , the user specifies a slicing direction and slicing distance . the algorithm then interpolates voxel density from the scaffold design at the specified slicing densities . a contouring algorithm is then used to extract wireframe contours at the specified density . these contours consist of joined polygon lines that are then written directly into either . s1c or . slf format . after creation of either a . stl , slc , or . slf data , the anatomically shaped scaffold with optimized porous architecture can then be built on a variety of solid free - form fabrication systems . the final step in creating the optimized scaffold is to fabricate the optimized design from a biomaterial . this biomaterial may be a ceramic , polymer or metal , so long as it is biocompatible . these optimal designs may be created by a variety of fabrication techniques including solid free - form fabrication and computer controlled milling . fabrication by solid free - form fabrication includes either direct fabrication from a biomaterial or fabrication of a mold into which a biomaterial may be cast . these solid free - form fabrication techniques include stereolithography ( sla ), receive laser sintering ( sls ), layered object manufacturing ( lom ), direct material deposition ( dmd ) and thermoplastic printing ( solidscape ). the above scaffold design procedure has been applied to design a mandibular condyle scaffold with internal architecture optimized to match three elastic young &# 39 ; s moduli of minipig mandibular condyle bone reported by teng and herring ( 1996 ). the following specific optimization formulation was used : e scaffold   min , d 1 , d 2 , d 3  ∑ i = 1 3  ( c i natural   tissue   eff - c i regen   tissue   eff c i natural   tissue   eff ) 2 + ∑ i = 1 3  ( c i natural   tissue   eff - c i scaffold   eff c i natural   tissue   eff ) 2 where the number of elastic constants to fit in the objective function was set to three ( the three orthogonal young &# 39 ; s moduli from teng and herring &# 39 ; s data ), the porosity bound was set to 60 % and the minimum and maximum scaffold young &# 39 ; s moduli were set to 1 and 15 gpa , respectively , to reflect the young &# 39 ; s modulus of available scaffold material ranging from biopolymers ( e - 1 cpa ) to bioceramics ( e = 15 gpa ). as shown in fig4 the results showed very close agreement between the scaffold moduli and the target bone moduli as well as the regenerate tissue moduli and the target bone moduli . the r 2 values in each case were 0 . 99 indicating excellent agreement between designed and target properties . the resulting scaffold design parameters and final scaffold porosity are shown in table 1 . table 1 : results for scaffold base modulus , three pore diameters and scaffold porosity when the scaffold architecture is optimized such that both scaffold and bone regenerate tissue elastic moduli match the target bone moduli from teng and herring . note that all scaffold porosity values match or exceed the minimum value of 0 . 60 or 60 % scaffold material pore 1 pore 2 pore 3 modulus diameter diameter diameter scaffold location ( gpa ) ( microns ) ( microns ) ( microns ) porosity suppostmed 10 . 7 . 633 . 516 . 777 . 63 supantmed 12 . 7 . 622 . 470 . 839 . 65 supostmid 9 . 3 . 591 . 520 . 767 . 71 supantmid 10 . 0 . 586 . 477 . 808 . 62 supostlat 14 . 3 . 723 . 512 . 782 . 66 supantlat 15 . 0 . 715 . 470 . 818 . 67 infpostmid 8 . 7 . 608 . 397 . 810 . 62 infantmid 15 . 0 . 563 . 536 . 857 . 67 average 12 . 0 . 627 . 489 . 818 . 64 the base scaffold moduli vary but typically had values closer to bioceramics . all pore diameters were within the bounds . finally , all scaffold porosity values met or exceeded the minimum value of 0 . 6 or 60 %. taken together , the results from fig4 and table 1 demonstrate that the current procedure can be used to optimize scaffold architectures such that both the scaffold and regenerate tissue match experimental target properties and the scaffold design parameters and porosity fall within desired limits . in addition , this approach provides for design and selection of the scaffold base material properties . referring to fig5 one of the optimized architectures was created in the shape of a mandibular condyle to demonstrate the ability to create anatomically shaped scaffolds with optimized interior porous architectures . the final scaffold design was created in both . stl format ( fig5 a ) and . slf format ( fig5 b ). the . slf format ( fig6 b ) has a large number of contours which makes it very difficult to see the details . the current invention provides the unique ability to optimize scaffold based material properties and scaffold interior architecture for a specific set of topologies , for example , intersecting cylinders . in addition , the invention allows constraints on the range of scaffold material properties , scaffold permeability , and the range of scaffold wall sizes . this type of optimization has not been previously presented for any type of biomaterial scaffold . also , the invention advantageously uses voxel based topologies to represent both interior scaffold architecture and exterior scaffold shape . this allows two or more architecture databases to be merged into an exterior scaffold shape design using boolean operations . this invention also uses voxel based techniques to design the initial set of scaffold architectures and homogenization theory to compute the range of effective properties . the current invention could be applied to design any type of tissue engineering scaffold or biomaterial matrix . these include , but are not limited to : 9 . in vitro tissue testing scaffolds including those used in bioreactors potential industries that may find this invention useful include orthopedic and cranial facial device industries , tissue engineering industries , and drug delivery and pharmaceutical industries . advantageously , the current invention allows the creation of these designs from anatomic images to be completed fairly rapidly , e . g ., 1 - 2 hours . coupling this with fabrication time , customized scaffolds can be turned around in a 1 - 2 day time frame . the description of the invention is merely exemplary in nature and , thus , variations that do not depart from the gist of the invention are intended to be within the scope of the invention . such variations are not to be regarded as a departure from the spirit and scope of the invention .

US-17841902-A

a rongeur surgical instrument is disclosed which has an actuating mechanism providing a variable degree of mechanical advantage for operation of the cutting element in the instrument . during the cutting stroke the rate of movement steadily decreases , while the degree of precision of movement and the amount of torque increase throughout the stroke . the instrument also has an improved shaft design which maintains cutting edge alignment with the footplate anvil surface , and also provides a mechanism for preventing cut portions of body material from aggregating near the distal end of the shaft and interfering with the cutting operation . in addition , the grip portion of the instrument has an adjustable spur member to allow the grip portion to comfortably fit a variety of hand sizes .

the preferred embodiment of the present invention has improvements embodied in the construction and operation of both the shaft members and the mounting and actuating mechanism . the description of the design and operational details will focus first on the shaft members , then on the mounting and actuating mechanism in and of itself , and finally on the operation of the improved rongeur surgical instrument as a whole . referring first to fig1 through 6 , a first shaft member 40 is illustrated . the first shaft member 40 as shown in fig1 through 3 has a proximal end on the right side of the drawings , and a distal end on the left side of the drawings . it is the distal end which will be the working end of the rongeur surgical instrument of the present invention . the proximal end of the first shaft member 40 is a wheel member 42 which is essentially round with a plurality of notches therein . the longitudinal axis of the first shaft member 40 is essentially perpendicular to the wheel member 42 . with the exception of a rectangular notch 44 in the top of the wheel member 42 , there are triangular notches 46 located at evenly spaced increments around the outer periphery of the wheel member 42 . the rectangular notch 44 extends much further into the wheel member 42 ( over half way through , as shown in fig3 and 5 ) than do the triangular notches 46 . in the preferred embodiment illustrated , there are seven of the triangular notches 46 in addition to the rectangular notch 44 , with 45 degrees between each adjacent pair of the notches 44 or 46 . the notches 44 and 46 will be used to position the first shaft member 40 with respect to a housing member to be discussed below in a desired rotational position in 45 degree increments . it will be apparent to those skilled in the art that more or fewer of the triangular notches 46 could be used if desired . extending distally from the wheel member 42 is a cylindrical segment 48 which has a diameter smaller than the diameter of the wheel member 42 . the cylindrical segment 48 has three distinct portions therein , all having the same diameter , and all having the rectangular notch 44 extending therein at the same depth as in the wheel member 42 . the first portion of the cylindrical segment 48 is immediately distal to the wheel member 42 , and is completely cylindrical except for the rectangular notch 44 therein . the second portion of the cylindrical segment 48 , which is immediately distal to the first portion , has a flat surface 50 on the top side thereof , with the balance of the cylindrical material removed . immediately distal to the second portion of the cylindrical segment 48 is a third portion , which has a flat surface 52 on the top side thereof . the flat surface 52 is lower than the flat surface 50 , with the third portion of the cylindrical segment 48 having even more material removed from the top of the cylinder . located immediately distal to the third portion of the cylindrical segment 48 is a long bottom shaft 54 which extends to the distal end of the first shaft member 40 . the long bottom shaft 54 has a flat top surface which is coplanar with the flat surface 52 of the cylindrical segment 48 . note that the rectangular notch 44 extends only into a short proximal portion of the long bottom shaft 54 . the long bottom shaft 54 is narrower than the width of the cylindrical segment 48 , as best seen in fig4 . for most of its length , the long bottom shaft 54 has a rounded bottom edge and flat side walls , as best seen in fig4 . located about two - thirds of the way from the proximal end of the long bottom shaft 54 toward the distal end thereof both sides of the long bottom shaft 54 are machined inwardly at 56 , as best shown in fig1 . these inwardly machined portions 56 are to allow retaining mechanisms located on a second shaft member to be discussed in conjunction with fig7 through 10 to be installed on the first shaft member 40 . located in both sides of the long bottom shaft 54 distally from the inwardly machined portions 56 nearly to the distal end of the long bottom shaft 54 are two slots 58 . the configuration of the slots . 58 are different from the slots used in the related patent application which was incorporated by reference above . the slots 58 thus extend longitudinally , and in cross - section as shown in fig6 widen as they extend into the sides of the long bottom shaft 54 . the narrowest portion of the slots 58 is thus adjacent the outside of the long bottom shaft 54 . located at the distal end of the long bottom shaft 54 is a footplate 60 , which extends transversely from the top of the long bottom shaft 54 . in fig2 , and 6 , the footplate 60 extends orthogonally to the flat top surface of the long bottom shaft 54 . however , in other embodiments , the footplate 60 could be located at an angle , typically with the footplate 60 declining away from the proximal end of the first shaft member 40 . for example , the footplate 60 may be mounted at a 45 degree angle declining away from the proximal end of the first shaft member 40 . note that as shown in fig3 the side of the footplate 60 facing proximally has a recess therein , to better enable the footplate 60 to act as an anvil in conjunction with a cutting member to be discussed below in conjunction with fig7 through 10 . located in the top surface of the long bottom shaft 54 spaced slightly proximally of the footplate 60 are a plurality of grooves 62 . as those skilled in the art know , bone or tissue chips , once removed by the operation of the rongeur , will be located in a tunnel defined in part by the top surface of the long bottom shaft 54 . as stated above , it is desirable to provide a mechanism allowing such bone and tissue chips to move proximally with respect to the first shaft member 40 , while inhibiting distal movement . the grooves 62 are this mechanism . the grooves 62 are configured so that the edge of each of the grooves 62 closest to the proximal end of the first shaft member 40 are tapered to facilitate the movement of bone or tissue chips in the proximal direction . however , the edge of each of the grooves 62 closest to the distal end of the first shaft member 40 are essentially orthogonal to the flat top surface of the long bottom shaft 54 . this configuration will impede the movement of bone or tissue chips in the distal direction . if desired , the sides of the grooves 62 closest to the distal end of the first shaft member 40 could even be undercut slightly to provide a sharper retaining edge . referring next to fig7 through 10 , a second shaft member 64 is illustrated . the second shaft member 64 as shown in fig7 through 9 has a proximal end on the right side of the drawings , and a distal end on the left side of the drawings . again , it is the distal end which will be the working end of the rongeur surgical instrument of the present invention . the second shaft member 64 has a ball 66 located at the proximal end thereof , which ball 66 will be used to drive the second shaft member 64 in reciprocating motion . the ball 66 is connected to a short shaft 68 , which in turn is connected to a long flat rectangular plate 70 . the flat rectangular plate 70 is oriented in a vertical manner , and has a thickness to allow the flat rectangular plate 70 to fit slideably into the rectangular notch 44 in the first shaft member 40 ( fig1 ). a long top shaft 72 which is attached to the distal end of the flat rectangular plate 70 extends essentially to the distal end of the second shaft member 64 . the long top shaft 72 has a flat bottom surface , and is of approximately the same width as the width of the long bottom shaft 54 of the first shaft member 40 ( fig1 ). for most of its length , the second shaft member 64 has a rounded top edge and flat side walls . in the preferred embodiment , the extreme proximal end of the second shaft member 64 has a wider diameter similar to the diameter of the cylindrical segment 48 of the first shaft member 40 ( fig1 ). the distal end of the long top shaft 72 is hollow to form a tunnel 74 therein , as best shown in fig9 ( the bottom of the tunnel 74 will be defined by the top surface of the long bottom shaft 54 of the first shaft member 40 shown in fig1 and 2 ). the distal end of the tunnel 74 is open , with the extreme distal portion of the long top shaft 72 being u - shaped in cross - section , as best shown in fig1 . the proximal end of the tunnel 74 communicates with an aperture 76 located in the top of the long top shaft 72 . the distal end of the long top shaft 72 is sharpened to form a cutting member 78 . it is this sharp - edged cutting member 78 which will be driven into engagement with the footplate 60 of the first shaft member 40 ( fig1 through 3 ) to cut bone or tissue . thus , it will be appreciated that the relative sizes and configurations of the cutting member 78 and the footplate 60 are directly related . for example , if the footplate 60 is mounted at a 45 degree angle declining away from the proximal end of the first shaft member 40 , the cutting member 78 would have a similar orientation . located on the sides of the long top shaft 72 of the second shaft member 64 near the distal end thereof are two side members 80 which extend below the flat bottom side of the long top shaft 72 . the side members 80 are designed to fit over the side of the long bottom shaft 54 of the first shaft member 40 ( fig1 ). on the facing inner sides of each of the side members 80 near the bottoms thereof is an inwardly extending tab 82 . the configuration of the inwardly extending tabs 82 are different from the tabs used in the related patent application which was incorporated by reference above . the inwardly extending tabs 82 extend longitudinally , and in cross - section as shown in fig1 they widen as they extend inwardly . the narrowest portion of the inwardly extending tabs 82 is thus immediately adjacent the side members 80 . the inwardly extending tabs 82 are designed for engagement with the slots 58 in the first shaft member 40 ( fig2 and 6 ). referring now to fig1 , 12 , and 13 , the assembly of the second shaft member 64 onto the first shaft member 40 is illustrated . in fig1 , the second shaft member 64 is illustrated above the first shaft member 40 in the proper manner for assembly . the inwardly extending tabs 82 on the side members 80 of the second shaft member 64 must be directly above the inwardly machined portions 56 on the sides of the first shaft member 40 . the flat rectangular plate 70 of the second shaft member 64 must also be above the rectangular notch 44 in the first shaft member 40 . the second shaft member 64 may then be lowered onto the first shaft member 40 , with the inwardly extending tabs 82 fitting around the inwardly machined portions 56 , and the flat rectangular plate 70 fitting into the rectangular notch 44 . fig1 shows the second shaft member 64 installed onto the first shaft member 40 in this manner , with the inwardly extending tabs 82 on the side members 80 of the second shaft member 64 engaged in the slots 58 in the first shaft member 40 . the flat rectangular plate 70 of the second shaft member 64 is also engaged in the rectangular notch 44 of the first shaft member 40 . note that in the position shown in fig1 , the distal end of the long top shaft 72 is in its fully proximal position on the flat surface 52 of the first shaft member 40 . further proximal movement of the second shaft member 64 without first lifting its proximal end will thus be prevented . fig1 illustrates the second shaft member 64 in its fully distal position on the first shaft member 40 . it may be seen that in this position , the cutting member 78 of the second shaft member 64 has engaged the footplate 60 of the first shaft member 40 . it will thus be apparent to those skilled in the art that the second shaft member 64 will reciprocate between the positions shown in fig1 and 13 in operation . note that the cutting member 78 of the second shaft member 64 will always be maintained in alignment with the footplate 60 of the first shaft member 40 , due to the interlocking design of the inwardly extending tabs 82 of the second shaft member 64 and the slots 58 of the first shaft member 40 . thus , the inwardly extending tabs 82 can no longer pull radially out of the slots 58 . note also the tunnel 74 in the second shaft member 64 ( fig9 ) and above the top surface of the long bottom shaft 54 of the first shaft member 40 will move in reciprocating fashion over the grooves 62 in the first shaft member 40 . thus , the grooves 62 will act to prevent bone and tissue chips from being moved distally out of the distal end of the second shaft member 64 by the reciprocating movement of the second shaft member 64 on the first shaft member 40 . this completes the description of the shaft members 40 and 64 of the rongeur surgical instrument of the present invention . referring next to fig1 through 18 , a housing member 84 is illustrated which is basically pistol - shaped . the housing member 84 has a grip portion 86 extending from the bottom and rear thereof . a spur member 87 extends rearwardly from the grip portion 86 at the rear and near the top thereof to provide support for the hand of a user ( not shown ). the housing member 84 is open on the top side thereof , as best shown in fig1 . the rear half of the top of the housing member 84 is open between the left and right side walls 88 and 90 of the housing member 84 , with the interior of the housing member 84 being both hollow and open to the bottom at the front of the grip portion 86 , as best shown in fig1 . located in the top side of the housing member 84 near the front is a cylindrical recess 92 , which will receive the bottom portion of the cylindrical segment 48 of the first shaft member 40 ( fig2 ). immediately to the rear of the cylindrical recess 92 in the housing member 84 is a larger diameter cylindrical recess 94 , which is for receiving the wheel member 42 of the first shaft member 40 ( fig2 ). the cylindrical recess 94 is of a length to admit the wheel member 42 without allowing the first shaft member 40 to move in an axial direction . located on each side of the housing member 84 at the top and around the cylindrical recess 92 is a notch 96 , best shown in profile in fig1 and 16 . the notches 96 are parallelogram - shaped , with the sides being angled upward and backward . this configuration of the notches 96 is for a latching mechanism which will be discussed below in conjunction with fig3 . located in the top of the housing member 84 immediately to the rear of and concentric with the cylindrical recess 94 is a smaller diameter cylindrical recess 98 . extending downwardly from the bottoms of both of the cylindrical recesses 94 and 98 is a notch 100 . the notch 100 , which is narrower than the diameter of the cylindrical recess 98 , is open at the rear thereof to the space between the left and right side walls 88 and 90 . located at the bottom of the notch beneath the cylindrical recess 94 is a small vertically oriented cylindrical recess 102 . located immediately to the rear of the cylindrical recess 98 and the notch 100 are two vertical slots 104 . one of the vertical slots 104 is located in the interior of the left side wall 88 , and the other of the vertical slots 104 is located in the interior of the right side wall 90 . the vertical slots 104 are open at the top of the housing member 84 , and extend about halfway down the interiors of the left and right side walls 88 and 90 . located at the bottom of the vertical slots 104 and extending rearwardly are two horizontal slots 106 . one of the horizontal slots 106 is located in the interior of the left side wall 88 , and the other of the horizontal slots 106 is located in the interior of the right side wall 90 . the fronts of the horizontal slots 106 are thus in communication with the bottoms of the vertical slots 104 . the horizontal slots 106 extend rearwardly , but do not extend to the rear of the left and right side walls 88 and 90 . located laterally in the housing member 84 are axially aligned apertures 108 which extend through the vertical slots 104 at intermediate positions therein . located near the rear of the housing member 84 at a level just below the horizontal slots 106 are two axially aligned apertures 110 which also extend laterally through the left and right side walls 88 and 90 of the housing member 84 . located in each of the left and right side walls 88 and 90 of the housing member 84 are two pairs of slots 112 and 114 . one of the slots 112 is horizontally located just below the top of the housing member 84 in each of the left and right side walls 88 and 90 . the slots 114 are located in the left and right side walls 88 and 90 above the front of the grip portion 86 , and extend upward and slightly toward the front of the housing member 84 . all of the slots 112 and 114 extend through the left and right side walls 88 and 90 of the housing member 84 . located in the front of the grip portion 86 near the bottom thereof is a threaded aperture 116 . located nearer the top of the grip portion 86 is another threaded aperture 118 . referring now to fig1 through 21 , a cover member 120 for enclosing the top of the housing member 84 ( fig1 ) is illustrated . the cover member 120 is mounted on a support arm 122 , which extends downwardly from the rear of the cover member 120 . the support arm 122 is of a width ( fig2 ) to fit between the left and right side walls 88 and 90 of the housing member 84 . extending laterally through the support arm 122 is a horizontally disposed slot 124 , which will be used to mount the cover member 120 onto the housing member 84 . located in the bottom side of the cover member 120 at the front is a cylindrical recess 126 for receiving the cylindrical segment 48 of the first shaft member 40 ( fig2 ). located to the rear of the cylindrical recess 126 is a larger diameter cylindrical recess 128 , which is for receiving the wheel member 42 of the first shaft member 40 ( fig2 ). the cylindrical recess 128 is of a length to admit the wheel member 42 , and also to allow the cover member 120 to move rearwardly slightly to allow the cover member 120 to be unlatched , as will become evident in the discussion of fig3 . located on each side of the cover member 120 at the bottom and around the cylindrical recess 126 is a tab 130 , best shown in profile in fig1 and 21 . the tabs 130 are essentially parallelogram - shaped ( with rounded lower corners ), with the sides being angled downward and forward . the tabs 130 are not as long as are the notches 96 in the housing member 84 ( fig1 and 16 ). this configuration of the tabs 130 is for a latching mechanism which , as mentioned above , will be discussed below in conjunction with fig3 . located to the rear of the cylindrical recess 128 in the cover member 120 is a smaller cylindrical recess 132 . behind this cylindrical recess 132 , the cover member 120 is thinner , designed to cover the top of the rear portion of the housing member 84 . referring next to fig2 and 23 , a trigger member 134 is illustrated which includes a gripping portion 136 designed to be squeezed by the four fingers of a hand . above the gripping portion 136 , the trigger member 134 is angled back , and has a support bar 138 connected as the cross bar of a &# 34 ; t &# 34 ; at the end of the trigger member 134 . the ends of the support bar 138 have apertures 140 and 142 laterally extending therethrough . the aperture 140 extends through the upper end of the support bar 138 , while the aperture 142 extends through the lower end of the support bar 138 . the apertures 140 and 142 in the support bar 138 are the mechanism through which the trigger member 134 will be installed for movement in the housing member 84 ( fig1 ) using the slots 112 and 114 . located in the upper end of the support bar 138 is a notch 144 splitting the upper end of the support bar 138 into two lateral halves . referring now to fig2 through 27 , a slide member 146 is illustrated . extending from the rear of the slide member 146 near the top thereof is an arm 148 located in a vertical plane . the arm 148 has a lateral aperture 150 extending therethrough , and is for engagement with the notch 144 in the trigger member 134 ( fig2 ). extending outwardly from the sides of the slide member 146 at the bottom and front thereof are horizontally oriented tabs 152 , which are for engagement with the horizontal slots 106 in the left and right side walls 88 and 90 of the housing member 84 ( fig1 and 18 ). located vertically in the top side of the slide member 146 is a cylindrical aperture forming a socket 154 , which is for engaging the ball 66 of the second shaft member 64 ( fig7 through 9 ). located at the front of the socket 154 is a vertically extending slot 156 communicating with the socket 154 . the slot 156 has a width designed to admit the shaft 68 through which the ball 66 is attached to the rest of the second shaft member 64 ( fig7 ). referring next to fig2 and 29 , a locking member 158 used to selectively inhibit rotation of the wheel member 42 at the proximal end of the first shaft member ( fig6 ) is illustrated . the locking member 158 has a flat base member 160 which is of a width for placement in the notch 100 in the housing member 84 ( fig1 and 17 ). located on top of the flat base member 160 at the front thereof is a wedge member 162 designed to fit into the triangular notches 46 of the rectangular notch 44 of the wheel member 42 ( fig4 ) to inhibit rotation of the wheel member 42 . extending upwardly from the rear of the flat base member 160 is an arm 164 which has a laterally extending aperture 166 therethrough . the aperture 166 will be used to pivotally mount the locking member 158 using the apertures 108 in the left and right side walls 88 and 90 of the housing member 84 ( fig1 , 16 , and 18 ). referring next to fig3 , a pin 168 used to support the locking member 158 ( fig2 and 29 ) is illustrated . the pin 168 has three sets of ridges located around the perimeter of the pin 168 , each of which sets of ridges is used for frictional engagement of the pin 168 in an aperture . a center set of ridges 170 located in the middle of the pin 168 will be used to engage the aperture 166 in the arm 164 of the locking member 158 . sets of ridges 172 located at the ends of the pin 168 will be use to attach operating mechanisms to the ends of the locking member 158 . referring next to fig3 , one of these operating mechanisms is illustrated . a lever 174 is illustrated which has an aperture 176 used for mounting the lever 174 onto one of the sets of ridges 172 on one end of the pin 168 ( fig3 ). the lever 174 may also have a raised portion 178 thereon to facilitate operation of the lever 174 . the assembly of the various components of fig1 through 31 may now be described . fig3 illustrates the housing member 84 illustrated in fig1 through 18 with most of the left side wall 88 cut away for clarity . assembled to the housing member 84 are the cover member 120 illustrated in fig1 through 21 , the trigger member 134 illustrated in fig2 and 23 , the slide member 146 illustrated in fig2 through 27 , the locking member 158 illustrated in fig2 and 29 , and the pin 168 illustrated in fig3 . several additional components are illustrated as well . the first component to be installed in the housing member 84 is the slide member 146 . the slide member 146 is installed by placing it between the left and right side walls 88 and 90 of the housing member 84 , with the tabs 152 of the slide member 146 fitting into the vertical slots 104 in the housing member 84 . the slide member 146 is moved downwardly , so that the tabs 152 of the slide member 146 move to the bottoms of the vertical slots 104 in the housing member 84 , which are in communication with the fronts of the horizontal slots 106 in the housing member 84 . the slide member 146 is then moved toward the rear of the housing member 84 , with the tabs 152 of the slide member 146 moving back in the horizontal slots 106 in the housing member 84 . the trigger member 134 may next be installed in the housing member 84 , using two pins 180 and four bearings 182 . one end of each of the pins 180 is peened , with the peened end being capable of retaining one of the bearings 182 thereon . the support bar 138 of the trigger member 134 is placed between the left and right side walls 88 and 90 of the housing member 84 with the aperture 140 in the support bar 138 aligned with the slots 112 in the housing member 84 , and with the aperture 142 in the support bar 138 aligned with the slots 114 in the housing member 84 . one of the bearings 182 ( not shown ) is installed onto a first one of the pins 180 , and the unpeened end of the first one of the pins 180 is inserted from the right side of the housing member 84 through the slot 112 ( fig1 ) in the right side wall 90 of the housing member 84 . the arm 148 of the slide member 146 is then placed in the notch 144 ( fig2 ) in the support bar 138 of the trigger member 134 , with the aperture 150 ( fig2 ) in the arm 148 aligned with the aperture 140 ( fig2 and 23 ) of the support bar 138 . the unpeened end of the first one of the pins 180 then goes through the aperture 140 in the support bar 138 of the trigger member 134 and the aperture 150 in the arm 148 of the slide member 146 . the arm 148 of the slide member 146 is thereby retained and will be driven by movement of the top end of the support bar 138 of the trigger member 134 . the unpeened end of the first one of the pins 180 next goes through the slot 112 in the left side wall 88 ( fig1 ) of the housing member 84 . another one of the bearings 182 is then installed on the unpeened end of the first one of the pins 180 . both of the bearings 182 on the first one of the pins 180 fit fully into the slots 112 in the housing member 84 , and the unpeened end of the first one of the pins 180 is then peened to retain it in place . another one of the bearings 182 ( not shown ) is installed onto a second one of the pins 180 , and the unpeened end of the second one of the pins 180 is inserted from the right side of the housing member 84 through the slot 114 ( fig1 ) in the right side wall 90 of the housing member 84 . the unpeened end of the second one of the pins 180 then goes through the aperture 142 ( fig2 ) in the support bar 138 of the trigger member 134 , and through the slot 114 in the left side wall 88 ( fig1 ) of the housing member 84 . the last one of the bearings 182 is then installed on the unpeened end of the second one of the pins 180 . both of the bearings 182 on the second one of the pins 180 fit fully into the slots 114 in the housing member 84 , and the unpeened end of the second one of the pins 180 is then peened to retain it in place . a spring member 184 having a roller wheel 186 located at one end thereof has the other end thereof secured to the front of the grip portion 86 of the housing member 84 with a screw 188 inserted into the threaded aperture 116 ( fig1 ). the spring member 184 biases the trigger member 134 into the position illustrated in fig3 . the gripping portion 136 of the trigger member 134 may be squeezed toward the grip portion 86 of the housing member 84 , with the spring member 184 bearing on the back of the gripping portion 136 via the roller wheel 186 to resist such movement , and to return the trigger member 134 to the position shown when the squeezing pressure on the trigger member 134 is released . it will also be appreciated by those skilled in the art that squeezing the gripping portion 136 of the trigger member 134 toward the grip portion 86 of the housing member 84 will cause the top end of the support bar 138 to drive the slide member 146 forward in the housing member 84 . upon releasing the squeezing pressure on the trigger member 134 , the spring member 184 will return the trigger member 134 to the position illustrated , also driving the slide member 146 rearwardly to the position shown in fig3 . a coil spring 190 is inserted into the cylindrical recess 102 in the housing member 84 . the locking member 158 is inserted into the notch 100 with the wedge member 162 located at the front as shown . the aperture 166 ( fig2 ) in the arm 164 of the locking member 158 is aligned with the apertures 108 in the housing member 84 , and the pin 168 is inserted through the aperture 108 in the right side of the housing member 84 , through the aperture 166 in the arm 164 of the locking member 158 , and then through the aperture 108 in the left side of the housing member 84 . the center set of ridges 170 ( fig3 ) of the pin 168 frictionally engage the aperture 166 in the arm 164 of the locking member 158 , maintaining the arm 164 and the rest of the locking member 158 in a mounted position on the pin 168 . the sets of ridges 172 ( fig3 ) on the ends of the pin 168 extend out of the apertures 108 on both sides of the housing member 84 . referring briefly to fig3 , one of the levers 174 will then be mounted on each of the sets of ridges 172 on the ends of the pin 168 ( the mounting of a lever 174 on the right side of the housing member 84 is the same as illustrated on the left side in fig3 ). with the levers 174 being used on both sides of the housing member 84 , operation of the locking member 158 may be done with the housing member 84 held in either hand of a user . referring now to both fig3 and 34 , by pushing end of the lever 174 having the raised portion 178 thereon upward , the wedge member 162 of the locking member 158 is moved downward against the force of the coil spring 190 , and out of the cylindrical recess 94 . referring again to fig3 , the installation of the cover member 120 may now be discussed . the cover member 120 is placed into position on the top of the housing member 84 as shown , with the slot 124 in the support arm 122 of the cover member 120 aligned with the apertures 110 ( fig1 and 16 ) in the housing member 84 . a pin 192 is installed in the apertures 110 , extending through the slot 124 and thereby capturing the cover member 120 . the pin 192 has an interference fit in the apertures 110 , but not in the slot 124 . a spring member 194 has one end thereof secured to the front of the grip portion 86 of the housing member 84 with a screw 196 inserted into the threaded aperture 118 ( fig1 ). the other end of the spring member 194 extends back between the left and right side walls 88 and 90 of the housing member 84 , and bears on the bottom of the support arm 122 , urging it forward . thus , it will be appreciated that the function of the spring member 194 is to urge the cover member 120 forward , to the limit of the slot 124 in the support arm 122 of the cover member 120 . it may be seen in fig3 that the tabs 130 of the cover member 120 are captured by the notches 96 of the housing member 84 when the cover member 120 is in its forward position , into which it is urged by the spring member 194 . note again that the lengths of the tabs 130 on the cover member 120 are shorter than the lengths of the notches 96 in the housing member 84 . this is to allow the cover member 120 to be pulled toward the rear of the housing member 84 , as shown in fig3 . in this position , the tabs 130 of the cover member 120 are no longer captured by the notches 96 of the housing member 84 , and the cover member 120 may be opened by rotating the front of the cover member 120 up and back , pivoting around the pin 192 . with the cover member 120 opened , the assembled first and second shaft members 40 and 64 may be installed in the manner illustrated in fig3 . the wheel member 42 of the first shaft member 40 fits into the cylindrical recess 94 ( fig1 and 16 ) of the housing member 84 , with the cylindrical segment 48 of the first shaft member 40 extending out of the housing member 84 through the cylindrical recess 92 ( fig1 and 16 ) at the front of the housing member 84 . when the cover member 120 is closed as shown in fig3 , the wheel member 42 of the first shaft member 40 will be retained between the cylindrical recess 94 in the top of the housing member 84 and the cylindrical recess 128 ( fig2 and 21 ) in the bottom of the cover member 120 . similarly , the cylindrical segment 48 of the first shaft member 40 will be retained between the cylindrical recess 92 in the top of the housing member 84 and the cylindrical recess 126 ( fig2 and 21 ) in the bottom of the cover member 120 . the tabs 130 of the cover member 120 are again retained by the notches 96 of the housing member 84 . it will be appreciated by those skilled in the art that the wedge member 162 of the locking member 158 ( fig3 ) will be urged by the coil spring 190 to engage one of the triangular notches 46 or the rectangular notch 44 ( fig5 ) in the wheel member 42 of the first shaft member 40 to retain the first shaft member 40 and the second shaft member 64 in a desired rotational configuration . this rotational configuration may be adjusted by pushing the raised portion 178 of one of the levers 174 upward to release the wedge member 162 of the locking member 158 from the engaged one of the triangular notches 46 or the rectangular notch 44 in the wheel member 42 , then rotating the first shaft member 40 and the second shaft member 64 to their desired position and releasing the lever 174 . the operation of the rongeur surgical instrument of the present invention may now be discussed with reference to fig3 and 35 . with the gripping portion 136 of the trigger member 134 in its unsqueezed position shown in fig3 , the distal end of the long top shaft 72 of the second shaft member 64 is in its fully proximal position on the flat surface 52 of the first shaft member 40 . the cutting member 78 is thus far from the footplate 60 . when the gripping portion 136 of the trigger member 134 is squeezed as shown in fig3 , the distal end of the long top shaft 72 of the second shaft member 64 moves to its fully distal position on the flat surface 52 of the first shaft member 40 . the cutting member 78 is brought into contact with the footplate 60 . during this operation any tissue or bone between the cutting member 78 and the footplate 60 will be cut . in comparing the positions of the rongeur surgical instrument of the present invention shown in fig3 and 35 , another difference is apparent . the pivot point is always at the location of the pin 180 and the bearings 182 in the slots 114 . with the instrument in the position of fig3 , the pivot point is at the bottoms of the slots 114 . in the position of the instrument in fig3 , the pivot point is at the tops of the slots 114 . it will thus be appreciated that during the actuation stroke , the pivot point will vary , becoming progressively shorter as the gripping portion 136 of the trigger member 134 is squeezed . thus , as the cutting member 78 nears the footplate 60 , a given movement of the gripping portion 136 of the trigger member 134 will produce progressively less and less movement of the cutting member 78 , giving the operation a higher degree of precision of operation near the end of the stroke . this also moves the cutting member 78 faster during the first part of the stroke , when precision of operation is not needed as much . this is graphically illustrated in the plot of fig3 , in which operation of a conventional rongeur is shown by the dotted line and the operation of the rongeur surgical instrument of the present invention is shown by the solid line . throughout the stroke , the conventional rongeur retains a uniform mechanical advantage . however , the rongeur surgical instrument of the present invention has a smaller mechanical advantage at the beginning of the stroke , and the mechanical advantage increases throughout the stroke . in addition to varying the speed and the precision of operation of the instrument , the amount of torque transmitted will also be varied throughout the stroke . at the beginning of the stroke , the torque will be at a minimum . this is fine , since little torque is needed , since the cutting operation does not take place at the beginning of the stroke . however , near the end of the stroke , the torque has increased ; since this is the point at which the cutting operation will take place , this represents a highly desirable effect . fig4 illustrates an alternate embodiment of the actuating mechanism . the trigger member 134 is modified at its opposite end where the &# 34 ; t &# 34 ; end is located . the trigger member continues to have an elbow bend going to the &# 34 ; t &# 34 ; end 252 . the &# 34 ; t &# 34 ; portion is longer and is forked beginning at the elbow bend . the forked portion 260 extends on both sides of the housing member 88 and fits around the housing member . the housing member 84 includes a rear projection 256 that is adjacent to the &# 34 ; t &# 34 ; end . the projection 256 has a hole and a pin 254 to secure the right half of the &# 34 ; t &# 34 ; 252 to the housing member . the stationary point for the actuating mechanism is located at the pin 254 . the left end of the &# 34 ; t &# 34 ; has a linkage 250 connected to the roller and pin 180 . there is another linkage 250 on the other side of the actuating mechanism that functions as a mirror image to linkage 250 . instead of being forked at the &# 34 ; t &# 34 ; portion , the &# 34 ; t &# 34 ; portion can be flat and able to fit in the housing 84 . in this version , the right side of the &# 34 ; t &# 34 ; would be fastened to the stationary point 254 by being placed between the walls of the housing member at the projection 252 . fig4 illustrates another alternate embodiment of the actuating mechanism . the trigger member 134 is the same configuration as shown in the preferred embodiment in fig3 . however , the stationary point for the actuating mechanism is now at 262 . there is a projection 263 above the spur 87 . the right half of the &# 34 ; t &# 34 ; moves along the slot 264 rather than remaining stationary and pivoting as is the case in the alternate shown in fig4 . an additional pair of linkages 260 are on both sides of the housing member 84 . the other ends of the pair of linkages 260 are secured to the roller by a pin 180 . the slotted opening 264 is changed slightly to allow the roller and pin 180 clearance to move as the actuating mechanism is being used . in an alternate embodiment , the housing member 84 of fig1 through 18 may be modified to replace the spur member 87 , which is mounted in a fixed position on the rear of the grip portion 86 ( fig1 and 16 ), with an adjustable spur member mounted on the grip portion 86 in a position which may be adjusted . this adjustment will vary the height of the spur member on the rear of the grip portion 86 . referring to fig3 through 39 , a housing member 198 having a grip portion 200 is illustrated which is identical to the housing member 84 of fig1 through 18 , with three exceptions . first , unlike the grip portion 86 , the grip portion 200 of the housing member 198 does not have a fixed spur member 87 mounted thereon . second , the rear of the grip portion 200 has a flat portion 202 near the location corresponding to the location of the spur member 87 on the grip portion 86 . third , the sides of the grip portion 200 have slots 204 and 206 in the left and right sides , respectively , thereof in front of the flat portion 202 . the flat portion 202 on the rear of the grip portion 200 of the housing member 198 extends upward and downward somewhat from the location of the spur member 87 on the grip portion 86 . the slots 204 and 206 are spaced away from and parallel to the flat portion 202 , and also upward and downward somewhat from the location of the spur member 87 on the grip portion 86 . in all other respects , the housing member 198 is the same as the housing member 84 , and reference numerals identical to those used on the housing member 84 are used on similar components on the housing member 198 . referring next to fig4 through 42 , a left adjustable spur half 208 is illustrated which has a main portion similar in configuration to the left half of the spur member 87 ( fig1 and 16 ). the left adjustable spur half 208 has an arm 210 extending from the lower left front portion thereof , which arm 210 is configured to fit around the left side of the portion of the grip portion 200 having the slot 204 therein ( fig3 through 39 ). on the right - facing side of the arm 210 is a tab 212 which is oriented to fit into the slot 204 . note that the length of the tab 212 is considerably less then the length of the slot 204 . extending through the main portion of the left adjustable spur half 208 is an aperture 214 , which is countersunk on the left side of the left adjustable spur half 208 . also located in the main portion of the left adjustable spur half 208 on the right side thereof and spaced away from the aperture 214 is an aperture 216 which does not extend through the left adjustable spur half 208 . referring next to fig4 through 45 , a right adjustable spur half 218 is illustrated which has a main portion similar in configuration to the right half of the spur member 87 ( fig1 and 16 ). the right adjustable spur half 218 has an arm 220 extending from the lower right front portion thereof , which arm 220 is configured to fit around the right side of the portion of the grip portion 200 having the slot 206 therein ( fig3 through 39 ). on the left - facing side of the arm 220 is a tab 222 which is oriented to fit into the slot 206 . note that the length of the tab 222 is considerably less then the length of the slot 206 . extending into the left side of the main portion of the right adjustable spur half 218 is a threaded aperture 224 , which does not extend through the right adjustable spur half 218 . the location of the threaded aperture 224 in the right adjustable spur half 218 corresponds exactly to the location of the aperture 214 in the left adjustable spur half 208 ( fig4 ). extending from the left side of the main portion of the right adjustable spur half 218 and spaced away from the aperture 224 is a pin 226 , the location of which pin 226 in the right adjustable spur half 218 corresponds exactly to the location of the aperture 216 in the left adjustable spur half 208 ( fig4 ). in addition , the pin 226 is sized to fit into the aperture 216 . referring now to fig4 and 47 , the assembly of the left adjustable spur half 208 and the right adjustable spur half 218 to the grip portion 200 of the housing member 198 is illustrated . the left adjustable spur half 208 is positioned with the tab 212 of the left adjustable spur half 208 in the slot 204 of the grip portion 200 , and the right adjustable spur half 218 is positioned with the tab 222 of the right adjustable spur half 218 in the slot 206 of the grip portion 200 . the right side of the main portion of the left adjustable spur half 208 is brought into contact with the left side of the main portion of the right adjustable spur half 218 , with the pin 226 of the right adjustable spur half 218 extending into the aperture 216 of the left adjustable spur half 208 . a flat head screw 228 is installed through the aperture 214 in the left adjustable spur half 208 into the threaded aperture 224 in the right adjustable spur half 218 . by not quite tightening the flat head screw 228 , the adjustable spur assembly consisting of the left adjustable spur half 208 and the right adjustable spur half 218 may be adjusted in height on the grip portion 200 of the housing member 198 . when the adjustable spur assembly is properly positioned , the flat head screw 228 may be tightened to fix the adjustable spur assembly in place on the grip portion 200 of the housing member 198 . it may therefore be appreciated from the above detailed description of the preferred embodiment of the present invention that it teaches a more positive mechanism for maintaining the relative alignment of the cutting member and the footplate in a rongeur surgical instrument . the mechanism for maintaining alignment of the cutting member and the footplate does not interfere in any way with the cutting operation of the surgical instrument , or with the surgeon &# 39 ; s vision of the cutting operation . in addition , this desirable design ambition is achieved without increasing the size of the members in any way , thereby maintaining a small distal shaft configuration . in another primary aspect , the present invention provides a variable degree of mechanical advantage to the trigger - actuated operation of the movement of the cutting member toward the footplate . during initial actuation of the trigger member to initiate movement of the cutting member toward the footplate prior to engagement of bone or tissue , the improved rongeur surgical instrument provides a lesser degree of mechanical advantage , together with a greater degree of movement of the cutting member . in contrast , during actuation of the trigger subsequent to engagement of bone or tissue between the cutting member and the footplate , the improved rongeur surgical instrument provides a greater degree of mechanical advantage , together with a lesser degree of movement of the cutting member . in still another primary aspect , the present invention provides a mechanism for inhibiting movement of bone or tissue chips , once cut , distally out of the tunnel in the cutting member . this mechanism thus provides a restriction on the movement of the bone or tissue chips , but without restricting in any way the cutting operation of the surgical instrument . thus , the mechanism for inhibiting movement of bone or tissue chips to the location of the cutting operation should enhance the ease of the cutting operation by not requiring the surgeon to pause to remove bone or tissue chips from the cutting members . the rongeur surgical instrument of the present invention also provides a grip which is adjustable to provide a custom fit to a wide variety of hand sizes . the variable fit of the grip may be modified to provide a comfortable accommodation for any hand size through a simple adjustment which may be quickly and easily accomplished . it can be appreciated that the invention disclosed and claimed herein can be used and incorporated herein with various tools and instruments other than a rongeur , such as staplers , tonsil and adenoid cutters , etc . the improved rongeur surgical instrument of the present invention is of solid construction , to be both durable and long - lasting in operation . finally , all of the aforesaid advantages and objectives of the present invention are achieved without incurring any substantial relative disadvantage . although an exemplary embodiment of the present invention has been shown and described , it will be apparent to those having ordinary skill in the art that a number of changes , modifications , or alterations to the invention as described herein may be made , none of which depart from the spirit of the present invention . all such changes , modifications , and alterations should therefore be seen as within the scope of the present invention .

US-78043191-A

a urine collection system includes an anti - flux mechanism to reduce the amount of urine that may flow from within the collection bag back into the urine meter . the urine collection system includes a urine meter , a collection member defining at least a first opening for receiving urine from the urine meter and a shield positioned adjacent the opening of the collection member . the shield is affixed to the collection member at predetermined connection points along a periphery of the shield whereby urine flows between the connection points from the urine meter to the collection member . the shield may be affixed to an internal surface of the bag . the shield may be spot welded to the collection member at the connection points . the shield may include at least a first slot configured to permit the passage of fluid therethrough .

referring initially to fig1 and 2 , a prior art urine collection system is shown generally as urine collection system 10 . urine collection system 10 is described in detail in commonly owned u . s . patent application publication no . 2007 / 0213639 , the contents of which is hereby incorporated by reference in their entirety , and will only be discussed to the extent necessary to enable the aspects of the present disclosure . urine collection system 10 includes a urine meter 20 and a collection member or bag 30 . urine meter 20 includes two large dump ports 22 , 23 which are in fluid communication with openings 32 , 33 formed in collection bag 30 . fluid “ f ” flows into urine meter 20 through tube “ t ” where the amount of fluid “ f ” may be measured before urine collection system 10 is tilted and fluid “ f ” drains into collection bag 30 . while the configuration of urine collection system 10 enables a user to easily drain fluid “ f ” from urine meter 20 into collection bag 30 , accident tilting of urine collection system 10 may also cause reflux of fluid “ f ” from collection bag 30 back into urine meter 20 through dump ports 22 , 23 . turning now to fig3 , a first embodiment of an anti - reflex mechanism according to the present disclosure is shown generally as shielded collection bag 100 . anti - reflux collection bag 100 is substantially similar to collection bag 30 discussed hereinabove , and will only be described as relates to the differences therebetween . anti - reflux collection bag 100 defines openings 132 , 133 for receiving fluid from a urine meter . anti - reflux collection bag 100 further includes shields 102 , 104 partially obstructing openings 132 , 133 . shields 102 , 104 may be constructed of vinyl or other suitable material . shields 102 , 104 are sized and dimensioned to cover openings 132 , 133 . shields 102 , 104 are affixed to the inner surface of collection bag 100 . shields 102 , 104 are positioned within collection bag 100 over openings 132 , 133 . once in position , shields 102 , 104 are attached to collection bag 100 at select points 102 a - c , 104 a - c about the perimeter of shields 102 , 104 , respectively . shields 102 , 104 may be attached to collection bag 100 using spot welding , adhesive or other suitable methods . as shown , shields 102 , 104 are each attached to collection bag 100 at three points 102 a - c , 104 a - c , respectively , however , fewer or more attachment points may be used . it is envisioned that attachment points 102 a - c , 104 a - c may be positioned at any suitable point along overlapping portions of collection bag 100 and shields 102 , 104 , respectively . by attaching shields 102 , 104 at select attachment points 102 a - c , 104 a - c , the remaining areas of overlap between collection bag 100 and shields 102 , 104 , namely overlap portions 106 , 107 remain unattached to collection bag 100 . in this manner , fluid “ f ” is permitted to flow from a urine meter , around or between attachment points 102 a - c , 104 c , and into collection bag 100 . overlap portions 106 , 107 may be configured to prevent sticking of shields 102 , 104 , respectively , to collection bag 100 . for example , overlap portions 106 , 107 may include knobs , ridges or other suitable configurations ( not shown ) to prevent shields 102 , 104 from sealing to bag 100 . overlap portions 106 , 107 may instead or further include a film or coating between shields 102 , 104 and collection bag 100 to prevent sticking of overlap portions 106 , 107 . shields 102 , 104 further include flaps 108 , 109 , respectively , configured to permit additional flow of fluid “ f ” from a urine meter into collection bag 100 . flaps 108 , 109 are configured to deflect inwardly from the urine meter as fluid “ f ” enters collection bag 30 while restricting movement of the flaps 108 , 109 in an outward direction toward the urine meter . in this manner , flaps 108 , 109 permit more fluid “ f ” to drain into collection bag 100 than is permitted to reflux back into the urine meter . flaps 108 , 109 may be positioned in any suitable location about shields 102 , 104 , respectively . shields 102 , 104 may include any number of flaps 108 , 109 , respectively , including no flaps at all . turning now to fig4 a - c , another embodiment of an anti - reflux mechanism according to the present disclosure is shown generally as anti - reflux guard 200 . anti - reflux guard 200 is configured to be secured within dump port 22 of urine meter 20 ( fig1 ). in this manner , guard 200 would be positioned between urine meter 20 and a collection bag 30 to control the flow of fluid “ f ” therebetween . a second guard ( not shown ) is a substantial mirror image of anti - reflux guard 200 and is configured to be secured within dump port 23 of urine meter 20 . in addition , openings 202 may be directional valves or one way openings permitting flow only in one direction from the urine meter to collection bag 100 . guard 200 defines a substantially planar member having a first side 202 a and a second side 202 b . as will be discussed in further detail below , first side 202 a of guard 200 is configured to engage dump port 22 of urine meter 20 ( fig1 ). guard 200 includes a plurality of horizontally spaced openings 202 . openings 202 define progressively larger internal dimensions or holes from bottom to top . although shown as circular openings , openings 202 may define any shape . the size and configuration of openings 202 may be varied to control the flow of fluid “ f ” into collection bag 30 ( fig1 ) and the reflux of fluid “ f ” back into urine meter 20 . the size and configuration of openings 202 may also be varied to control the passing of clots into collection bag 30 . in addition , openings 202 may be directional or one way valves or openings permitting flow only in the direction from urine meter 20 to collection bag 100 . guard 200 may be secured to dump port 22 of urine meter 20 in any suitable manner , including bonding , adhesive and friction or snap - fit . alternatively , guard 200 may be integrally formed with urine meter 20 . as shown , guard 200 is configured to be snap - fit within dump port 22 of urine meter 20 . guard 200 includes snap members 204 and locators 206 . locators 206 are located opposite snap members 204 and are configured to engage a first edge 22 a of dump port 22 . snap members 204 are configured to selectively engage a second edge 22 b of dump port 22 . guard 200 may include any number of snap members 204 and locators 206 . guard 200 further includes guides 208 , 209 configured to align guard 200 within dump port 22 . guides 208 , 209 are configured to engage third and fourth edges 22 c , 22 d , respectively , of dump port 22 . guard 200 may include any number of guides 208 , 209 . snap members 204 , locators 206 and guides 208 , 209 align and maintain guard 200 securely within dump port 22 . a seal or sealing substance ( not shown ) may be placed between guard 200 and urine meter 20 to increase the integrity of the seal therebetween . turning now to fig5 a - 6 , alternate embodiments of anti - reflux guard 200 are shown generally as anti - reflux guards 210 , 220 . anti - reflux guards 210 , 220 are substantially similar to anti - reflux guard 200 , and will only be described in detail as relates to the differences therebetween . anti - reflux guard 210 includes first and second sides 210 a , 210 b and defines a single large opening 212 . opening 212 is covered by a flap 213 . flap 213 is hingedly mounted to second side 210 b of guard 210 above opening 212 . flap 213 is sized and dimensioned to extend beyond opening 212 . guard 210 further includes snap members 214 , locators 216 and guides 218 , 219 configured to retain guard 210 within dump port 23 of urine meter 20 ( fig4 c ). when installed , flap 213 of guard 210 operates to permit the flow of fluid “ f ” through opening 212 into collection bag 30 ( fig1 ) and prevent the flow , or reflux , of fluid “ f ” back into urine meter 20 . as fluid “ f ” accumulates within urine meter 20 and encounters opening 212 , flap 213 swings away , thereby permitting fluid “ f ” to enter collection bag 30 . as fluid “ f ” reaches a predetermined level in collection bag 20 , the urine contacts the flap 213 , in effect , closing the flap 213 by biasing the flap edges extending beyond opening 212 against guard 200 . in this manner , fluid “ f ” is prevent from flowing back into urine meter 20 once it has been drained into collection bag 30 ( fig1 ). anti - reflux guard 220 includes horizontal slots 222 that get progressively taller from bottom to top . the size and configuration of horizontal slots 222 may be varied to control the flow of fluid “ f ” into collection bag 30 ( fig1 ) and the reflux of fluid “ f ” back into urine meter 20 . the size and configuration of horizontal slots 222 may also be varied to control the passing of clots into collection bag 30 . with reference now to fig7 a - e , yet another embodiment of an anti - reflux mechanism according to the present disclosure is shown generally as collection bag insert 300 . insert 300 is configured to be received within a collection bag 30 a . collection bag 30 a and insert 300 are configured for use with urine meter 20 and other suitable urine meters . it is envisioned that insert 300 may be modified for use with urine meters of alternative configurations , including urine meters with only a single dump port . insert 300 includes backboard 302 and a pair of flanges 304 , 306 extending from a first surface 303 a of backboard 302 . flanges 304 , 306 may be integrally formed with backboard 302 , or instead may be fixedly secured to backboard 302 using adhesive , boding or other suitable technique . backboard 302 defines a substantially planar base having a generally “ t ” shaped configuration . flanges 304 , 306 are located on a horizontal portion 302 a of backboard 302 and define openings 304 a , 306 a . flanges 304 , 306 are configured to engage dump ports 22 , 23 , respectively , of urine meter 20 . insert 300 further includes ribs 308 fainted on a second surface 303 b of backboard 302 and extending along vertical portion 302 b thereof as will be discussed below , when insert 300 is received with collection bag 30 a , ribs 308 form channels 309 between backboard 302 and collection bag 30 a . in use , collection bag 30 a , including insert 300 is secured to urine meter 20 by any suitable method . flanges 304 , 306 may be configured to extend from collection bag 30 a and be received with dump ports 22 , 23 ( fig1 ), respectively , of urine meter 20 . alternatively , flanges 304 , 306 may be configured to be positioned flush against dump ports 22 , 23 , respectively , of urine meter 20 . once collection bag 30 a is secured to urine meter 20 , fluid “ f ” ( fig2 ) may drain from urine meter 20 into collection bag 30 a . fluid “ f ” drains out of dump ports 22 , 23 of urine meter 20 into openings 304 a , 306 a of flanges 304 , 306 . fluid “ f ” drains from openings 304 a , 306 a between second side 303 b of backboard 302 and collection bag 30 through channels 309 formed by ribs 308 . the configuration of insert 300 reduces the amount of fluid “ f ” that may reflux back into urine meter 20 . although the illustrative embodiments of the present disclosure have been described herein with reference to the accompanying drawings , it is to be understood that the disclosure is not limited to those precise embodiments , and that various other changes and modifications may be effected therein by one skilled in the art without departing from the scope or spirit of the disclosure .

US-201414308953-A

the present invention is a robotics construction kit that serves as a platform for children to engage in problem - solving and innovative thinking in science , technology , engineering , and mathematics . by designing and building robotics constructions from an apparently simple set of blocks that encapsulate the kinetic , electronic , and software elements of robots , children and others can encounter , explore , and experiment with basic principles of science and computation . unlike existing robotics construction kits for education , the present invention embodies computation in every element , which affords understanding systems of distributed computation , rather than systems of top - down control .

as used herein in the specification and claims , including as used in the examples and unless otherwise expressly specified , all numbers may be read as if prefaced by the word “ about ”, even if the term does not expressly appear . also , any numerical range recited herein is intended to include all subranges subsumed therein . fig1 - 3 illustrate the present invention being a set of blocks 2 , also called modular units , with embedded electronic device 4 ( for example , printed circuit board ) and hermaphroditic electrical and magnetic connectors through the sides 6 of each block 2 . software ( reprogrammable or non - reprogrammable ) runs on the microcontroller on embedded electronic device 4 inside each block 2 . one embodiment of the present invention includes a reprogramming system that enables end - users to reprogram the reprogrammable software running inside predetermined blocks 2 . when blocks 2 are attached to one another to make a construction , the blocks 2 form a network and pass data from one block 2 to another block 2 , giving the construction 8 a unique and specific behavior . the present invention can be any size . for illustration purposes only , blocks 2 can be 40 mm plastic cube - shaped blocks that snap together with magnetic 23 and electric connectors 24 , 25 , 26 ( fig8 - 11 ). children use them to create constructions ( fig1 , 3 ) that respond to light , sound , proximity , and other external conditions , and produce light , sound , and motion . for example , the present invention assembled as a modular robot shown in fig3 moves on a tabletop and steers away from a light source . every block 2 contains a microcontroller and supporting electronics . the microcontroller in each block runs a program in firmware , which provides the default behavior of the blocks . all blocks initially run the same firmware program . in alternative embodiments of the present invention , users may replace the initial firmware using a reprogramming interface described below . there are four categories of blocks : sensors , operators , actuators , and utilities . different colors of plastic indicate the block categories . sensor blocks sense signals from the environment ( including light , sound , touch , motion and distance from objects ) and pass signals to connected neighboring blocks . operator blocks apply functions to those signals including arithmetic functions that compute a number from two or more numbers , such as sum , maximum , minimum , inverse and threshold . actuator blocks convert signals they receive into various types of action . for example , a motorized tread block ( fig4 ) drives around on a tabletop with a speed dependent on the signals it receives . other actuator blocks have rotating faces , bright leds and piezoelectric speakers . utility blocks include a power source block , including a battery , such as a lithium - ion or solar powered battery , that must be included in each construction . utility blocks can include a passive data - connection blocks that affect the physical form of a construction without affecting the flow or content of data . utility blocks can include a communication block being either hard wired or wireless that enable a nearby computer or mobile device to communicate with a construction . some utility blocks can be pass - through blocks that allow data to flow through them without changing the data . some utility blocks can be blocker blocks that restrict the flow of data through a construction . these last two may also be thought of as special operator blocks . now turning to fig5 a , 5b , and 6 , each block 2 is assembled from two nearly identical three - sided halves 10 a , 10 b that slide and mechanically interconnect , and electronically interconnect together ( fig5 a and 5b ), enclosing printed circuit boards 33 mounted on the inner surface 12 of block 2 ( fig6 ) forming a gap 14 between printed circuit board 33 and inner surface 12 of block 2 . except for special faces on sensor and actuator blocks , all block sides 6 are identical , and hermaphroditic connectors ( described below ) on each side 6 attach pairs of blocks physically and electrically and allow any block 2 to connect to any other block 2 in any of four orientations , or other orientations depending on the geometry configuration of the block . block mechanical interconnectivity can be achieved with any acceptable attachment device including screws ( not shown ) that are received into internally threaded holes 10 f and threaded or non - threaded holes 10 g in both block halves 10 a , 10 b , as illustrated in block halve 10 b in fig6 . block electronic interconnectivity can be achieved with any acceptable electronic coupling device including a interconnecting male electrical connector 10 c in block halve 10 a and female connector 10 d in block halve 10 b . also an electrical strip connected to block halves 10 a , 10 b can be used to electrically couple the two halves 10 a , 10 b . once the two halves 10 a , 10 b are coupled , all six sides of block unit 2 are in electronic communication with each other . in one embodiment of embedded electronic device 4 one or more printed circuit boards 4 a can be configured to be adjacent to an inner surface 12 of side 6 . in the case where there is more than one printed circuit board , solder joints 18 electrically couple three individual circuit boards 4 a , 4 b , 4 c , as shown in fig6 . each block 2 contains a core set of identical embedded electronic device 4 on one or more printed circuit boards : a microcontroller , programming header , shift register , and power management circuitry . in addition , some blocks contain additional electronics and mechanics specific to their functions . for example , the motorized tread block ( see fig4 and 7 ) contains a printed circuit daughterboard 4 b with an h - bridge motor controller integrated circuit to drive a small geared dc motor 22 . the wireless communication block contains a radio frequency transceiver to communicate with a pc or mobile device with a wireless communication protocol such as bluetooth or zigbee . each sensor block and each actuator block has a special face that houses its sensor or actuator . these special faces may or may not contain hermaphroditic connectors to attach to other blocks . for example , the special spinning face 45 of the rotation actuator block 47 ( see fig8 ) contains a hermaphroditic connector 20 that enables the block to connect to , and rotate , a neighboring or adjacent block . on the other hand , the special sensor face of the light sensor block does not contain a hermaphroditic connector , as it is intended to be exposed in order to detect light . now turning to fig9 , a light sensor block 48 can contain a photoresistor 21 mounted on one face that is wired to an analog input on the microcontroller , which senses the ambient light level . now turning to fig1 , distance sensor block 49 can contain a distance sensor 19 , such as a sharp gdp - series sensor , mounted on one face that transduces the distance of any object within its field of view into a resistance , which is wired to an analog input on the microcontroller . now turning to fig1 , an led bar graph display block 50 can contain an led bar graph display 17 mounted on one face that is wired to an analog output on the microcontroller . now turning to fig1 , knob block 51 can contain a knob 28 mechanically mounted on a rotary linear potentiometer 15 mounted on one face that is wired to an analog input on the microcontroller . now turning to fig7 , tread block 46 , for example , exposes two rubber - covered rollers 9 driven by a gear motor 22 inside the block ( see fig4 ). as mentioned above , the tread block 46 also contains a printed circuit daughterboard 4 b containing an h - bridge integrated circuit that is wired to an analog output of the microcontroller and which is used to control the action of the motor 22 . now turning to fig1 , flashlight action block 52 can contain a bright led 13 mounted on one face that is wired to an analog output on the microcontroller . now turning to fig1 , speaker block 53 can contain a speaker 17 such as piezoelectric speaker mounted on one face that is wired to an analog output on the microcontroller . now turning to fig8 , rotational actuator block 47 can contain a gear motor 22 and a printed circuit daughterboard 4 b containing an h - bridge integrated circuit that is used to control the action of the gear motor 22 that is wired to an analog output of the microcontroller and which is used to control the action of the motor 22 . the gear motor 22 is connected to a disk 45 , also called a rotating face 5 , on one side 6 of the rotational actuator block 47 , which contains a hermaphroditic connector 20 . this enables the gear motor 22 to rotate the disk 45 on the face of the block 47 while it is connected mechanically and electrically to another block 2 . the circuit board behind the rotating disk 45 has circular solder traces that enable the inner ring 25 and outer ring 26 of the hermaphroditic connector to maintain continuous electrical contact as the disk 45 rotates . the embedded electronic device 4 inside each block 2 includes a printed circuit board 33 having a motherboard 4 a , a daughterboard 4 b , and wing boards 4 c ( see fig6 ). each circuit board 33 is mounted on the inner surface 12 of a side 6 , and connects electrically to the hermaphroditic connector 20 having a portion extending beyond the outside surface 11 of side 6 ( see fig1 ). the circuit boards 33 inside each block 2 are electrically connected to one another and communicate power , ground and data signals . an electrical connector 20 can also use magnetic force to from an integral electrical and structural connector to hold parts together physically as well as electrically to connect pairs of blocks 2 . fig1 - 21 show photographs and drawings of connector 20 . by “ hermaphroditic ,” we mean that all connectors are identical : there are no “ male ” or “ female ” connectors . the connector is low cost and is used in applications where two components are required to connect both physically and electrically . the connector 20 shown here is four - way rotationally symmetric . it could easily be modified to support a different number of rotations , such as two or six ( or more ). the connector 20 shown herein supports three electrical contacts , in this case for conducting a power signal , a ground signal , and a data signal , but it could be easily modified for more or fewer contacts . the connector 20 has a front , or outer surface 11 , which contacts another connector when it is connected , and a back , or interior side , which contacts a circuit board . embedded magnets 23 on each face or side 6 of block 2 and concentric rings 25 , 26 and a center spring pin 24 connect the blocks 2 electrically . the magnets 23 on one block 2 and outer rings 26 on the other block 2 hold each pair of blocks 2 together physically by magnetic force . when a pair of connectors 20 are held together physically by the magnets 23 , and exerts an axial force that compresses the rings 25 , 26 , which holds the rings 25 , 26 firmly against the circuit board 33 behind them . this force also holds the outer rings 26 and spring pins 24 in contact with one another on the outer surface 11 of side 6 . the outer rings 26 can be made of any magnetic material , such as stamped steel . the rings 25 , 26 connect electrically using metal spring clips to contact circuit boards 33 mounted on the inner surface 12 of each side 6 . fig1 shows a photograph of the connector 20 mounted in a face or side 6 of a block 2 , exposing magnets 23 , portions of the inner and outer rings 25 , 26 , and center spring pin 24 . fig1 shows a drawing of the connector 20 with these parts labeled , and fig1 shows a cutaway view drawing of the connector 20 and circuit boards 33 mounted in a block half 10 b . fig1 shows an exploded view of the parts of the connector 20 including magnets 23 , spring pin 24 , inner and outer rings 25 , 26 , and side 6 . one embodiment of side 6 can be a plastic shell 32 ( see fig1 ). four flanged magnets 23 , shaped like top hats , can be inserted from the interior so that they cannot be pulled out of hole 16 a of plastic shell 32 from the exterior . when two opposing connectors 20 are connected together , the magnets 23 of one connector 20 contact the outer ring 26 of the other connector ( not shown ). this union holds the two connectors together physically and creates one electrical contact . in the center of the connector 20 , a spring pin 24 inserted through hole 16 b of side 6 is used as the second electrical contact . when two connectors 20 are held together , their respective center spring pins 24 contact and their respective springs compress to adjust for axial variability . one embodiment of the inner and outer rings 25 , 26 , respectively , can be bent or stamped pieces of spring steel that extend into holes 16 c , 16 d , respectively , of side 6 . holes 16 d are sized to receive extensions 16 e of outer ring of block 2 . extensions 16 e extend outward a predetermined distance from outer surface 11 of side 6 to sufficiently recess into holes 16 d such that magnets 23 of opposing block 2 contact outer ring 26 of block 2 to electrically connect the respective printed circuit boards 33 . when two opposing connectors 20 are connected , the inner ring 25 on one connector 20 contacts opposing inner ring 25 on the other connector to create the third electrical contact . fig1 shows a drawing of the inner ring 25 , with sprung wings 27 that contact the circuit board 33 at point a ( see fig2 ). fig2 shows a drawing of the outer ring 26 , with sprung wings 29 that contacts the circuit board 33 at point b ( see fig2 ). outer ring sprung wings 29 that contacts the magnets 23 on the connector 20 of the opposing block 2 and extensions 16 e that contacts magnets 23 on its mating connector ( not shown ). side 6 , such as a plastic shell 32 , including at least a number of apertures or holes equivalent to the number of extensions 16 e of inner and outer rings 25 , 26 , and for magnets 23 , and spring pin 24 to hold these components in place within connector 20 . on the back , or interior side , or inner surface 12 of the connector 20 , a printed circuit board 33 makes electrical contact with the spring pin 24 and the sprung wings 27 , 29 of inner and outer rings 25 , 26 , respectively . fig2 shows a printed circuit board indicating the locations a , b , c where inner ring 25 , outer ring 26 , and spring pin 24 make electrical contact , respectively . each block in a construction possesses a dynamic one - byte value that determines how it operates with regards to software , block data values and behaviors . these values originate in sensor blocks , travel through the construction from block to neighboring block and are consumed by actuator blocks . thus , sensors are data sources and actuators are data sinks . operator blocks change data values that pass through them , according to their pre - programmed functions . utility blocks ( except for blocker blocks ) simply pass data unchanged . a sensor block computes its value from environmental input . a light sensor block , for example , computes a value of 5 in a dark room and over 200 outside on a sunny day . for example , a touch sensor has a resting value of zero and 255 when it contacts another object . each actuator block derives its value from data it receives from its neighbors . the actuator block &# 39 ; s action depends on this value . for example , a tread block drives along a surface with a speed proportional to its value . a rotation block with a value of zero remains still , but with a value of 127 it rotates its active face at half speed . the default firmware computes the actuator block &# 39 ; s value as the weighted average of the values it receives from all sources . values originating closer to the block are weighted higher than values originating further away . the formula is as follows : v = sum ( v 1 / d 1 + v 2 / d 2 +. . . vn / dn )/ n where n is the total number of packets in the action block &# 39 ; s data store , v 1 , . . . n are the sensor values in arrived data packets , and d 1 , . . . n are the distances ( hop - counts ) for these data packets , respectively . an operator block computes its value as a function of the values it receives from its neighbors . the value of a sum block , for example , is the arithmetic sum of its neighbors &# 39 ; values . the value of a maximum block is the largest of its neighbors &# 39 ; values . a simple example illustrates the flow of data values and resulting behaviors . the robot ( shown in fig3 ) that steers away from light sources consists of two light sensor blocks , each atop a motorized tread action block , with a battery utility block joining them in the middle . each tread block receives data packets from both light sensors . the hop count from the more distant sensor block is higher , so each tread block &# 39 ; s speed is more dependent on the sensor nearest it . the side of the robot that is closer to the light will drive faster , causing the robot to steer away from the light . programs running in the blocks exchange data through the electrical connections on the block faces . they form a network that communicates data from sensor blocks to actuator blocks . blocks operate asynchronously , transferring data pairwise with no central clock . each sensor block &# 39 ; s value derives from its embedded sensor . every other block &# 39 ; s value is computed as a function of the number of steps from every sensor data source in the construction , with closer sensors having a greater influence than sensor that are farther away . two sensor blocks at either end of a chain of blocks , for example , create a gradient of values along the blocks between them . each data transfer between a pair of blocks is done as a packet . packets originate at sensor blocks , which produce the data values from their sensor readings . packets are consumed by actuator blocks , which use the data values to determine the actuator &# 39 ; s physical behavior . each packet contains the unique id of the originating sensor block , a time stamp that indicates when the packet was created , a hop - count , and a data value . each time a packet moves from one block to another , its hop - count is incremented by one . the hop - count therefore describes the distance the packet has traveled through the network from its sensor block source . a propagation algorithm in the firmware program running in each block manages the flow of packets through the block . on arrival of an incoming packet from a neighboring block , the propagation algorithm compares the incoming packet &# 39 ; s originating sensor block id with other packets in its store . if any packets in its store have the same id as the arriving packet , it compares the time stamps of the two packets . if the arriving packet is older than the packet in its store , it ignores the arriving packet . if the packet in its store is older , it deletes the packet in its store and adds the incoming packet to its store . each block constantly tries to establish a data connection with each of its neighbors , successively . whenever a connection between two blocks is established , each connected block adds to its data store the contents of its neighbor &# 39 ; s data store , eliminating the oldest packets originating from the same sensor , as described above . the reprogramming system enables users to change a firmware program that runs in any unit of a distributed modular robot shown in fig1 . a distributed modular robot is a collection , also called ensemble , of individual units also called modules , each comprising a microcontroller and additional electronics and mechanical components , and the having the ability to communicate with other units , some but not necessarily all of which include a sensor , such as a light , sound , or distance sensor , or an actuator such as a motor , speaker , or led . the overall behavior of a distributed modular robot is produced by local interactions among its units : a distributed modular robot has no single controlling unit . therefore to program and reprogram the robot &# 39 ; s behavior , a user must enter controlling code , called firmware , into individual units . the reprogramming system described herein enables a user to compose and compile a program on a computer or mobile device , also called the programming platform , and load the resulting compiled firmware code into some or all of the robot &# 39 ; s units . this enables a user to change the physical behavior of individual units and hence the behavior of the distributed modular robot . fig2 shows a diagram of the parts ( shown as rectangles ) and data exchange interactions ( shown as arrows ) of the reprogramming system . the reprogramming system includes an editor and compiler running in a web browser on a pc or mobile device 34 , a wireless communication unit 35 , the individual unit or units to be reprogrammed 36 , and a database that stores source code programs associated with each unit 37 . other embodiments of the present invention allowed the user to otherwise replace the unit &# 39 ; s source code by ( i ) entering a new source code in an editor on the computer or mobile device , or ( ii ) editing previously entered source code selected from a database . fig2 shows the flow of information from the user &# 39 ; s source code program stored on the internet data store 36 to the program installed in a target unit &# 39 ; s microcontroller memory 37 . users compose programs 38 in a programming language using an editor and compiler 39 , also called programming platform . the editor and compiler 39 operate in a web browser running on a pc or mobile device . the programming language may be textual , such as the programming language c , or visual , such as the programming language labview or scratch . the compiler , such as the gnu c compiler ( gcc ), translates user &# 39 ; s programs into firmware 40 for the target microcontroller 36 . the resulting firmware 40 is then loaded into the microcontrollers 36 of specific target units of the modular robot , where it is executed . the user &# 39 ; s compiled firmware program may use a runtime support system 41 that remains resident in the microcontroller &# 39 ; s local memory . fig2 shows the sequence of operations entailed in reprogramming a modular unit . the sequence begins ( step 1 ) when the user connects a computer or mobile device running a web browser to the wireless communication unit via a wireless radio - frequency link using a protocol such as bluetooth or zigbee . the wireless communication unit , which is connected to the ensemble of microcontroller robot modules , then asks the ensemble to describe its units and their connections ( step 2 , arrow a ). each unit in the ensemble reports which other units it is connected to , and this information is passed to the wireless communication unit ( step 3 , arrow b ). the wireless communication unit assembles this list of individual pairwise connections . it reports this list to the pc or mobile device , which displays it in the web browser ( step 4 ), for example as a graph ( see also fig2 ). the user now selects a node in the graph ( step 5 ) to indicate which unit in the ensemble is to be reprogrammed . the programming editor and compiler requests from the data store ( arrow c ) the source code for that unit . the data store provides the requested source code to the editor and compiler ( arrow d ), which displays it to the user ( step 6 ). the user modifies or replaces the source code ( step 7 ) and posts the new code back to the data store ( arrow e ). the programming editor and compiler compiles native code for the microcontroller ( step 8 ) and sends this code to the wireless communication unit ( arrow f ). the wireless communication unit passes the code , as a reprogramming packet , on through the ensemble of robot modules to its intended target unit ( step 9 ). when the target unit receives the reprogramming packet the target unit and one of its neighboring units collaborate to load the code into the target microcontroller . fig2 shows a representation of the text based programming editor and compiler running in a web browser on a mobile device . the programming platform includes an editable text area 43 where a user can type in new code or view code retrieved from a database . the wireless communication unit reports , to the editor and compiler , the currently connected units &# 39 ; identities and connections of the modular robot to the reprogramming environment . the programming editor and compiler displays this to the user , for example as a graph in which nodes represent units 36 and edges represent connections 30 between units ( fig2 ). in the editor and compiler the user can then select a node from this graph , for example by clicking on it . the editor responds to this by retrieving , from the database , the source code for the firmware that is currently running in the corresponding modular robot unit , called the target unit . the programming platform , using the target unit &# 39 ; s unique id as an index , retrieves source code from a database stored on a server and displayed in a text - editing area 43 on the pc or mobile device screen 31 . the user enters new source code in the text - editing area , compiles it , and downloads it into a unit . fig2 shows a representation of the user &# 39 ; s source code 38 for one unit displayed in a text editing area 43 for the user to modify . upon the user &# 39 ; s request , which is indicated for example by the user pressing a button in the editor and compiler &# 39 ; s screen interface , the editor and compiler posts the new source code to the database stored on the server , stamped with the current date and time . fig2 shows a representation of this database . the database contains source code for the firmware that is currently running on the unit , as well as previous versions of the firmware . the user can revert to a previous version of the firmware by selecting it in a menu ; the editor and compiler displays the source code for this previous version in a text - editing area and the user can compile and download the program into the unit . other embodiments of the present invention provide the capability of entering a new source code in an editor on the computer or mobile device or editing previously entered source code selected from a database . in addition to posting the new source code to the database , when the user requests it , the editor and compiler compiles the user &# 39 ; s program . if the code compiles without error , the editor and compiler sends the code to the wireless communication unit , which routes it to the designated target unit in the modular robot . the wireless communication unit waits for acknowledgement from the target unit that it has been successfully reprogrammed . when it receives this acknowledgement , the wireless communication unit conveys it to the programming editor and compiler , which in turn conveys it to the user . if the wireless communication unit receives no acknowledgement within a set time , the wireless communication unit conveys this information to the editor and compiler , which conveys to the user that reprogramming has failed . the user &# 39 ; s compiled program is copied from the wireless communication unit through the network of units in the modular robot to its designated target unit . fig2 shows a representation of this network . this communication is labeled as a reprogramming packet . when a unit in the modular robot receives a reprogramming packet that is targeted for another unit , it passes the packet to all the units it is connected to . when a neighbor unit 42 in the modular robot receives a reprogramming packet that is targeted for another unit ( target unit 40 ) that is directly connected to it , neighbor unit 42 passes the reprogramming packet to the target unit 40 and prepares to reprogram the target unit 40 . fig3 shows the sequence of events that is initiated when a neighbor unit 42 ( fig2 ) receives a reprogramming packet that is designated for one of its neighbors , the target unit 40 ( fig2 ). if the target unit 40 has more than one neighbor unit 42 , whichever neighbor unit 42 first connects with the target unit 40 initiates the reprogramming , and the target unit 40 ignores any other neighbor units 42 that try to connect to it . the reprogramming is accomplished using a bootloader program that is running in the target unit . when the target unit 40 receives a reprogramming packet addressed to it , it restarts its microcontroller in reprogramming mode , also called bootloader mode , which begins to execute the bootloader program that is stored in its memory . when the target unit 40 restarts , it signals to its neighbor unit 42 that it is ready and waits for reprogramming by its neighbor unit 42 . the neighbor unit 42 waits until it receives a ready message from the target unit 40 and then reprograms the microcontroller of the target unit 40 using the bootloader program that resides on the microcontroller . the neighbor unit 42 sends the target unit 40 a reprogram message . the target unit 40 resets itself and starts its bootloader program when it receives the reprogram message . the bootloader program sets the target unit 40 to receive a new application program from the neighbor unit 42 . the target unit 40 signals to the neighbor unit 42 when the reprogramming sequence is complete , and the target unit 40 passes an acknowledgement packet , also called ready packet , back to the wireless communication unit . both target and neighbor units then return to their ordinary modes of operation . while the disclosure has been described in detail and with reference to specific embodiments thereof , it will be apparent to one skilled in the art that various changes and modifications can be made therein without departing from the spirit and scope of the embodiments . thus , it is intended that the present disclosure cover the modifications and variations of this disclosure provided they come within the scope of the appended claims and their equivalents .

US-201013386707-A

polyols stabilize polymorphous form of rifaximin , in particular the β form . when polyols having at least two hydroxy groups are added to rifaximin powder , polymorph β is stable and remains stable in time independently from the environment humidity . in this invention a method to prepare formulations constituted by pure and stable polymorphous forms able to give a pharmaceutical product is described .

as previously described , the object of the present invention is the use of polyols above described to stabilize rifaximin polymorphous forms , in particular the β form as disclosed by viscomi g . c . et al ., in u . s . pat . no . 7 , 045 , 620b1 ( 2003 ), so as to obtain a pharmaceutical preparation containing the β form of rifaximin together with excipients well known in the state of the art , such as diluents , ligands , lubricants , disintegrants , dyes , flavors , and sweeteners , wherein the residual water content of the active ingredient rifaximin is lower than 4 . 5 % ( w / w ), and to maintain polymorph β unchanged during the production stage that can directly or indirectly lead to the drying of rifaximin , that is under conditions that , without the use of polyols , would not allow to conserve the β form , which would indeed be transformed into another polymorphous form of rifaximin , depending on the severity of the applied drying condition . we found that by putting in contact rifaximin β with a polyol aqueous solution at a concentration of 5 % ( w / w ) to 50 % ( w / w ), and preferably between 10 % ( w / w ) and 30 %, ( w / w ) for a period of time , generally from 1 to 24 hours , rifaximin in β form is obtained , which results stable even when the residual water content in the solid form is brought to a value lower than 4 . 5 % ( w / w ). the polyols described above or a mixture of them , which are the object of this invention , can be added to rifaximin β , either pure or mixed with a quantity of diluents known in pharmaceutical technology to improve the smoothness and to favour the interaction with polyols , or a mixture of them . for this purpose substances such as colloidal silica ( for example the colloidal silica known as aerosil ®) can be used and can be added to the active ingredient in a range comprised between 1 % ( w / w ) and 20 % ( w / w ) and preferably between 0 . 2 % ( w / w ) and 5 % ( w / w ). the interaction process between one of these polyols described above , or a mixture of them , and the rifaximin can be obtained by any procedure known in the pharmaceutical technology field which permits a close mixing of the components . one of these polyols , or a mixture of them , can be applied after a suitable water dilution with a granulation process in which the solution is opportunely added to the powder containing the active ingredient , or exclusively constituted by it , with suitable mixing . the operation can be carried out in a traditional granulator or in a high speed granulator where a rotary blade and a breaker are present to favour the mixing of the components . the addition of the solution of one or more polyols to the powder mixture can be done manually , taking care to slowly add the solution to the powder or to the powder mixture to favour the component interaction ; or more opportunely , it can be carried out by a suitable pumping system ; for example lobs pump , piston pump or peristaltic pump , and by the use of an atomizer allowing the nebulisation of the solution , thus favouring a better component interaction . when the granulation is effected , the excess water can be eliminated using a traditional drying system known in the pharmaceutical technology field by drying in static oven or by drying in a fluid bed apparatus . the drying temperature can range between 30 ° c . and 90 ° c ., preferably between 40 ° c . and 80 ° c . the drying time depends on the apparatus used , on the amount of powder to be dried and on the desired residual humidity . the application of the solution containing one of the above mentioned polyols , or a mixture of them , can be carried out also with a fluid bed apparatus . in this case , the powder containing the active ingredient , or exclusively constituted by it , is maintained in suspension by a warm air flux and at the same time the solution containing one of the above mentioned polyols or a mixture of them , is finely nebulised on the powder . in this case , the close mixture of the solution containing the polyols , or a mixture of them , with solid rifaximin , occurs at the same moment as the drying process . the person skilled in pharmaceutical technology is able to obtain a product with the desired residual water content by changing the critical parameters , such as air inlet temperature , air inlet capacity and application velocity of the solution . air inlet temperature is generally set between 20 ° c . and 90 ° c . and preferably between 30 ° c . and 80 ° c . the solution application speed is closely connected to air temperature that keeps the powder under suspension . the objective , well known to the expert in the art , is to maintain the mixture temperature constant during all the process . in fact an application speed that is too fast would lead to excessive wetting , with powder agglomeration , preventing the mixture necessary to obtain an effective action on the powder ; while an application speed that is too low could cause a mixture temperature increase with possible degradation of the active ingredient . the present invention can be obtained through any other pharmaceutical process providing a close mixture of the solution containing the above mentioned polyols , or a mixture of them , and subsequent drying . the preferred compounds having formula h —[ o — ch 2 — ch 2 ] n — oh ( where n can range between 2 and 10 ) and their mixture , and the compounds 1 , 2 , 3 - propanetriol and 1 , 2 - propanediol , can be added at concentrations comprised between 5 % ( w / w ) and 50 % ( w / w ), preferably between 10 % ( w / w ) and 30 % ( w / w ), as components of aqueous mixtures suitable for the film coating of solid oral pharmaceutical preparations , able to give a controlled release or gastro - resistance . preparation of rifaximin β form with residual water content lower than 4 . 5 % 199 grams of rifaximin β form are mixed for 5 minutes in a fluid bed apparatus having an inlet temperature of 80 ° c ., with 1 gram of aerosil ®. a suspension consisting of 390 grams of water and 13 grams of 1 , 2 - propanediol is sprayed on the mixture of rifaximin β form in a fluid bed apparatus , using a peristaltic pump with a 11 grams / minutes capacity and maintaining the temperature at a constant value of 80 ° c . during all the process . the mixture is dried at 80 ° c ., and drying is continued until the weight loss is constant . the residual water content in the microgranules is determined ( karl fisher ) and it is equal to 2 . 2 %. the microgranules thus obtained are submitted to x - ray spectroscopy and the diffractogram , which is reported in fig1 , corresponds to polymorph β of rifaximin which show peaks at the values of the diffraction angles 2θ of 5 . 3 , 6 . 7 , 7 . 7 , 8 . 9 , 10 . 4 , 12 . 3 , 17 . 7 , 18 . 2 , 18 . 6 and 20 . 7 . the same results are obtained when 1 , 2 - propanediol is replaced by erythritol or mannitol . this example demonstrates that in the absence of polyols , a rifaximin with a residual water content lower than 4 . 5 % does not take the polymorphous β form , and that the polyol addition allows to obtain rifaximin in a solid state in the β form with a residual content lower than 4 . 5 % ( the operations are the same as those described in example 1 , where the spayed solution does not contain 1 , 2 - propanediol ). 199 grams of rifaximin β form are mixed for 5 minutes in a fluid bed apparatus having an inlet temperature of 80 ° c ., with 1 gram of aerosil ®. 400 grams of water are sprayed on the mixture of rifaximin β form in a fluid bed apparatus , using a peristaltic pump with an 11 grams / minute capacity and maintaining the temperature at a constant value of 80 ° c . during all the process . the mixture is dried at 80 ° c ., and drying is continued until the weight loss is constant . the residual water content in the microgranules is determined ( karl fisher ) and it is equal to 1 . 1o / o . the microgranules thus obtained are submitted to x - ray spectroscopy and the diffractogram reported in fig2 corresponds to polymorph α of rifaximin . this example demonstrates the importance of the presence of the hydroxy group in a polyol to obtain a rifaximin in the polymorphous β form with residual water content lower than 4 . 5 %. the operations are the same as those described in example 1 , where 1 , 2 - propanediol is substituted by a polyol having the esterified hydroxy group , for example 1 , 2 , 3 - propanetriol triacetate . 199 grams of rifaximin are mixed for 5 minutes in a fluid bed apparatus having an inlet temperature of 80 ° c ., with 1 gram of aerosil ®. a suspension constituted by 382 . 75 grams of water and 12 . 75 grams of 1 , 2 , 3 - propanetriol triacetate , is sprayed on the mixture of rifaximin in a fluid bed apparatus , using a peristaltic pump with a 11 grams / minute capacity and maintaining the temperature at a constant value of 80 ° c . during all the process . the mixture is dried at 80 ° c . and drying is continued until the weight loss is constant . the residual water content in the microgranules is determined ( karl fisher ) and it is equal to 0 . 5 %. the microgranules thus obtained are submitted to x - ray spectroscopy and the diffractogram reported in fig3 corresponds to polymorph α of rifaximin . preparation of rifaximin β with a residual water content lower than 4 . 5 % in the presence of peg 400 199 grams of rifaximin are mixed for 5 minutes in a fluid bed apparatus having a inlet temperature of 80 ° c ., with 1 gram of aerosil ®. a suspension consisting of 360 grams of water and 40 grams of peg 400 ( polyethylene glycol with formula h —[ o — ch 2 — ch 2 ] n — oh , is sprayed on the mixture of rifaximin in a fluid bed apparatus , using a peristaltic pump with a 6 grams / minute capacity and maintaining temperature at a constant value of 80 ° c . during all the process . the mixture is dried at 80 ° c ., and drying is continued until the weight loss is constant . the residual water content in the microgranules is determined ( karl fisher ) and it is equal to 0 . 8 %. the microgranules thus obtained are submitted to x - ray spectroscopy and the diffractogram reported in fig4 corresponds to polymorph β of rifaximin . the same results are obtained using hydroxyethyl cellulose or tartaric acid instead of peg 400 . preparation of rifaximin b gastro resistant microgranules with a residual water content lower than 4 . 5 % in the presence of 1 , 2 - propanediol this example demonstrates that the polyol 1 , 2 - propanediol added to rifaximin to obtain rifaximin β with a residual water content lower than 4 . 5 ° k , ca n simultaneously operate as plasticizer in the preparation of films for covering granules without the addition of other compounds having this function . 25000 grams of rifaximin powder and 125 grams of aerosil ®, that acts as a fluidiser , are loaded in a fluid bed apparatus for the application of coated films on active ingredients with film glatt gpc 30 type , equipped with an 18 inch wurster system . at the same time , a suspension is prepared in a mixer under stirring as described in table 1 . the solid components are homogenously dispersed in demineralised water with a high speed ultra turrax homogenizer . the homogenized suspension is loaded in the wurster type apparatus with a peristaltic pump and nebulized on the rifaximin powder mixture and aerosil ® 200 at a pressure comprised between 1 . 0 and 1 . 5 bar , through a 1 . 8 mm nozzle . film coating application is performed under the same conditions as described in table 2 . 9 . 12 kg of gastroresistant rifaximin microgranules prepared according to the example 5 , 19 . 58 kg of sorbitol , 0 . 49 kg of aspartame , 0 . 21 kg of anhydrous citric acid , 2 . 10 kg of pectin , 2 . 10 kg of mannitol , 0 . 21 kg of neohesperidine dc , 1 . 12 kg of cherry flavour and 0 . 07 kg of silica gel are sieved on a 0 . 5 mm mesh sieve and then mixed for 20 minutes in a v mixer . the resulting mixture is partitioned and placed in thermo - welded bags containing 5 grams of product corresponding to 800 mg of rifaximin . the composition of the medicinal specialty contained in the thermo - welded bag is reported in the following table 3 . gastroresistance of microgranules contained in thermo - welded bags is evaluated after 12 months storage at 25 ° c . as disclosed in usp 28th ed ., page 2417 , obtaining the same results as those obtained on the microgranules prepared as in example 1 , that is a dissolution equal to 2 . 2 % in 0 . 1n hydrochloric acid and equal to 91 . 1 % in buffer at ph 6 . 8 . pharmaceutical preparation in the form of tablets containing rifaximin b prepared according to example 5 9 . 3 kg of gastroresistant rifaximin microgranules prepared according to the example 1 , 593 g of sodium starch glicolate , 100 g of magnesium stearate are sieved on a 0 . 5 mm mesh sieve and then mixed for 20 minutes in a v mixer . the resulting mixture is tabletted using a rotary tabletting machine ( fette 1200 ) equipped with oblong , scored 19 × 9 mm punches , yielding a final weight of 718 mg , corresponding to 400 mg of rifaximin . the tablets are then coated , using conventional pan equipment , with a hydroxypropylmethylcellulose film in order to improve appearance and to achieve taste - masking properties . the unitary film composition is reported in table 5 .

US-201615153636-A

a jump rope simulator for aerobic and anaerobic exercise having a hand - held unit comprising a handle , a base length connected to the handle , and one or more concatenated extension lengths attached to the base length . to exercise , the user grasps one or two units , imitates the motions of swinging a conventional jump rope , and jumps up and down , but there is no risk to the user of tripping over a rope as with a conventional jump rope . if the user desires , two units may also be linked together with an easily attachable connector to form a device similar to a conventional jump rope . a user can quickly convert between the two configurations of the jump rope simulator .

fig1 illustrates a jump rope simulator 100 in accordance with the preferred embodiment of the present invention . the jump rope simulator unit 100 has a handle that is l - shaped and padded on the long side 101 with a resilient material in an ergonomic shape that fits comfortably in a user &# 39 ; s hand during exercise workouts . the handle has a short side 103 that is attached to the long side of the handle 101 by a ball - bearing joint 102 which allows the short side of the handle 103 to rotate 360 degrees around the longitudinal axis of the long side of the handle . a sound mechanism is preferably built into the ball - bearing joint 102 such that for each rotation of the handle 103 around the long side of the handle , an audible sound is output . the rotatable handle is designed so that when the user rotates the individual unit , the far end of the unit is prevented from impacting the user &# 39 ; s legs . the long side of the handle 101 is preferably hollow and has a removable end - cap 120 . a weight 121 , available in various values , can be inserted inside the hollow handle . the weight adds extra resistance when the user is rotating the jump rope simulator in an aerobic and anaerobic workout . also shown in fig1 is a fixed length tube 104 permanently attached to the end of the short side of the handle 103 . the tube provides stability to the unit as it is being rotated by the user and also contributes to guiding the ends of the unit away from the user &# 39 ; s legs in conjunction with the l - shaped handle . along the body of the tube 104 , there are alternating sections that are smooth 105 and accordion - like with pleated folds 106 . the pleated folds provide the tube with some flexibility in bending when a user is rotating the jump rope simulator and also allow bending of the units so that the unit can be stored in a compact manner . attached to the bottom of the tube 104 is a sequence of several beads that are each preferably shorter in length than the tube 104 . only two beads are shown in fig1 , although any appropriate number of beads may be connected by the user to adjust the overall length of the unit to reach the floor and accommodate the user &# 39 ; s height . the bead 108 is connected to the tube 104 at the connector 107 , while the bead 110 is connected to the bead 108 at the connector 109 . each of the beads 108 and 110 also have accordion - like pleated folds in the body to provide for flexibility in the bead . at the bottom of the last bead on the unit is a ball - shaped safety nodule 112 which is attached to the last bead 110 by the connector 111 . the round safety nodule 112 is preferably made out of a soft material so that if the user inadvertently hits himself or another person while using the jump rope simulator , the safety nodule will cushion the impact . the safety nodule 112 is available in several different weights that provide variable resistance to the user during his aerobic and anaerobic workout with the jump rope simulator . as used herein , the term beads refers to any non - locking or interlocking segments , sections , tubular elements , collars or cylinders which can be used to extend the length of the jump rope simulator of the present invention . the length of the unit can be repeatedly adjusted by adding or removing beads from the unit . this allows the same unit to be repeatedly adjusted for use by users of different heights . conventional jump ropes typically only allow for a single length adjustment by cutting the rope . fig2 illustrates two units 202 and 203 of the jump rope simulator linked to each other with a removable connector 201 . in this configuration , the safety nodule 112 at the end of the unit shown in fig1 is removed from both of the units 202 and 203 , and the connector 201 is directly connected to the bead farthest away from the handle of each unit . the linking of the two units results in a device 200 that can be used in a similar manner as a conventional jump rope . the connector 201 is available in several different lengths to allow the user to modify the total length of the linked jump rope simulator to fit a particular user &# 39 ; s height . the connector 201 can be positioned anywhere between the two handles of each unit . fig3 is an exploded view of two beads 310 and 320 and a safety nodule 330 attachable to each other with a snap - fit type of connection . the two beads 310 and 320 each have a spherically - shaped protrusion 311 and 321 on one end and a socket 312 and 322 for accepting a spherically - shaped protrusion on the other end . the tubular body of each bead 313 and 323 has accordion - like pleated folds which allow for flexibility in bending the bead . as shown in fig3 , the spherically - shaped protrusion 321 on the top end of the bottom bead 320 plugs into the socket 312 in the bottom end of the top bead 310 in a snap - fit manner . this simple mechanism allows users to easily add or remove beads to adjust the length of the unit to accommodate the user &# 39 ; s height . plugged into the socket 322 located at the bottom end of the bottom bead 320 is a ball - shaped safety nodule 330 which is made out of a soft material . the safety nodule 330 also has a spherically - shaped protrusion 331 for plugging into the socket 322 . in addition the exploded view in fig3 shows a flexible cord 340 on which the beads are strung ; in ordinary use , after assembly the cord would be hidden from view . the flexible cord 340 ends in a knot 341 which securely fastens the safety nodule 330 to the unit . fig4 is an exploded view 400 of two beads 410 and 420 and a safety nodule 440 attachable to each other with a screw - coupler type of connector . both ends of each of the beads 411 , 412 , 421 , and 422 is a threaded female socket . a coupler screw 430 having two threaded male ends 431 and 432 is used to connect the two beads 410 and 420 . the tubular body 433 of the coupler screw 430 has accordion - like pleated folds to allow the connected beads to have flexibility in bending . this simple screw - type mechanism allows users to easily add or remove beads 413 and 423 to adjust the length of the unit to accommodate the user &# 39 ; s height . as shown in fig4 , the safety nodule 440 has a ball shape 441 and a threaded male end 442 . the threaded male end 442 of the safety nodule screws into the bottom 422 of the last bead in the series . fig5 is an exploded view 500 of the free end of the handle 510 and a screw - on weight 520 . the free end of the handle 510 has a threaded female socket 511 to accept the screw - on weight 520 . the screw - on weight 520 is disk - shaped and has a threaded male end 521 on one side which screws to the free end of the handle 510 . the other side of the screw - on disk - shaped weight has a threaded female socket 522 . this socket can accept another screw - on weight to increase the total weight of the handle or the handle end - cap 530 which also has a threaded male end . to assemble a jump rope simulator , a user takes the handle with attached tube and attaches a bead to the free end of the tube . the user continues attaching additional beads to increase the total length of the unit until a length appropriate for the user is reached . the ideal length allows the safety nodule to just touch the floor when the handle of the unit is held in a relaxed position by the user &# 39 ; s side . finally , at the end of the concatenation of beads the user attaches a safety nodule . use of the jump rope simulator as an exercise device is straightforward . for the configuration where the device is used as an individual unit or a pair of units , as shown in fig1 , the user simply grasps the handle in his hand and rotates the unit ( s ), simulating the feeling and rhythm of rotating a conventional jump rope . because of the sound mechanism within the ball - bearing joint 102 , the user also receives a simulated audible feedback as if a jump rope were hitting the floor on each rotation . the user can also jump or skip on each rotation of the rotating handle and exercise continuously without worrying about tripping over an actual rope and losing his balance , rhythm , and timing as would typically occur when a user trips over a conventional jump rope . however , should the user desire to exercise with a traditional style jump rope , two units of the simulator are easily connected together as shown in fig2 . the connection and detachment of the two units is very simple , thus allowing the user to choose which exercise device configuration meets his needs and to quickly switch between the two configurations as desired . multiple users have the ability to each utilize a pair of jump rope simulators in a group or class type environment in order to participate in a group workout . this allows the group of users to perform a series of exercises using the jump rope simulators of the present invention for aerobic and anaerobic exercise . this series of exercises can be performed to music to provide a rhythm and pace for the exercise . further , the level of exertion of the user &# 39 ; s exercise program can be changed by increasing or decreasing the amount of weight loaded in the handle or attached to the end of the handle . alternatively , the safety nodule at the end of the unit may be exchanged for another safety nodule having a different weight . the weight of the unit can also be increased or decreased by any other appropriate manner , including adding weight to the handle or to the end of the beads or safety nodule . the present invention discloses an exercise device wherein a user can simulate the motions and aerobic and anaerobic exercise benefits associated with using a traditional style jump rope without the risk of tripping over a physical rope . the jump rope simulator of the present invention has several advantages over the prior art . a user is able to easily and repeatedly modify the length of the jump rope simulator by adding or removing beads . a user is also able to easily and repeatedly modify the weight of the jump rope simulator either at the handle or at the safety nodule in order to increase or decrease the resistance of the unit as it is being rotated in the user &# 39 ; s hand . also , if the user desires , two of the jump rope simulator units are easily linked together with a simple connector to form a device similar to a conventional jump rope in form and function . the teachings of the present invention allow a user to quickly convert between the two configurations of the jump simulator . the present invention has been described in terms of specific embodiments incorporating details to facilitate the understanding of the principles of construction and operation of the invention . such reference herein to specific embodiments and details thereof is not intended to limit the scope of the claims appended hereto . it will be apparent to those skilled in the art that modifications can be made in the embodiment chosen for illustration without departing from the spirit and scope of the invention . specifically , it will be apparent to one of ordinary skill in the art that the device of the present invention could be implemented in several different ways and have several different appearances .

US-63996203-A

a holder for plastic and paper bags for receiving and retaining various types and sizes of bags for convenient storage for later re - use of the bags . the holder includes a container for plastic bags , the container including a top opening to receive collapsed or wadded plastic bags to be stored , and a bottom opening accessible to a user to allow withdrawal of a stored plastic bag for re - use . al least one hook is provided on the holder for hanging plastic or paper bags having openings that define handles , so that the handles can be hung on the hooks . a spring clip can be provided on the outer surface of the container for receiving and holding folded paper bags for later re - use .

referring to the drawings , and particularly to fig1 thereof , there is shown an embodiment of a holder 10 in accordance with the present invention . holder 10 includes a rear panel 12 that is adapted to be positioned in a substantially vertical orientation , such as against a panel or against a surface of a door of a kitchen cabinet or another form of storage cabinet . rear panel 12 can be flat and of generally rectangular form , as shown , defined by straight edges positioned perpendicularly to each other . alternatively , it can be of a curved form , such as an ellipse , or some other curved form , if desired for aesthetic reasons . the thickness of rear panel 12 can be of any desired value , depending upon the material from which holder 10 is made . for example , if made from a substantially rigid plastic material , such as nylon , polystyrene , or the like , rear panel 12 can have a thickness of the order of about one - eighth inch . alternatively , holder 10 can be formed from sheet metal , such as sheet aluminum , sheet steel that can be painted , sheet stainless steel , or the like . spaced from rear panel 12 is a front panel 14 that can also be a flat panel of generally rectangular form , as shown in the drawings . however , front panel 14 can also be curved to define a bowed cross section , in either the transverse or the longitudinal directions , or both , if desired for aesthetic reasons . positioned between each of rear panel 12 and front panel 14 and extending in a substantially longitudinal direction relative to those panels is a pair of laterally spaced side panels 16 . additionally , a bottom panel 18 extends transversely of and interconnects the lowermost ends of side panels 16 and also extends between rear panel 12 and front panel 14 . as shown in fig1 and 2 , the arrangement of rear panel 12 , front panel 14 , side panels 16 , and bottom panel 18 defines a tubular receptacle or container 20 that can have a generally rectangular cross section . container 20 has a first opening 22 positioned at the upper end of holder 10 to allow materials to be placed within the container . first opening 22 can be inclined relative to rear panel 12 , as shown , by forming front panel 14 to be shorter in a longitudinal direction than rear panel 12 , to facilitate access to the interior of container 20 . a second opening 24 is provided in container 20 adjacent bottom panel 18 and extends through front panel 14 . as shown in fig1 second opening 24 can be of elongated , generally rectangular form having a major axis that extends in the direction of bottom panel 18 . the longitudinal ends 26 of second opening 24 can be rounded , if desired , as shown in fig1 . extending downwardly from rear panel 12 are a pair of spaced hooks 28 that can be positioned below and adjacent to respective side panels 16 to allow items to be hung from holder 10 . a gusset 30 can be provided between the downwardly - extending portion of hooks 28 and bottom panel 18 of container 20 , if desired . although a pair of hooks 28 is shown in fig1 more or fewer hooks can be provided , such as a single hook centrally positioned along and extending below bottom panel 18 , or three hooks including one adjacent each end of bottom panel 18 and one centrally positioned along bottom panel 18 , and the like . a retaining clip 32 is provided on the outwardly - facing surface of front panel 14 . clip 32 includes a first leg 34 that extends outwardly from front panel 14 , and a second leg 36 that extends upwardly from first leg 34 and that has an upper end 38 that contacts and bears against front panel 14 . first leg 34 defines a support ledge against which edges of items held by clip 32 can rest . second leg 36 has a width less than that of container 20 , and can have a width of approximately one - half the width of container 20 . clip 32 is formed as a resilient member that provides a resilient , clamp - like holder , or a spring clip , for holding items against the outwardly - facing surface of front panel 14 . preferably , clip 32 has sufficient resilience to allow it to be deflected outwardly , away from front panel 14 a predetermined distance to hold a plurality of flat items in face - to - face or face - to - back relationship against front panel 14 . the lateral extent , or width , of clip 32 can be any convenient width that is sufficient to hold the number , size , and type of items intended to be placed between clip 32 and front panel 14 . holder 10 can be configured so that it can be hung vertically so that first opening 22 of container 20 faces in a generally upward direction and second opening 24 faces laterally outwardly from front panel 14 . accordingly , a u - shaped hangar 40 can be provided to fit over a door top edge . hangar 40 includes a top panel 42 that is substantially perpendicular to rear panel 12 and extends in a rearward direction , away from front panel 14 , and a leg 44 that extends downwardly from top panel 42 in a direction toward hooks 28 . hangar 40 is adapted to fit over the top of a door , such as , for example , a kitchen door or a cabinet door , to support holder 10 and thereby allow it to be supported by and to hang from the door top . an alternative arrangement for supporting holder 10 in an operative position involves the provision in rear panel 12 of mounting holes to allow holder 10 to be secured to and held against a vertical surface , such as a panel or a door . when so configured , holder 10 need not include hangar 40 . as shown in fig1 a pair of laterally spaced mounting holes 46 can be provided in rear panel 12 at a position opposite second opening 24 to receive mounting screws and to allow a screwdriver , or the like , to be utilized to fasten holder 10 to the vertical surface . alternatively , one or more similar holes ( not shown ) can be provided in rear panel 12 at a position adjacent to first opening 22 , above the topmost edge of front panel 14 . in use , holder 10 is supported substantially vertically , so that first opening 22 faces in an upward direction . as noted above , holder 10 can be hung over a door top , or it can be secured to a door face or to a wall surface by screws . plastic bags , such as crumpled bags 48 shown in fig2 can be inserted into container 20 through first opening 22 . the plastic bags need not be folded flat , nor need they be arranged in any particular manner relative to each other , and they can merely be wadded up and pushed or stuffed into first opening 22 . when it is desired to retrieve a plastic bag for re - use , the lowermost bag within container 20 can be withdrawn by pulling it through and from second opening 24 , which thereby serves as a dispensing opening for the plastic bags . in addition to plastic bags , holder 10 can also receive and hold bags having handles , such as paper or plastic shopping bags . the handles can be looped over one or more hooks 28 of holder 10 , so that one or more such handled bags hangs from holder 10 to allow ready access to the handled bags for re - use , as needed . further , holder 10 can also receive and hold one or more paper bags without handles . such bags are preferably in flat form , such as by returning the bags to their flat condition before having been opened , by folding the bags to their original folded form . one or more such flattened bags can be held by clip 32 against front panel 14 in face - to - face or face - to - back relationship , to allow several such paper bags to be retained for ready removal and re - use . although particular embodiments of the present invention have been illustrated and described , it will be apparent to those skilled in the art that changes and modifications can be made without departing from the spirit of the present invention . accordingly , it is intended to encompass within the appended claims all such changes and modifications that fall with the scope of the present invention .

US-31989902-A

the present disclosure relates to intravascular thrombectomy systems and methods for ablating a partial or complete blockage in a blood vessel . the system includes a catheter sleeve defining a lumen extending therethrough ; a pair of electrodes disposed at a distal end portion of the catheter sleeve , wherein the pair of electrodes are disposed on opposed sides of the lumen of the catheter sleeve ; and a guidewire slidably disposed within the lumen of the catheter sleeve , the guidewire including a capture element supported proximate a distal end thereof , wherein the guidewire is slidable with respect to the catheter sleeve to expose the capture element from the distal end portion of the catheter sleeve ; wherein the capture element includes a first condition retracted onto the guidewire and a second condition at least substantially spans the entire lumen of the vessel .

reference will now be made in detail to the present embodiments of the disclosure , examples of which are illustrated in the accompanying drawings . wherever possible , identical or similar reference numerals will be used throughout the drawings to refer to similar or like elements . the present disclosure provides for devices and methods for ablating a blockage and for preventing the introduction of emboli into the blood stream during and after surgery performed to reduce or ablate the blockage in the blood vessel . as used herein , and “ occlusion ,” “ blockage ,” or “ stenosis ” refers to both complete and partial blockages of the vessel . additionally , as used herein , “ proximal ” refers to that portion of the device or apparatus located closest to the user , and “ distal ” refers to that portion of the device or apparatus located furthest from the user . referring initially to fig1 - 3 , a thrombectomy catheter system , in accordance with an embodiment of the present disclosure , is generally designated 100 . thrombectomy catheter system 100 includes an elongate catheter sleeve 102 having a substantially tubular configuration . catheter sleeve 102 defines a lumen 103 ( see fig2 ) extending at least substantially entirely therethrough . catheter sleeve 102 includes a proximal end portion 106 connected to and / or supporting a handle , hub or manifold 104 , and a distal end portion 108 configured for passage of an elongated shaft 120 therethrough . catheter sleeve 102 is fabricated utilizing suitable technology to provide catheter sleeve walls having predetermined flexibility characteristics that can allow precise intravascular navigation , pushability and trackability . thrombectomy catheter system 100 includes at least one electrode 110 disposed at and / or supported at distal end portion 108 of catheter sleeve 102 . desirably , a pair of electrodes 110 a , 110 b is provided at distal end portion 108 of catheter sleeve 102 . each electrode 110 a , 110 b is electrically connectable to a source of electrosurgical energy , such as , for example , an electrosurgical generator “ g ”, via electrical conduits or wires 112 extending through lumen 103 of catheter sleeve 102 and through hub 104 . each electrode 110 may be electrically isolated and / or independent from one another . as is described in greater detail below , electrodes 110 a , 110 b are preferably used to emulsify emboli or thrombi entrained in fluid flows ( i . e ., vessels ) to prevent clogging of the channel or to ablate the embolus or thrombus to unclog the channel . as seen in fig1 - 3 , thrombectomy catheter system 100 further includes a shaft or guidewire 120 extendable through lumen 103 of catheter sleeve 102 . guidewire 120 includes a selectively deployable capture element 124 disposed proximate distal end 122 thereof . in one embodiment , capture element 124 is in the form of a filter or cage . capture element 124 includes a first condition wherein capture element 124 is collapsed or retracted onto guidewire 120 , and at least a second condition wherein capture element 124 is deployed or expanded to preferably span the entire lumen of the vessel or expand into apposition with the targeted vessel . transformation of capture element 124 may be impelled by external mechanical means , or by self - activating memory material provided within capture element 124 . such mechanical memory may be imparted to the material of capture element 124 by thermal treatment to achieve a spring temper in stainless steel , for example , or to set a shape memory in a susceptible metal alloy , such as a binary nickel - titanium ( nitinol ) alloy . other suitable methods of deploying and retracting capture element 124 will be readily apparent to one having ordinary skill in the art and are incorporated into the present disclosure without departing from the scope and spirit of the present disclosure . in one embodiment , in use , as will be described in greater detail below , guidewire 120 is inserted into the lumen of catheter sleeve 102 , through hub 104 , and slidably advanced therethrough until distal end 122 of guidewire 120 extends out through distal end portion of catheter sleeve 102 and capture element 124 is positioned at or near a desired location within the vessel . in an embodiment , catheter system 100 may also be a fixed - wire system or a rapid exchange system . turning now to fig4 a - 4d and 5 , an exemplary method of using thrombectomy catheter system 100 is shown and described . fig4 a schematically depicts a vessel “ v ” containing a blockage or clot “ b ” ( e . g ., a thrombus , embolus , etc .) completely or substantially restricting blood flow therethrough . as seen in fig4 b , distal end portion 108 of catheter sleeve 102 is introduced into vessel “ v ” using any suitable technique . a goal of the surgical procedure is to position capture element 124 of guidewire 120 distal of blockage “ b ”, and to position distal end portion 108 , and more particularly electrodes 110 , against and / or within blockage “ b ”. accordingly , as seen in fig4 c , catheter sleeve 102 is advanced through vessel “ v ” until electrodes 110 , disposed at distal end portion 108 , are in close proximity to , are in contact with , or are positioned within , blockage “ b ”. with continued reference to fig4 c , distal end 122 of guidewire 120 is advanced through blockage “ b ” until capture element 124 is disposed distal of blockage “ b ”. as seen in fig4 d , with capture element 124 of guidewire 120 located distally of blockage “ b ”, capture element 124 is deployed to span the entire lumen of vessel “ v ”. once capture element 124 has been deployed , energy ( e . g ., thermal , rf , ultrasonic , electrical , plasma , etc .) is delivered to blockage “ b ” via electrodes 110 . an effective amount of energy is delivered to electrodes 110 for an effective amount of time to ablate blockage “ b ”. during and following ablation of blockage “ b ”, any particularized thrombus and / or vapor , resulting from the ablation , is captured in capture element 124 of guidewire 120 . in one embodiment , capture element 124 of guidewire 120 functions to trap and remove particles and / or debris that may flow distally or downstream through vessel “ v ” during the thrombectomy procedure . as mentioned above , each electrode 110 may be electrically isolated and / or independent from one another . accordingly , it is envisioned and within the scope of the present disclosure for each electrode 110 to be independently controlled by electrosurgical generator “ g ”. during the procedure , it may be desirable to limit current flow to and between electrodes 110 when a low impedance path exists between electrodes 110 and a return or common electrode and / or when a high impedance path exists between electrodes 110 and a return or common electrode . desirably , the energy delivered to electrodes 110 is in the range from about 20 khz to about 20 mhz , and in the range of from about 5 volts to about 300 volts ( rms ). according to one embodiment and method , at least one or each electrode 110 may be configured to deliver plasma or the like . the surrounding blood or other suitable fluid media may be the medium for generating the plasma . in an embodiment , radio - opaque markers ( not explicitly shown ) may be provided along the length of catheter sleeve 102 and / or guidewire 120 . in this manner , the position and location of the various elements of thrombectomy catheter system 100 ( e . g ., electrodes 110 , capture element 124 , etc .) may be monitored using conventional monitoring techniques , such as , for example , fluoroscopy and the like . in one embodiment , thrombectomy catheter system 100 has an overall gauge that is less than about 0 . 060 inches . in this manner , thrombectomy catheter system 100 may enter and pass through present embolic protection devices that may be placed proximally of the blockage “ b ” during the thrombectomy procedure . turning now to fig6 , a thrombectomy catheter system , according to another embodiment of the present disclosure , is generally shown as 200 . thrombectomy catheter system 200 includes a catheter sleeve or body 202 having a distal end portion 208 . thrombectomy catheter system 200 further includes at least a pair of electrodes 210 a , 210 b disposed or supported thereon . desirably , electrodes 210 a , 210 b are spaced an axial distance from one another and are preferably located proximate distal end portion 208 . while only a pair of electrodes 210 a , 210 b are shown and described as being disposed on catheter sleeve 202 , it is within the scope of the present disclosure for any suitable number of electrodes to be disposed along the length of catheter sleeve 202 . if more than a pair of electrodes 210 a , 210 b is provided , it may be desirable for the electrodes to be evenly spaced from one another . additionally , each electrode 210 a or 210 b may be electrically isolated from one another . in an embodiment , radio - opaque markers 211 may be provided along the length of catheter sleeve 202 , desirably on either side of each electrode 210 a , 210 b . markers 211 provide the user , under fluoroscopic visualization , with the ability to identify when at least a distal - most electrode 210 is located distally of blockage “ b ”. in one embodiment , each electrode 210 a , 210 b may substantially surround catheter sleeve 202 . as seen in fig6 , thrombectomy catheter system 200 further includes a capture element 224 disposed and / or supported on distal end portion 208 of catheter sleeve 202 . capture element 224 may be located distally of a distal - most electrode 210 b . capture element 224 is substantially similar to capture element 124 and will not be discussed in great detail hereinbelow . capture element 224 is in the form of a filter or cage . capture element 224 includes a first condition wherein capture element 224 is collapsed or retracted onto catheter sleeve 202 , and at least a second condition wherein capture element 224 is deployed or expanded to preferably span the entire lumen of the vessel or expands into apposition with the targeted vessel . with continued reference to fig6 , an exemplary method of using thrombectomy catheter system 200 , for performing a thrombectomy procedure , is shown and described . once again , thrombectomy catheter system 200 is introduced into vessel “ v ” using any suitable technique . a goal of the surgical procedure of fig6 is to position capture element 224 through and distal of blockage “ b ”, and to position catheter sleeve 202 through blockage “ b ” such that at least one electrode , e . g ., distal - most electrode 210 b , is located distal or downstream of blockage “ b ” and such that at least one electrode , e . g ., proximal - most electrode 210 a , is located proximal of or upstream of blockage “ b ”. accordingly , in use , catheter sleeve 202 is advanced through vessel “ v ” and through blockage “ b ” until distal - most electrode 210 b is disposed distal of blockage “ b ” and capture element 224 is disposed distal of blockage “ b ”. as seen in fig6 , with capture element 224 of thrombectomy catheter system 200 located distally of blockage “ b ”, capture element 224 is deployed to span the entire lumen of vessel “ v ”. once capture element 224 has been deployed , energy ( e . g ., thermal , rf , ultrasonic , electrical , etc .) is delivered to blockage “ b ” via electrodes 210 a , 210 b . an effective amount of energy is delivered to and between electrodes 210 a , 210 b , from electrosurgical generator “ g ”, for an effective amount of time to ablate blockage “ b ”. during the ablation process , the effective amount of energy is transmitted through blockage “ b ” between distal - most electrode 210 b and proximal - most electrode 210 a . during and following ablation of blockage “ b ”, any particularized thrombus and / or vapor , resulting from the ablation , is captured in capture element 224 . in one embodiment , capture element 224 functions to trap and remove particles and / or debris that may flow distally or downstream through vessel “ v ” during the thrombectomy procedure . while the devices and methods of the present disclosure have been directed to thrombectomy procedures and the like , it is within the present disclosure for the devices disclosed herein to be used in connection with other procedures equally as well , such as , for example , vascular stenosis , plaque removal , artherectomy and the like . various modifications may be made to the embodiments of the presently disclosed apparatus , devices and methods . therefore , the above description should not be construed as limiting , but merely as exemplifications of embodiments . those skilled in the art will envision other modifications within the scope and spirit of the present disclosure .

US-78727410-A

the present invention provides a novel collapsible pen that is used in combination with a widely available modular unit used in the shipping industry . the present invention is economical to use by virtue of the fact that the pen may be stored inexpensively in a minimum of space in a disassembled state , may be assembled quickly , and may be easily and readily disassembled to permit alternate uses of the modular freight unit . the present invention consists of a collapsible pen erected on a standardized rectangular platform which has at least one side open to the air . the pen is made up of modular panels . the panels are attached to the rectangular platform , and can be used alone or in combination with any side or end walls present on the rectangular platform to create an enclosure .

the present invention consists of a livestock pen 1 for transporting livestock by rail , truck or on a container ship with other standardized freight containers . the pen has a base . the base consists of a rectangular platform 2 having a top 3 and a bottom 4 , and a perimeter extending around the top of the rectangular platform 2 , defined by two side edges 5 and 6 and two end edges 7 and 8 . the two side edges 5 and 6 and two end edges 7 and 8 meet at four corners . four posts 9 of equal height are attached to the rectangular platform . the four posts 9 are located at the four corners and extend from the top 3 of the rectangular platform 2 . the posts 9 together with the two side edges 5 and 6 and the two end edges 7 and 8 define four perimeter planar areas which extend perpendicular to the rectangular platform 2 and from the top 3 of the rectangular platform 2 at its perimeter . during transit of the rectangular platform 2 , at least one of the perimeter planar areas is open to the air , having no wall , panel or other fixed closure means which is part of the rectangular platform 2 . further the rectangular platform 2 is of standardized dimensions , formation and configuration such that the rectangular platform 2 is suitable for transport on a container ship stacked with other standardized freight containers . the pen 1 further has a plurality of panels erected on and connected to the rectangular platform 2 , creating an enclosed area on the rectangular platform for containing livestock . the international organization of standardization ( iso ) provides definitions of freight containers that are useful in defining the rectangular platform 2 of the present invention . these definitions are found in a publication called iso 830 freight containers - terminology , first edition , 198 - 11 - 15 , hereinafter called iso 830 : 1981 . iso 830 : 1981 first identifies a subgroup of freight containers called general cargo containers . at section 4 . 1 . 1 of iso 830 : 1981 the term “ general cargo container ” is defined as follows : “ this is a general term applicable to any type of container which is not intended for use in air mode transport and which is not primarily intended for the carriage of a particular category of cargo such as a cargo requiring temperature control , a liquid or gas cargo , dry solids in bulk or cargoes such as automobiles ( cars ) or livestock .” the rectangular platform 2 that serves as the base of the present invention is a sub - group of general cargo containers as defined . iso 830 : 1991 then goes on to distinguish general purpose containers from specific purpose containers . at iso 830 : 1991 section 4 . 1 . 1 . 1 a “ general purpose container ” is defined as a “[ f ] reight container , totally enclosed and weather - proof , having a rigid roof , rigid side walls , rigid end walls and a floor , having at least one of its end walls equipped with doors and intended to be suitable for the transport of cargo of the greatest possible variety .” the rectangular platform 2 of the present invention is not a general purpose container as defined . a “ specific purpose container ” is considered a “ general term applicable to all general cargo containers having constructional features either for the “ specific purpose ” of facilitating packing and emptying other than by means of doors at one end of the container , or for other specific purposes such as ventilation .” iso 830 : 1991 section 4 . 1 . 1 . 2 . the rectangular platform 2 of the present invention is a sub - group of specific purpose containers as defined . the term “ rectangular platform ” as used in the claims is considered to encompass the term “ platform based container open sided ” as defined in iso 830 : 1991 at section 4 . 1 . 1 . 2 . 3 , except any limitations as to series designations should be omitted from the definition of “ rectangular platform ”. the term “ platform based container open sided ” is “ applied to any general cargo container which does not have rigid side walls or equivalent structures capable of withstanding all of the loads that may be withstood or transmitted by a side wall of a general purpose container and which , for this reason has a base structure similar to that of a platform ( container ). ( see 4 . 1 . 1 . 2 . 4 ).” iso 830 : 1991 , section 4 . 1 . 1 . 2 . 3 . iso 830 : 1991 at section 4 . 1 . 1 . 2 . 4 defines a “ platform ( container )” as a “[ l ] oadable platform having no superstructure whatever but having the same length and width as the base of a container of the same series and equipped with top and bottom corner fittings , located in the plan view as on containers of series 1 , so that some of the same securing and lifting devices can be used .” iso 830 : 1991 discusses three main sub - types of platform based container open sided . the first is “ the platform based container open sided with complete superstructure ” which is defined as a “[ p ] latform - based container , having a permanently fixed longitudinal load - carrying structure between ends at the top .” iso 830 : 1991 , section 4 . 1 . 1 . 2 . 3 . 1 . this sub - type is further divided into “ those having a rigid roof and rigid end walls ( open sided ); . . . those having an open top and rigid end walls ; . . . [ and ] those having an open top and open ends ( skeletal ).” iso 830 : 1991 , section 4 . 1 . 1 . 2 . 3 . 1 . the second sub - type are “ platform based containers with incomplete superstructure and fixed ends ” which are defined as a “[ p ] latform based container without any permanently fixed longitudinal load - carrying structure between ends other than at the base .” iso 830 : 1991 , section 4 . 1 . 1 . 2 . 3 . 2 . the third sub - type defined is a “ platform based container with incomplete superstructure and folding ends .” this sub - type is defined at iso 830 : 1991 , section 4 . 1 . 1 . 2 . 3 . 3 , as a “[ p ] latform based container with incomplete superstructure ( as envisaged in 4 . 1 . 1 . 2 . 3 . 2 ) but having folding end - frames with a complete transverse structural connection between corner posts .” a description follows of the construction and attachment of the modular panels to a 40 ′ by 8 ′ by 8 ′ rectangular platform 2 of standardized dimensions , formation and configuration such that the rectangular platform 2 is suitable for transport on a container ship stacked with other standardized freight containers . such a construction constitutes the preferred embodiment of the present invention and is shown in fig2 . in the preferred embodiment , the rectangular platform 2 is a platform based container with an incomplete superstructure and fixed ends , wherein the fixed ends consist of fixed free - standing posts 9 . the platform based container open sided with an incomplete superstructure and fixed ends consisting of free - standing posts 9 of the preferred embodiment is built in conformance with the following international organization of standardization publications , the disclosure of which is incorporated by reference : iso 668 series 1 freight containers - classification , dimensions and ratings , fifth edition , dec . 15 , 1995 ; iso 1161 series 1 freight containers - corner fittings - specification , fourth edition , dec . 15 , 1984 ; iso 1496 - 5 series 1 freight containers - specification and testing - part 5 : platform and platform - based containers , second edition , dec . 15 , 1991 ; iso 1496 - 5 series 1 freight containers - specification and testing - part 5 : platform and platform - based containers - amendment 1 , second edition , mar . 1 , 1993 ; iso 1496 - 5 series 1 freight containers - specification and testing - part 5 : platform and platform - based containers - amendment 2 , second edition , sep . 1 , 1994 ; iso 6346 freight containers - coding , identification and marking , third edition , dec . 1 , 1995 . these publications are made available to the general public in the united states by the american national standards institute , located at 11 west 42nd street , new york , n . y ., 10038 . these publications detail iso construction standards for all platform based containers open sided . as shown in fig2 in the preferred embodiment , two side panels 10 are used to span the distance between the corner posts 9 of the rectangular platform 2 along its elongated side edges 5 and 6 . on a 40 ′ rectangular platform , a total of four side panels 10 are used . see fig2 . the four side panels 10 are similar in construction . variations in construction are determined by whether a side panel 10 will be fitted with a gate 11 , whether it will be fitted with a water trough 12 or other accessories , and whether it will be fitted with a winch assembly 13 or a hook assembly 14 . [ 0056 ] fig1 shows a preferred side panel 10 prior to being fitted with either a winch assembly 13 or a hook assembly 14 . phantom lines are meant to represent the alternate sites for the attachment of studs 15 depending on whether a gate 11 or gates 11 are built into the side panel 10 . if a gate 11 is to be positioned near an end of a side panel 10 , the first two studs 15 near that particular end of the panel shown in phantom are not used , and only the third and next stud 15 shown in phantom lines is used . if no gate 11 is to be positioned near a particular end of a side panel 10 , then studs 15 are placed at the first two sites demarcated in phantom lines near that particular end , and the next site shown in phantom lines is not used . the side panel 10 is framed with a top rail 16 and a kick plate 17 along the top and bottom edges of the side panel 10 respectively . the top rail 16 and the kick plate 1 7 are disposed generally parallel to each other . see fig1 . a plurality of vertically disposed studs 15 connect the top rail 16 to the kick plate 17 . the number of vertically disposed studs 15 used will depend on the desired spacing between the studs 15 and whether the side panel 10 will be formed with a gate 11 . the studs 15 should be spaced close enough to adequately support the paneling 18 against being pushed too far out by the animals and to provide sufficient rigidity to the side panel 10 . in the preferred embodiment , where cattle are to be transported , the studs 15 are generally spaced 16 . 5625 ″ apart . the studs 15 are welded to the top rail 16 and the kick plate 17 . preferably , the tops of the studs 15 are cut to form a saddle in which the top rail 16 can rest . the top rail 16 and studs 15 are made of hollow 6061 - t6 aluminum tubing . the top rail 16 tubing has a diameter of 2 ″. the studs 15 have a diameter of approximately 1 . 5 ″. the kick plate 17 is also made from 6161 - t6 aluminum , and is approximately ¼ ″ thick . the kick plate 17 is formed with a generally elongated planar main body 19 , having a top edge 20 , and with an outwardly extending lower flange 21 disposed at a right angle to the main body 19 of the kick plate 17 . see fig1 and 9 . this lower flange 21 rests on the rectangular platform 2 . because , in the preferred form , the impermeable membrane 22 for containing the livestock waste is tied to the kick plate 17 near its top edge 20 , the kick plate 17 needs to be tall enough to anchor the impermeable membrane 22 above the level of waste in the enclosure . see fig9 . as is shown in fig1 , openings 23 are provided in the kick plate 17 near its top edge 20 for anchoring the impermeable membrane 22 . as is shown in fig1 , notches 24 are made in the kick plate 17 at intervals along its length . the notches remove material from the lower flange 21 and portions of the main body 19 . these notches 24 are designed to receive straps 25 that will connect opposed side panels 10 when the enclosure is erected . on either side of each notch 24 , panel gussets 26 are welded to the kick plate 17 . see fig8 and 10 . the generally triangular panel gussets 26 connect to the main body 19 of the kick plate 17 and the lower flange 21 of the kick plate 17 along two sides . the panel gussets 26 are formed with openings for receiving first attachment fasteners 27 . the panel gussets 26 are used to connect either winch assemblies 13 or hook assemblies 14 to the kick plate 17 of the side panel 10 by means of the first attachment fasteners 27 . see fig8 and 10 . as shown in fig8 and 10 , the winch assemblies 13 and the hook assemblies 14 are each formed with two side plates 28 and a outwardly extending flange hook 29 that comprises the base for the assembly . these members can be welded together . the flange hooks 29 of the winch and hook assemblies 13 and 14 receive the side flanges 30 on the rectangular platform 2 and anchor the side panels 10 to the rectangular platform 2 . openings are formed in the side plates 28 of the winch and hook assemblies 13 and 14 . these openings align with the openings in the panel gussets 26 when the winch and hook assemblies 13 and 14 are installed properly . first attachment fasteners 27 pass through the openings in the side plates 10 and through the openings in the panel gussets 26 . the first attachment fasteners 27 are preferably machine bolts with threaded nuts . as shown in fig8 and 9 , the winch assemblies 13 are further formed with a mounting flange 31 disposed between the side plates 28 near the top of the side plates 28 . a winch 32 is mounted on the mounting flange 31 for tensioning the strap 25 that connects opposed side panels 10 . the winch 32 can be welded to the mounting flange 31 . the strap 25 as a tensioning member braces the side panels 10 against forces that would push them outward . in the preferred form , the hook assemblies 14 are formed with a pin 33 that can receive a hook 34 attached to the strap 25 that braces the lower ends of the side panels 10 . see fig9 . the pin 33 can be welded to the flange hook 29 of the hook assembly 14 . when the enclosure is erected on a rectangular platform 2 , an elongated strap 25 with a hook 34 is attached to the pin 33 of the hook assembly 14 and the free end of the strap 25 is run through the notch 24 in the side panel 10 to which the hook assembly 14 is adjacent . as shown in fig9 the strap 25 runs across the rectangular platform 2 to its other side and through a corresponding notch 24 in the kick plate 17 of the opposed side panel 10 . the free end of the strap 25 is threaded into the winch 32 and a lever is used to turn the winch 32 until the strap 25 is wound tightly onto the winch 32 and placed in tension such that it can brace the opposed side panels 10 against outward displacement forces . as mentioned earlier , preferably , some of the side panels 10 are formed with gates 11 for the ingress and egress of the animals and handlers . fig1 shows a detailed view of a gate 11 formed in a side panel 10 . the gate 11 is framed with a top strut 35 , a bottom strut 36 , two vertically disposed end struts 37 and an intermediate vertical strut 38 . the struts 35 , 36 , 37 and 38 are welded to each other . hinges 39 for the gate 11 are mounted on one of the end struts 37 of the gate 11 . the hinges 39 receive one of the studs 15 of the side panel 10 . annular rings 40 are welded onto the stud 15 received by the hinges 39 to appropriately position the hinges 39 . the other end strut 37 of the gate 11 is formed with a latching mechanism 41 . the latching mechanism 41 rotates on the end strut 37 and is manipulated with a handle 42 . tabs 43 on the latching mechanism 41 receive the other stud 15 of the side panel 10 that frames the gate 11 when the gate 11 is in its latched position . the latching mechanism 41 is provided with a locking mechanism 44 that prevents the latching mechanism 41 from rotating on the end strut 37 unless the latching mechanism 41 is raised above the locking mechanism 44 . as shown in fig2 in the preferred embodiment , the kick plate 17 of each side panel 10 at a selected end is further provided with a mid - panel connector gusset 45 . this mid - panel connector gusset 45 is similar to the panel gussets 26 welded to the kick plate 17 . the mid - panel connector gusset 45 is also welded to the kick plate 17 . the mid - panel connector gusset 45 is formed with openings for receiving second attachment fasteners 46 . the second attachment fasteners 46 connect the mid - panel connector gusset 45 to a gusset on the middle panel 47 and to the corresponding mid - panel connector gusset 45 on the adjacent side panel 10 . the second attachment fasteners 46 are also preferably machine bolts with threaded nuts . in the preferred embodiment , the kick plate 17 of each side panel 10 at a second selected end is formed with end panel attachment openings 48 for receiving third attachment fasteners 49 . see fig3 and 13 . positions for these openings 48 are shown in phantom in fig1 . the third attachment fasteners 49 connect the kick plate 17 of the side panel 10 to the adjacent end panel 50 . the third attachment fasteners 49 are also preferably machine bolts with threaded nuts . in the preferred embodiment , the top rail 16 of the side panel 10 is provided with a plurality of connection tabs . see fig1 . the connection tabs attach the top rail 16 to the other components of the enclosure . the first set of connection tabs are the side panel end tabs 51 which are located at the ends of the top rail 16 . the side panel end tabs 51 are each formed with an opening 52 for receiving a fourth attachment fastener 53 . the fourth attachment fasteners 53 are also preferably machine bolts with threaded nuts . preferably , the ends of the top rails 16 are notched and the side panel end tabs 51 are inserted into the notches and welded in place . the side panel end tabs 51 are generally planar and rectangular in configuration , and extend parallel to the rectangular platform . the side panel end tabs 51 are made from 6061 - t6 aluminum and are approximately ¼ ″ thick . the second set of connection tabs on the side panel top rail 16 are the side panel intermediate tabs 54 . see fig1 . in the preferred embodiment , there are three such side panel intermediate tabs 54 spaced at regular intervals along the top rail 16 . the side panel intermediate tabs 54 are also formed as generally rectangular planar members . each is formed with an opening 55 for receiving a fourth attachment fastener 53 . the side panel intermediate tabs 54 extend generally perpendicular to the studs 15 and generally parallel to the rectangular platform 2 when the enclosure is erected . the side panel intermediate tabs 54 are welded to the top rail 16 . the side panel intermediate tabs 54 are made from 6061 - t6 aluminum and are approximately ¼ ″ thick . as shown in fig2 and 3 the side panels 10 can be fitted with additional accessories . as shown in fig2 two of the side panels 10 are fitted with water troughs 12 . as shown in fig3 each of the side panels shown is fitted with a strut 56 disposed between two of the studs 15 for mounting a water trough 12 . next to each strut is a hose bib 57 for providing water to the trough 12 . preferably , the trough 12 is fitted with an automatic shut - off valve that is triggered when the level of the water in the trough 12 reaches a certain height . to provide rigidity to the preferred embodiment built on a 40 ′ rectangular platform 2 , a middle panel 47 is also used . the middle panel 47 traverses the rectangular platform 2 and is connected to all four side panels 10 . see fig2 . as is shown in fig1 , the middle panel 47 is framed with a top rail 58 and a bottom rail 59 along the top and bottom edges of the middle panel 47 respectively . the top rail 58 and the bottom rail 59 are disposed generally parallel to each other . a plurality of vertically disposed studs 60 connect the top rail 58 to the bottom rail 59 . the number of vertically disposed studs 60 used will depend on the desired spacing between the studs 60 . the studs 60 should be spaced close enough to adequately support the paneling 18 against being pushed by the animals and to provide sufficient rigidity to the middle panel 47 . in the preferred embodiment , where cattle are to be transported , the studs 60 are generally spaced 15 ″ apart . the studs 60 are welded to the top rail 58 and the bottom rail 59 . preferably , the tops and bottoms of the studs 60 are cut to form a saddle in which the top rail 58 and the bottom rail 59 can rest . the top rail 58 , bottom rail 59 and studs 60 are made of hollow 6061 - t6 aluminum tubing . the tubing for the top and bottom rails 58 and 59 has a diameter of 2 . 5 ″. the studs 60 also have a diameter of approximately 2 . 5 ″. as shown in fig1 and 16 , side panel connector gussets 61 are welded to the two outermost studs 60 of the middle panel 47 . these gussets 61 are generally planar and triangular and lie in line with the bottom rail 59 . they are connected on the outside of the outermost studs 60 along one edge , preferably by welding . the generally triangular side panel connector gussets 61 are formed with openings 62 for receiving second attachment fasteners 46 . the side panel connector gusset 61 is similar to the mid - panel connector gussets 45 welded to the kick plates 17 of the adjacent side panels 10 . when the pen 1 is erected , the side panel connector gusset 61 of the middle panel 47 will lie between the two adjacent mid - panel connector gussets 45 with the openings in the three gussets 61 and 45 in alignment . see fig2 . the second attachment fasteners 46 are inserted through the aligned openings and tightened so that the gussets 61 and 45 are held firmly together . as shown in fig1 , in the preferred embodiment , the top rail 58 of the middle panel 47 is provided with a plurality of connection tabs . the connecting tabs attach the top rail 58 to the other components of the enclosure . the first set of connection tabs are the mid - panel end tabs 63 which are located at the ends of the top rail 58 . the mid - panel end tabs 63 are each formed with two openings 64 for receiving fourth attachment fasteners 53 . preferably , the ends of the top rail 58 are notched and the mid - panel end tabs 63 are inserted into the notches and welded in place . the mid - panel end tabs 63 are generally planar in configuration , and extend parallel to the rectangular platform . the mid - panel end tabs 63 are made from 6061 - t6 aluminum and are approximately ¼ ″ thick . the mid - panel end tabs 63 will overlap adjacent side panel end tabs 51 when the pen 1 is erected , such that the openings 64 and 52 in the overlapping mid - panel and side - panel end tabs 63 and 51 will be alignment to receive fourth attachment fasteners 53 . the fourth attachment fasteners 53 are tightened such that the mid - panel and side panel end tabs 63 and 51 are clamped together . the second set of connection tabs on the middle panel top rail 58 are the mid - panel intermediate tabs 65 . see fig1 . in the preferred embodiment , there are two such mid - panel intermediate tabs 65 disposed on either side of the top rail 58 at its middle point . the mid - panel intermediate tabs 65 are also formed as generally planar members . each is formed with an opening 66 for receiving a fourth attachment fastener 53 . the mid - panel intermediate tabs 65 extend generally perpendicular to the studs 60 and generally parallel to the rectangular platform when the enclosure is erected . the mid - panel intermediate tabs 65 are welded to the top rail 58 . the mid - panel intermediate tabs 65 are made from 6061 - t6 aluminum and are approximately ¼ ″ thick . in the preferred embodiment , two end panels 50 are also provided that are similar to the middle panel 47 in size , but have kick plates 67 instead of bottom rails . see fig1 , 18 and 19 . each end panel 50 is framed with a top rail 68 and a kick plate 67 along the top and bottom edges of the end panel 50 respectively . see fig1 . the top rail 68 and the kick plate 67 are disposed generally parallel to each other . a plurality of vertically disposed studs 69 connect the top rail 68 to the kick plate 67 . the number of vertically disposed studs 69 used will depend on the desired spacing between the studs 69 . in the preferred embodiment , where cattle are to be transported , the studs 69 are generally spaced 15 ″ apart . the studs 69 are welded to the top rail 68 and the kick plate 67 . preferably , the tops of the studs 69 are cut to form a saddle in which the top rail 68 can rest . the top rail 68 and studs 69 are made of hollow 6061 - t6 aluminum tubing . the top rail 68 tubing has a diameter of 2 . 5 ″. the studs 69 have a diameter of approximately 2 . 5 ″ as well . the kick plate 67 is also made from 6161 - t6 aluminum , and is approximately ¼ ″ thick . the kick plates 67 of the end panels 50 are formed in a similar fashion as the side panel kick plates 17 , however , there is no need in the preferred embodiment to provide the end panel kick plate 67 with either winch or hook assemblies . the kick plate 67 is formed with a generally elongated planar main body 70 , having a top edge 71 , and with an outwardly extending lower flange 72 disposed at a right angle to the main body 70 of the kick plate 67 . see fig1 . this lower flange 72 rests on the rectangular platform 2 . because , in the preferred form , the impermeable membrane 22 for containing the livestock waste is tied to the kick plate 67 near its top edge 71 , the kick plate 67 needs to be tall enough to anchor the impermeable membrane 22 above the level of waste in the enclosure . see fig9 and fig1 . as is shown in fig1 , openings 73 are provided in the kick plate 67 near its top edge 71 for anchoring the impermeable membrane 22 . as shown in fig1 , attached to the kick plates 67 of the end panels 50 at their outer edges are side panel connector gussets 74 . the side panel connector gussets 74 are welded to the kick plate 67 . these gussets 74 are generally planar and rectangular and lie perpendicular to the kick plate 67 . these gussets 74 are formed with openings 75 for receiving third attachment fasteners 49 . when the pen 1 is erected , the side panel connector gusset 74 of the end panels 50 will lie adjacent to selected ends of the kick plates 17 of the side panels 10 . the openings 75 formed in the side panel connector gusset 74 will align with the end panel attachment openings 48 in the selected ends of the side panel kick plates 17 . with the openings 75 and 48 in alignment third attachment fasteners 49 can be inserted therethrough to rigidly connect the end panel 50 to the side panel 10 . if the side panel connector gusset 74 of the end panel 50 does not register with the kick plate 17 of the side panel 10 , a spacer can be placed between them to make the connection more rigid . see fig1 , in the preferred embodiment , the top rail 68 of each end panel 50 is provided with a plurality of connection tabs . the connecting tabs attach the top rail 68 to the other components of the enclosure . the first set of connection tabs are the end panel end tabs 76 which are located at the ends of the top rail 68 . the end panel end tabs 76 are each formed with an opening 77 for receiving a fourth attachment fastener 53 . preferably , the ends of the top rails 68 are notched and the end panel end tabs 76 are inserted into the notches and welded in place . the end panel end tabs 76 are generally planar and rectangular in configuration , and extend parallel to the rectangular platform 2 . the end panel end tabs 76 are made from 6061 - t6 aluminum and are approximately ¼ ″ thick . the end panel end tabs 76 and the side panel end tabs 51 connect to an intermediate member called a corner bracket 78 . see fig2 and 21 . the corner bracket 78 is formed as a generally l - shaped member , with an opening in each of the legs . the interior angle of the l - shaped member is meant to receive the two interior sides of the corner post 9 of the rectangular platform 2 . abutment plates may be provided on the two interior angle edges of the l - shaped corner bracket 78 to provide strength . the abutment plates would be welded to the l - shaped corner bracket 78 and disposed perpendicular to it . when the pen 1 is erected , the corner brackets 78 are attached to adjacent end tabs 76 and 51 of the end panels 50 and side panels 10 with fourth attachment fasteners 53 inserted through the aligned openings and in the corner brackets 78 and the end tabs 76 and 51 . the other connection tab on the end panel top rail 68 is the end panel intermediate tab 79 . in the preferred embodiment , the end panel intermediate tab 79 is disposed at the middle point of the top rail 68 . see fig1 . the end panel intermediate tab 79 is also formed as a generally planar member with an opening 80 for receiving a fourth attachment fastener 53 . the end panel intermediate tab 79 extends generally perpendicular to the studs 69 and generally parallel to the rectangular platform 2 when the enclosure is erected . the end panel intermediate tab 79 is welded to the top rail 68 . the end panel intermediate tab 79 is made from 6061 - t6 aluminum and is approximately ¼ ″ thick . on all of the panels , rigid polyethylene paneling 18 is mounted by means of brackets 81 . see fig3 , 5 and 6 . the polyethylene paneling 18 is mounted in abutment , such the animals for the most part will not be able to see outside of the enclosure . the polyethylene paneling 18 also helps to contain waste . to give the enclosure further rigidity , a top frame is provided . the top frame serves , in part , as a bracing member . in the preferred embodiment , this top frame consists of two identical trusses 82 . each truss 82 connects two opposed side panels 10 as well as the middle panel 47 and an end panel 50 . see fig2 . the trusses 82 connect to the intermediate tabs 54 , 79 and 65 of the side panels 10 , the end panels 50 and the middle panel 47 with fourth attachment fasteners 53 . as shown in fig2 , in the preferred embodiment , a truss 82 is constructed in the following manner . a truss end tab is 83 provided that is substantially planar and is formed with an opening 84 for receiving a fourth attachment fastener 53 . two first tube braces 85 of substantially equal length are connected to the first truss end tab 83 . preferably , notches are formed in the ends of the fist tube braces 85 that will connect to the truss end tab 83 . the truss end tab 83 is received in those notches and welded to the first tube braces 85 . the first tube braces 85 extend away from the truss end tab 83 forming an interior angle between them that is less than 180 degrees . each of the free ends of the first tube braces 85 is attached to a separate truss corner tab 86 . the truss corner tab 86 is also substantially planar and is formed with an opening 87 for receiving a fourth attachment fastener 53 . like the connection between the truss end tab 83 and the first tube braces 85 , each truss corner tab 86 is preferably inserted into a notch in a first tube brace 85 and then welded to it . a second tube brace 88 spans between the truss corner tabs 86 , connecting them and forming a triangular frame with the first tube braces 85 . the connection between the second tube brace 88 and the two truss corner tab 86 is also made by notching the ends of the second tube brace 88 and fitting the truss corner tabs 86 into the notches and welding . third tube braces 89 of substantially equal length are connected to each of the truss corner tabs 86 . these third tube braces 89 extend from the truss corner connectors 86 on intersecting paths to create a similar triangular frame disposed opposite the first triangular frame created by the first tube braces 85 and the second tube brace 88 . the third tube braces 89 are connected by a truss center tab 90 that is received in notches in the free ends of the third tube braces 89 and welded to them . also extending from each of the truss corner tabs 86 is a fourth tube brace 91 . these fourth tube braces 91 are of substantially equal length and extend generally parallel to each other and away from the first tube braces 85 . the fourth tube braces 91 are each connected to a truss corner tab 86 in a similar fashion as described above and each is also connected to a truss middle tab 92 in a similar fashion as described above . the truss middle tab 92 is also a generally planar member with an opening 93 for receiving a fourth attachment fastener 53 . each of the truss middle tabs 92 is connected to the truss center tab 90 by fifth tube braces 94 . the two fifth tube braces 94 are substantially equal in length and are disposed in a line . each fifth tube brace 94 together with an adjacent fourth tube brace 91 and an adjacent third tube brace 89 creates a triangular frame . the fifth tube braces 94 connect to the truss middle tabs 92 and to the truss center tab 90 in the manner as described above for similar connections . the remaining portion of the truss 82 is constructed in a similar manner and is a mirror image of the first portion of the truss 82 already described . two additional third tube braces 89 are connected to the truss center tab 90 , and extend away from the truss center tab 90 , each in line with a third tube brace 89 connected to the truss center tab 90 . two additional fourth tube braces 91 extend away from the truss middle tabs 92 , each in line with a fourth tube brace 91 . each additional third tube brace 89 connects to an intersecting , additional fourth tube brace 91 by means of a truss corner tab 86 . the two additional truss corner tabs 86 are connected by an additional second tube brace 88 , creating another triangular framing element between the two additional third tube braces 89 and the additional second tube brace 88 . finally , two additional first tube braces 85 are connected to each of the additional two truss corner tabs 86 and intersect at an additional truss end tab 83 . the components of the truss are also preferably made out of 6061 - t6 aluminum with the tube braces being approximately 1 . 25 ′ to 1 . 5 ″ inches in diameter . the truss 82 is designed so that when the pen 1 is erected , one of the truss end tabs 83 will overlap with an end panel intermediate tab 79 , such that the openings 80 and 84 in the tabs 79 and 83 align and can receive a common fourth attachment fastener 53 . the other truss end tab 83 will overlap a middle panel intermediate tab 65 and the openings 66 and 84 in the tabs 65 and 83 will align to receive a fourth attachment fastener 53 . further , when the truss 82 is attached to the side panels 10 , the fourth tube braces 91 will parallel the top rails 16 of the side panels 10 . each of the truss corner tabs 86 will connect to a side panel intermediate tab 54 by means of a fourth attachment fastener 53 . each of the truss middle tabs 92 will also connect to separate side panel intermediate tab 54 by means of a fourth attachment fastener 53 . after the side panels 10 , the end panels 50 , and the middle panel 47 have been connected to each other , impermeable membranes 22 are installed in each of the enclosures formed . in the preferred embodiment , the impermeable membrane 22 is a tarp with grommets spaced around its edges . the tarp is made from vinyl - coated nylon . the tarp is large enough to cover one - half of the rectangular platform 2 as well as extend up to the top edges 20 and 71 of the kick plates 17 and 67 of the side and end panels 10 and 50 and to a similar height on the middle panel 47 . the tarp is rectangular in shape and folded over itself at the corner intersections of the side panels 10 with the end panel 50 and the middle panel 47 . ties are looped through the grommets in the tarp and through the openings 23 and 27 in the kick plates 17 and 67 . the middle panel 47 is provided with intermediate cross bars 95 for securing the tarp . see fig5 . after the tarp is laid down and secured , stall mats 96 are placed over the tarp to protect it . see fig9 . if the voyage will be of a long duration , a feeding trough 97 can be placed in each of the enclosures created by the middle panel 47 that divides the pen 1 into two enclosures . see fig2 . the feeding troughs 97 can be secured to the middle pane 47 . i the pen 1 can also be provided with mesh or tarp spread over the top frame to provide shade to the animals . it is preferred during most voyages that the rectangular platforms 2 with animals be shipped near deck level so that handlers can reach the animals . since container ships usually stack many levels of containers in each column , the rectangular platforms will generally have containers stacked above them that can provide shade to the animals during the voyage . the preferred embodiment of the present invention involves erecting panels on a rectangular platform 2 having corner posts 9 . the corner posts 9 provide longitudinal resistance to movement of the panels , as well as aiding the straps 22 and flange hooks 29 in providing lateral or transverse resistance . additional anchoring points and lashing points on the rectangular platform 2 can be used to anchor the panels against longitudinal and lateral or transverse forces with methods generally known in the art . as is shown in fig2 , panels may be eliminated from the pen 1 and the enclosure still maintained . fig2 shows a rectangular platform 2 ′ with incomplete superstructure and fixed ends , wherein the fixed ends consist of a complete end structure ( end walls 98 ). because end walls 98 are present on the rectangular platform 2 ′, end panels 50 are not needed to complete the enclosure . fig2 shows a cross bar 99 connecting two opposed corner brackets 78 to provide further stability to the structure . as shown in the drawings , the rectangular platforms 2 and 2 ′ are provided with corner fittings 100 to allow stacking of the rectangular platforms 2 and 2 ′ with other standardized freight containers , and to allow easy attachment of the rectangular platforms 2 and 2 ′ to trucks and rail cars designed to carry standardized freight containers .

US-15199298-A

an implantable orthopedic prosthesis is provided that includes a shell having a substantially concave inner surface defining a cavity and a substantially annular groove formed therein . the prosthesis further includes a polymeric insert that is positionable within the cavity of the shell , and that has a substantially convex outer surface and a circumferential protrusion projecting therefrom . the protrusion has a substantially trapezoidal cross - section wherein at least one of the sides of the trapezoid is substantially parallel to the axis of symmetry of the insert . the cross - section of the protrusion is substantially congruent to the cross - section of the groove of the shell , and the inner surface of the shell is substantially congruent with a corresponding portion of the outer surface of the insert when the insert is properly positioned within the cavity of the shell .

referring to the drawings , fig1 - 9 , a preferred embodiment of the present invention is illustrated in the form of an implantable orthopedic prosthesis , particularly an acetabular component of a total hip joint prosthesis . the illustrated acetabular component is useful as part of that well - known type of total hip joint prosthesis that includes an acetabular component comprising an acetabular shell and an associated bearing liner , and a femoral component comprising a femoral stem and an associated spherical head . the spherical head , fixed to the femoral stem , articulates in a ball - and - socket arrangement within the bearing liner , with the bearing liner being essentially fixed within the acetabular shell . the femoral stem and acetabular shell are fixed to bone of the proximal femur and pelvic acetabulum , respectively . only the acetabular shell and bearing liner are described in detail herein , as the various types and configurations of femoral stems and heads are well understood in the art . the illustrated acetabular shell and bearing liner are particularly resistant to disconnection and displacement from each other when implanted . referring to fig1 an acetabular shell 10 is shown in cross - section in a plane along the axis of symmetry . acetabular shell 10 is shaped generally as a hemispherical cup having a shell wall 12 defined by a convex proximal surface 14 and a concave distal surface 16 . acetabular shell 10 has a proximal dome region 18 at the apex of shell wall 12 and an annular rim 20 at the distal end of shell wall 12 . concave distal surface 16 of shell wall 12 defines a shell cavity 22 having an opening 24 into and through which a bearing insert , described further below , can be received . an annular lip 25 extends radially inwardly from concave distal surface 16 and , in cooperation with an annular protrusion on the bearing insert as described further below , provides a means for affixing the bearing insert against axial displacement from within shell cavity 22 . such means also includes an annular flange , described further below , on the bearing insert having notches for receiving the legs 26 that extend axially from rim 20 . the interengagement of the legs 26 of shell 10 and the notches of the bearing insert flange affix the bearing insert against rotation within shell cavity 22 about the axis of symmetry 27 of acetabular shell 10 passing through the center of proximal dome region 18 at the apex of shell 10 . convex proximal surface 14 is provided with a macro - texture comprising circumferential grooves 28 filled and covered with a porous coating 29 comprised of titanium powder sintered in place . the porous coating 29 accepts the ingrowth or ongrowth of bone , and enhances adhesion of bone cement . the porous coating 29 , while preferred , is not necessary for the understanding or practice of the present invention . referring again to fig1 acetabular shell 10 includes a dome hole 30 centered in dome region 18 at the apex of shell 10 in coaxial alignment with axis 27 . dome hole 30 is internally threaded to serve as an engagement interface for an instrument ( not shown ) for holding and positioning acetabular shell 10 during implantation . typically , such an instrument is used by the implanting physician to securely grasp the acetabular shell 10 and place it in the reamed acetabulum . such an instrument usually includes an elongate handle for controlling anteversion and adduction of the acetabular shell as it is implanted , and for transmitting axial driving forces to the shell . acetabular shell 10 can also be provided with a plurality of screw holes ( not shown ) through shell wall 12 between concave distal surface 16 and convex proximal surface 14 . a bone screw ( not shown ), having a head and a threaded shank , can be inserted through a screw hole from within the shell cavity 22 and screwed into the pelvic bone underlying the acetabulum to secure acetabular shell 10 in place . the concave distal surface 16 of shell 10 , as shown in fig1 starting at the dome region 18 and proceeding toward the rim 20 , includes a spherical wall portion 40 followed by a first right - cylindrical wall portion 42 , and a next subsequent frusto - conical wall portion 44 that slopes distally and radially outwardly . next following frusto - conical wall portion 44 is a second right - cylindrical wall portion 46 . at the distal extent of right - cylindrical wall portion 46 , a shoulder 48 extends radially inwardly , followed by a third right - cylindrical wall portion 50 that extends distally therefrom . finally , a second frusto - conical wall portion 52 slopes distally and radially outwardly from wall portion 50 . shoulder 48 , right - cylindrical wall portion 50 , and second frusto - conical wall portion 52 together define the annular lip 25 first mentioned above . referring to fig2 , 4 , 5 and 6 , a polyethylene bearing insert 60 , first mentioned above , is shown in detail . fig2 and 4 are top , side and bottom views , respectively of bearing insert 60 , and fig5 is a cross - sectional view of the same . fig6 is a perspective view of bearing insert 60 . in general , bearing insert 60 is designed to fit congruently against concave distal surface 16 of acetabular shell 10 , in order to minimize the opportunity for bearing insert 60 to flex under load that otherwise would be made possible by a significant gap between bearing insert 60 and acetabular shell 10 . such flexing , were it to occur , could result in micro - motion of the bearing insert 60 relative to acetabular shell 10 , causing the generation of polyethylene wear debris from friction between the bearing insert 60 and the acetabular shell 10 . by maintaining a high degree of congruence , the bearing insert 60 is fully supported and restrained against relative movement . to aid in maintaining congruent contact between bearing insert 60 and shell 10 , bearing liner 60 is provided with an integral connection means proximate the rim thereof that engages the geometrical features of the acetabular shell 10 as described above . the connection means , while allowing ease of insertion as described further below , also results in a strong connection between bearing insert 60 and acetabular shell 10 that is highly resistant to dislocation , separation , or disengagement . such strength of connection is highly advantageous after implantation of the acetabular component because the bearing insert is often subjected to forces by the head and femoral stem components that , under some circumstances , tend toward dislodging the bearing insert 60 from the acetabular shell , which could result in failure of the implanted component . again referring to fig2 - 6 , bearing insert includes a convex spherical wall portion 62 followed by a first right - cylindrical wall portion 64 , and a next subsequent frusto - conical wall portion 66 that slopes distally and radially outwardly . next following frusto - conical wall portion 66 is a second right cylindrical wall portion 68 . at the distal extent of right - cylindrical wall portion 68 , a second frusto - conical wall portion 70 slopes distally and radially inwardly from wall portion 68 , followed by a third right - cylindrical wall portion 72 that extends distally therefrom . at the distal extent of cylindrical wall portion 72 , an annular rim 74 extends radially and includes a lip 76 that extends upwardly ( proximally ) and radially outwardly . frusto - conical wall portion 66 , cylindrical wall portion 68 , and frusto - conical wall portion 70 , together form an annular protrusion 78 that engages the annular groove 79 in shell 10 , which is defined by frusto - conical wall surface 44 , cylindrical wall surface 46 , and shoulder 48 . as shown best in fig2 annular protrusion 78 is not continuously annular , but rather is periodically relieved about its circumference by a plurality of notches 80 . as preferred , about fifty percent of the circumference of annular protrusion 78 is relieved by notches 80 , evenly spaced . as shown best in fig2 and 4 , annular rim 74 , also is not continuously annular , but rather is periodically relieved about its circumference by a plurality of notches 82 . as preferred , about twenty - five percent of the circumference of annular rim 74 is relieved by notches 82 , evenly spaced . referring to fig7 bearing insert 60 is shown inserted within acetabular shell 10 . frusto - conical wall portion 70 of the annular protrusion 78 of bearing insert 60 engages shoulder 48 of acetabular shell 10 to retain bearing insert 60 therein . as bearing insert 60 is inserted into acetabular shell 10 , annular protrusion 78 deforms elastically , as permitted by the relieved areas 80 , in order to proceed past annular lip 25 of shell 10 . once past , annular protrusion 78 rebounds into the annular groove 79 in shell 10 . also , as bearing insert 60 is inserted into shell 10 , lip 76 of annular rim 74 engages rim 20 of shell 10 , and is elastically deformed distally , as permitted by relieved areas 82 and as shown best in fig7 . the deformed annular rim 74 maintains spring pressure against rim 20 via lip 76 to hold annular protrusion 78 tightly against shoulder 48 of shell 10 . referring to fig8 and 9 , a test arrangement is shown schematically , by which the resistance of bearing liner 60 against displacement from shell 10 is measured . in fig8 a push out test is illustrated , whereas in fig9 a lever out test is shown . by measuring the force required to dislodge bearing insert 60 from shell 10 , either by an axial force 90 or a levered force 92 about a fulcrum 94 near the rim 20 of the shell , the strength of the connection between bearing insert 60 and shell 10 can be characterized . as shown in fig8 the push out test was performed on a 28 mm polyethylene insert fully seated in a 53 mm shell . the push out pin 96 was moved axially at a linear velocity of 0 . 2 inches per minute until failure of the insert to shell connection . an axial load of about 750 lbs was required to dislodge the bearing insert 60 . as shown in fig9 the lever arm was moved about the fulcrum at an angular velocity of 1 . 3 radians per minute at a fulcrum located 2 . 2 inches from the bearing liner , until failure of the insert to shell connection . a torque load of about 580 inch - pounds was required to dislodge the bearing insert .

US-22655699-A

a folding device used to fold a cardiac valve is disclosed . also shown are methods and system for holding and delivering a cardiac valve during implantation . the folding device facilitates folding either a stented or unstented prosthetic valve prior to insertion into a valve annulus . a delivery system is provided to allow a user to measure the patient annulus to select the prosthetic valve size and insert a folded prosthetic valve into a target site . methods for using the folding device and delivery system are also disclosed .

fig1 through 23 show embodiments of systems and methods for folding and delivering a cardiac valve . as shown in fig1 and fig2 , the present invention is directed towards a folding device 2 . the folding device 2 may be securely attached to an unfolded prosthetic valve 1 . a surgeon or an assistant folds the unfolded valve 1 by pushing the exposed side walls of the prosthetic valve 1 towards the center of the folding device 2 while simultaneously using fingers to compress the sides of the folding device 2 . the folding device 2 bend inwards and the prosthetic valve 1 folds by caving in on itself . the valve 1 may be inserted into the folding device 2 in the operating room . alternatively , the valve 1 may be inserted and attached into the folding device 2 during the manufacturing process . as such , the folding device 2 also protects the valve 1 during shipment . the folding device 2 helps make sure foldable valves are folded consistently . the folding device 2 also helps transfer the prosthetic valve 1 in a folded configuration to the target valve annulus . the folding device 2 may also be used as a stand - alone device to fold and deliver a prosthetic valve 1 . the folding device 2 may also be used in conjunction with a valve delivery system to deliver a folded valve 1 to a target site . fig1 and fig2 show the cardiac valve 1 loosely disposed within the folding device 2 . the folding device 2 is generally semi - cylindrical , to partially envelope the cardiac valve 1 . in one embodiment of the present invention , locking bars 3 are attached to the folding device 2 . the locking bars 3 are generally long slender rods used to lock the folding device 2 into a top loading valve receptacle 17 shown in fig1 . in another embodiment of the present invention , the locking bars 3 are hollow cylinders that can be loosely disposed on the two rods 22 part of the guide rail valve receptacle 15 shown in fig1 a and fig1 b . in yet another embodiment , the folding device has curved edges and snaps onto the two rods 22 part of the guide rail valve receptacle 15 shown in fig1 a and fig1 b . sutures 9 may be tied between a plurality of suture holes 4 on opposite sides of the folding device 2 to retain the valve 1 positioned within the folding device 2 . such sutures 9 help retain the position of the prosthetic valve 1 within the folding device 2 . as such , the sutures 9 also help with consistent folding of the prosthetic valve 1 . fig2 shows an embodiment of the present invention wherein the folding device has a stopper ring 5 is attached to the folding device 2 . the stopper ring 5 is used to guide and limit the insertion of the folding device 2 into a valve receptacle 10 . fig3 a and 3b show end and top views , respectively , of the folding device 2 . the folding device 2 is generally curved to match the substantially circular geometry of the cardiac valve 1 . the folding device may include a single or plurality of suture slots 8 . suture slots 8 may be used to tie guiding sutures between the unfolded prosthetic valve 1 and the valve annulus , or alternatively between the folded prosthetic valve 6 and the valve annulus . in a preferred embodiment of the present invention , the folding device 2 is made out of a flexible material such that the folding device can stay in intimate contact with the cardiac valve 1 during folding . in one embodiment of the present invention , the folding device 2 is made out of a plastic material . in another embodiment of the present invention , the folding device 2 is made out of a metal . in yet another embodiment of the present invention , the folding device 2 is made out of a composite material . the folding device can be cleaned , sterilized in an autoclave , and reused . in another embodiment , the folding device 2 is disposable . fig4 a and 4b show end and top views , respectively , of an expanded heart valve 1 loosely disposed in the folding device 2 . temporary sutures 9 are tied between suture holes 4 to secure the valve 1 within the folding device 2 . fig4 b also shows a handle 11 attached directly to the folding device 2 . in one embodiment of the present invention , there is no handle 11 attached directly to the folding device 2 . fig5 a and 5b show end and side views , respectively , of an expanded heart valve 1 loosely disposed in the folding device 2 . fig6 a and 6b show end and side views , respectively , of a heart valve 1 being folded within the folding device 2 . a folding bar 20 used to push the exposed portion of the valve 1 downward into the folding device 2 , thereby transforming the unfolded valve 1 into a folded valve 6 . the folding bar 20 is used with the folding device 2 to ensure consistent folding of the valve . fig7 a and 7b show end and side views , respectively , of a folded heart valve 6 loosely disposed in the folding device 2 . fig8 and 9 also show the folded valve 6 disposed within the folding device 2 . the folding device 2 helps maintain the valve 6 in a folded configuration . fig9 shows the folding device 2 loosely disposed within a retainer ring 7 . the retainer ring 7 helps maintain the folding device 2 in a folded configuration and allows the folded valve 6 to be transferred to the target site . by utilizing the systems and methods for folding a heart valve described herein , the size ( i . e . largest diameter that can be measured ) of the valve during the implantation process is reduced by approximately 1 to 50 %. after the valve 1 has been folded , the temporary suture 9 attached to the suture holes 4 may be removed . in one embodiment of the present invention , the folded valve 6 and folding device 2 may be transferred to a front loading valve receptacle 10 . in another embodiment of the present invention , the folded valve 6 is transferred alone directly from the folding device 2 into a front loading valve receptacle 10 . in another embodiment of the present invention , the folded valve 6 and folding device 2 may be transferred to a guide rail valve receptacle 15 . in another embodiment of the present invention , the folded valve 6 and folding device 2 may be transferred to a top loading valve receptacle 17 . in another embodiment of the present invention , the folded valve 6 and folding device 2 may be transferred to a retainer ring valve receptacle 18 . the folding device 2 and the folded valve 6 may be maintained in a folded position by inserting the folding device 2 into a retainer ring 7 . the retainer ring 7 maintains the shape of the collapsed valve and folding device 2 . in one embodiment of the present invention , the retainer ring 7 is adapted to connect to a handle 11 . as such , the combined folding device 2 , retainer ring 7 , and handle 11 functions as a valve delivery system . in another embodiment of the present invention , the valve 1 is pushed into a retainer ring 7 adapted to connect to a handle 11 . as such , the combined retainer ring 7 and handle functions as a valve delivery system . fig1 through 23 show different variations of the disclosed delivery systems . fig1 shows a delivery system that includes a front loading valve receptacle 10 adapted to receive a handle 11 . the folded cardiac valve 6 is loosely disposed within the front loading valve receptacle 10 . a plunger 12 is loosely disposed within the handle 11 . fig1 shows the same delivery system shown in fig1 . fig1 also shows the folded valve 6 shown in fig9 being transferred into the front loading valve receptacle 10 . here , the folded valve 6 is loosely disposed within the folding device 2 . the folding device 2 is loosely disposed within the retainer ring 7 . the stopper ring 5 limits the insertion of the folding device 2 into the front loading valve receptacle 10 . next , the folded valve 6 is inserted by sliding in the front loading valve receptacle 10 . the stopper ring 5 and the folding device 2 is then removed , leaving the folded valve 6 loosely disposed within the front loading valve receptacle 10 . the folded valve 6 may now be delivered to the annulus of the patient . fig1 a and 12b show end and side views , respectively , of a valve delivery system . the delivery system includes a front loading valve receptacle 10 adapted to receive a handle 11 . fig1 a and 13b show end and side views , respectively , of a valve delivery system including a front loading valve receptacle 10 , handle 11 , and plunger 12 . the plunger 12 is loosely disposed within the handle 11 . the plunger 12 may assist with the unfolding and delivery of the folded valve 6 . moving the plunger 12 in the direction of the folded valve 6 releases the folded valve 6 from the front loading valve receptacle 10 . fig1 a and 14b show end and side views , respectively , of a valve delivery system . the delivery system includes a front loading valve receptacle 10 adapted to receive a handle 11 . a plunger 12 is loosely disposed within the handle 11 . in fig1 b , the handle 11 is curved and not aligned with the plunger 12 over its entire length . this allows the user to grasp the handle 11 with the fingers of one hand and operate the plunger 12 with the thumb of the same hand . a folded valve 6 is shown loosely disposed within the front loading valve receptacle 10 . fig1 a and 15b show end and side views , respectively , of a valve delivery system including a front loading valve receptacle 10 , handle 11 , and plunger 12 . here , the plunger 12 has been moved in the direction of the arrow . the plunger 12 , attached to the plunger plate 14 , pushed the valve 1 out of the front loading valve receptacle 10 , thereby releasing the valve . in one embodiment of the present invention , the folded cardiac valve 6 is released by retracting the handle 11 while keeping the plunger 12 stationary . the plunger plate 14 , which is attached to the distal portion of the plunger 12 , prevents the folded valve 6 from moving while retracting the handle 11 and the front loading valve receptacle 10 . a knob 13 attached to the proximal portion of the plunger 12 facilitates manipulation of the plunger 12 . in another embodiment of the present invention , a plunger 12 , plunger plate 14 , and a plunger knob 13 are not utilized . in this embodiment , the valve 1 is released by pulling the entire delivery system away from the target site . in one embodiment of the present invention , the front loading valve receptacle 10 includes one or more distal suture slots 21 that may be used to gain access to the folded valve 6 suture ring area , for example to insert sutures into the folded valve 6 for use during later implantation . in another embodiment of the current invention , the front loading valve receptacle 10 does not include any distal suture slots 21 . the valve receptacle 10 shown in fig1 through fig1 may be characterized as a front or distal valve receptacle since the folded valve 6 is inserted distal to the valve receptacle 10 . fig1 a and 16b show a delivery system with a different valve receptacle . fig1 a and 16b show the folded valve 6 disposed within the folding device 2 . the two locking bars 3 are loosely disposed around the two guide rails 22 that form the guide rail valve receptacle 15 . once the valve 1 has been folded , the folded valve 6 and the folding device 2 may be attached to the guide rail valve receptacle 15 by sliding the folding device 2 and the folded valve 6 between the two guide rails 22 part of the guide rail valve receptacle 15 . in one embodiment of the present invention , the cardiac valve 1 is released by retracting the handle 11 while keeping the plunger 12 stationary . a plunger plate 14 is attached to the distal portion of the plunger 12 . the plunger plate 14 prevents the valve from moving while retracting the handle 11 . a knob 13 is attached to the proximal portion of the plunger 12 . in another embodiment of the present invention , a plunger 12 , plunger plate 14 , and a plunger knob 13 are not utilized . rather , the valve 1 is released by pulling the delivery system away from the target site . in order for such a method of releasing the folded valve 6 to work properly , the folded valve 6 must exert a retaining force against the annulus as it unfolds , thereby preventing the folded valve 6 from moving with respect to the annulus . alternatively , the user can employ a suture or similar means to retain the folded valve 6 at the target site . in one embodiment of the present invention , the guide rail valve receptacle 15 includes one or more suture slots 21 that may be used gain access to the folded valve 6 , such as to insert sutures into the valve for use during implantation . in another embodiment of the current invention , the guide rail valve receptacle 15 does not include any suture slots 21 . fig1 shows the folded valve 6 loosely disposed within the folding device 2 . the folding device 2 is in turn loosely disposed within the retainer ring 7 . the combined folding device 2 and retainer ring 7 shown in fig9 is here dubbed a folding device valve receptacle 16 . the folding device valve receptacle 16 is adapted to receive a handle 11 . in one embodiment of the present invention , the cardiac valve 1 is released by retracting the handle 11 while keeping the plunger 12 stationary . a plunger plate 14 is attached to the distal portion of the plunger 12 . the plunger plate 14 prevents the valve from moving while retracting the handle 11 . a knob 13 is attached to the proximal portion of the plunger 12 . in another embodiment of the present invention , a plunger 13 , plunger plate 14 , and a plunger knob 13 is not utilized . as such , the valve 1 is released by pulling the delivery system away from the target site . in one embodiment of the present invention , the handle is curved to allow better view of or easier access to the target implantation site . in one embodiment of the present invention , the folding device valve receptacle 16 includes one or more suture slots 21 that may be used to gain access to the suture ring of the folded valve 6 , such as to insert sutures into the valve suture ring for use during implantation . in another embodiment of the current invention , the folding device valve receptacle 16 does not include any suture slots 21 . fig1 shows a delivery system with a different valve receptacle . fig1 shows the folded valve 6 loosely disposed within the folding device 2 , also shown in fig8 . once the valve 6 is folded within the folding device 2 , the folding device 2 may be inserted into the top loading window of the top loading valve receptacle 17 . fig1 shows the folding device 2 loosely disposed within the top loading valve receptacle 17 . the top loading valve receptacle 17 is adapted to receive a handle 11 . fig1 a and 19b show end and side views , respectively , of a valve delivery system that includes a top loading valve receptacle 17 , handle 11 , plunger 12 , a plunger plate 14 , and a curved handle 11 . fig2 a and 20b show the same delivery system seen in fig1 a and 19b , respectively . in fig2 a , the folding device 2 and valve 6 is also shown inserted into the top loading valve receptacle 17 . in one embodiment of the present invention , the cardiac valve 1 is released by retracting the handle 11 while keeping the plunger 12 stationary . a plunger plate 14 is attached to the distal portion of the plunger 12 . the plunger plate 14 prevents the valve from moving while retracting the handle 11 . a knob 13 is attached to the proximal portion of the plunger 12 . in another embodiment of the present invention , a plunger 13 , plunger plate 14 , and a plunger knob 13 are not utilized . here , the valve 1 is released by pulling the delivery system away from the target site . in one embodiment of the present invention , the handle is curved to allow better view or easier access to the target implantation site . in one embodiment of the present invention , the top loading valve receptacle 17 includes one or more suture slots 21 that may be used gain access to the folded valve , such as to insert sutures into the valve for use during implantation . in another embodiment of the current invention , the top loading valve receptacle 17 does not include any suture slots 21 . a valve delivery system is provided that includes a retainer ring 7 adapted to receive a handle 11 . when the retainer ring 7 is adapted to receive a handle 11 and used to transfer and deliver a valve , the retainer ring 7 is dubbed a retainer ring valve receptacle 18 . in one embodiment , the folded cardiac valve 6 is loosely disposed within the retainer ring valve receptacle 18 . in another embodiment , the folded cardiac valve 6 is loosely disposed within a folding device 2 , which in turn is disposed within the retainer ring valve receptacle 18 . the folded cardiac valve 6 is released by pulling the delivery system away from the target site , thereby leaving the unfolded cardiac valve 1 disposed in the annulus . in another embodiment , a plunger 12 and plunger plate 14 may be used to release the folded valve 6 . fig2 shows such a delivery system . a retainer ring valve receptacle 18 is adapted to receive a handle 11 . the folded prosthetic valve 6 is shown folded within the folding device 2 . in one embodiment , the folded prosthetic valve 6 is moved directly into the retainer ring valve receptacle 18 as shown in fig2 . in another embodiment , the folding device 2 and folded prosthetic valve 6 may jointly be inserted into the retainer ring valve receptacle 18 as shown in fig2 . in yet another embodiment , the folding device 2 is removed from the delivery system shown in fig2 , leaving the folded valve 6 loosely disposed within the retainer ring valve receptacle 18 as shown in fig2 . the folding device 2 , handle 11 , front loading valve receptacle 10 , guide rail valve receptacle 15 , folding device valve receptacle 16 , top loading valve receptacle 17 , retainer ring valve receptacle 18 , plunger 12 , plunger plate 14 , and retainer ring 7 may be made of metal , plastic , or polymeric plastic materials that can be cleaned or sterilized in an autoclave . the delivery system may be disposable or reusable . components of the delivery system or folding device may also be made out of a transparent material thereby making folding and valve delivery easier . in one embodiment of the present invention , the handle 11 is curved to allow better view of or easier access to the target implantation site . in one embodiment , the handle 11 is straight . in another embodiment , the handle 11 is centered in relation to axis of the folded valve 6 . in another embodiment , the handle is offset to the side in relation to the axis of the folded valve 6 . in one embodiment of the current invention , a front loading valve receptacle 10 , can be adapted and used to size the valve annulus or orifice before using the delivery system to deliver the folded valve 6 . the external diameter of the front loading valve receptacle 10 may be used to size the valve annulus or orifice . front loading valve receptacles 10 of different diameters may be inserted into the valve annulus until a diameter matching the valve annulus is found . annulus size is determined by the diameter of the front loading valve receptacle 10 , which may be engraved onto the valve receptacle 10 . once the proper valve size is selected , the valve 1 may be folded using the folding device and inserted into the front loading valve receptacle 10 . in another embodiment of the present invention , a folding device valve receptacle 16 can be adapted and used to size the valve annulus or orifice before using the delivery system to deliver the folded valve 6 . in another embodiment of the present invention , a top loading valve receptacle 17 can be adapted and used to size the valve annulus or orifice before using the delivery system to deliver the folded valve 6 . in another embodiment of the present invention , a retainer ring 7 can be adapted and used to size the valve annulus or orifice before delivering the folded valve 6 . in another embodiment of the present invention , a retainer ring valve receptacle 18 can be adapted and used to size the valve annulus or orifice before using the delivery system to deliver the folded valve 6 . front loading valve receptacle 10 , guide rail valve receptacle 15 , folding device valve receptacle 16 , top loading valve receptacle 17 , and retainer ring valve receptacle 18 , described herein may be manufactured in different sizes to accept valves from 1 mm to 70 mm . in one embodiment , the valve receptacles described herein , are interchangeable . that is , a particular handle may accept different valve receptacle sizes . obviously , numerous variations and modifications can be made within departing from the spirit of the present invention . therefore , it should be clearly understood that the forms of the present invention described above and shown in the figures of the accompanying drawings are illustrative only and are not intended to limit the scope of the present invention .

US-47109206-A

expandable , percutaneously deployable , prosthetic heart valves and systems for minimally invasive replacement of damaged or diseased native aortic valves comprise an expandable , tubular stent body and a unidirectional valve assembly . embodiments of the stent body comprise an annulus anchoring section , a sinus section , and an outflow section , with the outflow section flared outwardly from the sinus section in an expanded configuration . embodiments of the stent body are self - expanding , comprising , for example nitinol . the valve assembly disposed within the sinus section of the stent body and sutured thereto . embodiments of the valve assembly comprise three leaflets , each leaflet comprising a curved outer edge sutured to the sinus section of the stent body , and a coapting free edge . embodiments of the valve leaflets comprise pericardium , for example , porcine pericardium . embodiments of the prosthetic heart valve have a contracted configuration dimensioned for percutaneous delivery thereof .

the present invention discloses a number of expandable heart valves for implantation in a host annulus , or host tissue adjacent the annulus . the valves may be implanted in any of the four valve positions within the heart , but are more likely to be used in replacing the aortic or mitral valves because of the more frequent need for such surgery in these positions . the patient may be placed on cardiopulmonary bypass or not , depending on the needs of the patient . a number of expandable prosthetic heart valves are disclosed that are initially rolled into a tight spiral to be passed through a catheter or other tube and then unfurled or unrolled at the implantation site , typically a valve annulus . the heart valves comprise one - or two - piece stent bodies with a plurality of leaflet - forming membranes incorporated therein . various materials are suitable for the stent body , although certain nickel - titanium alloys are preferred for their super - elasticity and biocompatibility . likewise , various materials may be used as the membranes , including biological tissue such as bovine pericardium or synthetic materials . it should also be noted that specific stent body configurations disclosed herein are not to be considered limiting , and various construction details may be modified within the scope of the invention . for example , the number and configuration of lockout tabs ( to be described below ) may be varied . those of skill in the art will recognize that the means and techniques for delivering and implanting the prosthetic heart valves disclosed herein are numerous and not the specific focus of the present application . in general , the heart valves in a first , contracted configuration are delivered through a tube such as a percutaneously - placed catheter or shorter chest cannula and expelled from the end of the tube in the approximate implantation location . the heart valve is then expanded via a balloon , mechanical means , or self - expanded from internal elastic forces , into a second , expanded configuration that engages the native host tissue , such as the target valve annulus . depending on the native valve being replaced , the prosthetic heart valve may have varying axial lengths . for example , in the aortic position , a portion of the valve may extend upward into and even contact the aorta to better stabilize the commissure regions of the valve . in other words , the particular design of the valve may depend on the target valve location . with reference to fig1 and 2 a - 2 b , an exemplary one - piece prosthetic heart valve 20 ( complete in fig2 a ) of the present invention is shown . the valve 20 comprises a stent body 22 that is shown isolated in fig1 , and a plurality of leaflet - forming membranes 24 . the stent body 22 is shown in both fig1 and 2a in its expanded configuration generally defining a tube centered about an axis . the membranes 24 fasten within the stent body 22 so as to form a one - way valve therewithin , and orient the valve to have an inflow end 28 and an outflow end 30 . in a preferred embodiment , there are three such membranes 24 each having a free edge 32 that extends inward from the stent body 22 and coapts or meets the other two free edges generally along radial lines spaced apart 120 ° with respect to each other to close the valve during the back flow cycle of blood flow , as seen in fig2 a . when blood flows in the opposite direction , from the inflow to the outflow end , the free edges 32 of the membranes 24 move radially outward away from each other to open the valve . with specific reference to fig1 , the tubular stent body 22 comprises three sections , starting at the inflow end 28 and moving toward the outflow end 30 : an annulus anchoring section 40 , a sinus section 42 , and an outflow section 44 . the three sections 40 , 42 , and 44 are desirably formed from a single generally sheet - like piece of material that can be cohesively rolled into a tight spiral and expanded into the tubular configuration shown . in this regard , the stent body 22 includes an axially - oriented first side edge 50 that mates with an axially - oriented second side edge 52 along longitudinal seam 53 . the two side edges 50 , 52 abut or overlap and lock together using one or more , preferably two or more cooperating tabs 54 and slots 56 . in the illustrated example , two series of slots 56 a , 56 b are provided around the circumference of the stent body 22 adjacent the first side edge 50 , while a pair of engaging tabs 54 a , 54 b are provided adjacent the second side edge 52 . the annulus anchoring section 40 is desirably substantially solid and free of perforations so as to more reliably retain its tubular shape upon outward expansion against the native heart valve annulus . in a preferred implantation technique , the prosthetic heart valve 20 expands outward and compresses against the native leaflets which present a relatively uneven base . even if the leaflets are excised , the circularity of the annulus depends on the skill of the surgeon . minimizing any openings in the anchoring section 40 enhances its rigidity so as to ensure a relatively tubular support structure for the leaflet - forming membranes 24 . however , anchoring barbs 60 may be provided in the anchoring section 40 , and may be formed by integrally cut tabs as shown . in addition , a pair of openings 62 may be optionally provided in the side wall of the tubular stent body 22 to reduce the roll - up stiffness . with reference to fig2 a , the sinus section 42 comprises a plurality ( preferably three ) of generally axially extending commissures 70 and curvilinear cusps 72 defined by relatively large sinus apertures 74 in the stent body 22 . in the illustrated embodiment , the sinus apertures 74 are generally semi - circular with a straight , circumferential edge 76 defined by the beginning of the outflow section 44 . a plurality of small attachment apertures 78 track along the edge of the sinus apertures 74 , extending around the curvilinear cusps 72 and substantially up the entire commissures 70 . the membranes 24 fasten to the stent body 22 using the attachment apertures 78 . more particularly , as seen in fig2 b , an outer edge portion 80 of each membrane 24 folds upward in the outflow direction to lie against an inner surface 84 of the stent body 22 . this folded attachment helps reduce localized stresses caused by the sutures through the membrane 24 , and enhances coaptation of the free edges 32 at the commissures 70 . fasteners such as sutures 82 secure the outer edge portion 80 flush against the inner surface 84 . the sutures typically loop through the membrane 24 twice at each attachment aperture 78 in a single mattress stitch , though various other stitching techniques are known . in a preferred embodiment , the attachment apertures 78 are spaced apart a minimum distance of about 0 . 004 - 0 . 0075 inches for strength . a small lip 86 of the outer edge portion 80 desirably projects beyond the sinus aperture 74 to help protect the membrane 24 from rubbing directly against the material of the stent body 22 during operation of the valve . that is , there is membrane - to - membrane cushioned contact at the sinus apertures 74 when the membranes 24 are forced outward in the opening cycle of the valve . additionally , all exposed edges of the stent body 22 are electropolished or coated with a layer of lubricious material ( e . g ., ptfe or “ teflon ”) to eliminate any sharp corners and thus reduce wear on the flexible membranes 24 . the free edge 32 of each membrane 24 meets the stent body 22 at one of the commissures 70 . because adjacent arrays of attachment apertures 78 converge in the outflow direction along each commissures 70 , the free edges 32 of adjacent membranes 24 coapt at or closely adjacent to the stent body inner surface 84 , as best seen in fig2 a . this configuration eliminates leakage between the free edges 32 when the valve closes . the outflow section 44 desirably comprises at least a circular band 90 of material that joins the outflow ends of the commissures 70 . in the illustrated embodiment , the outflow section 44 further includes a second band 92 axially spaced from the first band 90 and joined thereto with a lattice , mesh or grid 94 . the outflow section 44 may not be in contact with any tissue of the heart , but rather project into the respective outflow chamber as a support for the three commissures 70 . that is , substantial inward radial loads are imposed on the commissures 70 during the closing cycle of the valve , and the outflow section 44 maintains the spacing between the commissures to ensure proper coaptation of the membrane free edges 32 . the grid 94 defines more spaces than connecting struts , and thus minimizes interference with proper blood flows in the outflow chamber . the outflow section 44 may be rigid , or may be somewhat flexible to mirror aortic wall movement . in fig2 c , an alternative stent body 22 ′ has a flared outflow section 44 ′ section that conforms to and contacts the aortic wall in an aortic valve replacement setting . the aortic wall and sinuses diverge outward from the annulus , in which the annulus anchoring section 40 ′ resides . therefore , the outward flaring of the outflow section 44 ′ permits contact with the aortic wall and better stabilizes the valve in its implantation position . further , the backflow volume on the outflow side of the leaflets will be slightly increased which may enhance valve closing . the outflow section 44 ′ may be formed to spring open to the flared shape , or may be plastically deformed into the flared shape using a non - cylindrical expansion balloon . for example , the outflow section 44 ′ may be annealed nitinol that self - expands to the flared shape upon being released from within a delivery tube . further embodiments of stents having the flared outflow section are shown and described below . with reference to fig3 a - 3c , an exemplary two - piece stent body 100 comprises a generally ring - shaped primary stent 102 and a tubular secondary stent 104 coupled therewithin . the primary stent 102 is shown isolated in fig4 a and 4b and includes a first side edge 106 , a second side edge 108 , and a pair of opposed end edges 110 a , 110 b . a pair of alignment tabs 112 projects radially outward from the end edges 110 a , 110 b adjacent the second side edge 108 . the alignment tabs 112 provide guides for use during unfurling of the primary stent 102 to maintain concentricity about a central axis . that is , as the primary stent 102 transitions between a first , contracted configuration ( i . e ., a tight spiral ) and a second , expanded configuration , the alignment tabs 112 prevent the stent from unrolling to form a cone . desirably , in the first , contracted configuration , the primary stent 102 is spirally - wound about an axis such that at least one winding of the stent body 100 surrounds another winding , and preferably there are numerous windings to reduce the radial profile of the stent 102 . desirably , the second side edge 108 resides at the center of the tightly rolled second configuration such that as the stent 102 unrolls , the end edges 110 a , 110 b slide by and are constrained within the tabs 112 . in addition , the primary stent 102 includes lockout structure in the form of a pair of tabs 114 projecting radially inward near the first side edge 106 and a pair of notches 116 in the second side edge 108 . the tabs 114 fit within the notches 116 and lock the two side edges 106 , 108 together . desirably , a bi - directional locking arrangement is provided to prevent contraction of the stent but also further expansion . there are preferably two locking tabs / slots along the mating edges , desirably located symmetrically about an axial midplane of the stent . referring to fig3 a - 3c , the secondary stent 104 includes a generally solid inflow section 120 , a sinus section 122 , and an outflow band 124 . the sinus section 122 is relatively more solid than the sinus section 42 of the first embodiment , and includes a plurality , preferably three , oval - shaped sinus apertures 126 . a leaflet - forming membrane ( not shown ) fastens around the inflow edge of each of the sinus apertures 126 in such a manner so as to coapt within the tubular stent body 100 and define the valve occluding surfaces . more specifically , a membrane fastening strip 128 follows the edge contour of each membrane with a pair of commissure regions 130 and a curvilinear cusp region 132 and provides an anchor to which the membrane may be attached . the fastening strip 128 may be made of pericardium , and may be fastened to the inner surface of the secondary stent 104 using stitching or other suitable expedient . in an exemplary embodiment , secondary stent 104 includes at least one locking tab 140 that projects outwardly through a locking window 142 in the primary stent 102 to retain the two stents in cooperating relationship . the secondary stent 104 includes a first side edge 144 and a second side edge 146 that overlap and are locked together using suitable tabs / notches ( not further described herein ). in use , the primary stent 102 is first delivered and then unfurled and secured in the native annulus , after which the secondary stent 104 is delivered and then unfurled and locked within the primary stent . one or more alignment tabs 150 may be provided on the secondary stent 104 to engage alignment slots 152 and ensure the secondary stent unfurls concentrically around the axis . further , the outwardly projecting alignment tabs 112 and locking tab ( s ) 140 may double as anchoring barbs projecting into the native tissue . alternatively , a ratchet type of locking arrangement can be provided for the primary stent 102 or secondary stent 104 to enable greater size adjustment . for instance , multiple engaging teeth may be formed on either stent 102 or 104 to enable substantially continuous size adjustment beyond a minimum annulus diameter . the ratchet teeth may be on circumferentially opposed surfaces or a bent end tab may engage teeth provided on a circumferential edge of the stent . likewise , coupling structure between the primary and secondary stents may be used other than the tabs / slots shown . for instance , a hook and loop connection may be realized by expanding the secondary stent within the primary stent . fig5 a and 5b show in greater detail exemplary alignment tabs / slots and locking tabs / notches . these figures illustrate an exemplary primary stent having a first side edge 160 and a second side edge 162 , although the same concepts may be applied to a secondary stent . a pair of alignment tabs 164 projects radially outward from the second side edge 162 and a second pair of alignment tabs 166 projects radially outward from the body of the stent . a series of circumferential slots 168 are provided along the length of the stent such that the tabs 164 , 166 are received therein during the unfurling process . the slots 168 guide the tabs 164 , 166 to prevent the stent from unfurling into a cone . once the stent has fully expanded , a pair of locking tabs 170 projecting radially inward from near the first side edge 160 engages a pair of notches 172 in the second side edge 162 . fig6 a - 6d illustrate a still further primary stent 180 that is similar to , but slightly axially longer than , the primary stent 102 described above . again , the stent 180 includes overlapping first and second side edges 182 a , 182 b , respectively , and circumferentially disposed end edges 184 a , 184 b . as seen best in fig6 b and 6c , three alignment tabs 186 project radially outward from the second side edge 182 b into alignment slots 188 . as before , these alignment tabs and slots prevent the primary stent 180 from unfurling unevenly to form a cone . it should be noted that the middle alignment slot 188 is circumferentially staggered with respect to the two alignment slots near the end edges 184 a , 184 b such that at least one alignment tab 186 resides in one of the slots at all times . additionally , two pairs of alignment tabs 190 project radially outward from the end edges 184 a , 184 b at the second side edge 182 b , further insuring against misalignment during the unfurling process . a pair of locking tabs 192 projects inward from the primary stent 102 near the first side edge 182 a and engages a cooperating pair of locking notches 194 formed in the second side edge 182 b . as can be appreciated from fig6 b , the locking tabs 192 and notches 194 prevent the primary stent 180 from contracting once it has been fully expanded . finally , fig6 d is a detail of an inwardly directed coupling tab 196 that may be used to couple a secondary stent to the primary stent 180 . in the illustrate embodiment , there are three such coupling tabs 196 distributed evenly about the stent . fig7 illustrates a secondary stent 200 of the present invention in plan view , before being rolled into its contracted configuration . the stent 200 has a generally rectangular periphery defined by a first side edge 202 a , a second side edge 202 b , and a pair of linear end edges 204 a , 204 b . again , the secondary stent 200 comprises a generally sheet - like body that can be rolled into a relatively tight configuration and unrolled into a tube . three sinus apertures 206 a , 206 b , 206 c formed in the secondary stent 200 each having a curvilinear cusp 208 and a pair of generally linear commissures 210 of either side of the cusp . the commissures 210 are joined by an outflow band 212 . a pair of combined alignment and locking tabs 216 is sized to translate within respective alignment slots 218 to insure even unfurling of stent 200 . a pair of locking notches 220 is formed at the end of the alignment slots 218 closest to the first side edge 202 a . the locking tabs 216 have an enlarged head joined by a neck to the body of the stent 200 and the locking notches 220 also include a tapered neck 222 that permits passage of the tab neck in only one direction so as to lock it therein . fig8 is a detailed isolation of overlapping side edges of a secondary stent showing alignment tabs 230 disposed on side edges of the inner layer of the stent . these alignment tabs 230 therefore can replace the alignment tabs 216 and slots 218 of the secondary stent 200 of fig7 , although alternative locking structure must be provided . fig9 illustrates a still further secondary stent 250 of the present invention , and fig1 illustrates the same stent coupled with the primary stent 180 of fig6 a . the secondary stent 250 includes many of the same features described above , including a generally solid inflow section 252 , a sinus section 254 , and an outflow band 256 ( again , the leaflet - forming membranes are not shown to better illustrate the stent ). the body of the stent 250 includes two pairs of side alignment tabs 258 that prevent the stent 250 from unfurling into a conical form . one or more lockout tabs 260 extend outward from one side edge of the stent 250 and engage one or more apertures 262 in the other side edge to secure the edges in an overlapping relationship as shown . a plurality of coupling windows 264 is located at evenly - spaced circumferential intervals around the body of the stent 250 to receive and retain coupling tabs 196 extending inward from the primary stent 180 ( see fig6 d ). note in fig1 that the alignment tabs 258 closely conform to the inflow end of the primary stent 180 and further help retain the stent assembly together . also , these alignment tabs 258 may serve as anchoring barbs to retain the valve in the host annulus . fig1 a - 11e illustrate another primary stent 270 that features a plurality ( at least three ) of outwardly angled anchoring spikes 272 . the stent 270 includes a band - like body 274 having a first side edge 276 a and a second side edge 276 b , with opposed and parallel end edges 278 a , 278 b extending therebetween . the anchoring spikes 272 extend axially away and then radially outward from the respective end edges 278 a , 278 b a distance of between about 1 - 2 mm . there are desirably at least three anchoring spikes 272 extending from each end edge 278 a , 278 b , and more preferably six . in addition , a plurality of body anchoring barbs 280 is disposed at regular intervals around the body 274 . these barbs 280 may be small portions of the body 174 stamped into spikes and bent outward from the body 274 . the barbs 280 desirably have a length of about 1 mm . fig1 b and 11c illustrate a two - way lockout structure on the side edges 276 a , 276 b including tabs 282 and receptacles 284 . in addition , alignment tabs 286 and slots 288 are provided as described above . fig1 shows the primary stent 270 of fig1 a - 11e coupled to an alternative secondary stent 290 . the secondary stent 290 has relatively large , semi - circular sinus apertures 292 and membrane attachment strips 294 on its inner surface . note that the sinus apertures 292 have a curvilinear cusp edge 296 that coincides approximately with an end edge 278 b of the primary stent 270 . this maximizes exterior reinforcement for the secondary stent 290 without interfering with the motion of the leaflet - forming membranes ( not shown ). fig1 a - 13c schematically illustrate a secondary stent 300 unfurling within a primary stent 302 . the primary stent 302 includes coupling tabs 304 bent inward from the body of the stent that have an axially - opening notch 306 on one side . the tabs 304 are slightly circumferentially offset with respect to one another , and axially spaced nearly the entire axial dimension of the primary stent 302 . as best seen in fig1 c , the secondary stent 300 has a pair of v - shaped slots 308 located on a first side edge 310 that couple with the tabs 304 . more specifically , the slots 308 terminate in a bridge 312 between the slot and a cutout 314 , and the coupling tab 304 is designed to frictionally engage the bridge by virtue of the shape of the notch 306 . the first side edge 310 is thus unrolled and the tabs 304 coupled to the slots 308 by a relative axial displacement of the secondary stent 300 and primary stent 302 . once coupled , the secondary stent 300 is fully unfurled and locked in its expanded configuration within the primary stent 302 . the secondary stent 300 may be coupled to the primary stent 302 using relative axial and / or circumferential motion with or without a tactile feedback signaling completion of the coupling operation . fig1 - 18 illustrate various steps in the process of rolling a primary stent of the present invention ( i . e ., converting a flat sheet - like material into the first , contracted configuration of the stent ). a rolling base 320 includes a raised rolling platform 322 surrounded by a pair of linear rolling tracks 324 . a stent roller 326 includes a central mandrel 328 and a pair of rolling wheels 330 that ride within the tracks 324 . an initially flat sheet - like primary stent 334 is placed on the rolling platform 322 and secured thereto at a first side edge 336 . fig1 c illustrates one means for securing the first side edge 336 , that is , angled pins 338 through holes in the first end . alternatively , a clamp 340 as seen in fig1 may be tightened over the first side edge 336 . with reference to fig1 a and 15b , the stent roller 326 is temporarily secured to a second side edge using a pin 342 aligned with the mandrel 328 . a plurality of lockout tabs 344 are seen projecting between the pin 342 and the mandrel 328 such that rotation of the roller 326 lifts the second side edge upward from the platform 322 . the pin 342 extends through a small cavity in both rolling wheels 330 adjacent the mandrel 328 and may be easily removed once the rolling operation is complete . fig1 a shows the stent 334 in its rolled configuration after the stent roller 326 has translated the length of the rolling platform 322 . the rolling tracks 324 are slightly ramped upward toward the platform 322 to accommodate the gradually increasing diameter of the stent 334 as it is rolled . a plurality of linear grooves 350 in the rolling platform 322 provide clearance for any radially outwardly projecting tabs on the stent 334 . fig1 b shows a suture 352 or other such retaining means tied around the rolled stent 334 to enable removal of the stent and roller 326 from the platform 322 . finally , fig1 a and 18b schematically illustrate the steps for removing the rolled stent 334 from the roller 326 . specifically , one of the wheels 330 is removable and the rolled stent 334 is then freed for use . the inner bore illustrated may be substantially smaller if a smaller mandrel 328 is used . the same sequence of rolling may be used for both the primary and secondary stents with the membranes . the membranes lie relatively flat against the secondary stents and present little obstacle to rolling . the rolled stent 334 desirably has a diameter of less than about 20 mm . an aspect ratio of the stents of the present invention may be defined as the axial length over the final , expanded diameter . some of the primary stents as described above may have a relatively small aspect ratio , desirably less than about 2 . once the rolled stent 334 is formed , it is loaded within a delivery tube or catheter and urged down the tube to the implantation site ( of course , the suture 352 will be removed ). a pusher or other such device may be used to advance the rolled stent 334 . once at the site , the tube may be retracted and the rolled stent 334 caused to unfurl on its own , the stent may be delivered over an inflation balloon to enable plastic deformation / expansion , or the stent may be expanded with a subsequently introduced balloon or mechanical expander . fig1 illustrates a still further one - piece expandable heart valve stent 400 of the present invention in its flattened configuration having a somewhat more solid or robust outflow section 402 than shown previously coupled to a sinus section 404 and anchoring section 406 on the inflow end of the stent . the stent 400 comprises a single sheet - like body 408 of a rolled superelastic metal alloy , preferably nitinol . for orientation purpose , the body 408 is initially formed in the y - z plane as shown , and is elongated in the y direction with a generally rectangular outline . the body 408 is designed to be rolled up on itself about a z - axis into a relatively tight spiral , and later unrolled to form a tube with a first side edge 410 a connecting to a second side edge 410 b . in the illustrated embodiment , the left side of the stent body 408 forms the inner winding of the spiral while the right side is the outer winding . desirably , and as mentioned above , the first side edge 410 a and second side edge 410 b overlap in the enlarged tubular configuration . the body 408 also defines relatively linear first and second end edges 412 a , 412 b that form the circular outflow and inflow rims , respectively , of the tubular stent . the stent 400 includes alignment structure for ensuring proper unrolling about the central z - axis , and also locking structure for maintaining the final tubular shape . specifically , a pair of guide / lockout tabs 414 a , 414 b engage a guide slot 416 that extends along the y - axis in the outflow section , closely adjacent the sinus section 404 . a single such guide slot 416 as shown located generally in the center of the body 408 with respect to the z - axis is believed sufficient to hold the stent in the final tubular shape , although two or more may be used as described previously . the guide / lockout tabs 414 a , 414 b each include an enlarged generally semi - circular head 418 and a narrow neck 420 connecting the head to the body 408 . a first tab 414 a extends from the first end edge 410 a while a cutout in a mid - portion of the body 408 forms a second tab 414 b . the spaced tabs 414 a , 414 b align with the guide slot 416 and are annealed out of the plane of the body 408 so as to fit within the slot . specifically , the tabs 414 a , 414 b are annealed so that they bend inward with respect to the rolled spiral of the stent body 408 and can then be introduced into the slot 416 . once in the slot 416 , the head 418 of each tab 414 a , 414 b projects through to the outside of the body 408 and retains the tabs in engagement with the slot . the neck 420 has a width that is slightly smaller than the slot width for easy longitudinal movement therewithin . as the stent body 408 unfurls from its tightly coiled contracted state to its expanded state , the tabs 414 a , 414 b travel along the slot 416 ( from the left to the right in the drawing ). as this process occurs , the maintenance of the tabs 414 a , 414 b within the slot 416 ensures that the stent body 408 will not misalign and unroll into a conical shape . ultimately , the tabs 414 a , 414 b travel past two pairs of similarly spaced lockout notches 422 annealed out of the plane of the body 408 toward the inside of the now tubular stent . the interference between these lockout notches 422 and the heads 418 of the tabs 414 a , 414 b retains the stent 400 in its open , expanded configuration . a plurality of engaging pairs of bridge tabs 424 and apertures 426 maintain a uniform width of the guide slot 416 to retain the tabs 414 a , 414 b therein during unrolling of the stent body 408 . each tab 424 is annealed so as to bend and lock into the corresponding aperture 426 . maintenance of the guide slot 416 width ensures a continuous engagement of the tabs 414 a , 414 b and guide slot 416 during the unrolling process . the stent body 408 further includes a plurality of edge tabs 430 located along both end edges 412 a , 412 b adjacent the first side edge 410 a . although shown flattened in the plane of the stent body 408 , the edge tabs 430 are also annealed to bend generally perpendicular to the stent body . the edge tabs 430 are disposed closely to and constrain the end edges 412 a , 412 b during the unrolling process to further help prevent misalignment . a pair of stop slots 432 is formed in the anchor section 406 to limit the extent that the stent body 408 unrolls . one side of each slot 432 is annealed out of the plane of the stent body 408 so that they engage each other after the body has unrolled to the tubular final shape . the outflow section 402 includes an array of diamond - shaped apertures 434 forming an open lattice , mesh or grid pattern that reduces the stent surface area and thus the risk of thrombosis after implantation . the open mesh pattern is somewhat stiffer than , for example , the grid pattern shown in the stent of fig1 , and helps stabilize the valve commissures 440 about which flexible leaflet membranes 442 ( shown in phantom ) are attached . a plurality of triangular - shaped cutouts 444 aligned in the y - direction in the outflow section 402 “ ratchet ” against one another during unrolling of the stent body 408 and thus incrementally prevent closing of the stent . still with reference to fig1 , the sinus section 404 incorporates three membrane apertures 450 defining the aforementioned commissures 440 and intermediate curvilinear cusps 452 . a series of attachment holes 454 closely surrounds each aperture 450 and is used to suture or otherwise attach each membrane 442 to the stent 400 . the edge of each membrane 442 is folded as described above with respect to fig2 b to help prevent wear and ensure longevity . the opposed ends of the sinus section 404 are shaped to conform to the outer two membrane apertures 450 . that is , a pair of opposed extension flaps 456 a , 456 b on the anchoring section 406 overlap and each blends along a curvilinear edge 458 a , 458 b toward the outflow section 402 . these curvilinear edges 458 a , 458 b provide reliefs to avoid occluding either of the outer two membrane apertures 450 when the stent is locked open and the flaps 456 a , 456 b overlap . although not shown , a plurality of anchoring barbs are desirably provided in at least the anchoring section 406 to secure the unrolled valve into position in the valve annulus and aortic root . further , the outflow section 402 may be annealed so as to flare outward and contact the ascending aorta for further anchoring . fig2 a illustrates a still further one - piece expandable heart valve stent 500 of the present invention in its flattened configuration with an outflow section 502 coupled to a sinus section 504 and anchoring section 506 on the inflow end of the stent . the stent 500 again comprises a single sheet - like body 508 of a rolled superelastic metal alloy , preferably nitinol . for orientation purpose , the body 508 is initially formed in the y - z plane as shown , and is elongated in the y direction with a generally rectangular outline . the body 508 is designed to be rolled up on itself about a z - axis into a relatively tight spiral , and later unrolled to form a tube with a first side edge 510 a connecting to a second side edge 510 b . in the illustrated embodiment , the left side of the stent body 508 forms the inner winding of the spiral while the right side is the outer winding . that is , the stent body 508 is rolled from the left end in the direction of arrow 511 . desirably , the first side edge 510 a and second side edge 510 b overlap in the enlarged tubular configuration . the body 508 also defines first and second end edges 512 a , 512 b that form the circular outflow and inflow ends , respectively , of the tubular stent . the stent 500 includes alignment structure for ensuring proper unrolling about the central z - axis , and also locking structure for maintaining the final tubular shape . specifically , guide / lockout tabs 514 a , 514 b engage guide slots 516 a , 516 b aligned therewith along the y - axis . a first pair of tab 514 a and slot 516 a is located in the outflow section , closely adjacent the sinus section 504 , while a second pair of tab 514 b and slot 516 b is located in the anchoring section , closely adjacent the second end edge 512 b . the guide / lockout tabs 514 a , 514 b are each formed with an enlarged head 518 and a pair of necks 520 on either side of the head connecting it to the body 508 . each head 518 is annealed to bend about the necks 520 out of the plane of the stent body 508 and fits through an entrance opening 522 into the respective slot 516 . in the illustrated embodiment , the heads 518 are bent out of the page and the stent body 508 is rolled about the z - axis out of the page so that the heads 518 project radially outwardly through the entrance openings 522 . as seen in fig2 a and 20b , each slot 516 includes a pair of lockout tabs 524 near the slot end closest to the second end edge 510 b . small angled cutouts 526 diverging on either side of the slot 516 form the lockout tabs 524 . each tab 524 is annealed to bend out of the plane of the stent body 508 , in this case into the page . as the stent body 508 unrolls , the heads 518 of the tabs 514 a , 514 b slide from left to right along the slots 516 and cam over the bent tabs 524 . the tabs 514 a , 514 b are thus prevented by the tabs 524 from retreating along the slots 516 a , 516 b . the maintenance of the tabs 514 a , 514 b within the slots 516 a , 516 b ensures that the stent body 508 will not misalign and unroll into a conical shape . a plurality of bridges 528 maintains a uniform width of the guide slots 516 a , 516 b to retain the tabs 514 a , 514 b therein during unrolling of the stent body 508 . each bridge 528 crosses over the respective slot 516 a , 516 b and is secured thereto at points 530 , such as by ultrasonic welding . alternatively , bridges formed as an integral part of the stent body 508 are contemplated . maintenance of the guide slot 516 width ensures a continuous engagement of the tabs 514 a , 514 b and guide slots 516 a , 516 b during the unrolling process . the bridges 528 are located on the inner side of the stent 508 in its rolled configuration . the outflow section 502 includes an array of cross members 534 forming a lattice , mesh or grid pattern with diamond - shaped openings that reduces the stent surface area and thus the risk of thrombosis after implantation . adjacent the mesh pattern , a solid band 536 of the stent body 508 within which the guide slot 516 a is formed helps stabilize the valve commissures 540 about which flexible leaflet membranes 542 ( shown in phantom ) are attached . still with reference to fig2 a , the sinus section 504 incorporates three membrane apertures 550 defining the aforementioned commissures 540 and intermediate curvilinear cusps 552 . a series of attachment holes 554 closely surrounds each aperture 550 and is used to suture or otherwise attach each membrane 542 to the stent 500 . the edge of each membrane 542 is folded as described above with respect to fig2 b to help prevent wear and ensure longevity . the right end of the sinus section 504 is shaped to conform to the left membrane apertures 550 . that is , a curvilinear edge 558 provides a relief to avoid occluding the left membrane aperture 550 when the stent is locked open and the end edges 510 a , 510 b overlap . although not shown , a plurality of anchoring barbs are desirably provided in at least the anchoring section 506 to secure the unrolled valve into position in the valve annulus and aortic root . further , the outflow section 502 may be annealed so as to flare outward and contact the ascending aorta for further anchoring . fig2 a illustrates a heart valve 600 of the present invention having a stent 602 similar to the stent 500 described above with reference to fig2 a . a pair of lockout / guide tabs 604 a , 604 b engages an aligned pair of guide slots 604 a , 604 b to both ensure proper unrolling and secure the unrolled valve in its expanded configuration . the tabs 604 a , 604 b and slots 606 a , 606 b may be configured as described above with respect to either of the embodiments of fig1 or 20 a , or may be a similar expedient . in this regard , entrance openings 608 and lockout tabs 610 may be provided to enable the tabs 604 a , 604 b to enter the slots 606 a , 606 b and be retained therein in an open , unrolled configuration of the valve 600 . a plurality of bridges 612 seen on the inside of the stent 602 through the slots 606 a , 606 b maintain the width of the slots as described above . the stent 602 includes an outflow section 620 having a mesh 622 that is annealed to flare outward into contact with the aorta and increase the stiffness of valve commissures in a sinus section 624 . the sinus section 624 includes three membranes 626 attached around generally semi - circular apertures 628 to form the occluding surfaces of the valve when fully unrolled . fig2 b illustrates the stent 602 by itself in a partial state of unrolling , while fig2 c shows the stent fully unrolled . note the flared configuration of the mesh 622 on the outflow section 620 and the overlapped sides of the stent . fig2 and 23 illustrate two different two - piece expandable heart valve stents that are coupled using guide wires . in fig2 , a generally tubular primary stent 700 is first unrolled and implanted in the body . a secondary stent 702 of various configurations described above is then delivered in its contracted state into proximity with the primary stent 700 and unrolled and coupled thereto . to ensure proper rotational alignment between the primary stent 700 and secondary stent 702 , a plurality of guide wires 704 are threaded through features ( not shown ) within the secondary stent 702 and coupled to corresponding features on the primary stent 700 . for example , the guide wires 704 may be threaded or otherwise registered with coupling tabs ( not shown ) on the secondary stent 702 and also with coupling apertures 706 on the primary stent 700 . in this way , the secondary stent 702 advances along the guide wires 704 and is rotationally oriented thereby to ensure mating engagement of the coupling features . the distal end of a delivery tube 708 is illustrated through which the guide wires 704 are pulled . fig2 likewise shows a generally tubular primary stent 720 being coupled to a secondary stent 722 using a plurality of guide wires 724 . the secondary stent 722 includes a tubular mesh portion 726 and a scalloped wireform portion 728 on an outflow end . although not shown , the wireform portion 728 receives valve leaflets or an intact bioprosthetic valve as is well known in the art . the tubular mesh portion 726 fits within and couples to the tubular primary stent 720 , while the wireform portion 728 remains completely or substantially completely extended out of the outflow end of the primary stent . again , the distal end of a delivery tube 730 is illustrated . the heart valves of the present invention may be implanted using several minimally - invasive approaches , and in one or more stages . for example , the single stent valves described herein may be delivered using a pusher or along with a balloon catheter through a large bore cannula or catheter ( i . e ., tube ). the two piece valves may be delivered through a single tube , or through two different tubes in sequence . in one embodiment , the stent having the flexible membranes thereon may be stored in an unfurled configuration to reduce stress on and damage to the membranes , and rolled into a compact tube just prior to use . one or two balloons may be used , or the stents can be primarily self - expanding with a balloon or other expansion device used to provide a final deployment force , such as for anchoring barbs in the annulus or locking the rolled stents in the open configuration . while the foregoing describes the preferred embodiments of the invention , various alternatives , modifications , and equivalents may be used . moreover , it will be obvious that certain other modifications may be practiced within the scope of the appended claims .

US-201213529955-A

a liquid crystal display includes a liquid crystal display panel having a plurality of pixels on a display line . a set of drivers drives a set of pixels , the set of drivers receiving display data and providing video signals to the set of pixels . a clock provides a clock signal to the set of drivers to latch the display data based on a frequency of the clock signal , and receives a feedback signal from the set of drivers prior to an end of the display data received by the set of drivers . a delay circuit stops the clock signal to the set of drivers , based on the feedback signal , after delaying for a first time period that is no less than a predetermined time period between the feedback signal and the end of the display data received by the set of drivers .

a preferred embodiment of the present invention will be explained by referring to fig1 to fig5 . in the present embodiment , the present invention will be explained by taking as an example a signal processing system combining a signal broadcast from a broadcasting station and a signal output from a home game system for various processing and a home system for the same . first , an explanation will be made of the configuration of the signal processing system . fig1 is a block diagram of the configuration of a signal processing system 100 of the present embodiment . the signal processing system 100 has a broadcasting station system 200 , a home system 300 , and a communication network 400 . the broadcasting station system 200 has a server 210 , a video reproduction apparatus 220 , a video camera 230 , a selector / controller 240 , an authoring / encoder system 250 , a transmitter 260 , and a computer 270 . the server 210 is a large capacity hard disk drive which stores digital data of various types of broadcast use stock such as program content . the data stored in the server 210 is suitably reproduced according to a broadcast schedule managed by a not illustrated scheduler and output to the selector / controller 240 . the video reproduction device 220 plays back a video tape on which is recorded various broadcast use stock such as program content set according to need and outputs the same to the selector / controller 240 . the video camera 230 is a camera for capturing picture and sound for when broadcasting a live program such as news or for when using a live picture of a later explained host etc . in a broadcast . the captured video signals and audio signal are output to the selector / controller 240 according to need . the selector / controller 240 creates a broadcast use signal , that is , prepares the program , based on the video signal and audio signal input from the server 210 , video reproduction device 220 , and the video camera 230 and outputs the same to the authoring / encoder system 250 . the selector / controller 240 selects the required video signal and audio signal automatically or manually by the operation of a program producer based on a control signal from the not illustrated scheduler and information such as a request from the viewer transmitted from the home system 300 of the viewer mentioned later via a public telephone line 420 to the computer 270 of the broadcasting station system 200 and combines them or otherwise processes them according to need to create the broadcast use program data , and outputs the same to the authoring / encoder system 250 . note that the production of this program in the selector / controller 240 is carried out for every channel sent by the broadcasting station system 200 . here , the configuration of the broadcast signal created at the selector / controller 240 is shown in fig2 . as shown in fig2 , the broadcast signal transmitted from the broadcasting station system 200 basically has main video data , main audio data , command data , television complementary data , and game complementary data . the main video data is the video data for usual viewing of a television program by a viewer . the main audio data is the audio data for usual viewing of a television program by a viewer . the command data is the data from the broadcasting station system 200 for directly controlling the home system 300 per se or a game system 320 or a synthesizer 330 of the home system 300 mentioned later . the television complementary data is sub information of the main video data and the main audio data and is data such as picture , sound , and text to be displayed and output to a monitor 340 of the home system 300 according to need . the game complementary data is data such as sub information relating to the processing to be performed in the game system 320 and not stored in the home system 300 . specifically , it is data such as unique game characters for only the broadcast , information of special rules , and unique background images . the authoring / encoder system 250 encodes the program data input from the selector / controller 240 by for example mpeg , converts the same to a predetermined broadcast format such as xml and mpeg , and outputs the same to the transmitter 260 . the transmitter 260 encodes , modulates , and otherwise processes for transmission the broadcast use program data converted to the predetermined broadcast format input from the authoring / encoder system 250 so as to convert the same to a signal suitable for the broadcasting means used and actually transmits the same . in the present embodiment , it is assumed that the broadcasting station system 200 performs digital satellite broadcasting by a satellite line 410 via a broadcast satellite . accordingly , the transmitter 260 transmits the created broadcast use signal toward the broadcast satellite . the computer 270 is connected to the public telephone line 420 and performs a desired information processing . it receives a response relating to the broadcast content broadcast by the broadcasting station system 200 , that is , a signal transmitted from the home system 300 of each viewer via the public telephone line 420 , stores the information from the viewers , and determines the action to be taken in the broadcasting station system 200 in accordance with the received content . then , according to need , the computer 270 instructs the selector / controller 240 to produce the program data based on that action . the home system 300 has a communication portion 310 , a game system 320 , a synthesizer 330 , and a monitor 340 . the communication portion 310 receives the broadcast data sent from the broadcasting station system 200 via the satellite line 410 , demodulates it and decodes the transmission use code to create a digital baseband signal , and transmits the same via an ieee1394 interface to the synthesizer 330 . further , when information such as a certain instruction or data to be transmitted to the broadcasting station system 200 is input from the synthesizer 330 via the ieee1394 interface , the communication portion 310 transmits the information via the public telephone line 420 to the computer 270 of the broadcasting station system 200 . the game system 320 is a home television game system and has a game system console 321 , a controller 322 , storage medium i / f 323 , and an ic card i / f 324 . the game system console 321 runs the game according to game software stored on the storage medium mounted in the storage media i / f 323 and moves the game along based on data similarly read from the storage medium and operation signals of the user input from the controller 322 . it creates a video signal to be displayed on the monitor and an audio signal to be output from the monitor 340 and outputs the same via the ieee1394 interface to the synthesizer 330 . further , the game system console 321 performs predetermined processing according to commands of command data received from the broadcasting station system 200 and input from the synthesizer 330 mentioned later . when further additional data is necessary when executing the commands , the data is transmitted from the broadcasting station system 200 as complementary data . the game system console 321 executes the processing by using this . the controller 322 is a joy stick or directional button pad or other game controller provided with various inputting means suitable for playing the game . when playing a usual television game , the player operates the controller 322 to run the game . further , when the home system 300 receives a broadcast from the broadcasting station system 200 and performs some sort of operation with respect to the received content , the viewer inputs instructions from this controller 322 while viewing the monitor 340 . the storage medium i / f 323 is loaded with a storage medium storing the program and data for the game . it suitably reads out the program and data in response to requests from the game system console 321 and outputs the same to the controller 322 . the ic card i / f 324 is an i / f for writing or reading data with respect to the mounted ic card . in this game system 320 , an ic card is used for example for storing the results of the game , storing the interim progress of the game , inputting personal data to the game system console 321 , or storing data from the game system console 321 . the synthesizer 330 extracts the data of the main video data , main audio data , command data , television complementary data , and the game complementary data from the received broadcast signal having the structure shown in fig2 input from the communication portion 310 . further , the synthesizer 330 receives from the game system 320 for example a signal of the results of the game , a signal obtained from the package medium , and a signal created based on the command data and the game complementary data extracted from the broadcast signal in the synthesizer 330 . the synthesizer 330 combines the extracted main video data , main audio data , and television complementary data with the data input from the game system 320 according to need based on for example the extracted command data to create one video signal and audio signal able to be output from the monitor 340 and outputs the same to the monitor 340 . further , the synthesizer 330 outputs at least the command data for the game system 320 among the command data and the game complementary data to the game system 320 . further , when the data input from the game system 320 is an instruction for transmitting certain information to the broadcasting station system 200 , the synthesizer 330 outputs the instruction to that effect to the communication portion 310 the monitor 340 displays the video signal input from the synthesizer 330 on a screen and outputs the audio signal input from the synthesizer 330 . next , an explanation will be made of the operation of the signal processing system 100 having such a configuration . first , an explanation will be made of the basic operation of the signal processing system 100 . first , the selector / controller 240 of the broadcasting station system 200 creates the main video data and the main audio data by for example combining the picture captured from the video camera 230 with video stock data obtained from the server 210 and the video reproduction apparatus 220 . further , it adds data used for replacement of the main video data and main audio data or for performing certain processing with respect to the main video data and the main audio data as the television complementary data . further , it adds the data provided for the processing performed in the game system 320 of the home system 300 and used for replacement of the video data and audio data supplied from the package medium in the game system 320 or for performing certain processing with respect to the video data and audio data as the game complementary data . then , while making suitable use of the television and game complementary data , it creates command data for the game system 320 and the synthesizer 330 for enabling the desired av data processing in the home system 300 and thereby creates the broadcast use signal shown in fig2 . then , the created broadcast use signal is authored and encoded in the authoring / encoder system 250 , encoded , modulated , and otherwise processed for transmission in the transmitter 260 , and transmitted to the home system 300 via the satellite line 410 . the home system 300 receives the broadcast from the broadcast system 200 in a state with the medium storing the desired television game software loaded in the storage medium i / f 323 of the game system 320 . the synthesizer 330 demultiplexes the signal received at the communication portion 310 to the main video data , main audio data , command data , and the television complementary data and outputs the command data and the game complementary data for the game system 320 to the game system 320 . the game system 320 performs the desired processing on the data read from the package medium , an application executed according to the software read from the package medium , or the input game complementary data based on the input command data and operation of the controller 322 by the viewer so as to create the video signal and the audio signal to be output to the monitor 340 or to be provided for a further processing in the synthesizer 330 and outputs them to the synthesizer 330 . the synthesizer 330 performs desired processing on the received main video data and main audio data or television complementary data and further the video data and the audio data input from the game system 320 based on the input command data , for example , the combination of a plurality of the data , to create the final video signal and audio signal to be output to the monitor 340 . then , the created video signal and audio signal are output from the monitor 340 . as a result , new content obtained by combining content seemingly close to usual program data based on the main video data and the main audio data and content obtained by the desired processing of for example the game in the game system 320 is created and output from the monitor 340 . further , when the viewer operates the controller 322 of the game system 320 based on information output from for example the monitor 340 in order to transmit for example the selection or request of new information , selection of reception conditions , and notification of the reception state from the home system 300 to the broadcasting station system 200 , a signal based on this operation is transmitted from the game system 320 to the synthesizer 330 and transmitted from the communication portion 310 via the public telephone line 420 to the computer 270 of the broadcasting station system 200 . in the broadcasting station system 200 , the computer 270 performs the processing relating to this signal and instructs the selector / controller 240 to change the structure of the broadcast signal according to need . next , the various services which become possible in a signal processing system 100 having such a configuration and operation will be successively explained by giving concrete examples . first , such a signal processing system 100 can make a character of a television game appear in a television program and thereby provide a new form of entertainment . such processing will be explained next . first , in the broadcasting station system 200 , the selector / controller 240 combines for example a picture of the host captured from the video camera 230 with the video stock obtained from the server 210 or the video reproduction device 220 to create the broadcast use signal having the main video signal as shown in for example fig3 a . at this time , it uses the main video data , main audio data , and television complementary data to create a broadcast use signal of a configuration enabling the picture of the host captured from the video camera 230 to be easily separated from the rest of the video signal . the method may also be considered of storing background data of the region where the host of the main video data will be displayed as the television complementary data so that the host will be erased by combining for example the television complementary data and the main video data or conversely making the main video data video data without a host and separately sending the video of the host as the television complementary data . further , the method may also be used of adding an address of a position occupied by the host in the main video data as the complementary data . next , the selector / controller 240 creates instructions on timing of use , situation of use , etc . of the television complementary data as command data and adds it to the broadcast use signal . then , the broadcast use signal created in this way is authored and encoded in the authoring / encoder system 250 , encoded , modulated , etc . for transmission in the transmitter 260 , and transmitted via the satellite line 410 to the home system 300 . the home system 300 loads for example a medium storing the television game software containing the desired character shown in fig3 b in the storage medium i / f 323 of the game system 320 and receives the broadcast from the broadcasting station system 200 . the synthesizer 330 demultiplexes the received signal into the main video data , main audio data , command data , television complementary data , etc . then , basically the main video data and the main audio data are output to the monitor 340 for viewing of the program . upon a switch command of the command data or instruction by the viewer from the controller 322 , however , the synthesizer 330 cuts out the host ( replaced object ) data 500 of the main video data shown in fig3 a and instead inserts the data of the character ( replacement object ) 510 read from the storage media i / f 323 of the game system 320 as shown in fig3 b in the video signal . as a result , the monitor 340 display a picture as shown in fig3 c obtained by combining the picture of the character read from the television game package software via the storage medium i / f 323 with a picture of a television broadcast showing the real world or persons . due to this , the character of a game can be made to appear in a picture of the real world . by doing this , the viewer can newly experience a view of a game character , which had previously been limited in movement to the finite world stored in the package software in advance , moving around in the real world , and therefore can experience a new form of entertainment using package software which he or she had finished playing . further , the signal processing system 100 can transmit new data by such a broadcast to a game run by software stored on a package medium in the game system 320 and therefore expand the conditions , development , etc . of the game . such processing will be explained next . the method of creation of the broadcast signal , the method of the broadcast , etc . are the same as the methods explained above , but in this case , a broadcast signal containing the data to be newly added to the game as the game complementary data and containing commands for installing the complementary data as the command data is broadcast . the home system 300 receiving such a broadcast signal demultiplexes the game complementary data and the command data at the synthesizer 330 and inputs the same to the game system 320 . the game system console 321 of the game system 320 introduces the complementary data into the game software already loaded thereon based on the commands of the command data . below , a concrete explanation will be made of how a game can be expanded by such processing . for example , when what is being played on the game system 320 is a fight game , by transmitting data of a new fight opponent as the game complementary data and superposing a command for incorporating the game complementary data as the command data , the game system 320 can run the game while introducing a new fight opponent which did not exist in the package software . further , when what is being played on the game system 320 is a role playing game etc ., by transmitting data of a new stage as the game complementary data and superposing a command for incorporating the game complementary data as the command data , the game system 320 can run the game while additionally introducing a new stage which did not exist in the package software . further , when what is being played on the game system 320 is a game such as a baseball game or a soccer game , by transmitting character data employing players active in the real world as the game complementary data and superposing a command for incorporating the game complementary data as the command data , the game system 320 can introduce for example a rookie player newly starting to be active in the real world into the game and enable enjoyment of a more realistic and on - the - scene game . in addition , by broadcasting stock prices , exchange rates , a weather , rankings in professional baseball , hit charts and music thereof , and other various information of the real world or any other information in accordance with the game as the game complementary data and superposing a command for introducing the game complementary data as the command data , it is possible to enjoy a game incorporating real - time information of the real world . further , it is possible to create a game predicated on introduction of information of the real world from the start , for example , a game simulating the purchase of stock , bets on horse races , or bets on soccer tournaments . further , by broadcasting game complementary data for making for example the image data of the game higher in definition and command data for reflecting that complementary data , it is possible to enjoy a game on a higher definition screen which could not be experienced by only the package software . further , by having the signal processing system 100 combine processing with respect to a television program as mentioned above and processing with respect to the game system , it is possible to provide a program combining information from the package media and information by the broadcast . such processing will be explained next . the method of creating the broadcast signal , the method of broadcast , the processing in the home system 300 , etc . are the same as the methods explained above . in this case , a broadcast signal is broadcast adding data for expanding the program data as the television complementary data , adding data to be newly added to the processing of the game in the game system 320 etc . as the game complementary data , and adding commands for controlling the program data and the data of the game , including commands for controlling the game system 320 from the broadcasting station system 200 , as the command data . due to this , it is possible to provide a program combining game software and a broadcast program while controlling the game system 320 of the home system 300 from the broadcasting station system 200 . for example , when broadcasting a game strategy program or a game - production documentary , by broadcasting commands for operating an actual game system 320 included in the broadcast signal , it is possible to proceed with the program while remotely controlling the game system 320 by command data from the broadcasting station system 200 end . by proceeding with the program while combining the image created by operating the game system 320 of the user and the real picture wherein the host etc . appear , it is possible to for example more effectively illustrate the strategy in the game or inside stories of production . further , in for example a game strategy program , by transmitting information enabling a beginner who is not proficient in a game to more easily enjoy the game , that is , operational information enabling one to beat a better player even with a low capability level in a fight game , auxiliary information speeding up the progress of a role playing game , settings of special rules not existing in the package software , etc ., it is possible to provide a service enabling a considerably beginning class user to experience the thrill of a game designed for a higher class user or a high stage that cannot be reached by his or her own capability . note that , in this case , a user who doesn &# 39 ; t have the game software can enjoy only the main picture and the main sound . further , by having the signal processing system 100 broadcast content different from the main video data and the main audio data in the television complementary data , it is possible to provide the following types of broadcasts . for example , when broadcasting a game strategy program , it is possible to broadcast a program for a beginning class user as the main video and main audio data and broadcast a program for a high level user as the television complementary data and to have the user operate the controller 322 of the game system 320 to select one of the same . by doing this , the user can view a program matching his or her own level . further , in a broadcast such as a usual drama , it is possible to provide several story lines different from the main video and main audio data using the television complementary data . then , by having the viewer select any of these or according to the status of a game being played by the viewer or randomly for every home system 300 based on a command transmitted as the command data , one story line is selected and output to the monitor 340 . by doing this , it is possible to broadcast a drama unfolding with several branching story lines as the program content . such a format imparts a game - like unpredictability , bidirectionality , and multiple story lines to television broadcast content which everyone had previously identically viewed passively . further , it is also possible to have the signal processing system 100 operate in cooperation with media distributed to the home as package media by the above configuration . by employing such a format , the following processing can be carried out . first , characters or game screens which can not be seen by a usual game operation are stored in advance in the package software . then , these characters or game screens are called up by the command data when broadcasting a specific program by the main video and main audio data . by doing this , it is possible to provide content newly enjoyable by only viewers watching a broadcast , upgrade the version of the game to a new stage after a while from the release of the package software , or provide other services . next , an explanation will be made of a format in the case when using the signal processing system 100 having such a configuration as an advertisement medium . first , there is an advertisement format that provides advertisement information different between the main video and main audio data and the television complementary data and the game complementary data by a broadcast or package medium or a combination of the same and selectively outputs it to the monitor 340 by the selection of the viewer or unspecifically according to the state etc . of a game being played by the viewer or according to some sort of conditions described in the command data . by doing this , a tv commercial rich in unpredicted or unexpected changes can be realized . further , a format is also possible wherein , when a viewer watching an advertisement by the above format becomes interested in the product , the viewer can operate the controller 322 of the game system 320 to request a catalog , place an order for the product , answer a questionnaire , apply for a prize , etc . to the computer 270 of the broadcasting station system 200 via the synthesizer 330 , communication portion 310 , and the public telephone line 420 . further , it is also possible to provide points for the purchases of products or viewing of advertisements and therefore offer a so - called “ point service ”. by utilizing such a format , two - way communication of tv commercials and television shopping can be realized . further , a format can also be considered wherein advertisement information of a specific advertiser is additionally broadcast as game complementary data at predetermined time intervals and the broadcasted advertisement of the advertiser is displayed on the screen of a game when a user is playing a game in the game system 320 of the home system 300 . the position of the advertisement in the game may be fixed to a predetermined position on the game screen or may be set to a billboard or wall or a label of a product in the game depending on the game software . by doing this , it is possible to change the sponsor according to the time or date even in the same game . further , since the advertisement information may be transmitted later by broadcasting , the software of the game can be produced taking a long time as in the conventional case and respecting the wishes of the creators . further , in a format where the user can play a game with different sponsors assigned for predetermined times as mentioned above , it is also possible to collect score information etc . of ending information of the game of the viewers at the computer 270 of the broadcasting station system 200 and assign rankings according to the scores or order of arrival . then , the sponsor can then provide privileges or prizes to for example the viewers of the highest rankings . by doing this , it is possible to encourage the combination of tv commercials and the game and make this type of advertisement more effective . next , an explanation will be made of use of the signal processing system 100 having such a configuration as a system for purchasing show tickets . here , an explanation will be made of a system adding entertainment to the processing for purchasing of the ticket , running a game preceding the purchase of the ticket , and selling tickets on a priority basis to viewers finishing the game fastest by referring to the flow charts of fig4 and fig5 . first , game software for purchasing tickets is distributed to the viewers in advance by broadcast or package media . then , at the time of start of the sale of the tickets , the broadcasting station system 200 broadcasts a “ ticket sale program ” and starts the sale of the tickets in parallel to this broadcast . below , first , an explanation will be made of the processing in the home system 300 by referring to the flow chart of fig4 . the viewer desiring to purchase a ticket receives the “ ticket sale program ” broadcast by the broadcasting station system 200 and starts the game ( step s 10 ). the synthesizer 330 of the home system 300 confirms the sale information of the ticket based on the broadcasted data ( step s 11 ) and checks whether or not it has been sold out ( step s 12 ). when it has not yet been sold out , it confirms the ending information of the game being performed in the game system 320 ( step s 13 ) and checks whether or not the game is ended ( step s 14 ). if the game has not been ended , it repeats the processing from the confirmation of the sale information of step s 11 . when the game has been terminated at step s 14 , it transmits the ending information of the game and an user id indicating the id of the viewer via the communication portion 310 to the broadcasting station system 200 ( step sis ). then , it confirms acquisition / reception information from the home system 300 indicating whether or not the ticket could be acquired or which seat could be acquired etc . ( step s 16 ). when a ticket could be acquired ( step s 17 ), it writes ticket acquisition right information in an ic card loaded in the ic card i / f 324 of the game system 320 ( step s 18 ) and terminates the series of ticket acquisition processing ( step s 19 ). at step 12 , when the tickets had been already sold out even though the game has not yet been terminated , it displays sold out information on the monitor 340 ( step s 20 ) and terminates the series of the ticket acquisition processing ( step s 21 ). further , at step s 17 , when the game could be ended , but the tickets have been already sold out , it displays the sold out information on the monitor 340 ( step s 22 ) and terminates the series of the ticket acquisition processing ( step s 23 ). next , an explanation will be made of the processing in the broadcasting station system 200 by referring to the flow chart of fig5 . in the broadcasting station system 200 , after starting the broadcast of the “ ticket sale program ” ( step s 30 ), the computer 270 performs processing . first , it checks the sold out information of the tickets ( step s 31 ). when they have not been sold out ( step s 32 ), it searches for game ending information transmitted from a home system 300 via the public telephone line ( step s 33 ) and checks whether or not the game ending information has arrived ( step s 34 ). when game ending information has arrived ( step s 34 ), it receives the id of the user ( step s 35 ), checks again the sold out information of the tickets ( step s 36 ), confirms again that the tickets have not been sold out ( step s 37 ), updates the remaining seat data base of the tickets ( step s 38 ), and transmits ticket acquisition right information to the user of the received id ( step s 39 ). after transmitting the ticket acquisition right information at step s 39 and when the game ending information has not arrived at step s 34 , the operation routine returns to step s 31 , after which the processing from the checking of the sold out information is repeated again . further , when the tickets have been sold out at step s 37 , it transmits the sold out information to the user of the id transmitting the game ending information ( step s 40 ), transmits a sold out information screen ( step s 41 ), and terminates the ticket sale program . further , when the tickets have been sold out at step 32 as well , it transmits the sold out information screen ( step s 41 ) and terminates the ticket sale program . note that the program transmitted from the broadcasting station system 200 has for example the host confirming the state of remaining seats of the tickets etc . over a monitor . in the conventional method of telephone reservations , when the telephone lines are congested and one cannot get through , one cannot find out that the tickets have been sold out , so has to continue to try to call until getting through and only then learns the tickets are sold out . by using the above system , however , it is possible to easily confirm when tickets have been sold out . further , the viewer can confirm the seat which he or she has acquired in the television program . note that , for ticket sales , it is also possible for example to enable persons who have purchased tickets to view a message of thanks from the performing artist conversely to enable viewers who were not able to purchase tickets view a message of apology from the performing artist . further , a similar method can be applied to the sale of for example the limited distribution goods or software other than tickets . as explained above , according to the signal processing system 100 of the present embodiment , by combining the signal processing of for example a television game using package media and real - time signal processing by a broadcast , a , variety of new services can be provided . for example , it becomes possible to view a received broadcast while actually operating the game software , therefore , a game strategy program or other program for explaining the package software can be provided in a more impressive manner . further , by complementing the software of a television game by data from a broadcast or adding information of the real world , it is possible to provide a user with fresh entertainment expanded at any time after the user has experienced the finite information recorded in the software in advance . further , new game entertainment of game software linked with the real world can be provided . further , a secondary new additional value can be given to once sold package software and a corresponding new business can be created . further , the selectivity , unpredictability , and other elements of a game can be introduced into a television broadcast and therefore another new form of entertainment can be provided . further , in television commercials , commercials of a format never before existing , for example , enabling a user interested in the advertised product or the like to request further detailed information , actually order a catalog of the product or the product itself , or select information of interest from among a plurality of choices , or commercials having unpredictability can be provided . note that the present invention is not limited to the present embodiment and includes various suitable modifications . for example , the interface between the components in the home system 300 is not limited to an ieee1394 interface . any interface , for example , a usb can be used too . further , in the embodiment , the home system 300 was configured by four components of the communication portion 310 , game system 320 , synthesizer 330 , and monitor 340 contained in different housings . however , it is possible to employ a configuration where any combination of them , for example the communication portion 310 and synthesizer 330 or the communication portion 310 , game system 320 , and synthesizer 330 , is contained in one housing . further , any configuration can be used when mounting the same . further , in the present embodiment , the broadcasting station system 200 broadcasted to the home system 300 by a digital satellite broadcast , but the broadcast method is not limited to this . it may be an analog satellite broadcast or digital or analog ground wave broadcast . further , it may be a broadcast over a cable television system and an internet broadcast system . further , the route for feedback of a signal from the home system 300 to the broadcasting station system 200 is not limited to one using a public telephone line as in the present embodiment . use can be made of any communication system , for example a dedicated line or the internet or a system utilizing the two - way characteristic of a cable television system . note that this feedback communication route is not indispensable in the present invention . the system of the present invention can stand even when transmitting a signal in one direction by a broadcast . further , in the present embodiment , the explanation was made of various types of broadcast services and the information services according to the present invention , but the processing relating to charging for the provided services and contents was not described . however , it is also possible to incorporate a mechanism for charging for the provided service and contents in the signal processing system 100 by any method . such a system is also within the scope of the present invention . for example , it is also possible to utilize the charging mechanisms of existing satellite broadcasts and other pay broadcasts so as to collect charges for provision of the additional value . summarizing the effects of the invention , it is possible to provide a data transmission method and system which can combine audio and video content obtained by a television broadcast and audio and video content obtained by running for example package software in for example a television game system or operation and control information etc . from that television game system so as to have these functions complement each other and provide functions effective for a variety of objectives such as publicity and shopping or provide more enjoyable and less boring content of programs , games , etc . suitable for the interests of the viewer . further , it is possible to provide an information processing method and system which can combine the audio and video content obtained by a television broadcast and the audio and video content obtained from a television game system or the like or operation and control information , etc . thereof and perform suitable processing based on the audio and video content for publicity , shopping , and other objectives in new formats . further , it is possible to provide a data transmitter suitable for use in such data transmission system and information processing system . further , it is possible to provide a signal processor suitable for use as for example a home terminal in such data transmission system and information processing system . further , it is possible to provide a content data processing method suitable for application to such data transmission system and information processing system . further , it is possible to provide a data serving method suitable for application to such data transmission system and information processing system .

US-73333200-A

a package for blood and / or intravenous solutions which is nontoxic , autoclavable , retains its strength when dropped , sufficiently flexible and is of substantially reduced material cost which comprises an outer layer blend of propylene - ethylene copolymer and butene - 1 - ethylene copolymer , which is laminated to an inner layer blend of butene - 1 - ethylene copolymer and propylene - ethylene copolymer . the copolymers are random and the thickness ratio of the inner layer blend to the outer layer blend is 4 : 1 .

fig1 is a front view of the package as it is hung for use as a container of blood and / or intravenous solutions . fig2 is a side view of the outer layer blend of polymers which is laminated to the inner layer blend of polymers and which shows the layer structure at the sealed portion of the package . fig3 shows the layer structure of the inner and outer polymer blends . the outer layer blend comprises amounts of polypropylene copolymer and polybutene - 1 copolymer which are sufficient to lend desirable film thickness as well as desirable autoclavable and drop test results . the polypropylene copolymer of the outer layer blend comprises from about 50 % by weight to about 95 % by weight propylene - ethylene copolymer or propylene homopolymer and is preferably from about 85 % by weight to about 90 % by weight propylene - ethylene copolymer or propylene homopolymer . the polybutene - 1 copolymer of the outer layer blend comprises from about 5 % by weight to about 50 % by weight butene - 1 - ethylene copolymer and is preferably from about 10 % to about 15 % by weight butene - 1 - ethylene copolymer . the inner layer blend comprises amounts of polypropylene copolymer and polybutene - 1 copolymer which are sufficient to lend desirable film thickness as well as desirable autoclavable and drop test results . the propylene copolymer of the inner layer blend comprises from about 10 % by weight to about 40 % by weight propylene - ethylene copolymer or propylene homopolymer and the polybutene - 1 copolymer of the inner layer blend comprises from about 60 % by weight to about 90 % by weight butene - 1 - ethylene copolymer . the polypropylene copolymer of the inner layer blend preferably comprises from about 10 % by weight to 15 % by weight propylene - ethylene copolymer or propylene homopolymer and the polybutene - 1 copolymer of the inner layer blend preferably from about 85 % by weight to about 90 % by weight butene - 1 - ethylene copolymer . the propylene - ethylene copolymer of the outer layer blend as well as the inner blend comprises from about 0 % by weight to about 8 % by weight of the ethylene content and the butene - 1 - ethylene copolymer comprises from about 2 % by weight to about 8 % by weight of the ethylene content . the propylene - ethylene copolymer preferably comprises 3 % by weight ethylene content and the butene - 1 - ethylene copolymer comprises preferably about 5 % by weight ethylene content . both the polybutene - 1 copolymer and polypropylene copolymer of the outer layer blend and the polybutene - 1 and the polypropylene copolymer of the inner layer blend should be random copolymers . the inner layer b is coextruded with outer layer a as shown in fig3 . the thickness of inner layer b to outer layer a is from about 1 : 1 to about 6 : 1 and preferably about 4 : 1 . suggested hot bar sealing conditions are where the coextruded blend of polymers are at a temperature of 340 ° f . to 360 ° f ., and where both sides of the package are heated with the use of teflon cloths . three to 3 . 5 seconds is a sufficient dwell time at a pressure of 20 - 30 psi . as may be seen in fig4 and fig5 as the ethylene content increases , the seal drop test and film drop test results are better . all data are based on two mil blown film . fig6 illustrates the steps in the method for producing a package according to this invention . in accordance with this method , from about 85 % by weight to about 90 % by weight propylene copolymer and from about 10 % by weight to about 15 % by weight butene - 1 copolymer are mixed together in the form of pellets and then extruded at a melt temperature of about 400 ° f . to 500 ° f . separately , a mix of from about 10 % by weight to about 15 % by weight propylene copolymer and from about 85 % by weight to about 90 % by weight butene - 1 copolymer is prepared from pellets of the copolymers and is extruded at a melt temperature of 380 ° f . to 450 ° f . the two mixes of propylene copolymer and butene - 1 copolymer pellets are initially contained in hopper 10 and hopper 12 where they are respectively extruded through extruder 14 ( the inner blend ) and extruder 16 ( the outer blend ). the resulting propylene / butene - 1 copolymer 18 and butene - 1 / propylene copolymer 20 are each separately pelletized through pelletizers 22 and 24 , respectively . the resulting pellets of each are separately extruded through extruders 26 and 28 , respectively , and through coextrusion die 29 into sheets 30 . coextrusion die 29 may be of the slot or circular type . the coextrusion die 29 is at approximately 380 ° f . to 500 ° f . coextruded sheets 30 are passed between chilled rollers 32 and 34 , respectively , to cool and flatten said coextruded sheets 30 . the rollers 32 and 34 may be chilled by filling them with cold water . the cooled and flattened sheets 33 are wound on a take - up device 35 and are then sealed on at least two sides by a sealing device 36 to produce the desired package 38 . the two - layer blend that is the subject of this invention ( wbs - 289 ) was tested for comparison with the pvc material usually used . the pvc iv solution bag was supplied by abbott laboratories , while the polybutylene / polypropylene blends of this invention were extrusion melt compounded and fabricated into film by a film casting process . the results of such comparison testing may be seen in table 1 below . the corresponding astm test number is included next to each test , unless the test is one that is recognized as standard in the industry . the bag drop test results in table 1 are for the blown tube sealed on four sides and testing was conducted after the autoclave experiments . table i______________________________________comparison of shell wbs - 289 blend with pvcfor intravenous solution bagsastmtest test wbs vinylno . description 289 ( pvc ) ______________________________________ -- film thickness , cm 0 . 025 0 . 038 ( 10 mil ) ( 15 mil )-- density , g / cm . sup . 3 0 . 91 1 . 27e96 water vapor transmission 3 . 10 21 . 70 rate / g / m . sup . 2 / 24 hrs .-- usp class vi method extractables , mg / cm . sup . 2 total by water 0 . 00020 0 . 0020 chloroform 0 . 00000 0 . 00069 ( cannot detect ) d1003 film haze , % 33 10 55 ( embossed )-- autoclave @ 121 ° c . pass pass -- bag drop test pass pass ( 1000 cc , 183 cm height ) d882 secant modulus ( 2 %)* 1400 478 kg / cm . sup . 2d882 tensile break ,* kg / cm . sup . 2 232 246d1003 haze , %, presterilization 34 18 ( two plys & amp ; wet ) not embossed embossed 31d1003 haze , %, post sterilization 73 79 ( two plys & amp ; wet ) not embossedd882 seal strength *, kg / cm . sup . 2 180 124______________________________________ *= thickness corrected as may be seen in table 1 , the polybutylene / polypropylene blend ( wbs - 289 ) exhibited far better values in water vapor transmission resistance , had much less extractables , and greater seal strength demonstrated by the lower film thickness and density values , than the values exhibited by the vinyl ( pvc ). autoclavability at 121 ° c . was successful for wbs - 289 as was the bag drop test . the wvtr has been decreased seven - fold , and the extractables have been decreased ten - fold for total by water and more than five hundred - fold for chloroform ( cannot detect ). the film thickness has been reduced from 15 ml to 10 ml and the density lowered by more than one - third , which results in a substantial savings of material cost , as may be seen in table ii , below . table ii______________________________________ thickness , material mil density , g / cm . sup . 3______________________________________wbs - 289 10 0 . 91vinyl ( pvc ) 15 1 . 27savings wbs - 289 33 % 28 % total savings = 61 % material cost______________________________________

US-57873984-A

provided is a topical cream composition for the delivery of mometasone furoate comprising low dose mometasone furoate for the treatment of corticosteroid responsive dermatoses . the composition of the present invention can be safely applied over large surface areas of the skin , and can be used therapeutically for extended periods of time . treatment with the composition of the present invention carries reduced and / or fewer side effects compared with commercially available mometasone furoate cream products . the cream composition of the present invention is safe for the use of babies and infants under 2 years old . additionally provided are methods of preparing and using the composition of the invention .

the composition of the present invention can be administered topically using methods that are well known in the art , e . g ., by directly applying or spreading the composition on an affected area , which can include surfaces of the skin , and the like . the composition of the present invention preferably includes from about 0 . 05 wt % to less than 0 1 wt % mometasone furoate , e . g ., from about 0 . 075 wt % to less than 0 . 1 wt % mometasone furoate ( e . g ., about 0 . 075 wt % mometasone furoate ), and a pharmaceutically acceptable vehicle that includes an oily phase and at least about 20 wt % water ( e . g ., from about 30 wt % to about 65 wt % water , e . g ., about 60 wt % water ). the vehicle is preferably chosen from components that are suitable for use in contact with mammalian skin without producing undue toxicity , incompatibility , instability , allergic responses or the like . it will be appreciated that the precise amount of mometasone furoate to be used in the composition of the present invention , the choice of vehicle components and the amount of composition to be administered to a particular patient , can vary depending on a variety of factors . such factors may include , e . g ., the nature of the skin being treated , the age and physical condition of the subject being treated , the severity of the condition , the duration of the treatment , the nature of any concurrent therapy that may apply , the nature of the active agent ( s ) and topical carrier ( s ) employed , and the like . in a preferred embodiment , the composition of the present invention includes about 0 . 075 wt % to less than 0 . 1 wt % mometasone furoate , a polyol , a gelling agent , at least about 20 wt % water , and an oily phase . exemplary compositions of the present invention include about 0 . 075 wt % mometasone furoate , a polyol , a gelling agent , at least about 30 wt % water ( e . g ., about 60 wt % water ), and an oily phase ( e . g ., about 15 wt % of an oily phase ). the composition of the present invention is suitable for topical administration to mammalian skin , preferably human skin . the skin can be covered with hair and / or can have wrinkles . the composition of the present invention can be used for topically treating corticosteroid - responsive skin conditions and / or diseases , such as , e . g ., inflammation , psoriasis , hyperkeratotic dermatosis , pruritic manifestations of corticosteroid - responsive dermatoses , eczema , atopic dermatitis and the like . the composition of the present invention preferably includes from about 12 wt % to about 30 wt % of a polyol . in a preferred embodiment , the composition of the present invention includes about 15 wt % of a polyol . any polyol suitable for topical administration can be used in the composition of the present invention . preferred polyols include propylene glycol and hexylene glycol . other suitable polyols can include commercially available or known polyols such as , e . g ., pentaerythritol , ethylene glycol , polyethylene glycol , polypropylene glycol , sorbitol , glycerol , polyglycerol , saccharides , cyclodextrins , synthetic polyhydric polymers , and the like , and combinations thereof . preferably , the polyol used in the composition of the present invention has humectants properties ( e . g ., propylene glycol , hexylene glycol , sorbitol , glycerine , etc .). the composition of the present invention preferably includes from about 0 wt % to about 0 . 9 wt % of one or more gelling agents . in a preferred embodiment , the composition of the present invention includes about 0 . 5 wt % of one or more gelling agents . suitable gelling agents can include , e . g ., pharmaceutically acceptable natural , synthetic , and semisynthetic gelling agents . preferably , the gelling agent includes a polyacrylic acid , such as , for example , a carbomer , e . g ., carbomer 910 , carbomer 934 , carbomer 940 , carbomer 941 and the like , and combinations thereof . other suitable gelling agents can include , e . g ., carboxymethylcellulose , ethylcellulose , gelatin , hydroxyethyl cellulose , hydroxypropyl cellulose , magnesium aluminum silicate , methylcellulose , poloxamers , polyvinyl alcohol , sodium alginate , alginic acid , tragacanth , acacia , bentonite , poly ( amino amine )- xanthan gum , and the like , and combinations thereof . in some embodiments , the composition of the present invention includes two or more gelling agents . preferred combinations of gelling agents include combinations of xanthan gum and a carbomer . in some particularly preferred formulations , the composition includes about 0 . 4 wt % of xanthan gum or less , and / or about 0 . 5 wt % of carbomer 940 or less . the composition of the present invention also can include a neutralizing agent , which can serve to activate the gelling agent . one skilled in the art can easily determine the appropriate neutralizing agent to be used for activating a particular gelling agent . a neutralizing agent can be any ph adjusting agent . suitable neutralizing agents include basic neutralizing agents , which also be used to increase the ph of the composition . suitable neutralizing agents also can include acids , as well as buffers . exemplary neutralizing agents include sodium hydroxide , potassium hydroxide , triethanolamine , sodium phosphate dibasic , dibasic sodium phosphate heptahydrate , phosphoric acid , and the like , and combinations thereof . the composition of the present invention preferably includes at least about 20 wt % water , e . g ., at least about 30 wt % water , about 30 wt % to about 65 wt % water , about 40 wt % to about 65 wt % water , about 50 wt % to about 60 wt % water , e . g ., about 60 wt % water . preferably , at least a substantial portion of the water in the composition of the present invention is bound water . more preferably , substantially all of the water in the composition of the present invention is bound water . the composition of the present invention can exist in any form suitable for topical administration , e . g ., an oil - in - water emulsion , a liposomal suspension , a cubosomal suspension , a vesicular suspension , or the like . preferably , the composition of the present invention exists as an oil - in - water emulsion . the composition of the present invention can further include one or more emulsifiers , e . g ., from about 7 wt % to about 20 wt % of one or more emulsifiers . preferably , the composition of the present invention includes about 9 wt % of one or more emulsifiers . suitable emulsifiers that can be used in the composition of the present invention include , for example , sorbitans , alkoxylated fatty alcohols , alkylpolyglycosides , soaps , alkyl sulfates , monoalkyl and diallyl phosphates , alkyl sulphonates , acyl isothionates , and the like , and combinations thereof . preferred emulsifiers include emulsifying waxes , and combinations thereof . in particularly preferred embodiments , the compositions can include about 6 wt % to about 10 wt % emulsifying wax . the compositions of the present invention includes an oily phase , e . g ., from about 5 wt % to about 50 wt % oily phase ( e . g ., from about 11 wt % to about 15 wt % oily phase ). an exemplary composition of the present invention includes about 12 wt % oily phase . the oily phase preferably includes one or more pharmaceutically acceptable oil components suitable for topical administration such as , e . g ., fatty acids , fatty alcohols , fatty acid esters , silicones , and the like , and combinations thereof . preferably , the components of the oily phase have emollient or skin softening properties . preferred oily phase components include , e . g ., cetostearyl alcohol , oleic acid , caprylic capric triglyceride , and the like , and combinations thereof . in particularly preferred embodiments , the compositions can include about 10 wt % or less cetostearyl alcohol , about 1 wt % to about 3 wt % oleic acid , and / or about 10 wt % to about 12 wt % caprylic capric triglyceride . the composition of the present invention also can include one or more additional active ingredients , including pharmaceutically active and cosmetically active ingredients , which can be water insoluble or only slightly soluble in water . suitable additional active ingredients can include , e . g ., anti - inflammatory agents , analgesics , anti - histamines , antiinfective agents ( e . g ., anti - viral , anti - fungal agents , anti - mycotic agents , anti - bacterial agents , components such as dibasic sodium phosphate heptahydrate and the like ), antiacne agents , anti - psoriasis agents , wound healing agents , anti - wrinkle agents , skin rejuvenating agents , anti - pigmentation agents , anti - proliferative agents , growth factors , cytoxic agents , chemotherapeutic agents , and the like , and combinations thereof . such ingredients , if included , will typically be present in relatively amounts of about 0 . 5 wt % or less . if desired , the composition of the present invention can include one or more additional suitable corticosteroids , preferably in low doses . exemplary additional corticosteroids can include commercially available or known corticosteroids such as , e . g ., alcometasone , clocortolone , dexamethasone , hydrocortisone , hydrocortisone 21 - acetate , prednisone , hydrocortisone 17 - valerate , hydrocortisone 17 - butyrate , betamethasone valerate , triamcinolone acetonide , flucinonide , desonide , flucinolone acetonide , dexamethasone , dexamethasone 21 - phosphate , prednisolone , prednisolone 21 - phosphate , haloprednone , cortisone acetate , hydrocortisone cyclopentylpropionate , cortodoxone , flucetonide , fludrocortisone acetate , flurandrenolone acetonide , medrysone , amcinafal , amcinafide , betamethasone , betamethasone benzoate , chloroprednisone acetate , clocortolone acetate , descinolone acetonide , desoximetasone , dichlorisone acetate , difluprednate , flucloronide , flumethasone , flumethasone pivalate , flunisolide acetate , flucortolone , fluorometholone , fluperolone acetate , fluprednisolone , fluprednisolone valerate , meprednisone , methyl prednisolone , paramethasone acetate , prednisolamate , prednival , triamcinolone , triamcinolone hexacetonide , cortivazol , formocortal , nivazol , methylprednisone , and the like , and combinations thereof . the composition of the present invention also can include other well - known pharmaceutically and / or cosmetically acceptable additives , such as , e . g ., antioxidants , ph adjusting agents , chelating agents , preservative agents , occlusive agents , emollients , thickeners , solubilizing agents , tonicity agents , penetration enhancing or modifying agents , crystallization inhibiting agents , anti - irritants , and the like , and combinations thereof . suitable ph adjusting agents , which can be used in the composition of the present invention can include , for example , malic acid , lactic acid , citric acid , glycolic acid , benzoic acid , ascorbic acid adipic acid , glycines , phosphoric acid , calcium hydroxides , magnesium aluminometasilicates , buffer systems , and the like , and combinations thereof . if desired , one or more ph adjusting agents can be added to maintain desired ph levels . suitable chelating agents , which can be used in the composition of the present invention can include , for example , ethylenediaminetetraacetic acid ( edta ), edta derivatives and salts , and the like , and combinations thereof . suitable preservative agents , which can be used in the composition of the present invention can include , for example , benzyl alcohol , alkanols , disodium edta ( ethylenediamine tetraacetate ), edta salts , edta fatty acid conjugates , isothiazolinone , parabens ( e . g ., methylparaben and propylparaben ), glycols , sorbates , diazolindinyl urea , and the like , and combinations thereof . in a preferred embodiment , compositions of the present invention can comprise about 1 % to about 3 % benzyl alcohol . suitable occlusive agents , which can be used in the composition of the present invention and can be incorporated in the oily phase of the composition of the present invention , can include , for example , petrolatum , mineral oil , beeswax , silicone oil , lanolin and oil - soluble lanolin derivatives , saturated and unsaturated fatty alcohols such as behenyl alcohol , hydrocarbons such as squalane , animal and vegetable oils ( e . g ., almond oil , peanut oil , wheat germ oil , linseed oil , jojoba oil , apricot pit oil , walnut oil , palm nut oil , pistachio nut oil , sesame seed oil , rapeseed oil , cade oil , corn oil , peach pit oil , poppyseed oil , pine oil , castor oil , soybean oil , avocado oil , safflower oil , coconut oil , hazelnut oil , olive oil , grape seed oil , sunflower seed oil ), and the like , and combinations thereof . some occlusive agents also can serve as emollients . suitable emollients , which can be used in the composition of the present invention include , for example , dodecane , squalane , cholesterol , isohexadecane , isononyl isononanoate , ppg ethers , petrolatum , lanolin , safflower oil , castor oil , coconut oil , cottonseed oil , palm kernel oil , palm oil , peanut oil , soybean oil , polyol carboxylic acid esters , derivatives thereof , and the like , and combinations thereof . suitable thickening agents , which can be used in the composition of the present invention can include , for example non - ionic water - soluble polymers such as , e . g ., hydroxyethylcellulose ( commercially available under the trademark natrosol ® 250 or 350 ), cationic water - soluble polymers such as polyquat 37 ( commercially available under the trademark synthalen ® cn ), fatty alcohols , fatty acids and alkali salts thereof , and the like , and combinations thereof . it will be appreciated that some thickening agents also can be used as gelling agents . suitable solubilizing agents , which can be used in the composition of the present invention , can include , e . g ., complex - forming solubilizer citric acid , ethylenediaminetetraacetate , sodium meta - phosphate , succinic acid , cyclodextrin , polyvinylpyrrolidone , diethylammonium - ortho - benzoate , or micell - forming solubilizers such as tweens and spans ( e . g ., tween 80 ), and the like , and combinations thereof . other suitable solubilizers can include , e . g ., polyoxyethylene sorbitan fatty acid ester , polyoxyethylene n - alkyl ethers , n - alkyl amine n - oxides , poloxamers , organic solvents , phospholipids , cyclodextrins , and the like , and combinations thereof . suitable penetration enhancing or penetration modifying agents can include , e . g ., dimethylsulfoxide ( dmso ), dimethyl formamide ( dmf ), allantoin , urazole , ndimethylacetamide ( dma ), decylmethylsulfoxide ( c 10 mso ), polyethylene glycol monolaurate ( pegml ), propylene glycol ( pg ), propylene glycol monolaurate ( pgml ), glycerol monolaurate ( gml ), lecithin , the 1 - substituted azacycloheptan - 2 - ones , particularly 1 - n - dodecylcyclazacycloheptan - 2 - one ( available under the trademark azone ® from whitby research incorporated , richmond , va . ), alcohols , glycerin , hyaluronic acid , transcutol , and the like , and combinations thereof . certain oil components ( e . g ., certain vegetable oils such as , e . g ., safflower oil , cottonseed oil and corn oil ) also can exhibit penetration enhancing or penetration modifying properties . suitable anti - irritants can include , e . g ., aloe vera , chamomile , alpha - bisabolol , cola nitida extract , green tea extract , tea tree oil , licoric extract , allantoin , caffeine or other xanthines , glycyrrhizic acid and derivatives thereof , and the like , and combinations thereof . the present invention additionally provides a method of producing a topical cream composition , which preferably includes mixing an active phase with an oily phase ; combining a water phase with the mixture of oil and active phases , and homogenizing the phases to produce a substantially uniform dispersion ; optionally adjusting the ph to obtain a ph of from about 4 . 0 to about 5 . 5 ; and , optionally , further diluting with water , to produce the composition . the active phase preferably includes a polyol and from about 0 . 05 wt % to less than 0 . 1 wt % mometasone furoate ; the oily phase preferably includes a fatty acid , a fatty alcohol , a fatty acid ester , or a combination thereof ; and the water phase preferably water and one or more gelling agents . the composition prepared in accordance with the method of the present invention preferably includes at least about 20 wt % water . in a particularly preferred embodiment , the method of the present invention includes preparing a water phase that includes water and one or more gelling agents ; preparing an active phase that includes a polyol and about 0 . 075 wt % mometasone furoate ; preparing an oily phase that includes a fatty acid , a fatty alcohol , and a fatty acid ester ; mixing the active phase with the oily phase ; combining the water phase with the mixed active and oily phases and homogenizing the phases ; adjusting the ph to a ph of from about 4 . 0 to about 5 . 5 ; and adding sufficient purified water ( qs as needed ) to produce a composition that includes at least about 20 wt % water . preferably , at least a substantial portion of the water in the composition of the present invention is bound water . more preferably , substantially all of the water in the composition of the present invention is bound water . one skilled in the art will appreciate that additional components , including but not limited to additional active ingredients , can optionally be included in the appropriate phase of preparation . the composition of the present invention can be formulated in various dosage forms suitable for topical , transdermal , or buccal administration such as , for example , a foam , an aerosol , a spray , a gel , a cream , a lotion , an ointment , a suspension , an emulsion , a paste , a solution , and the like . the composition of the present invention is preferably formulated as a topical cream . the present invention further provides a method for treating a corticosteroid - responsive disease or condition associated with a patient &# 39 ; s skin , which method includes topically applying to the patient ( e . g ., on the patient &# 39 ; s skin at or near the affected area ) a therapeutically effective amount of a mometasone furoate composition of the present invention . preferably , the disease or condition is a corticosteroid - responsive dermatosis . in a preferred embodiment , the disease or condition is an atopic dermatitis or a type of eczema . the method of the present invention can be used for treating pediatric patients , e . g ., pediatric patients under 2 years of age , under 18 months of age , under 1 year of age , or under 6 months of age . in accordance with the method of the present invention , the composition can be safely applied to a relatively large percentage of the patient &# 39 ; s total skin surface area ( e . g ., greater than about 20 % of the patient &# 39 ; s total skin surface area ), even in pediatric patients under 2 years of age , with a reduction in toxicity and / or side effects otherwise exhibited by elocon ® cream . for instance , the composition can be applied in any amount sufficient to contact up to about 80 % of the patient &# 39 ; s total skin surface area , e . g ., about 20 % to about 80 %, about 20 % to about 70 %, about 20 % to about 60 %, about 20 % to about 50 %, about 20 % to about 40 %, or about 20 % to about 30 %. in accordance with the method of the present invention , the patient can be treated over a relatively long period of time with a reduction in toxicity and / or side effects otherwise exhibited by elocon ® cream . for instance , the composition of the present invention can be topically applied to the patient at least once per day for more than 3 weeks , e . g ., about 3 weeks to about 6 months , about 3 weeks to about 5 months , about 3 weeks to about 4 months , about 3 weeks to about 3 months , about 3 weeks to about 2 months , or about 3 weeks to about 6 weeks . the following examples further illustrate the invention but , of course , should not be construed as in any way limiting its scope . this example illustrates a method of preparing an exemplary composition of the present invention . 100 grams of an aqueous cream composition containing 0 . 075 % mometasone furoate are prepared by the following process . the water phase is prepared first : xanthan gum , and carbomer 940 are dispersed in purified water . next , dibasic sodium phosphate heptahydrate is mixed into the dispersion . emulsifying wax and benzyl alcohol are added to the dispersion and heated . to prepare the active solution , mometasone furoate usp is dissolved in heated propylene glycol . next , the oily phase is prepared : oleic acid , cetostearyl alcohol , and caprylic capric triglyceride are combined and mixed . the active solution and the oily phase are added to the water phase . the resulting emulsion is cooled . emulsion ph is checked and adjusted with phosphoric acid as needed . purified water is added to the emulsion to reach 100 % ( q . s .). the components of the exemplary composition ( formula a ) are listed in table 1 . the presence of bound ( entrapped ) water in formula a , prepared as described in example 1 above , is determined by dsc measurements performed in the endothermic scanning mode by controlled heating of previously frozen samples . the dsc curve expected to result from analysis of formula a is characterized by an asymmetric broad peak at − 6 . 30 ° c . the enthalpy change ( δh ) associated with a thermal transition ( the total energy ), is evaluated by integrating the area of this peak . enthalpy ( δh ) of free water melting is − 324 j / g . the actual enthalpy change demonstrated for formula a is significantly smaller than − 162 j / g , the predicted δh of a composition such as formula a , which contains about 50 % water . the temperature and enthalpy values indicate that the vast majority of the water in formula a exists as bound water . this example illustrates comparative mometasone furoate 0 . 1 % composition ( formula b ). the components of comparative formula b are listed in table 2 . the results of the test show , as presented in fig1 , that the penetration of the active pharmaceutical ingredient from formula b exhibits a similar penetration relative to the active pharmaceutical ingredient from the elocon 0 . 1 % composition . this example illustrates an exemplary 0 . 075 % mometasone furoate cream composition of the present invention ( formula c ). the components of exemplary formula c are listed in table 3 . the results of the test show , as presented in fig2 , that formula c exhibits reduced penetration relative to formula b . hence , the reduced penetration improves the safety of the 0 . 075 % cream composition by reducing the toxicity of the composition . this example compares the effect of the exemplary formulation of the present invention , formula a mometasone furoate cream ( 0 . 075 %, see example 1 ), with formula b mometasone furoate cream ( 0 . 1 %, see example 2 ) and elocon ® 0 . 1 % cream on 12 - o - tetradecanoylphorbol - 13 - acetate ( tpa , sigma ) induced skin inflammation response in female imprinting control region ( icr ) mice . female icr mice ( 40 ) were divided into 6 groups and the dorsal skin was treated with the following compositions ( 100 μl volume each ) once daily for 10 days and 30 minutes prior to treatment with tpa every other day : group components group 1 none ( untreated ) group 2 mometasone cream 0 % ( placebo ) 0 μg tpa ( acetone vehicle alone ) group 3 5 μg tpa ( 8 . 5 nmol in acetone )* group 4 mometasone cream 0 . 075 % 5 μg tpa ( in acetone ) group 5 mometasone cream 0 . 1 % 5 μg tpa ( in acetone ) group 6 elocon ® 0 . 1 % cream 5 μg tpa ( in acetone ) * mice were treated with 5 μg tpa every other day a skin biopsy ( 3 cm × 3 cm ) was performed on each mouse and the effect of each composition on scores of dermal inflammatory cell infiltration and epidermal hyperplasia following inducement by administration of tpa to the external skin was determined . the scoring used for dermal inflammatory cell infiltration represents the percentage of tissue in the section involved in focal , multifocal or diffuse distribution of lesions ( 0 not present ( 0 %), 1 = slight ( 0 - 10 %), 2 = mild ( 11 - 20 %), 3 = moderate ( 21 - 40 %), and 4 marked ( 41 - 100 %)). the scoring used for epidermal hyperplasia represents the increase in the thickness of the epidermal layers ( thickness of the epithelium from basal layer to stratum corneum ) in treated animals compared to control animals ( 0 = not present ( 0 ), 1 = slight ( 2 × control ), 2 mild ( 3 × control ), 3 = moderate ( 4 × control ), and 4 = marked ( 5 × control )). the results of the histopathological analysis test are summarized in fig3 . mometasone cream 0 . 075 % ( group 6 ) significantly reduced mean histopathology score of dermal inflammatory cells infiltration and epidermal hyperplasia induced by 5 μg ( 8 . 5 nmol ) tpa ( group 3 ). there were no significant differences between the dermal therapeutic effects ( anti - inflammatory and antiproliferative effects ) of mometasone cream 0 . 075 % ( group 6 ) and elocon ® 0 . 1 % cream ( group 4 ). the therapeutic effects of mometasone 0 . 075 % ( group 6 ) and mometasone cream 0 . 1 % ( group 5 ) were comparable . the results of the histopathological analysis test show that the mometasone cream 0 . 075 % composition of the invention significantly reduced scores of dermal inflammatory cell infiltration and epidermal hyperplasia induced by 5 ug ( 8 . 5 nmol ) tpa compared to placebo . in addition , there were no significant differences between therapeutic effects of mometasone cream 0 . 075 % of the invention and elocon ® 0 . 1 % cream and the therapeutic effects of mometasone cream 0 . 075 % of the invention and mometasone cream 0 . 1 % were comparable . all references , including publications , patent applications , and patents , cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein . the use of the terms “ a ” and “ an ” and “ the ” and similar referents in the context of describing the invention ( especially in the context of the following claims ) are to be construed to cover both the singular and the plural , unless otherwise indicated herein or clearly contradicted by context . the terms “ comprising ,” “ having ,” “ including ,” and “ containing ” are to be construed as open - ended terms ( i . e ., meaning “ including , but not limited to ,”) unless otherwise noted . recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range , unless otherwise indicated herein , and each separate value is incorporated into the specification as if it were individually recited herein . all methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context . the use of any and all examples , or exemplary language ( e . g ., “ such as ”) provided herein , is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed . no language in the specification should be construed as indicating any non - claimed element as essential to the practice of the invention . preferred embodiments of this invention are described herein , including the best mode known to the inventors for carrying out the invention . variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description . the inventors expect skilled artisans to employ such variations as appropriate , and the inventors intend for the invention to be practiced otherwise than as specifically described herein . accordingly , this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law . moreover , any combination of the above - described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context .

US-53540609-A

a skewer gripping device for use with a skewer has a food engaging surface and a locating portion . the locating portion has a clamping screw associated therewith . in use , food is placed on the skewer between two gripping devices , which clamp the food in position . the gripping devices act to hold the skewer away from a hot surface , and thus prevent contact of the food and the hot surface .

referring to the figures , there is shown a food skewer 10 having a first end 12 and a second end 14 . the skewer 10 is looped at the first end 12 to form a handle . the skewer 10 is pointed at the second end 14 to allow for the insertion of food thereon . two skewer gripping devices 20 are mounted on the skewer 10 . each skewer gripping device 20 includes a substantially hexagonal plate 22 . the hexagonal plate 22 is substantially perpendicular to a longitudinal direction of the skewer 10 . the hexagonal plate 22 has a front face 24 which serves , in use , as a food engaging surface and a rear face 26 . the hexagonal plate 22 has an outer periphery in the form of an outer edge 28 . the hexagonal plate 22 has a centrally located aperture 30 a substantially cylindrical locating portion 32 extends outwardly from the central aperture 30 of the hexagonal plate 22 , away from the rear face 26 in a direction perpendicular to the plate 22 . the locating portion 32 is hollow , and communicates with the central aperture 30 . the locating portion 32 and central aperture 30 are sized so as to allow the skewer 10 to slide within the location portion 30 . the locating portion 32 includes an internally threaded radial aperture 34 located along its length . an externally threaded clamping screw 36 having a bulbous head 38 is receivable within the aperture 34 . the action of the clamping screw 36 within the locating portion 32 comprises a gripping means against the skewer 10 . the gripping means has a first configuration in which the clamping screw 36 is not tightened within the aperture 34 , and does not bear against the skewer 10 . when the gripping means is in the first configuration , the locating portion 32 and thus the gripping device 20 is able to readily slide along the skewer 10 . the gripping means has a second configuration in which the clamping screw 36 is tightened within the aperture 34 , and bears against the skewer 10 . in this configuration , the clamping screw 36 provides a frictional force against the skewer 10 and prevents sliding of the gripping device 20 along the skewer 10 . it will be appreciated that a user can tighten the clamping screw 36 , and thus adjust the gripping means between the first and second configurations , using the bulbous head 38 . in use , a first gripping device 20 is located on the skewer 10 by threading the second end 14 of the skewer 10 through the rear end of the locating portion 32 . with the gripping means in the first position , the gripping device 20 can be slid up the skewer 10 to a desired location adjacent the first end 12 of the skewer 10 . the screw 36 can then be tightened , fixing the gripping device 20 in location with its food engaging surface 24 oriented towards the second end 14 of the skewer 10 . food stuffs can then be threaded onto the second end 14 of the skewer 10 in the usual manner . the first food item is threaded along the skewer until it bears against the food engaging surface 24 . subsequent foodstuffs are then added such that each food item is packed against adjacent food items . when the skewer 10 is sufficiently loaded with food , a second gripping device 20 is introduced onto the skewer 10 in a similar fashion to the first gripping device 20 . the second gripping device 20 is oriented such that its food engaging surface 24 is oriented towards the first end 12 of the skewer 10 , and is thus in opposition to the food engaging surface 26 of the first gripping device 20 . the second gripping device 20 is pushed against the foodstuffs on the skewer until a sufficient clamping force is distributed along the foodstuffs between the opposed food engaging surfaces 24 . the clamping screw 36 of the second gripping device 20 is then tightened to bring the gripping means into the second configuration . it will be appreciated that the outer periphery 28 of each of the gripping devices 20 now extends about the skewer 10 . when the skewer 10 is placed on a hot surface such as a grill plate , the outer peripheries 28 of the gripping devices 20 rest on the hot surface and the skewer 10 is displaced from the hot surface by at least the minimum radial extent of the gripping devices 20 . in a preferred mode of use , the foodstuffs placed on the skewer 10 do not extend past the minimum radial extent of the gripping devices 20 . in use , therefore , foodstuffs placed on the skewer are spaced from the hot surface and are thus cooked by convection and radiation rather than conduction of heat . in the preferred mode of use , the gripping devices 20 are arranged on the skewer 10 such that the outer peripheries 28 are aligned . in this way , the hexagonal peripheries 28 of the embodiment of the drawings provide 6 stable angular orientations for the skewer 10 in relation to the hot surface . the skewer 10 can thus be readily rotated through each of the angular orientations to provide even cooking of the food on the skewer 10 . the clamping of the foodstuffs between the food engaging surfaces 24 prevents rotation of the food relative to the skewer 10 . although the preferred embodiment of the drawings shows each periphery as hexagonal in shape , it will be appreciated that any shape could be used . clearly , a regular polygonal shape is preferred . modifications and variations as would be apparent to a skilled addressee are deemed to be within the scope of the present invention .

US-56751905-A

a knee joint flexibility rehabilitation apparatus may comprising a tubular strut having a first support foot and a bracket attached thereto , the tubular strut forming a first aperture ; a height - adjustment bar translatably and rotatably disposed in the tubular strut , the height - adjustment bar forming a plurality of second apertures extending through the cross - section of the height - adjustment bar ; a support bar fixed substantially perpendicularly to the height - adjustment bar , the padded support bar being configured to receive a knee joint posterior ; a support strut pivotably connected to the bracket , the support strut having a second support foot attached thereto , the support strut pivotable away from parallel the tubular strut to form an acute angle thereto ; and a pin removably disposed in one of the plurality of second apertures to fix the height - adjustment bar against translation in one direction .

disclosed is a passive manipulative knee joint flexibility therapy apparatus and method , specifically adapted for knee joint flexibility rehabilitation following knee joint surgery or other type of knee joint treatment , such as knee joint replacement or replacement or repair of any torn or damaged previously described ligaments , bone fracture and bone fracture surgery , or internal fixation surgery , or for treatment of arthritic conditions , or meniscus repair , or for knee injury recovery , regaining normal knee joint flexibility , range of motion and strength . the apparatus capable of reducing muscle spasm , pain and swelling ; having such arrangement to provide appropriate content stable support of the posterior intersection concerning the femur and tibia of a non - operative , arthritic , injured , fractured , or post - operative recovering knee joint ; prompting deliberate gravity assisted passive flexion towards gradual knee joint muscle and tendon stretching , and mechanical decompression of the knee joint to alleviate pain , pressure , swelling , and general discomfort . the disclosed apparatus arrangement may comprise a padded knee posterior support bar disposed atop an adjustable linearly sliding rod ; whereby said rod may travel a controlled distance while contained inside a slightly larger collaborating support strut tube . a locking mechanism may be used , thereby establishing and maintaining a desired height position of the posterior knee support bar . further , the disclosed apparatus may utilize opposed parallel horizontal members as stabilizing structure ; being estranged , such members may form a stable apparatus foundation ; having each support base tube incorporate a perpendicular strut affixed mid span ; uniting the opposing strut ends uniquely via a pivot fulcrum point ; forming a triangle . further , the apparatus is collapsible to a somewhat flat arrangement for easy of storage or shipment . the above brief description sets forth rather broadly certain features of the disclosed apparatus in order that the description thereof that follows may be better understood , and in order that the present contributions to the art may be better appreciated . there are , of course , additional features of the disclosed apparatus that will be described hereinafter and which will , in whole or in part , form the subject matter of the claims appended hereto . thus , it is to be understood that the disclosed subject matter is not limited in its application to the details of the construction and to the arrangements of the components set forth in the following description or illustrated in the drawings . the disclosed subject matter is capable of other embodiments and of being practiced and carried out in various ways , including being fabricated with fixed dimensions , non - folding components , or other structural locking mechanisms . also , it is to be understood , that the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting . as such , the concept , upon which this disclosure is based , may readily be utilized as a basis for designing other structures , methods , and systems for carrying out several purposes of the present invention . it is important , therefore , that the claims be regarded as including such equivalent constructions insofar as they do not depart from the spirit and scope of the subject matter described herein . various objectives may be therefore apprehended , one or more of which the disclosed subject matter may provide : one objective may be to provide a new and unique economically realized passive knee joint flexibility rehabilitation apparatus wherein the various elements of the apparatus may be examined . another objective may be reduction of spasm ( s ) of the knee joint musculature . another objective may be to provide such an arrangement for which to appropriately and contentedly support the posterior intersection relationship of the femur and tibia allowing for knee joint decompression . another objective may be to promote gravity assisted passive flexion specific towards gradual knee joint muscle and tendon stretching . another objective may be to provide a padded horizontal posterior knee support bar ; where a pad could be realized from such material as neoprene , polysulfide , silicone , urethane , gel , but not limited thereto ; where the horizontal knee posterior support bar may have a predetermined length and have rounded ends . another objective may be mechanically affix a padded horizontal knee posterior support bar , and provide proper longitudinal position relative to individual recovering patient knee anatomy during gravity assisted passive flexion . another objective may be to provide the opposed end of said adjustable sliding rod strut tube to be perpendicularly introduced in to a somewhat larger diameter horizontal tube ; considered as a base foot ; being realized from such material as ferrous or nonferrous metal , plastic , wood , carbon fiber , composite , fiberglass , but not limited thereto ; with said tube incorporating a purposefully predetermined receiving hole or harbor mid span ; being somewhat dimensionally reduced of that of the strut tube outer wall dimension ; wherein the strut tube end being firmly pressed in to the accommodating receiving harbor ; having this press fit amalgamation permanently affixed by means of mechanical , fusion or chemical bonding , but not limited thereto . another objective may be to provide said adjustable sliding rod strut tube as being perpendicularly introduced in to said horizontal tube base foot ; to include a dual purpose mounting bracket located an established distance below said adjustable sliding rod entry ; being located 90 degrees in reference to said horizontal tube base foot ; whereas said mounting bracket appendage may be angled at a somewhat 4 o &# 39 ; clock position ; being permanently affixed mechanically , chemically , or fusion bonded , but not limited to ; with said mounting bracket realized from such material as ferrous or nonferrous metal , plastic , wood , carbon fiber , composite , fiberglass , but not limited thereto ; having said mounting bracket realized by means of casting , forming , molding , fabricating , stamping , machining , but not limited thereto . another objective may be to provide said permanently affixed mounting bracket as being a predetermine length ; having a profile with an inside dimension equaling that of a cooperating second strut tube outside dimension , in which such profile may comprise a square channel profile ; with the channel opening positioned facing downward towards said horizontal tube base foot ; incorporating laterally opposed apertures located at identical predetermined points aside said square channel . another objective may be to provide a second said strut tube being a predetermined length perpendicularly introduced in to a second somewhat larger diameter horizontal tube ; considered as a base foot , realized from such material as ferrous or nonferrous metal , plastic , wood , carbon fiber , composite , fiberglass , but not limited thereto ; having said horizontal tube base foot incorporate a purposefully predetermined receiving hole or harbor mid span ; being somewhat dimensionally reduced to that of the said second strut tube outer wall dimension ; wherein the strut tube end being firmly pressed in to the accommodating receiving harbor ; having this press fit amalgamation permanently affixed by means of mechanical , fusion or chemical bonding , but not limited thereto . another objective may be to provide the second said strut tube being perpendicularly introduced and permanently affixed to the somewhat larger diameter tube ; considered as a base foot ; having the opposing strut tube end include laterally opposed apertures equal to the diameter of the apertures referenced in said dual purpose mounting bracket ; having said apertures located parallel considering said base foot horizontal relationship . another objective may be to provide the second said strut tube ; having the opposing end include laterally opposed apertures ; incorporate an arc end ; whereas the arc chord equaling said strut tube outside diameter ; whereby arc height and outside tube radius being equivalent ; having said arc chord midpoint being the same as of said opposed aperture centers . another objective may be to provide the adjustable sliding strut tube and second strut tube compilation , having an arc end , as united by inserting the arc end of said second strut tube into the accommodating dual purpose channel shaped said mounting bracket ; wherein once inserted alignment of the cooperating said laterally opposed cooperating of each component , may align , thus affording the insertion of a bolt , screw , or pin , but not limited to ; being realized as a pivot fulcrum . another objective may be to provide the adjustable sliding strut and the second strut compilation as utilizing said pivot fulcrum the second strut compilation to swing into a somewhat flat collapsed configuration , whereas the strut feet are in close horizontal parallel proximity . another objective may be to capitalize upon pivot fulcrum utilization , whereby spreading the strut support feet a predetermined distance ; having that distance governed by rigid contact interface between the pivoting strut tube outer surface engaging the internal top surface of the affixed said dual purpose mounting bracket channel ; whereby realizing a stable acute triangle support frame structure . another objective may be to provide a new knee joint gravity assisted passive flexion apparatus , which may be easily and efficiently manufactured and marketed . another objective may be to provide knee joint gravity assisted passive flexion apparatus , which is of durable and reliable construction . another objective may be to provide a new knee joint gravity assisted passive flexion apparatus , which may be susceptible of a low cost of manufacture with regard to both materials and labor , and which accordingly may then be susceptible of low prices of sale to the consuming public , thereby making such knee joint gravity assisted passive flexion assembly available to the buying public . with reference now to the drawings , a novel and unique apparatus for knee joint flexibility and rehabilitation will be more fully disclosed . such an apparatus , and method of using such apparatus , may meet one or more of the foregoing objectives . fig1 provides a perspective view of an embodiment of such an apparatus . the apparatus may have a supple pad 1 encompassing nearly the full length of a knee posterior support bar 2 , but not necessarily in full circumference ; having said pad 1 feasibly detained , by some form of bonding agent ( e . g ., glue , double - sided tape , stitching , velcro , or some other commercially available attachment means ) or simply by friction or mechanical pressure . the knee posterior support bar may be substantially horizontally oriented . the bar 2 and a linearly travelling adjustable rod 3 may be mechanically joined . said linearly travelling rod 3 may contain one or more holes 4 which may be used to lock the rod 3 in vertical position with a pin 5 or any other suitable locking mechanism . a sliding bar strut tube 6 may serve as a structural support component affixed to horizontal strut support tube foot 7 , for example , at mid span juncture 8 , or at an end of the support tube foot 7 . said strut tube 6 may also serve as the housing in which said sliding rod or bar 3 may translate a determined linear distance , upon having said sliding rod 3 inserted into said tube housing 6 at induction point 9 . finally , the sliding bar strut tube housing 6 may have affixed thereto a multi - task bracket 10 . the bracket 10 may be located below said induction point 9 , such as at reference point 11 , and may be disposed at angle to strut support tube foot 7 . said rod 3 may freely rotate in said strut tube 6 . in some embodiments , the rod 3 may be fixed against rotation by insert the pin 5 through a hole 18 in the strut tube 6 and further inserted into one of the holes 4 aligned therewith . such fixation may further prevent translation of the rod 3 . the pivotal support strut tube 12 may serve as a structural support member affixed to horizontal strut support tub de foot 13 , such as at mid - span juncture 14 . the opposite end of said strut tube 12 may be introduced into the accommodating landing 15 of said bracket 10 . such introduction may be fixed or pivotable . a pivotable introduction may be accommodated by a pivot point , such as provision of a pivot pin inserted , indicated by reference 16 . thereby having the two collaborate opposing horizontal strut support tube feet 7 & amp ; 12 spread apart , utilizing the indicated pivot point 16 , to where the pivotal support strut tube 12 engages the multi - task bracket 10 at intended engagement landing point 15 , may provide a stable , rigid , gravity assisted passive flexion knee joint flexibility rehabilitation posterior support apparatus . fig2 illustrates two exemplary vertical positions of the support bar 2 . an exemplary method of using the apparatus of fig1 is described in connection with discussion of fig2 and 3 . a recovering patient 30 may be place in a supine position atop a physical therapy treatment table 32 , or other such firm stable surface , whereby having the patient may optionally bend the non - rehabilitating leg at an upward directed 45 degree angle with their foot flatly placed or may optionally have the non - rehabilitating leg resting at full horizontal extension . thereupon , introducing the apparatus for knee joint flexibility rehabilitation , being approximately centered beneath the recovering knee 34 posterior 36 ; whereby the strut support tube foot 7 may impinge upon or be disposed on the table adjacent the patient &# 39 ; s buttock ( s ) 38 ; whereby the compilation of the sliding bar strut tube housing 6 and the linearly traveling adjustable sliding rod 3 may slightly engage the back of the patient &# 39 ; s lower thigh 40 ; whereby encouraging the lower leg thigh to mimic the compilation &# 39 ; s acute angle . the patient &# 39 ; s recovering knee joint 34 posterior 36 may then rest upon the horizontal knee posterior support bar 2 , having the desired height of said support bar 2 established . accommodating a desired height of said support bar 2 may be accomplished by removing locking pin 5 , thus affording said sliding rod 3 free linear movement 17 in either an ascending or descending direction . reengagement of the locking pin 5 may be accomplished by aligning rod 3 hole 4 with support 6 hole 18 and inserting said locking pin 5 . of course , if both of a patient &# 39 ; s knee joints require rehabilitation , two such apparatuses may be advantageously used at the same time . in other embodiments , the support bar 2 may be of a length sufficient to support both of a patient &# 39 ; s knee joints , and more than one rod 3 and more than one strut tube 6 may be used to support a single support bar , or more than one support bars 2 in an apparatus . should free rotating motion of the sliding rod 3 be desired , the locking pin 5 may be inserted in the appropriate hole 4 of rod 3 above support ring 19 , whereby the vertical load of the patient &# 39 ; s leg may be transmitted through the locking pin 5 to the top of the support ring 19 . the linearly traveling adjustable sliding rod 3 being so disposed , the knee posterior support bar 2 may be temporarily in parallel with opposing horizontal strut support tube feet 7 & amp ; 13 , respectfully . the patient &# 39 ; s lower leg 42 may now be extended out over the horizontal knee posterior support bar 2 , whereby said support bar 2 may serve as a fulcrum . the compilation engagement of the pivot support strut tube 12 , and sliding bar strut tube housing 6 multi - task bracket 10 ; utilizing a pivot pin , referenced as 16 , may have said strut tube 12 in cantilever ; thereby establishing an acute angle support structure . further , considering a phantom centerline 20 commencing from the center of the knee posterior support bar 2 end 21 ; traveling vertically downward ceasing imaginarily between the opposing horizontal strut support tube feet 7 & amp ; 13 , simulating opposing right angles having said centerline 20 as the adjacent ; revealing said tube foot 13 opposite angle line 22 extends further forward than does opposite angle line 23 of said tube 7 . having this acute triangle configuration may beneficially negate any forward catapulting or pitching effect that could be realized during gravity assisted passive flexion of a knee joint . now , again , referencing fig1 contemplating the length of the horizontal knee posterior support bar 2 to that of the horizontal strut support tube feet 7 & amp ; 13 being equivalent or longer , may conclusively diminish any involuntary lateral or rolling movement of the horizontal knee posterior support bar 2 . continuing on with fig4 being an exploded illustration of the embodiment of fig1 , an end cap 24 may be inserted into each end of supports 7 and 13 respectively . the strut and support tubes , rods and / or bars may comprise any suitable cross - sectional configuration , such as round , square , polygonal , channel , angular or the like . the feet may comprise tubular , angular , channel or plate structural members . the foregoing thus describes a new knee joint flexibility rehabilitation apparatus . the knee joint flexibility rehabilitation apparatus may be specifically intended for gravity assisted passive flexion of the knee joint . the knee joint flexibility rehabilitation apparatus may be used to provide knee rehabilitation treatment specific for knee joint stiffness , flexibility and strengthening . the knee joint flexibility rehabilitation may be used to provide knee rehabilitation treatment specific for swelling reduction , pain reduction , spasm reduction , and compression reduction . the knee joint flexibility rehabilitation apparatus may be used to provide knee rehabilitation treatment specific for injury recovery , arthritic relief therapy , bone fracture recovery and surgery recovery . the knee joint flexibility rehabilitation apparatus may provide an arrangement that is appropriate for and contently supports the posterior intersection relationship of the femur and tibia of a post - operative recovering knee joint others . the knee joint flexibility rehabilitation apparatus may promote deliberate gravity assist passive flexion specific towards gradual knee joint decompression and muscular and tendon stretching . although the disclosed subject matter and its advantages have been described in detail , it should be understood that various changes , substitutions and alterations can be made herein without departing from the invention as defined by the appended claims . moreover , the scope of the claimed subject matter is not intended to be limited to the particular embodiments of the process , machine , manufacture , composition , or matter , means , methods and steps described in the specification . as one will readily appreciate from the disclosure , processes , machines , manufacture , compositions of matter , means , methods , or steps , presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized . accordingly , the appended claims are intended to include within their scope such processes , machines , manufacture , compositions of matter , means , methods or steps .

US-201514758776-A

the invention provides a method for molding three - dimensional products from a mass of foodstuff starting materials which are suitable for consumption , in particular a meal mass . the method comprises the steps of filling a mold cavity , which is open on one side , with the mass of foodstuff starting materials which are suitable for consumption , which mold cavity is defined by a boundary comprising walls and base , in order to mold a molded three - dimensional product , and the removal of the molded three - dimensional product from the mold cavity . in the method according to the invention , during removal the adhesion forces between the molded product and the boundary are eliminated virtually simultaneously along all the interfaces .

fig1 diagrammatically depicts a perspective view of an embodiment of a moulding device 10 according to the invention , while fig2 shows a side view of this device . the moulding device 10 comprises a frame 14 which can be moved with the aid of wheels 12 . a moulding drum 16 is mounted on the frame 14 in such a manner that it can be rotated about a horizontal axis and is coupled to a drive , for example an electric motor . the moulding drum 16 comprises mould cavities , which are not visible in fig1 and 2 . a mass feed member 18 for feeding mass which is to be moulded to the mould cavities of the moulding drum comes into close contact with the outer circumference of the moulding drum 16 . the mass is fed from a displaceable storage device 19 with introduction funnel 20 and then via a releasable connecting pipe 22 to the mass feed member 18 by means of an ( optionally continuously ) operating pump ( not shown ). in the vicinity of the underside of the moulding drum 16 , there is a release device 24 for releasing moulded products from the mould cavities of the moulding drum 16 , as well as a discharge belt 26 beneath it . via this discharge belt 26 , the products can be fed to other processing stations , for example a protein - coating device , a freezing device or a packaging installation . the moulding device 10 also comprises a control unit 28 for controlling the various components . with a view to making the device , in particular the moulding drum 16 and the mass feed member 18 , accessible for maintenance and cleaning purposes , the mass feed member 18 is secured to a subframe 30 , which can be rotated about a pivot pin 34 with the aid of a piston / cylinder assembly 32 , so that the mass feed member 18 can be moved out of a working position illustrated in fig1 and 2 into an at - rest position ( not shown ) at a distance from the moulding drum 16 after coupling 36 between connecting pipe 22 and mass feed member 18 has been released . in the embodiment shown in fig3 a ) and b ), rectangular recesses 42 are provided in the outer circumference 40 of the moulding drum 16 , which is in this case hollow . exchangeable inserts 44 of corresponding dimensions can be secured in these recesses 42 . for this purpose , bores 46 are provided at the corners of an insert 44 , aligned with threaded holes 47 in the base 48 of the recess 42 , and bolts 50 can be fitted into them . in the base 48 of a recess 42 there is an opening 52 which is in communication , via one or more axial connecting passages and distribution device ( not shown ), with an opening 54 in an end piece 56 of the moulding drum 16 . this opening 54 is in communication with excess - pressure means ( not shown ), such as a compressor , for supplying a forcing fluid via a flexible hose 57 , and with reduced - pressure means ( not shown ), for example a vacuum pump , via a flexible hose 58 . in its top side , the insert 44 comprises a mould cavity 60 of a shape which corresponds to the shape of the product which is to be produced . in the embodiment shown in fig4 , the insert 44 together with spacer 62 , forms an assembly 64 . insert 44 comprises the mould cavity 60 delimited by vertical walls 66 and base 68 , while spacer 62 is a flat plate in which there is a through - opening 72 , the dimensions of which are larger than the mould cavity 60 . the insert 44 is made from a porous material , such as sintered steel . the pores are denoted by reference numeral 73 . they open out in the base 68 and peripheral wall 66 . therefore , in the assembled state , there is a space between the underside of this insert 44 and the base 48 of the recess 42 , this space also being delimited by the peripheral wall 74 of the opening 72 in spacer 62 , which space is in communication with , on the one hand , the pores 73 in the insert 44 and , on the other hand , the opening 52 , so that during operation the mould cavity 60 can be efficiently evacuated , and during the release operation a forcing fluid can be supplied between product and boundary . the insert 44 is a rectangular body with a flat underside and sides , apart from the top side 75 , which is curved . the radius of curvature of the curved upper side 75 is identical to the radius of curvature of the moulding drum 16 . fig5 illustrates the way in which this embodiment of a device 10 according to the invention operates . the mass which is to be moulded is forced into the mould cavity 60 , which is in a filling position , via the mass feed member 18 , while air is being sucked out of this mould cavity 60 through the pores in the insert 44 in question , the opening 52 and a connecting passage 76 with the aid of reduced - pressure means . this mould cavity 60 is filled during the rotation ( direction of rotation indicated by an arrow ) of the moulding drum 16 past the filling position . as a result of further rotation , a mould cavity 60 moves into a release position where a moulded product 78 , under the force of gravity , drops out of the mould cavity 60 onto a discharge belt 26 moving beneath it . the release is assisted by supplying compressed air or other pressure medium , for example water , to the mould cavity 60 via the connecting passage 76 and the porous insert 44 . the compressed air is supplied by excess - pressure means ( not shown ). fig6 shows the latter aspect in more detail . from the connecting passage 76 , compressed air is passed through the opening 52 in the base 48 of the recess 52 in the drum 16 into distribution space 82 , from where the compressed air ( indicated by arrows ) forces its way through the pores in the boundary of the insert 44 and expels a product . for the sake of simplicity , fig3 - 6 in each case illustrate a combination of excess - pressure means and reduced - pressure means . as will be clear from the general description given above , the two aspects can also be employed separately . fig1 shows an embodiment of a mould cavity 60 with a permeable boundary with a complete pore structure for the base 68 and peripheral wall 66 . in addition to the pores 73 , passages 200 are provided in the base 68 . in the situation illustrated , the pores 73 are fed with a gaseous forcing fluid , such as compressed air , via a separate feed 202 . the passages 200 are provided with a liquid forcing fluid , such as water , via a separate feed 204 . as an alternative to a separate supply , it is also possible to use a mixture of liquid and gaseous forcing fluids . fig1 shows yet another embodiment , in which the boundary of a mould cavity 60 is of layered structure . an innermost boundary layer 206 comprises a pore structure , while the outermost boundary layer 208 is provided with passages 200 . a forcing fluid is introduced into a distribution chamber 212 via feed 210 . from there , the fluid flows through the passages 200 and then via the pores 73 and into the mould cavity . fig1 and 17 show two different pore structures . one is composed of sintered , substantially round metal grains ( fig1 ) and one is composed of sintered , irregularly shaped metal particles . in the case of the pore structure shown in fig1 , the risk of a meat mass or small pieces of meat sticking in the pores is lower than in the case of the structure shown in fig1 , since the depth of penetration of the mass is lower on account of the relatively high resistance caused by the irregular nature of the pores . fig1 shows a boundary part with irregular passages 200 which taper from the outside towards the mould cavity 60 . fig1 shows a boundary of a mould cavity 60 in which the boundary comprises a coating layer 220 which is given a surface charge by a reversible chemical reaction , repelling the oppositely charged particles ( indicated as dipoles ) from the product starting material . fig2 illustrates a method in which an additional electromagnetic repulsion force is generated in order to release a product from the mould cavity 60 with the aid of an electromagnet 222 . fig7 shows another embodiment of a moulding device 10 according to the invention , in which components which correspond to those shown in fig1 - 6 are denoted by the same reference numerals . the moulding drum 16 comprises recesses 42 which are distributed over its circumference and in which a filler piece 81 is positioned . in this case , the mould cavity 60 is delimited by the top side 83 of filler piece 81 and side walls 84 of the recess 42 . the top side 83 in this case has a surface which is provided with a contour , so that an attractively shaped appearance can be imparted to the product . the mould cavities 60 of the moulding drum 16 can once again be selectively coupled to either reduced - pressure means or feed means , as described for a different embodiment with reference to fig5 and 6 . for this purpose , an opening 52 , which is aligned with bore 85 in filler piece 81 , is provided in the base 48 of the recess 42 . a web or strip 86 is wound around the moulding drum 16 . this strip 86 has a sandwich structure and comprises an upper layer 88 made from a plastics material , in which flexible premoulds 90 are provided , substantially corresponding to a mould cavity 60 , and a lower layer 92 , which during operation is in contact with the outer circumference of the moulding drum 16 and is made from a more rigid material , in which there are round openings 94 , the diameter of which in this case substantially corresponds to that of the premoulds 90 and therefore to that of the mould cavities 60 . the two layers 88 and 82 are connected to one another in a suitable way . one end 96 of the web 86 of a sandwich structure is provided with securing means which interact with securing features on the drum 16 . an example is a row of small openings 98 which are positioned over short projections on the drum 16 . the free end 102 of the web may be fixed to the drum 16 or to itself , for example using adhesive tape or the like . to protect the web 86 , there is a wear - resistant material , for example stainless steel , protective strip 104 , in which openings 106 which likewise correspond to the flexible premoulds are provided . one end of the protective strip 104 has a flanged edge 108 which , during operation , engages in an axial groove 110 provided in the outer circumference of the drum 16 . the other end 112 has spring securing means 114 at its corners , and these means can be fixed to projections on the drum 16 , so that the protective strip 104 can be clamped taut around the drum 16 and in this way also holds the flexible strip 86 beneath it in place . during operation , at the filling position the flexible premoulds 90 in the mould cavities 62 are filled with mass or a portion of mass , it being possible for the air which is present beneath the flexible premould 90 in the mould cavity 60 to be sucked out , for example via the central bore 85 in filler piece 81 and opening 52 connected to it in the base 48 of recess 42 , which opening can be connected to reduced - pressure means via an axial connecting passage in the manner described above . at the release position ( fig8 ), the flexible premould 90 is pushed out of the mould cavity 60 with the aid of compressed air , which is led to the mould cavity 60 in the manner which has likewise already been described , and the moulded product 78 can be released , if desired with the assistance of a release device , for example a spindle belt which is to be described below . the release device 24 shown in fig8 - 10 is arranged beneath the moulding drum 16 at the release position and in the situation illustrated comprises an endless conveyor . this conveyor comprises two endless chains 120 which are arranged parallel to one another and are guided in a fixed path over toothed wheels 122 . toothed wheels 128 arranged on a common driven axle 126 engage in the vicinity of the centre of a top part 124 , moving towards the drum 16 , of the conveyor . a drive unit is denoted overall by reference numeral 130 . the links 132 of the chains 120 ( cf . fig1 ) are lengthened on the inner side by an extension piece 134 which projects inwards . extension pieces 134 of corresponding links 132 of the two endless chains 120 are connected to one another by thin transverse spindles 136 , in such a manner that the transverse spindles 136 , at the reversing point , pass through the centre of the axis of the toothed wheel 122 in question . this results in the formation of a pointed nose which is responsible for further removing moulded products 78 from the mould cavity 60 . fig1 diagrammatically depicts an embodiment of a mass feed member 18 , in which identical components are once again denoted by identical reference numerals . the mass feed member 18 comprises a virtually semicircular housing 140 with a through - passage 142 extending in the radial direction ( cf . also fig1 ) with an inlet 144 for the mass which is to be moulded from a storage device 19 and an outlet 146 for the mass to pass to a mould cavity 60 . side walls 148 and 150 of the housing 140 are provided with openings 152 extending in the radial direction . radially movable lamellae 154 , for example made from metal , are arranged between corresponding openings 152 in the side walls 148 , 150 . the central part of the mass feed member 18 comprises a filler block 156 which is fixedly connected to the housing and in which the through - passage 142 is provided . that side of the mass feed member 18 which faces towards the moulding drum 16 comprises a plate 158 made from a flexible plastic , for example teflon , in which the outlet 146 to a mould cavity 60 is provided . between the inner wall of the housing 140 and the lamellae 154 there is a pressure cushion 160 which can be pressurized using a suitable pressure medium , such as compressed air or pressurized water or other liquid . in this way , during operation , the teflon plate 158 is pressed onto the moulding drum 16 in such a manner as to form a seal , the lamellae 154 forming a large number of ribs which extend in the axial direction of the moulding drum 16 and impart the required rigidity , while the teflon plate 158 is able to adapt to possible deviations in the radius of the moulding drum 16 . on one side of the through - passage 152 there is a cutting blade 170 for cutting through tough pieces , such as muscle fibres . in the embodiment of the moulding drum 16 illustrated in this figure , there are provided , in its outer wall , recesses 42 which have a widened base 162 , extend in the longitudinal direction and into which corresponding inserts 44 with a mould cavity 60 can be pushed from the corresponding end of the moulding drum 16 . fig2 shows a perspective illustration of an exchangeable moulding drum 16 as an embodiment of a moulding surface according to the invention . the moulding drum 16 , which can rotate about an axle 250 , comprises a cylindrical drum wall 252 . the outer side of the cylindrical drum wall 252 comprises recesses 42 . in each recess 42 there is an insert 44 , which insert 44 comprises a mould cavity 60 which is defined by a boundary provided with holes , namely walls 66 and base 68 . in the embodiment illustrated , all the mould cavities 60 are identical in shape . it is also possible for the shape of the mould cavities to differ , for example for each annular drum - wall part to have identically shaped mould cavities , while the shape of the mould cavities differs from one annular drum - wall part to another . it is therefore relatively easy to make a range of products of different shapes and then package these products . fig2 shows a moulding drum similar to that shown in fig2 , except for the fact that the exchangeable inserts 44 are elements which extend in the longitudinal direction of the drum and are each provided with four mould cavities 60 . fig2 shows a particularly preferred embodiment of a moulding drum 16 according to the invention which can be exchanged in its entirety . the moulding drum 16 comprises a piece of porous metal , the surface pores of which have been sealed at the outer surface and the inner surface . the mould cavities 60 are formed by spark erosion , with the result that the boundary , comprising base 68 and side walls 66 , has acquired the porous structure , since the pores are uncovered as a result . it is easier to replace one moulding drum with another than to exchange the removable inserts as used in the embodiments shown in fig2 and 22 .

US-201414305742-A

a surgical system that ablates soft tissue . the system may include a fiber laser oscillator as the gain medium that emits electromagnetic radiation . the system may process the electromagnetic radiation , and direct the electromagnetic radiation on to the soft tissue to be ablated . due at least in part to the nature of the electromagnetic radiation emitted by the fiber laser oscillator , the system may provide various enhancements , such as a higher power conversion efficiency , a longer lifetime , less heat dissipation , a more compact design , and / or other enhancements , for example . the system may also generate electromagnetic radiation with a relatively high beam quality . this may reduce beam divergence and beam spot size on targeted soft tissue , thereby enhancing power density in the electromagnetic radiation guided to the soft tissue . this enhanced power density may facilitate effective ablation .

fig1 illustrates a surgical system 10 configured to ablate soft tissue of a patient , according to one or more implementations . surgical system 10 may be particularly configured to ablate prostate tissue , or other soft tissue . in some implementations , system 10 may include a source 12 , an output assembly 14 , a power assembly 16 , a cooling assembly 18 , a processor 20 , and / or other components . in some implementations , source 12 may output electromagnetic radiation at a predetermined output wavelength and a predetermined output power . output assembly 14 may be configured to deliver the output electromagnetic radiation to soft tissue of the patient to ablate the soft tissue . for example , output assembly 14 may include an optical fiber . in some instances , the optical fiber may include a side - firing tip . output assembly 14 may be configured to deliver the output electromagnetic radiation to prostate tissue of the patient to ablate the prostate tissue . power assembly 16 may receive an input power from an external power source and may , at least in part , drive source 12 and / or other components of system 10 with the input power . cooling assembly 18 may cool source 12 during operation . processor 20 may control operation of system 10 . as is illustrated in fig1 , source 12 may include a generation assembly 22 , an amplification assembly 24 , a wavelength adjustment assembly 26 , and / or other components or assemblies . generation assembly 22 may generate electromagnetic radiation at a predetermined fundamental wavelength and a predetermined fundamental power . amplification assembly 24 may be optically coupled with generation assembly 22 to receive electromagnetic radiation from generation assembly 22 and may amplify the power of the received electromagnetic radiation to that the electromagnetic radiation that is output to ablate the soft tissue will be output at the predetermined output power . wavelength adjustment assembly 26 may be optically coupled to amplification assembly 24 , and may adjust the wavelength of the received electromagnetic radiation to the predetermined output wavelength . in some instance , the output wavelength may be shorter than the fundamental wavelength . in some implementations , processor 20 may execute a generation module 28 , an amplification module 30 , a cooling / temperature module 32 , a temperature tuning module 34 , and / or other modules . although processor 20 is shown in fig1 as a single unit , it may be appreciated that processor 20 may include a plurality of processors operatively linked to each other , and that various ones of the linked processors may be physically located locally to each other , or may be remote from each other . for example , in one implementation , processor 20 may include a processor integral with the other components system 10 and a central processing unit of a host computer system being employed to control and / or read out data from system 10 . in another implementation , processor 20 may include only the processor formed integrally with the other components of system 10 . other configurations exist . further , each of modules 28 , 30 , 32 , and / or 34 may be implemented in hardware , software , firmware , or in some combination thereof . modules 28 , 30 , 32 , and / or 34 may be executed locally to each other , or one or more of modules 28 , 30 , 32 , and / or 34 may be executed remotely from other ones of modules 28 , 30 , 32 , and / or 34 . generation module 28 may operate to control and receive feedback from generation assembly 22 . for instance , as will be discussed further below , generation module 28 may include one or more drivers configured to communicate with various components of generation assembly 22 . amplification module 30 may operate to control and receive feedback from amplification assembly 24 . for instance , as will be discussed further below , amplification module 30 may include one or more drivers configured to communicate with various components of amplification assembly 30 . cooling / temperature module 32 may operate to determine one or more temperature related to the operation of system 10 . for example , cooling / temperature module 32 may receive information from one or more sensors ( not shown ) located at source 12 , and based on this information may determine an overall temperature of source 12 , individual temperatures of one or more of assemblies 22 , 24 , or 26 , and / or individual temperatures of one or more components of assemblies 22 , 24 , or 26 . further , cooling / temperature module 32 may be operate to control and / or receive feedback from cooling assembly 18 . as will be discussed further below , temperature tuning module 34 may operate to tune one or more components of wavelength adjustment module 26 to an operating temperature . the tuning performed by temperature tuning module 34 may enhance the performance of wavelength adjustment assembly 26 , protect one or more of the components of wavelength adjustment assembly 26 , and / or provide other advantages . referring to fig2 , generation assembly 22 is illustrated in accordance with one or more implementations . as shown , generation assembly 22 may include one or more pump sources 36 , a fiber laser oscillator 38 , an optical isolator 40 , an amplitude modulator 42 , and / or other components . pump source 36 may provide pump energy to fiber laser oscillator 38 . the pump energy may cause fiber laser oscillator 38 to lase , thereby emitting electromagnetic radiation with the fundamental wavelength . amplitude modulator 42 may be optically coupled to fiber laser oscillator 38 , via optical isolator 40 , to receive electromagnetic radiation emitted by fiber laser oscillator 38 . amplitude modulator 42 may modulate the amplitude of the received electromagnetic radiation to provide electromagnetic radiation in pulses . the pulses of electromagnetic radiation may be provided at a predetermined frequency and / or with a predetermined pulse width . since amplitude modulator 42 modulates only the amplitude of the electromagnetic radiation , electromagnetic radiation included in the pulses provided by amplitude modulator 42 may generally have the fundamental wavelength . the electromagnetic radiation included in the pulses of amplitude modulator 42 may have the fundamental power . pump source 26 may be controlled by a pump driver executed by generation module 28 ( as shown in fig1 ). pump source 36 may include one or more diode lasers that emit electromagnetic radiation . the electromagnetic radiation emitted by the one or more diode lasers may be guided to fiber laser oscillator 38 , and may provide the pump energy requisite to lase fiber laser oscillator 38 . in some instances , the one or more diode lasers may include a plurality of broad - area laser diodes . the broad - area laser diodes may emit electromagnetic radiation with a wavelength between about 915 nm and 976 nm . in some implementations , fiber laser oscillator 38 may include a double or triple clad fiber to enable the energy from pump source 36 to be applied to fiber laser oscillator 38 as a cladding pump . it should be appreciated that alternative configurations of pump source 36 are also contemplated . as fiber laser oscillator 38 lases , it may produce electromagnetic radiation at a wavelength of about 1080 nm that has a relatively high beam quality ( e . g ., substantially single transverse mode ( tem00 ) radiation ) with an enhanced input power to optical output power efficiency , particularly when compared with other , more conventional oscillator media ( e . g ., solid state gain media , etc .). this may prove useful in the context of soft tissue ablation for several reasons . for instance , electromagnetic radiation with a high beam quality may enhance soft tissue ablation , so the generation of electromagnetic radiation by fiber laser oscillator 38 with substantially a single transverse mode and at a relatively high power conversion efficiency may enable source 12 to generate electromagnetic radiation that is effective in ablating soft tissue while being powered only from a standard wall outlet via power assembly 16 . this may facilitate the implementation of system 10 for soft tissue ablation in a variety of treatment settings where more substantial power supplies may not be readily available ( e . g ., in a hospital , a doctors office , a patients home , etc .). as another example of an enhancement provided by the use of fiber laser oscillator 38 , source 12 may not dissipate as much energy in the form of heat . in other systems used for soft tissue ablation that employ a more standard oscillating medium , the amount of heat produced as a bi - product may require an extensive cooling system to ensure that theses systems are not damaged by the dissipated heat ( e . g ., they may require liquid cooling and / or a secondary cooling loop ). the implementation of fiber laser oscillator 38 in system 10 may enable cooling assembly 18 to keep the various components of system 10 at safe operating temperatures without employing a liquid cooling system and / or a secondary cooling loop . this may reduce the overall size and weight of system 10 , and therefore make the use of system 10 more convenient . fiber laser oscillator 38 may include a yb - doped fiber , or other types of fiber laser oscillators , as the oscillator . the electromagnetic radiation emitted by fiber laser oscillator 38 may be near infrared . for example , the electromagnetic radiation may have a wavelength of between about 1000 nm to about 1100 nm . in some instance , fiber laser oscillator 38 may include one or more diffractive elements that narrow the linewidth of the emitted electromagnetic radiation . the linewidth of the electromagnetic radiation may be narrowed by the one or more diffractive elements to about 1080 nm . in one implementation , the one or more diffractive elements may include one or more bragg gratings . isolator 40 may be located between fiber laser oscillator 38 and amplitude modulator 42 . isolator 40 may protect fiber laser oscillator 38 from undesired feedback . amplitude modulator 42 may include a high frequency acousto - optical modulator and may be controlled by an amplitude modulator driver executed by generation module 28 ( shown in fig1 ). as was mentioned above , amplitude modulator 42 may chop a beam of electromagnetic radiation received from fiber laser oscillator 38 into a train of pulses of electromagnetic radiation . the train of pulses may form a quasi - continuous wave beam of electromagnetic radiation that may eventually be delivered to the patient by output assembly 14 . the pulses formed by amplitude modulator 42 may have a predetermined frequency and / or a predetermined pulse width . the predetermined frequency may be between about 0 . 1 khz and about 1000 khz . in one implementation , the predetermined frequency may be between about 5 khz and about 100 khz . the predetermined pulse width may be between about 0 . 1 ns and about 100 ns . in one implementation , the predetermined pulse width may be between less than about 30 ns . due in part to the predetermined frequency and / or predetermine pulse width , in combination with subsequent processing of the electromagnetic radiation in the pulses ( e . g ., by amplification assembly 24 and wavelength adjustment assembly 26 ), the electromagnetic radiation in the pulses may eventually be delivered to the patient with a predetermined pulse fluence and / or a predetermined peak power . in some instances , the predetermined pulse fluence may be between about 250 mj / cm 2 and 1000 mj / cm 2 . in some implementations , the predetermined peak power may be between about 50 kw and about 100 kw . turning to fig3 , amplification module 24 is illustrated , according to one or more implementations . as can be seen , amplification module 24 may form a multi - stage amplifier system . the multi - stage amplifier system may include a first amplifier 44 , an isolator 46 , a second amplifier 48 , and / or other components . first amplifier 44 may receive electromagnetic radiation at the fundamental wavelength and the fundamental power from source generation assembly 22 , and may amplify the power of the received electromagnetic radiation . second amplifier 48 may be optically coupled to first amplifier 44 , via isolator 46 , to receive the electromagnetic radiation amplified by first amplifier 44 . second amplifier 48 may amplify the power of the received electromagnetic radiation . in some instances ( not shown ), the multi - stage amplifier system may include more ( e . g ., three or more ) amplifiers than the amount shown in fig3 . in other instances , amplification module 24 may include only a single amplification stage . isolator 46 may be located between first amplifier 44 and second amplifier 46 . isolator 46 may protect first amplifier 44 from undesired feedback . in some implementations of the invention , first and second amplifiers 44 and 48 may be formed as high - power , high - gain fiber amplifiers . in these implementations , amplifiers 44 and 48 may include large core yb - doped fiber amplifiers . first and second amplifiers 44 and 48 may be controlled by a corresponding driver or drivers executed by amplification module 30 ( as shown in fig1 ) to provide the electromagnetic radiation received from generation assembly 24 with a predetermined gain . the use of amplification assembly 24 in conjunction with generation assembly 22 may further enhance the power conversion efficiency of system 10 in providing electromagnetic radiation to output assembly 14 . in some implementations , system 10 may convert the input power used by power assembly 16 to power system 10 to optical power output to the patient via output assembly 14 with an efficiency of greater than about 6 %. in some of these implementations , the input power may be converted with an efficiency of between about 8 % and about 14 %. fig4 illustrates wavelength adjustment assembly 26 , in accordance with one or more implementations . in the implementation ( s ) of fig4 , wavelength adjustment assembly 26 may include a refractive optical element 50 and a pair of crystals 52 . refractive optical element 50 may include a focusing lens that may concentrate electromagnetic radiation received by wavelength adjustment assembly 26 onto crystals 52 . crystals 52 may adjust the wavelength of the received electromagnetic radiation . wavelength adjustment assembly 26 may act as a second harmonics generator by receiving electromagnetic radiation from amplification assembly 24 and adjusting the wavelength of the received electromagnetic radiation from the fundamental wavelength to the output wavelength . in some instances , wavelength adjustment assembly 26 may effectively half the wavelength ( e . g ., double the frequency ) of the received electromagnetic radiation . crystals 52 may include nonlinear crystals arranged in a cascading configuration . crystals 52 may be replaced by a single crystal , provided the single crystal is made long enough . crystals 52 may be composed of a nonlinear material such as ktp or lbo . lbo may be more resistant to heat , and thus may be more compatible with use in wavelength adjustment assembly 26 . turning to fig5 , an illustration of one or more alternate implementations of wavelength adjustment module 26 is shown . in the implementation ( s ) of fig5 , wavelength adjustment module 26 may perform substantially the same function as the implementation ( s ) described above with respect to fig4 . however , in the implementation ( s ) of fig5 , wavelength module 26 may include collimating optics 54 , a crystal array 56 , and / or other components . collimating optics 54 may include a positive lens 58 and a negative lens 60 . collimating optics 54 may down collimate electromagnetic radiation received from amplification assembly 24 . down collimating the electromagnetic radiation may enable the beam size of the electromagnetic radiation to be reduced . this reduction in beam size may enhance the efficiency of adjustment of the wavelength . crystal array 56 may include a block array of a plurality of individual crystals 58 . in some implementations , crystal array 56 may include three or more crystals . the crystals may be phase matched . for instance , the crystals may be type i or type ii phase matched . the optical surfaces of the crystals may be coated with an anti - reflection coating for one or both of infrared and visible electromagnetic radiation . in some implementations , the phase matched crystals in crystal array 56 may be mechanically and / or temperature tuned to meet the phase matching condition for the linewidth of the electromagnetic radiation emitted by fiber laser oscillator 38 to enhance the adjustment of the wavelength of the electromagnetic radiation ( e . g ., frequency doubling from near infrared to green ). in some instances , this tuning may be monitored and controlled by temperature tuning module 34 ( as shown in fig1 ). the conversion efficiency of wavelength adjustment module 26 , due at least in part to the temperature and / or mechanical tuning of the crystals in crystal array 56 , may be greater than about 50 %. other embodiments , uses and advantages of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein . the specification should be considered exemplary only , and the scope of the invention is accordingly intended to be limited only by the following claims .

US-45482806-A

an airless applicator may deliver high / low viscosity liquids or semi - liquids , and contains a valve controlling flow between a product reservoir and an intermediate pooling area , while a narrow opening between the intermediate pooling area and a product dispensing chamber controls flow therebetween . this arrangement prevents backflow to the product reservoir , precluding an influx of contamination therein . product delivery is by specially adapted applicator heads . in one embodiment , a plurality of prongs , and openings into the product dispensing chamber , permit application of mascara onto eyelashes . alternating prong heights increases effectiveness in applying mascara onto all sides of a user &# 39 ; s lashes . other applicator heads are configured for lip product applications such as for lipstick , and for eye products such as eyeliner and eye shadow . an air - tight sealing cap having a spring biased inner cap member may prevent moisture from escaping from the product dispensing chamber and prevent entry of contaminants therein .

fig1 shows a first embodiment of the present invention , which includes an applicator device 10 with a cap 11 . assembly of the applicator device 10 is shown in the cross - sectional view of fig3 , and is broken down into its component parts — a body 17 and an applicator head 14 — as seen in fig4 . the invention disclosed herein provides for various embodiments of the applicator head that may assemble into the body 17 in one of several ways to provide for careful dispensing of amounts of product to be delivered onto discrete surfaces of an object , or to provide for more generous delivery of a product onto a receiving surface , but while still be permitting deliberation with respect to where the product is applied . the invention also includes multiple product pooling areas to resist the spread of contaminants into the primary product pool , as well as a spring - biased dual cap that also serves to prevent the entry therein of contaminants , when secured onto the applicator , as well as serving to prevent the loss of essential moisture and oils from the product . the body 17 ( fig3 and 4 ) may generally be comprised of cylinder 60 that rotatably receives a handle 70 so that the handle is free to rotate relative to the cylinder . as seen in fig3 , a cylindrical portion of the handle 70 may be received within cylinder 60 and thereby be able to rotate , and may be retained therein by use of an annular protrusion 71 on the handle 70 being received by an annular recess 63 on the cylinder 60 . the handle 70 may be threadably coupled to a piston rod 80 , so that rotation of the handle causes the piston rod to advance within the cylinder 60 . the piston rod 80 may engage and drive a piston 90 , which may be slidably disposed within the cylinder , to advance the piston therein . installation of applicator head 14 into body 17 forms a product reservoir 101 , between the piston 90 and generally the end or bottom of the head 40 , and advancement of the piston may cause the enclosed volume of the reservoir to decrease , forcing product to be pumped therefrom . the applicator head 14 may be installed into the body 17 through one of several different mechanical means . in one embodiment , the applicator head 14 may be installed into , and retained within , body 17 by use of a friction fit . in another embodiment , the applicator head 14 may be threadably installed into body 17 by use of internal threading on the cylinder &# 39 ; s upper internal surface 61 , and use of external threading on the tubular extension 31 of the applicator head 14 . in yet another embodiment , shown in fig5 and 6 , the applicator head 14 may be snapped into cylinder 60 of the body 17 . the snap - in arrangement may be accommodated by having one or more annular protrusions 32 on the tubular extension 31 of the applicator head 14 , and corresponding annular indentations or recesses on the cylinder &# 39 ; s upper internal surface 61 . alternatively , the indentations may be formed on the applicator head 14 , while the annular protrusions are formed on the cylinder &# 39 ; s upper internal surface 61 . any of these installation means for the applicator head 14 may be adapted to permit removal of the head and allow interchangeability of one applicator head in favor of another applicator head . alternatively , the applicator head 14 may be securely and permanently attached to the body 17 , which may better act to preserve the integrity of the product contained therein , by reducing or eliminating the possibility of contaminants being introduced into the product supply , and by better serving to retain moisture and essential oils therein . the applicator head 14 of the current invention may comprise a tubular extension 31 originating from an annular pedestal 30 ( fig8 ). the pedestal 30 may overhang the tubular extension 31 so as to form a shoulder 33 . installation of the applicator head 14 may occur with the tubular extension 31 being mated with the cylinder &# 39 ; s upper internal surface 61 ( fig4 ) until shoulder 33 of the applicator head 14 reaches the end wall 62 of cylinder 60 . an o - ring seal may be accommodated at the meeting of shoulder 33 and end wall 62 of cylinder 60 , or may be accommodated where tubular extension 31 mates with the cylinder &# 39 ; s upper internal surface 61 . extending upward from pedestal 30 may be a v - shaped neck 34 . the v - shaped neck 34 and tubular extension 31 may be formed as a single housing , or may be separately formed and then be mated together using male and female connectors 18 and 19 on respective parts ( fig8 ). pedestal 30 may be integral to either the v - shaped neck 34 of tubular extension 31 . the tubular extension 31 may include a cylindrical opening 38 beginning on the bottom surface 40 — a first end of the housing — and may interconnect with an opening at a second end of the housing to form a conduit . where the cylindrical opening 38 begins on surface 40 , there may also be a counter - sunk opening 37 to transition between the cylindrical opening 38 and the flat surface 40 . inserted into cylindrical opening 38 to occupy at least a portion of the conduit may be a valve cylinder 41 . the portion of the conduit beyond the valve cylinder may comprise a product dispensing chamber 102 . where the cylindrical opening 38 transitions into the product dispensing chamber 102 , within the v - shaped neck 34 , a lip 39 may be formed to retain the valve cylinder . valve cylinder 41 being installed therein may generally comprise a cylindrical outer wall 43 having a first end 44 and a second end 47 ( fig9 ). the first end 44 may have a tapered surface 45 between the cylindrical outer wall 43 and the first end 44 . the first end may also have an opening 46 into an inner wall 49 , which may be parallel to the outer wall 43 and taper 45 . the inner wall 49 may transition to a second inner wall 49 a having a greater diameter than inner wall 49 , and create a first lip 42 . an opening 48 in the second end 47 may create a second lip 50 at the second end 47 of the valve cylinder 41 . the valve cylinder 41 may be inserted into the cylindrical opening 38 of tubular extension 31 as seen in fig8 , which may interconnect to at least one opening at a second end of the housing to form a conduit . the first end 48 of the valve cylinder 41 may be flush with the end 39 of cylindrical opening 38 . the external diameter of outer wall 43 and the internal diameter of cylindrical opening 38 may be sized so as to be engaged in an interference fit ( friction fit ) rather than a clearance fit , whereby the valve cylinder 41 may be inserted through either a press - fit installation process or a cryogenic installation process . the interference fit would serve to positively retain the valve cylinder 41 within the cylindrical opening 38 . within the valve cylinder 41 may be cylindrical member 54 , having a first end 55 , a second end 56 , an outer wall 57 , and an inner wall 58 . the cylindrical member 54 may be positioned within the valve cylinder 41 between the first lip 42 and second lip 50 . a blocking member , which may for example be a cylindrical piston , is preferably a spherical valve ball 51 being disposed within the valve cylinder 41 , as seen in fig8 , and may be biased by a helical compression spring 52 to normally block the opening 46 of the valve cylinder 41 . the ball 51 may selectively block or close off the flow of product through the valve cylinder 41 , so that valve cylinder product pool 103 may operate as an intermediate pooling area , to serve in maintaining product integrity within the reservoir 101 . the valve cylinder product pool 103 , being formed by the spherical ball on one end , and the shoulder 50 of valve cylinder 41 on the other end , in conjunction with the selective blocking of the valve cylinder , serves to reduce or eliminate the possibility of such contamination . by twisting the handle 70 , the mechanical connection with the piston rod 80 drives the piston 90 , which in turn forces product contained within the product reservoir 101 against the spherical ball 51 to counter the biasing provided by spring 52 . the product may then flow past the spherical ball 51 into the valve cylinder product pool 103 . the valve arrangement serves to isolate the product within the product reservoir 101 and maintain its integrity , so there can be no back - flow of product which could cause contamination by matter acquired from the receiving surface . moreover , the valve arrangement and dual reservoir arrangement of the head ( product dispensing chamber 102 and valve cylinder product pool 103 ) also serves as a barrier to keep air from entering the chamber , and thus serves to maintain product moisture and consistency , and eliminate any entry of air - borne contamination in the form of dust , pet dander , mold , pollen , bacteria , etc . it should be noted that the isolation provided between the product dispensing chamber 102 and valve cylinder product pool 103 may be increased by significantly reducing the size of the opening 48 in the second end 47 of valve cylinder 41 . the size need only be large enough to permit passage therethrough of the cosmetic product , and where the cosmetic product is less viscous , the size may be reduced even further . the v - shaped neck 34 may have a flat face 36 ( a second end of the housing ) that terminates in a tip 35 . protruding from the flat face 36 may be a plurality of prongs 20 . in a first embodiment , the prongs may comprise a conical outer surface 21 which , as seen in fig7 , may protrude outward from the flat face 36 to end in a curved tip 24 . the prongs may be manufactured from any suitable material . material selection may be dictated by the particular application . where the applicator may be used to dispense make - up products such as mascara , the nozzle may be made from materials including , but not limited to a thermo plastic elastomer ( tpe ). with the prongs so constructed , product may be dispensed with a careful turn of the handle 70 . the threading on the handle 70 and on the piston rod 80 may be of such a pitch and coarseness / fineness to produce the appropriate degree of movement of the piston , to result in a desired amount of product delivery , which may depend upon the viscosity of the product being dispensed . as seen in fig5 and 11 , the conical prongs 20 may surround a single elongated opening 29 in the flat face 36 , or alternatively , the prongs may surround a plurality of smaller openings , such as the openings 29 a , 29 b , 29 c , and 29 d that may be seen in fig5 a for head 14 a . the elongated opening 29 or openings 29 a - 29 d may directly interconnect to the dispensing chamber 102 , which may interconnect with the valve cylinder product pool 103 that may further isolate the product contained therein by increasing the overhang provided by shoulder 50 so that opening 48 is reduced in size to tend to prohibit product from re - circulating back through the opening . the length and width of each of the one or more openings 29 or openings 29 a , 29 b , 29 c , and 29 d may vary to produce a smaller or larger opening surface area depending upon the type of product being dispensed , and its particular viscosity , as well as a desired flow rate . the shape of the openings also need not be rectangular to be characterized by length and width , and may instead be circular , elliptical , or some other shape , even being an irregular shape . also , the total number of prongs may vary , and may be adjusted for a particular application , as well as their location relative to the opening , and the density of prongs for a given area on the flat face 36 may also vary for a particular application , as seen in the applicator head 15 in fig1 . as seen in fig1 - 2 , a cap 11 may be snapped onto the applicator head to protect product contained within the product dispensing chamber applicator against contamination . the snapping of the cap may be through the use of any of the mechanical attachment means discussed previously — receiving the cap onto the head in a friction fit ; or snapping the cap onto the head using an annular protrusion being received in an annular recess ; or a threaded connection . additionally , as seen in fig1 a - 2a , a cap 11 a may be threadably received onto the applicator head , to provide an air - tight seal . also , the caps 11 or 11 a may comprise an insert , where the insert serves to wipe the prongs during placement and / or removal of the cap from said applicator head . in yet another embodiment , seen in fig1 c , there may preferably be an alternating series of longer and shorter prongs , 20 l and 20 s , that extend away from the flat surface 36 , and which serve to aid a user in applying the mascara , by permitting the longer prongs to initially contact and deflect a portion of the user &# 39 ; s lashes , while the adjacent shorter prongs 20 s follow and serve to better apply mascara to the inside surfaces of the exposed lashes , which may be a portion of the lash that is generally more difficult to reach . the difference in height of the prongs may preferably be at least 0 . 030 inches to permit the longer prongs to contact one or more lashes and cause deflection before the shorter prongs contact the un - deflected lashes . the height difference may preferably be not much more than 0 . 060 inches , otherwise the amount of displacement of the longer prongs 20 l may be such that some of the deflected lashes may spring back to their initial position . there may be at least a single row of the alternating series of prongs disposed about each side of a plurality of openings 29 a - 29 e ( in the case of five openings , as seen in fig1 c ), or there may be , as seen in fig5 a , two or more rows of prongs disposed about each side of the plurality of openings . a long prong 20 l may also be disposed between openings 29 a and 29 b , between 29 b and 29 c , and between openings 29 c and 29 d . also in this embodiment , a screw - on cap may also be used , and which contains an insert 12 that may be made of a flexible material that has a flange 13 that extends at least part - way across the opening of the cap , and thereby serves to wipe the prongs , during placement on and / or removal of the cap from , the applicator head . this prevents agglomeration and drying of mascara product upon the prongs , which would tend to degrade the fidelity with which the applicator may be used to apply mascara onto a person &# 39 ; s lashes . while any excess product transferred to the insert may agglomerate thereon , such agglomeration would not serve to degrade application of product onto the user . as seen in fig1 - 18 , other embodiments of the head may be used , and may be specifically tailored for the application of different cosmetic products and other types of products , and may be used for the application of oral products ( e . g ., teeth whitener ), eye products ( e . g ., eye shadow , eye liner ), lip products , nail products , etc . the applicator head 114 is shown enlarged in fig1 a and may comprise , instead of the v - shaped neck 34 , a hollow outer cylinder 119 a that extends from the annular pedestal 30 to serve as a protective housing . a hollow inner cylinder 114 b may extend to be concentric with the opening 48 in the second end of valve cylinder 41 , and may serve to conduct product away from the valve cylinder product pool 103 . a hollow cylinder 114 c may be larger than and concentric with the inner cylinder 114 b , and may extend further than cylinder 114 b , to serve in the application of the product . the applicator head 214 , which is shown enlarged in fig1 b , may similarly be installed into the body 17 , but may have an application member being particularly constructed for applications requiring or preferring use of a generally flat dispensing surface to apply the products . the applicator head 214 may comprise the same valve components as the applicator head 14 , including the valve cylinder 41 , spherical valve ball 51 , helical compression spring 52 , etc . however , the product dispensing chamber 102 may be generally cylindrical , and may have a tapered region 105 into a neck region 106 , that may open into a dispensing surface supply pool 107 . the second end of the head may also have a generally flat face 36 , which may serve in the application of the lip product . the flat surface 36 may have one or more small openings 108 that interconnect with the dispensing surface supply pool 107 . by twisting the handle 70 , lip product may pass from the reservoir 101 , past the spherical valve ball 52 , through the valve cylinder 41 , and through the product dispensing chamber 102 and dispensing surface supply pool 107 to be deposited out from a plurality of openings 108 onto the flat surface 36 for application onto a user &# 39 ; s lips . the plurality of openings 108 may be distributed evenly about the flat surface 36 . in a variation of this embodiment , the exposed portion of the applicator head 214 may comprise a felt surface , or at least the flat surface 36 may comprise a felt surface for an even and streak - free application of product . a different arrangement is offered by head 314 , which is shown in fig1 , and which may be usable for applying cosmetic products along a narrow path , such as , for example , eyeliner . the head 314 may have a conical housing 314 c , and instead of a flat application surface 36 , it may also have a wedge - shaped , or conical application member 36 t . the tapered application member 36 t may be disposed directly over the product dispensing chamber 102 so as to block the free flow of product therefrom . however , the material of the tapered application member 36 t may comprise properties such that it may be capable of being permeated by the product , which may be a liquid or a semi - liquid , to supply the tip with product for application in a desired location . the material of the tapered application member 36 t may comprise felt . fig1 a , 16 a , 17 a , and 18 a also show another cap embodiment 111 being secured upon each of the applicator heads that were shown in fig1 - 18 . cap 111 , which is shown by itself and enlarged in fig2 , may comprise an outer cap member 120 , an inner cap support member 121 , a helical spring 122 , and an inner cap 123 . the outer cap member 120 may receive an assembly of the other cap components as follows . the inner cap member 123 may comprise a shaft portion 123 s , at the end of which may be a stop in the form of an integral retaining head 123 r . the helical spring 122 may be slid onto the shaft portion 123 s of the inner cap 123 , after which the shaft portion 123 s may be inserted through a hole in the inner cap support member 121 , by press / shrink fit installing the integral retaining head 123 r through the hole , as the integral retaining head may be hat - shaped to prevent its returning back through the hole . that assembly of cap components may then be installed within the outer cap member 120 , and be secured therein using any suitable means known in the art , including , but not limited to , using adhesive , and / or mechanical fasteners such as rivets , screws , etc . also , it may be recognized that the outer cap member 120 and the inner cap support member 121 may be formed as a single part , particularly where it is made using a plastic injection molding process or as a cast part . the inner cap 121 , when being secured upon one of the applicator heads seen in fig1 - 18 , may thus have a bottom surface 123 b be spring biased into contact with a sill portion 30 s of the annular pedestal 30 . the cap 111 may be secured to the applicator by a securing means 125 that may include threadably receiving the cap onto the applicator head , by the use of corresponding internal and external threading on the cap and applicator . alternatively , the securing means may comprise receiving the cap onto the head in a friction fit ; or snapping the cap onto the head using an annular protrusion or lip on one applicator part , and an annular recess on the corresponding applicator part . an alternate embodiment of cap 111 is shown by the illustration of cap 211 in fig1 . an outer cap 220 with outer surface 220 t may be open at a first end 226 exposing an interior surface 220 i , and may be closed at a second end 227 . the open first end 226 may receive the other components therein . the inner cap support member 221 with outer surface 221 t may be open at a first end 226 exposing an interior surface 221 i , and may be generally closed at a second end 228 . the second end 228 of the inner cap support member 221 may be formed to have a flat wall with an orifice therein . the inner cap 223 may comprise a cap portion and a shaft portion . the cap portion may be open at a first end 229 and be generally closed at a second end 230 . the shaft portion may have a first end being fixed to and extending out from the second end 230 of the cap portion , and the second end of the shaft portion may comprise a hat - shaped stop member , which may be integral , or may be mechanically attached onto the shaft ( swaged , etc ). with the helical spring 222 being received over the shaft portion of the inner cap 223 , the combination spring and inner cap may be received through the open end 226 of the cap support member 221 , with the shaft portion being slidable received through the orifice of the cap support member . the spring may thereby bear against the wall of the cap support member 221 , and against the second end 230 of the cap portion of the inner cap 223 . the stop 223 r may thereafter serve to limit the outward biased travel of the inner cap 223 back towards the open end 226 of the cap support member . the cap support member 221 with the inner cap 223 and helical spring 222 assembled together , may then be received through the open end 226 of the outer cap 220 . the shape of the outer cap member 220 may comprise and elongated contoured cavity 220 c , which may provide added space so that a force may counter the biasing of the spring to move the shaft portion of the inner cap , as described in the following sections , into the cavity . the shape of the inner cap 221 may also be contoured so as to have a flared section 223 f proximate to first end 228 , which may also have an annular protrusion or lip at a convex portion of the flared contouring ( see fig2 ). installation of cap 211 may be upon an applicator head , as seen in fig2 - 22 , where the applicator head housing may be conical such as for applicator head 314 , and where the shape of the inner cap 223 may have corresponding contouring . as seen in fig2 , as the airtight sealing cap 211 is concentrically translated onto the applicator head 314 , the convex surface of the inner cap member 223 at the flare 223 f contacts a portion of the conical surface 314 c of the applicator head 314 , and the spring biases the inner cap member into airtight contact with the applicator head . the outer cap portion may continue its translation until a securing means 225 on the cap support member 221 is secured to a corresponding securing means 225 a on the applicator head 314 . the helical spring 222 biasing the inner cap 223 into the tapered applicator head housing may cause slight elastic deformation of the annular periphery of the inner cap member , which may be manufactured in a thin enough section to accommodate such deformation by the spring 222 . this may result in the applicator head better receiving the cap 211 in an air - tight seal , as the elastic deformation may serve to overcome any slight deviations due to manufacturing tolerances , etc ., in either the shape of the cap or the applicator head , which may otherwise permit air passage therebetween . a small annular recess 314 r may also be provided in the conical applicator head 314 for receiving a small corresponding annular protrusion 223 p at the convex portion of the inner cap 223 , which may also serve in the airtight sealing , by limiting relative movement , at a certain point , between the inner cap 223 and the conical surface 314 c , so that the continued translation thereafter ( once the minor deformation is completed ) and corresponding increased biasing force ( based upon the spring formula f = kx ) then serves to apply a greater contact force between the two parts to encourage better sealing therebetween . the examples and descriptions provided merely illustrate a preferred embodiment of the present invention . those skilled in the art and having the benefit of the present disclosure will appreciate that further embodiments may be implemented with various changes within the scope of the present invention . other modifications , substitutions , omissions and changes may be made in the design , size , materials used or proportions , operating conditions , assembly sequence , or arrangement or positioning of elements and members of the preferred embodiment without departing from the spirit of this invention as described in the following claims .

US-201414323178-A

a cushioned horseshoe with a lightweight , metal plate and a unitary resilient tread bonded to the entire adjacent surface of the plate and molded to form a raised toe calk , cushioned raised heel calks and raised , self - cleaning traction cleats disposed on a unitary resilient base . the shoe is designed for use on turf , fast track or mud track and for use on any one of the horse &# 39 ; s hooves . cushioning is provided directly to the critical heel area of the hoof by providing heel cushion holes in the heel areas of the plate to permit the heel calks to project through the plate and to resiliently engage the horse &# 39 ; s hoof while still maintaining a rigid contact between the remainder of the hoof and the plate to permit the plate to be securely nailed to the hoof .

referring now to fig1 there is shown an exploded view of the horseshoe of the present invention including an aluminum plate 10 , an optional metal toe piece 20 and a tread 30 . one surface of plate 10 , the tread bearing surface , is bonded to tread 30 , and the other surface of plate 10 , the hoof engaging surface , abuts the hard outer surface of the horse &# 39 ; s hoof . plate 10 is made of lightweight flexible metal which is hard but not brittle and which can be cold forged to allow the finished horseshoe to be custom fitted to the horse &# 39 ; s hoof and which is sufficiently flexible to accommodate the natural deformation of a horse &# 39 ; s hoof . we prefer to use commercially available hardened aluminum alloy like 2014 t - 3 or 2024 t - 3 but other materials like magnesium could also be used . plate 10 has a uniform thickness of between 0 . 156 inch to 0 . 160 inch . this thickness is about half of that used for previous aluminum plate shoes . plate 10 has three heel cushion holes 12 centered on each heel portion of plate 10 . plate 10 has a uniform width of about 19 / 32 of an inch . heel cushion holes 12 are about 7 / 32 of an inch in diameter . heel cushion holes 12 are countersunk from both surfaces of plate 10 to eliminate sharp edges . plate 10 has a plurality of generally rectangular conventional nail holes 14 having a length of approximately 5 / 32 of an inch and a width of approximately 3 / 32 of an inch . size 4 , size 4 1 / 2 and size 5 shoes may have three nail holes on each side of the shoe . size 6 , size 7 and size 8 shoes may have four nail holes on each side of the shoe . the inside edge of plate 10 adjacent the surface on which the tread will be placed , i . e ., the tread bearing surface , has a concave bevel 16 having a radius of about 3 / 16 of an inch and an arc of about 25 degrees . bevel 16 helps disburse the impact forces experienced by plate 10 when the horse &# 39 ; s hoof hits the ground about the entire toe area of plate 10 . without bevel 16 , the impact forces would tend to localize at a single point so that plate 10 would tend to break in the toe area . edge 18 of the heel portions of plate 10 are radiused to approximately 0 . 015 inch from the tip of the heel extending back to at least past the third heel cushion hole on both surfaces of both heels . radius 18 prevents the rubber tread in this area from being cut during impact and also removes sharp edges from the shoe in order to minimize the possibility that the shoe on one foot will clip and cut the adjacent leg of the horse . an optional metal toe piece 20 having a plurality of downwardly extending fingers 22 may be used . in the preferred embodiment there are two sets of three such fingers 22 , each set offset an equal distance from the vertical center plane of toe piece 20 . toe piece 20 is bent to match the contour of the horseshoe in the toe area , i . e ., about 30 ° to 35 °. toe piece 20 is punched through the central portion of plate 10 so that fingers 22 protrude through a predetermined distance . the protruding end of each finger 22 is then slotted and flattened to hold toe piece 20 securely to plate 10 and then sanded to provide a smooth surface to the bottom of the horse &# 39 ; s hoof so as to minimize irritation in this area . we prefer steel toe pieces although other hard metals may be used . a strip of resilient material having a width equal to the width of plate 10 is bonded to plate 10 and molded into tread 30 . we prefer high quality natural rubber tread material of a quality used to retread motor vehicle tires . the tread must be strong enough to withstand the severe forces , especially shearing forces , experienced during running and to withstand the associated thermal stresses generated within the tread . we have found that orco plus retread rubber sold by oliver tire and rubber company of oakland , california and flemmington , new jersey is satisfactory . referring now to fig2 there is shown a completed horseshoe which includes the optional metal toe piece 20 . the rubber tread 30 includes a base portion 28 bonded to the entire tread bearing surface of plate 10 which supports a raised toe calk 32 formed completely about toe piece 20 , three spaced apart raised traction cleats 34 on each side of the toe piece 20 and one raised large rubber heel calk 36 on each heel . the base has a significant thickness in the area 38 intervening between the raised toe calk 32 and raised cleats 34 and heel calks 36 . this provides better bonding of the tread to plate 10 and cures the significant disadvantage of the prior art wherein individual cleats may be jarred loose from the plate during running . molded tread 30 is countersunk in the area surrounding nail holes 14 so that the nail head may tightly and rigidly engage plate 10 in the area immediately surrounding nail holes 14 . countersinking the rubber around nail holes 14 in this way prevents the nail from vibrating loose as the rubber tread flexes while the horse is running . cleats 34 and heel calks 36 each project the same distance from the tread bearing surface of plate 10 . the surface of the cleats 34 and heel calks 36 that engages the running surface is aligned generally parallel to the tread bearing surface of plate 10 . toe piece 20 projects from the tread bearing surface of plate 10 a greater distance than cleats 34 and heel calks 36 so that when the horse is standing on the running surface cleats 34 and heel calks 36 touch the surface and toe piece 20 digs in to the surface . when optional toe piece 20 is used , toe calk 32 projects from the tread bearing surface of plate 10 a lesser distance than cleats 34 or heel calks 36 so that when the horse is standing toe calk 32 clears the running surface . in the embodiment which omits metal toe piece 20 , toe calk 32 is molded to project from the tread bearing surface of plate 10 a distance equal to that of cleats 34 and heel calk 36 . it can be seen that the walls of each cleat 34 are not vertical but are disposed at an angle to the tread bearing surface of plate 10 and that lateral walls 40 and 42 slant toward each other in a direction away from plate 10 . also transverse walls 44 and 46 slant toward each other in a direction away from plate 10 . thus , the space between adjacent cleats 34 is wider at the tip of the cleats than at the base of the cleats . this feature makes the cleat self - cleaning so that dirt , turf or mud will tend to be thrown free of the tread while the horse is running . heel calks 36 and toe calk 32 ( in the embodiment which omits toe piece 20 ) have similarly slanting walls . it can be seen in fig3 and 5 that the rubber projections of heel calks 36 project through the heel cushion holes 12 and plate 10 to provide additional cushioning to the horse &# 39 ; s hoof in the critical heel area of a thickness equal to the entire thickness of the tread plus the thickness of plate 10 . in the partially broken away side view of the heel portions of the completed horseshoe , shown in fig3 it is evident that in addition to providing increased cushioning in the heel area , the rubber projections 48 of heel calk 36 help hold heel calk 36 onto the plate 10 so that it is less apt to be jarred loose during running . the countersinking on the hoof engaging surface of plate 10 provides a cavity into which projections 48 are molded to form a flange 50 to provide additional holding power for heel calk 36 and tread 30 . in fig3 it is also evident that the trailing edge 52 of heel calk 36 extends down around the edges of the heel portions of plate 10 so as to limit the amount of metal showing in this area and to help minimize the danger of the shoe clipping the adjacent leg of the horse during running . in fig4 it is shown that rubber tread 30 is molded into concave bevel 16 in the toe area to provide added thickness and to enhance cushioning . it can be seen that the cushioned horseshoe of the present invention provides a horseshoe which is adaptable to turf , fast track or mud racing . providing a significant thickness of rubber about the entire working surface of the horseshoe provides better bonding for the tread and minimizes the possibility of individual cleats being jarred loose during running . providing a heel cushion which projects through plate 10 in the critical area of the heel provides added protection and comfort for the horse &# 39 ; s hoof while maintaining a secure contact between the hoof and the shoe . it will be understood that the particular horseshoe illustrated in this preferred embodiment is susceptible of considerable modification without departing from the inventive concept herein disclosed . consequently , it is not intended that this invention shall be limited to the precise detail disclosed but only as set forth in the following claims .

US-74347976-A

a rounding apparatus for rounding dough pieces comprises a conveyer having a surface for supporting thereon and transporting dough pieces ; and a plurality of rounder bars any one of which is selectively brought into contact with the surface of the conveyor to engage with the dough pieces conveyed by the conveyor thereby rotating the dough pieces on the surface of the conveyor to round the dough pieces .

the best mode for implementing a rounding apparatus according to the present invention is described below , with reference to the drawings . the present mode will be described using an example of a rounding apparatus provided with two stages of rounder bars 1 . shown in fig1 and 2 , respectively , are simplified plan and side views of the entire rounding apparatus . a dividing apparatus 100 , at the left side of the drawing , continuously supplies dough pieces containing a set amount of dough to a rounding apparatus a . that is , dough brought into the system from above through a hopper 101 is pressed out horizontally through a collar , using a screw . as the dough is pressed out , it is divided into individual dough pieces , each containing a prescribed amount of dough , by a cutter 102 rotating at a given cycle period . dough pieces divided in this manner are supplied to a rounding apparatus positioned downstream of the dividing apparatus . the rounding apparatus a has a conveyer 6 for moving dough thereon , and rounder bars 1 for gradually rounding the dough . the conveyer 6 and rounder bars 1 are installed on a main frame 3 of the rounding apparatus a . provided at the bottom of the main frame 3 are casters 7 for enabling the entire rounding apparatus a to be moved . the rounder bars 1 are placed in contact with the conveyer 6 in the direction of motion thereof . as shown in these drawings , a first stage rounder bar 1 ( v ) is provided at the first half of the conveyer . this first stage rounder bar 1 is followed by a second stage rounder bar 1 ( w ) placed downstream thereof . the first stage rounder bar 1 ( v ) is generally aligned with the direction of travel of the conveyer 6 , but inclined at an angle thereto ( slanting from the right side of the conveyer toward its center , as shown in fig1 ). the second stage rounder bar 1 ( w ) is similarly aligned with the direction of travel of the conveyer 6 , at an incline from the left side of the conveyer toward its center , as shown in fig1 . as mentioned above , the conveyer 6 and rounder bars 1 are installed on the main frame 3 of the rounding apparatus a . this installation of the rounder bars 1 on the conveyer 6 is such that it enables them to be rotated by a switching mechanism to a standby position at a given height of separation over the conveyer 6 , as appropriate . fig5 ( a ) and 5 ( b ) show a switching mechanism for a rounder bar 1 of a rounding apparatus a of the present invention . fig5 ( a ) shows the switching mechanism , and fig5 ( b ) shows the main frame 3 on which the switching mechanism is rotatably supported . fig6 shows the same rounder bars 1 of the rounding apparatus a of the present invention after switching . as will be understood from the drawings , first , the main frame 3 is provided with gate - shaped support members 3 ′ straddling the conveyor 6 in a position traversing the conveyor . each of the support members 3 ′ has a hanger provided on a center horizontal cross member thereof . a rotating member 2 is rotatably supported by the hangers . the rotating member 2 can be removed from the hangers by removing split portions 31 of the hangers . multiple rounder bars 1 can be installed on a rotating member , but in this case there are two : an ‘ in - use ’ rounder bar 1 ( x ); and a ‘ switchable alternate ’ rounder bar 1 ( y ). the switchable alternate rounder bar 1 ( y ) is positioned so that it can be switched onto the conveyer 6 in place of the currently in - use rounder bar 1 ( y ), when required . this will be described in detail later . a bracket 4 is mounted on the rotating member 2 . formed in this bracket 4 is an elongated arc - shaped slot 41 that extends through an arc of 90 degrees . a securing bolt 5 extends through this slot 41 of the bracket 4 and is threadably engaged with the frame . the bracket 4 can be easily secured to the main frame 3 by tightening a handle 51 on this securing bolt 5 . the switchable alternate rounder bar 1 ( y ) and the in - use rounder bar 1 ( x ) are installed on the rotating member 2 to form a right angle therebetween . normally , the in - use rounder bar 1 ( x ) is placed in contact with the conveyer 6 by tightening the securing bolt 5 when it is positioned at one end of the elongated slot 41 ( point p 1 ) as shown in fig5 ( a ). if , from this state , the rotating member 2 is rotated as far as possible in the counter - clockwise direction the securing bolt 5 will then be positioned at the other end of the slot 41 of the bracket 4 ( point p 2 ). this rotation lifts the in - use rounder bar 1 ( x ) above the conveyer 6 , and lowers the switchable alternate rounder bar 1 ( y ) onto the conveyer 6 in its place . now , the securing bolt 5 is tightened , securing the bracket 4 to the main frame 3 , to thus lock the switchable alternate rounder bar 1 ( y ) firmly in position on the conveyer . the cross - sectional shapes of the dough - shaping surfaces 11 of the rounder bars are arc - shaped curves that differ from one rounder bar to another . fig4 ( a ), 4 ( b ) and 4 ( c ) are cross - section views of the rounder bar and show the relationship between the dough - shaping surface 11 of a rounder bar 1 and the dough ( shown in dotted lines ). the example shown here is of a first stage rounder bar in which the dough is being rotated and rounded as it moves along from a to b to c in contact with the dough - shaping surface . first , a divided dough piece d is received ( fig4 ( a )); then , the dough is momentarily pressed downward to consolidate it ( fig4 ( b )); and finally , the dough is urged upward to form the desired spherical shape ( fig4 ( c )). a large number of thin vertical grooves ( anti - slip grooves 16 ) are formed in the dough - shaping surface 11 . the reason for this is that dough , while being in contact with the dough - shaping surface 11 , tends to slip thereon , thereby failing in performing proper rounding function . typical grooves of this kind are shown in fig7 . the first stage rounder bar 1 ( v ) shown here has vertical grooves formed throughout the entire length of the surface . the first half of the second stage rounder bar 1 ( w ) also has the same kind of vertical grooves as the first stage rounder bar 1 ( v ), but its second half has narrow horizontal grooves . although proper dough - rounding action is obtained in the first stage rounder bar 1 ( v ) and the first half of the second stage rounder bar 1 ( w ), the dough - shaping surface 11 leaves undesirable vertical groove marks in the surface of the dough . these groove marks are repaired / removed by the horizontal grooves in the second half ( the groove mark repair section 17 ) of the second stage rounder bar 1 ( w ). note that the rounder bar has a removable bottom edge piece 12 that is separate from the main rounder bar unit . fig3 shows a side view of a rounder bar , and fig4 ( a ), 4 ( b ) and 4 ( c ) show cross - sectional views of the same rounder bar at sections a — a , b — b , and c — c of fig3 . as can be seen from these drawings , a blade - shaped bottom edge piece 12 is supported in the main unit of the rounder bar by spring pressure in such a manner that the bottom edge piece 12 is urged against the conveyor under pressure applied by springs 13 through pins 14 . the bottom edge piece 12 is attached to the rounder bar main unit by fastening bolts 15 such as to limit the downward travel of the bottom edge piece 12 to a set length . when the rounder bar is set on the conveyer 6 , its bottom edge piece 12 receives constant spring pressure urging it against the surface of the conveyer 6 . the reason the rounder bar must be kept in firm contact with the conveyer 6 is that if a gap were allowed to exist at this point , dough would get caught in the gap and be damaged . the disadvantage of this is that constant contact between the rounder bar 1 and the surface of the conveyer 6 results in friction that quickly wears down the tip of the bottom edge piece 12 , and when this wear becomes excessive , it requires replacement . in the rounder bar of the present invention , however , when replacement becomes necessary , only the bottom edge piece 12 need be replaced ; not the entire rounder bar . this is cost - effective , and the replacement procedure is also quite easy in that it requires only removal of the fastening bolts 15 . next , the operation of the rounding apparatus a for rounding a dough piece d will be described . fig8 is a simplified diagram of this operation . first , a dividing apparatus 100 divides dough into dough pieces d containing a set amount of dough . these divided dough pieces d are continuously supplied to a conveyer 6 of a rounding apparatus a . when thus supplied , the dough pieces d are loaded onto the conveyer in a position corresponding to that of a dough - shaping surface 11 of a rounder bar 1 placed on the conveyer . as they move , the dough pieces d loaded on the conveyer come into contact with the dough - shaping surface 11 of the rounder bar 1 , which causes them to rotate . when this occurs , as the conveyer moves ( from left to right in the drawing ), the dough pieces d move sideways across the conveyer ( from up to down normally on fig8 ). as each dough piece d is thus rotated in contact with the dough - shaping surface 11 of the rounder bar 1 , its surface is gradually rounded until it comes to the end of the first stage rounder bar 1 ( v ), at which point the first stage rounding operation is complete . in this first stage rounder bar 1 ( v ), the dough receives proper rounding action because vertical grooves formed in the dough - forming surface keep the dough from slipping . the dough piece d is now handed off from the first stage rounder bar 1 ( v ) to the second stage rounder bar 1 ( w ). because the dough - shaping surface 11 in this rounder bar 1 ( w ) and the dough - shaping surface 11 of the first stage rounder bar 1 ( v ) face each other along the direction of the conveyor , the transfer of the dough piece d is smooth . the dough piece d then goes on to be rounded by the shaping surface 11 of the second stage rounder bar 1 ( w ). in this stage , as the conveyer 6 moves ( from left to right ) the dough pieces d move sideways across the conveyer ( from down to up normally on fig8 ). in this second stage rounder bar 1 ( w ), in the first half of the dough - shaping surface 11 ( the anti - skid section ), the dough pieces d are rounded without slipping because of the vertical grooves formed therein . in the second half ( the groove mark repair section ), the marks in the dough caused by the vertical grooves of the preceding rounding process are repaired / removed by horizontal grooves 17 formed in this section of the dough - shaping surface 11 . completion of the above process marks the end of the operation to effect proper rounding of the dough pieces . when it is desired to change over to process dough for a different lot , the in - use rounder bar 1 ( x ) is rotated up to a standby position , while at the same time , a switchable alternate rounder bar 1 ( y ) that had been in the raised standby position is rotated down to be placed in contact with the conveyer . although the preferred mode for carrying out the invention was described above , the present invention is not limited to the above mode . a variety of modifications thereto are possible while still remaining within the scope of the stated objectives . for example , although the above example described only first and second stage rounder bars 1 , a third , fourth , or even more stages of rounder bars could be added , depending on the product . also , the number of available switchable alternate rounder bars for each stage needs not be limited to two . the number of switchable alternate rounder bars is limited only by the amount space available on the rotating frame for installing them . also , there are dividing machines that simultaneously output several divided dough pieces from several output opening . rounding apparatus following such dividing machines can be provided with rounder bars arranged in rows , as shown in fig9 ( a ). in addition , although the example described two serial stages of rounder bars , there could be more stages , or there could be only one stage , as shown in fig9 ( b ). according to the present invention as described above , alternate rounder bars can easily be switched into position for use , thus greatly reducing setup time . this makes it possible to quickly support a variety of different lots , for a major improvement in productivity .

US-96741601-A

the invention describes an adaptive , sensory - motor encoder for a visual prosthesis or for an acoustic prosthesis and equipped with a central control unit for signal processing functions , monitoring functions , control functions and external intervention functions as well as with a group of adaptive spatio - temporal filters for the conversion of sensor signals into stimulation impulse sequences , whereby a bi - directional interface is provided for coupling the encoder with an implantable microstructure for stimulation of nerve or glial tissue on the one hand , and on the other hand for function monitoring of brain function .

fig1 shows schematically a visual prosthesis using the example of a retinal implant with an adaptive , sensory - motor encoder with image shifting mounted in an eye glass frame ; a interface , implanted in the eye in proximity to the ganglion cell layer for stimulation and recording as a micro - contact structure ( 2 ) with accessory electronics and a bi - directional , wireless signal and energy transfer system between the encoder and the interface . the individual spatio - temporal filters ( rf filters ) of the encoder with each approximately round cutouts of the photosensor array ( 4 ) in the input layer ( left ) and the related signal outputs in the output layer ( middle ) represent typical receptive field characteristics , for example , of ganglion cells of the primate retina , or of neurons in the visual cortex and are individually adjustable as to function by parameter vectors . the interface receives not only stimulation signals from the encoder but also sends recorded neural impulse signals to the recorder . the components that are additionally associated with the encoder such as , for example , the central control unit or the pre - processing module connected upstream of the rf filters are not shown in fig1 . fig2 shows the layout of the encoder ( 1 ) with dialogue system in a coupling with the central visual system , either as a model ( implementation in a normal - sighted person ), or as an actual system from the level of the implanted micro - contacts up to visual perception ( implementation in the implant carrier ). the angle as exemplar image pattern on the photosensor array ( left ) represents at the same time a desired pattern on the monitor , which moves upwards to the right on the connecting internal image pattern array that is done electronically in the encoder , the angle in the example moves from another starting position in another direction , in order to indicate the function of a technical image shift . the screen to the right shows the appropriate actual image pattern and represents either a second monitor ( normal - sighted person ), or a virtual projection of the visual perception area ( implant carrier ). the elliptical disc moving from upper left to downward right represents the corresponding perceived actual image pattern . the man ( lower right ) articulates his subjective evaluation of the comparison of the desired and actual patterns over a multichannel evaluation input . the dialogue module as neural network with a decision system ( below ) forms the output signals of the evaluation input on a parameter vector for adjustment of the rf filter . with replacement of image , patterns with sound patterns and the visual system with the auditory system fig1 applies correspondingly to the use of encoders for acoustic prostheses . fig3 shows schematically a suitable design form of the encoder with respect to the positioning of a multidimensionally functioning head movement sensor ( k ) above the ear , a multidimensionally functioning eye movement sensor ( a ) and the encoder that has been integrated into an eye glass frame with indicated moved image pattern . a throat collar ( h ) for the production of local tactile sensations , for example by vibration it provides the user with information regarding the location of an object relative to the user . if an object lying in front of him wanders to the left out of the field of vision , then the vibration area produced on the throat also moves to the left , as indicated in fig3 . fig4 shows an illustrated example of micro - contacts ( 6 ) that impinge on nerve tissue ( 8 ). in the present example three micro - contacts ( 16 , 17 , 18 ) are implanted in the nerve tissue ( 8 ) and there positioned more or less randomly close to certain nerve cells . the micro - contact structure ( 6 , 16 , 17 , 18 ) is uniformly essentially coarser than the matrix of the nerve cells ( 8 ). micro - contacts ( 16 , 17 , 18 ) are supplied with signals ( s 1 , s 2 and s 3 ) by way of the stimulator ( 12 ). in order to created targeted neural excitation , a stimulation focus , for example ( f ), must be reached that cannot be directly affected by a micro - contact . the stimulation focus ( f ), however , can be reached if the signals ( s 1 , s 2 , s 3 ) are passed to the electrodes ( 16 , 17 , 18 ) using different strengths , time course and , above all , time spacing . the overlap or superimposition of the signals in the area of the intended stimulation focus ( f ) exceeds the excitation threshold of individual or a few nerve cells , while the addition of the signal flows in the rest of the area of the nervous tissue remain below the excitation threshold . by changing the temporal sequence and of the temporal signal flow of the various signals tuned to each other the stimulation focus ( f ) can also be shifted to ( f ′). for the pre - compensation of these stimulation functions that attain a stimulation focus that is not in direct connection with an electrode , an adaptive process is required . since it is not precisely known which stimulation focus ( f ) an ( f ′) for a particular neural stimulation must be addressed , the adaptive sensory - motor control unit can offer only a particular signal pattern that the implant carrier then assesses by way of a sensory perception or another sensor data evaluation . a second signal pattern that has been changed in comparison to the first one , is then also subsequently assessed as to whether it attains the targeted neural excitation or not . the user needs only say whether the later signal pattern is better or worse than the preceding one . using this control mechanism of a neural network an optimal signal time function for the electrodes ( 16 , 17 , 18 ) for stimulation of the stimulation focus ( f ) is determined in the course of the control process . fig5 shows a scene perceived under practical conditions by the photosensors in which a patio door ( 30 ) is observed from inside a room . the door ( 30 ) exhibits a window ( 31 ), a keyhole ( 32 ) and a door panel ( 33 ). in front of the door dangles a spider ( 34 ) and through the window ( 31 ) a beach scene ( 35 ) is visible . the illumination differences in this scene lie between approximately 10 − 1 cd / m 2 in the area of the door latch to 10 0 cd / m 2 in the area of the spider and 10 1 cd / m 2 in the area of the door panel on up to 10 4 - 10 5 cd / m 2 in the outdoors area . such brightness differences are not simultaneously visible using conventional cameras and otherwise even with the human eye . the brightness adjustment occurs always only in the currently observed area . fig6 shows in diagrammatic form how the pre - processing module of the camera ( 1 ), because of its pattern recognition functions , delimits the individual areas from one another and converts them using different functions in the brightness layers of the camera imaging . on the x - axis the brightness ( i . e ., luminance ) is represented in cd / m 2 over a total of 9 decades , just as they occur in the actual picture in fig5 . the y - axis shows the 256 relative units of the brightness information , as attributed to the image representation by the camera or its pre - processing module , 256 units corresponding to a brightness modulation of 8 bits . an initial brightness curve l 32 shows the area of the brightness of the door latch ( 32 ), illustrated on the 256 relative brightness levels of the camera imaging . corresponding brightness curves l 33 for the door panel ( 33 ), l 34 for the spider ( 34 ) and l 35 for the outdoors area ( 35 ) are likewise illustrated . the pre - processing module recognizes in the detailed imaging different and delimited from one another with sharp contours areas with the four different brightness areas . these areas are constructively separated from one another and each transposed with optimal resolution to the 256 brightness levels of the camera imaging . in the result the scene is shown to the observer as an image in fig5 in which the image areas ( 32 , 33 , 34 ) are illustrated with equal brightness and with the corresponding structuring in the various brightness levels . such an illustration can be unusual but it offers a richness of detail in various regions that can not be simultaneously illustrated with the human eye or with conventional camera systems . the illustration in fig5 also shows objects at various distances . thus , for example , the objects ( 32 , 33 and 34 ) are at a distance of 2 m from the observer , whereas the palm ( 36 ) in the outdoors area ( 35 ) can be at a distance of 40 m . using conventional camera objectives it is generally not possible to simultaneously present both objects ( 34 and 35 ) with the same sharpness . the available definition ranges are inadequate to accomplish this . using the pre - processing module the adaptive sensory - motor encoder can initially put the remote area ( 35 ) into definition and recognize and store the contour - defined delimited regions ( the palm ) there . then a second range ( i . e . distance ) can be selected in which the spider ( 34 ) is set up sharply defined , whereby the area ( 35 ) becomes unsharp i . e . ( blurred ). the pre - processing module can recognize this condition and instead of the blurred region ( 35 ) will incorporate the previously determined and captured sharp image unit constructively into the image focused at short distance . this sequence can be cyclically repeated in a kind of focus scanning so that from different focal distances sharp areas are continuously determined , captured and incorporated into the overall sharp image . the definition that is virtually attainable in this way is many times better than that of a normal optical system . with adequate frequency of reiteration of the process the image produced can be distinguished by the use only by the particular definition . according to the invention an encoder is recommended that optimizes the diverse functions by neural networks in dialogue with the implant carrier , in which various functional modes can be selected and the positions of objects picked up can be used and which warns of obstacles , reports technical recognition of patterns as well as functionally increases the number of selectively addressable stimulation sites and monitors the neural activity of individual neurons . the implanted structure can operate almost with sensory - motor autonomy by using suitable sensory and motor components as well as an adaptive control system . the adaptive encoder is characterized in comparison to the conventional visual prosthesis systems by a number of essential advantages . firstly an encoder is recommended here that is pre - trained by normal - sighted persons and then can be individually adapted by the implant carrier to his functional requirements . for the first time , an encoder is disclosed here that provides eye movement functions as well as compensation of undesired eye movements . furthermore , for the first time an encoder is disclosed that functionally increases the number of selectively reachable stimulation sites and that can later be adapted to new stimulation conditions . further , for the first time an encoder is disclosed , that functions bidirectionally ; thus , along with the stimulation functions it allows also monitoring and evaluation of the neural activity of the neurons to be stimulated . corresponding advantages result with the utilization of the adaptive encoder versus the previously developed auditory prosthesis systems . the adaptability of the imaging functions of the individually adjustable spatio - temporal filters of the encoder using receptive field properties ( rf filters ) in the entire neurophysiological relevant functional range will be assured in conjunction with neural networks or other parameter setting processes when used for visual or acoustic prostheses . the individual imaging functions of the individual rf filters ascertained in perception - based dialogue are sufficiently similar to the receptive field properties expected by the visual system ; thus they adapt to the function of the visual system created by the tandem connection of encoder and coupled central vision system . this means on the one hand that the spatio - temporal function range prepared by the rf filters incorporates the neurophysiologically relevant function range and , on the other hand , that the rf filters permits , with the aid of a neural network , a continuous movement in the function range with suitable adjustment procedures . the same applies with use of the encoder in acoustic prostheses . already in its use in normal - sighted persons a reasonable default setting of the rf filter has been undertaken using corresponding neurophysiological data on the function of the visual system or the auditory systems of primates . in addition , the dialogue process is being tested using the associated components under realistic conditions by stimulation of the perception process . the same applies with use of the encoder in acoustic prostheses . the rf filters associated with the individual micro - contacts are individually tuned to optimal visual or auditory perception quality in the dialogue between the encoder and the implant carrier . in contrast with an encoder with static pre - processing ; that is , one without the opportunity for individual pre - programming , the individual rf filters are adjusted as separate encoder channels on the basis of the single relevant criterion ; namely the visual or auditory perception targeted . subsequent function changes ; for example , as a result of the relocation of micro - contacts , or of changes in the functional parts of the central visual system can be compensated in the entire perception process by appropriate adaptation of the rf filter functions . an advantage of tuning the rf filters function in the dialogue with the implant carrier consists in the consideration of aspects of function that only the implant carrier can bring in and then only in implicit form by subjective evaluation of his visual perceptions and their implementation in encoder adjustment in the optimization process . the same applies to an acoustic prosthesis . the asynchronous impulse sequences of the individual rf filter outputs of the currently functionally separate encoder channels are tuned to one another as stimulation signals for selective stimulation sites in the dialogue with the implant carrier in consideration of the recorded neural impulses . because the temporal coupling or synchronization of the neural impulses of several neurons for neurobiological signal coding in sensory systems is co - employed , this technically ( also by evaluation of the recorded neural activity of neurons to be stimulated ) effected , temporal coupling brings with it the advantage of enhancement of the quality of the visual perception . the number of selectively reachable stimulation sites and their definition ( separation sharpness ) in the case of a fixed number of implanted micro - contacts is functionally increased . with a given relatively small number of implanted and permanently functional micro - contacts , whose position relative to the neurons can not be modified , it is of considerable advantage , functionally speaking ; that is , by production of suitable signals , to increase the number of selectively reachable stimulation sites or neurons and thus at the same time the number of separately accessible encoder channels with a sufficient reserve in rf filters . this effects an improvement of the visual perception quality . the detection of eye and head movements has the advantage of determination of the current position of visual objects in space . furthermore , there is an advantage in that undesired actual eye movements can be compensated by appropriate simulated eye movements and , further , suppress visual perception conflicts such as , for example , apparent movements or vertigo . the production of the individual movement functions as programs that can be selected as separate or combined programs and has the advantage that the implant carrier himself can select the programs depending on his uses for the visual perception quality , instead of being subject to an automatic function . nevertheless the choice can be made between automatic and option operation . it is very important to the implant carrier to be able to perceive the current position of a perceived visual or auditory object in order to be able to accordingly correct his orientation in space and , if necessary , his activities . furthermore , it is of considerable benefit that the implant carrier is warned automatically of obstacles or hazards and the technical recognition of patterns or objects is reported in support of orientation in space . with the encoder a direct connection to a part of the nervous system is established that is already spontaneously active . thus , neural impulses from individual neurons are generated without technical stimulation . monitoring of the neural activity of individual neurons to be stimulated is of considerable advantage for optimum adaptation of the stimulation impulse sequences to the respective spontaneous activity , for precise determination of the stimulation parameters for assured and simultaneous biologically compatible conversion of stimulation impulses into neural impulses as well as for improved optimization of the temporal tuning and synchronization of the neural activities of several neurons . with technical adaptation of the operating range it is possible to adapt , in the bright - adapted or dark - adapted brightness range , the function to the image pattern or the sound pattern , to accordingly vary the spatio - temporal filter parameters , or to technically compose a operating range that , for example , consists of partial areas of the larger photosensor function range that are separated from one another &# 39 ; s by decades . pre - processing of incoming image patterns , particularly with respect to rapid selection and change opportunities of the respective pre - processing function is made possible . with the pre - processing module connected the function of an encoder consisting of only a limited number of rf filters is facilitated by the essential simplification of the image pattern or sound pattern and accordingly the perception quality is improved .

US-36703000-A

a game structure capable of being used to simulate to a degree any of a series of games such as basketball , volleyball or the like can be constructed so as to utilize a housing having a transluscent or transparent front surface . in a game structure as disclosed a carriage is mounted in the housing in back of the front surface so as to be capable of being moved back and forth along a path . a member simulating a member which is moved as a game is played is supported on the carriage so as to be moved as the carriage is moved . this member is of such a character as to be capable of being viewed through the front surface of the housing . two separate structures are provided for moving the carriage . one of these is mounted adjacent to one end of the housing and the other is mounted adjacent to the other end of the housing . each of these structures for moving the carriage is capable of being actuated so as to exert repetitive blows against the carriage as it is repetitively actuated in order to cause the carriage to move .

the toy game structure 10 of the invention illustrated includes a housing 12 formed so as to include a transluscent or transparent front surface 14 , a bottom or base 16 , opposed ends 18 connected by the surface 14 and the bottom 16 , a top 20 and a removable back cover 22 serving to enclose various operative parts as hereinafter indicated . indicia 24 simulating a basketball court and further indicia 26 simulating the baskets used with such a court are provided on the front surface 14 . a support platform 28 forming part of the bottom or base 16 is located within the housing 12 intermediate the ends 18 . this platform 28 includes an elongated slot 30 extending parallel to the front surface 14 . rubber bumpers 32 are mounted on the platform 28 in alignment with the slot 30 and spaced from the ends 34 of the slot 30 . this platform 28 is used to support a carriage 36 having wheels 38 which rest upon the platform 28 . a small guide member 40 extends downwardly from the carriage 36 through the slot 30 for the purpose of insuring that the carriage 36 will only move in a linear path parallel to the front surface 14 . preferably an enlarged head 42 is provided on the guide 40 for the purpose of preventing movement of the carriage 36 generally away from the platform 28 . with this structure the bumpers 32 limit the movement of the carriage 36 toward the ends 18 of the housing 12 . these bumpers 32 are preferably formed of an elastomeric material such as a rubber composition so as to absorb any shock resulting from the carriage 36 hitting against them so as to minimize vibration . the carriage 36 is provided with parallel , upstanding , spaced supports 44 . each of these supports 44 is provided with an upwardly directed groove serving as a bearing opening 46 . if desired one of these supports 44 may include a small , pivotally mounted shaft retainer 48 which frictionally bears against the support 44 upon which it is located . these bearing openings 46 support a shaft 50 extending from both sides of a light unit 52 . the retainer 48 is adapted to be utilized to hold the shaft 50 so as to prevent the light unit 52 from moving away from the carriage 36 . this light unit 52 includes a bottom section 54 serving as a housing holding batteries 56 . this bottom section 54 preferably also includes a small counter weight 58 tending to balance the entire light unit 52 so that it may be pivotted between positions in which an arm 60 extending from the bottom section 54 is directed generally toward either of the ends 18 . the arm 60 carries a small housing 62 carrying a light bulb ( and socket ) 64 remote from the shaft 50 . an opening 66 in the housing 62 is used to convey light from the bulb 64 to immediately in back of the front surface 14 so that the light from the bulb 64 will be visible through this front surface 14 . preferably this front surface 14 will be transluscent so that the light from the bulb 64 will be visible through the front surface 14 while various other operative parts within the housing 12 are concealed from view . it is , however , possible to form an effective game structure 10 in which the front surface 14 is transparent . the important factor is to make the game structure 10 in such a manner that this light bulb 64 or any other equivalent element substituted for it such as a colored disk ( not shown ) is visible through the front surface 14 as the game structure 10 is used . this opening 66 is preferably formed as indicated in fig6 so as to have various internal ribs 68 effectively simulating the stitching on a common ball such as a basketball . the light unit 52 also includes various conventional conductors 70 and a conventional switch 72 mounted on the bottom section 54 and on the arm 60 for the purpose of controlling the operation of the bulb 64 . a small door 74 of conventional design may be provided on the back cover 22 for the purpose of facilitating access to the switch 72 . the carriage 36 also includes two separate levers 76 each of which is pivotally mounted on the carriage 36 through the use of conventional fasteners 78 serving as pivots . lugs 80 on the carriage 36 limit the downward movement of these levers 76 and the retainer 48 limits the upward movement of the levers 76 in such a manner that these levers 76 will always tend to fall back against the lugs 80 after they have been engaged . these levers 76 are located adjacent to a plate 82 which is mounted within the housing 12 parallel to the front surface 14 immediately above the bottom 16 within the back cover 22 . this plate 82 is formed so as to include two identical ramps 84 located adjacent to slots 86 which extend parallel to these ramps 84 . each of the ramps 84 leads upwardly at an angle from adjacent to an end 18 . each of the ramps 84 terminates at a stop 88 formed in the plate 82 . these ramps 84 are adapted to carry what are referred to herein as strikers 90 . these strikers 90 are mirror images of one another . each of these strikers 90 includes a body portion 92 carrying a shaft 94 mounting a comparatively heavy roller 96 . it will be noted that these body portions 92 include enlarged sides 98 which effectively straddle the ramps 84 so as to serve to guide the strikers 90 so that they will only move in a linear manner along the ramps 84 . the rollers 96 employed are sufficiently heavy so as to be capable of returning the strikers 90 through the action of gravity toward positions as shown in fig3 in which these strikers 90 are at the lowermost portions ( not separately numbered ) of the ramp 84 adjacent to the end 18 . each of the body portions 92 includes a hammer - like end 100 which is adapted to engage one of the levers 76 in order to impart motion to the carriage 36 . it will be realized that when a lever 76 is engaged by a hammer - like end 100 of a striker 90 that this lever 76 will be rotated slightly in an amount depending upon the degree of the impact by the hammer - like end 100 . the initial rotation of a lever 76 will not normally result in movement of the carriage 36 . if the force applied by a hammer - like end 100 is great enough a lever 76 will be moved into engagement with the shaft retainer 48 and this in turn will cause movement of the carriage 36 . an important feature of the present invention which is considered to aid in the game structure 10 effectively simulating the game of basketball relates to the fact that the light unit 52 includes a shock absorbing rubber projection 102 which extends outwardly from the remainder of this unit 52 to a sufficient extent so as to be capable of engaging a sloping surface 104 on either of the levers 76 when the light unit 52 is in either of the two substantially horizontal positions that this unit 52 can assume . with this type of structure when the projection 102 is at rest against a sloping surface 104 of a lever 76 and when this lever 76 is engaged by the hammer - like end 100 of the striker 90 the movement of the lever 76 which is so engaged by the striker 90 will result in pivotting of the light unit 52 relative to the carriage 36 . thus , this rotation of the light unit 52 is in a sense independent of the movement of the carriage 36 although the light unit 52 is supported on the carriage 36 so as to be capable of being moved as the carriage 36 is moved . bell crank type levers 106 which are mirror images of one another are mounted upon shafts 108 so that arms 110 of these levers 106 project outwardly through openings 112 in the ends 18 . these arms 110 are preferably shaped much as handles so that they may be manually engaged so as to be rotated against stops 114 located on the ends 18 . during such rotation internal arms 116 on these levers 106 will hit against the strikers 90 when such strikers 90 happen to be at or adjacent to the end ( not separately numbered ) of a ramp 84 adjacent to an end 18 . the impact of an arm 116 with a striker 90 is intended to propel such a striker 90 so as to impart movement to the carriage 36 and the light unit 52 in the manner described in the preceding . because of their function the striker 90 , the ramp 84 and the lever 106 may be collectively referred to as a moving means . such movement as is caused by appropriate actuation of the levers 106 so that repetitive blows are delivered to the strikers 90 through the actuation of the levers 106 will cause the carriage 36 to move back and forth along a linear path parallel to the front surface 14 . concurrently the light unit 52 will pivot back and forth relative to the carriage 36 and the front surface 14 . as this occurs the light emitted from the bulb 64 will on occasion pass adjacent to the areas ( not separately numbered ) on the front surface 14 containing indicia 26 simulating baskets . this will , of course , correspond to &# 34 ; baskets &# 34 ; being made in a conventional game of basketball . in order to improve playability of the game structure 10 it is considered desirable to incorporate within this game structure 10 two counters 118 which will count the number of &# 34 ; baskets &# 34 ; made during the use of the game structure 10 . each of these counters 118 includes an assembly ( not separately numbered ) of a framework 120 carrying a rotatable drum 122 located about a shaft 124 . the shafts 124 are mounted on the frameworks 120 so as to extend to the front surface 14 adjacent to the bottom 16 . there small hands 126 are located on the shafts 124 so as to point to dials 128 containing numbers . the shafts 124 are also secured to conventional crown ratchet wheels 130 which are intended to be utilized in controlling the rotation of the shafts 124 and the drums 122 . elongated actuators 132 are pivotally mounted by pins 134 on the frameworks 120 so that the lowermost ends 136 of these actuators 132 are adjacent to the ratchet wheels 130 . conventional escapement teeth 138 are provided on the actuators 132 so as to coact with the ratchet wheels 130 in order to permit a limited amount of rotation of each shaft 124 each time a corresponding actuator 132 is deflected so as to bring its end 136 generally toward a ratchet wheel 130 . small coil springs 140 extending between the drums 122 and the framework 120 will normally tend to bias the ratchet wheels 130 so that they are held against rotation by escapement teeth 138 and so that during each movement of an end 136 toward the ratchet wheel 130 there will be restricted motion of a shaft 124 . the springs 140 can , of course , be placed under tension by rotating the hands 126 so as to reset the counters 118 . the teeth ( not separately numbered ) of the ratchet wheels 130 slide against the escapement teeth 138 in order to permit such resetting of the counters 118 . each of the actuators 132 is supplied with a tapered surface 142 which is adapted to be engaged by the arm 60 as the light unit 52 is moved and rotated so as to pass adjacent to the basket indicia 26 . such engagement of its tapered surface 142 will cause an actuator 132 to be pivotted in order to permit the end 136 to be moved so that the escapement teeth 138 coact with the ratchet wheel 130 in order to permit limited movement of a hand 126 and a counter 118 . small coil springs 144 are normally connected between the actuators 132 and the framework 120 for the purpose of biasing these actuators 132 in positions in which the escapement teeth 138 prevent rotation of the ratchet wheels 130 and in positions in which the surfaces 142 are located so that they can be engaged by the arm 60 . if desired , however , these springs 144 may be dispensed with when the actuators 132 are balanced so as to automatically pivot back to a &# 34 ; normal &# 34 ; position through the action of gravity . the actuators 132 also include stop walls 146 located at the lowermost extremities of the tapered surfaces 142 . these stop walls 146 are designed to prevent the resilience of the projection 102 from causing the light unit 52 to bounce back away from a substantially horizontal position after a &# 34 ; basket &# 34 ; has been made as indicated by the light unit 52 passing relative to an indicia 26 as indicated . the action of a spring 144 will automatically return an actuator 132 to a position in which the light unit 52 cannot be pivotted relative to the carriage 36 until such time as one of the strikers 90 moves so as to cause movement of the carriage 36 to a sufficient extent so that a stop wall 146 will no longer preclude rotation of the light unit 52 relative to the carriage 36 . it is believed that it will be apparent from the preceding that the game structure 10 is of such a character that it can be manufactured without significant difficulty at a comparatively nominal cost . this game structure 10 is of a comparatively simple mechanical character which contributes to the game structure 10 being capable of prolonged use by children without mechanical malfunction . there are obviously a number of ways that the particular game structure 10 can be modified . the particular game structure 10 is primarily designed or intended for use by two children . it is considered that an effective toy or game may be manufactured utilizing the principles of this invention so that only one of the moving means for moving the carriage 36 are employed . such a modified unit would substantially correspond to an individual shooting baskets by himself or herself .

US-73339276-A

an optical tomographic measuring device that includes : an illuminating component , a plurality of light - receiving components , a storage component , a specifying component , an acquiring component , and a constructing component is provided . the specifying component specifies a position of the measurement plane in the body length direction . the acquiring component acquires , from the storage component , an optical characteristic distribution that corresponds to the position specified by the specifying component . the constructing component constructs a density distribution of fluorescence in the measurement plane , on the basis of intensities of the fluorescence received at the respective light - receiving components and the optical characteristic distribution acquired by the acquiring component .

an exemplary embodiment of the present invention is described hereinafter with reference to the drawings . the schematic structure of an optical tomographic measuring system 10 relating to the present exemplary embodiment is shown in fig1 . the optical tomographic measuring system 10 has an optical measuring device 14 and a data processing device 16 that carries out predetermined data processing on measurement data that is obtained at the optical measuring device 14 . note that the optical tomographic measuring , system 10 may be a structure in which the functions of the optical measuring device 14 and the functions of the data processing device 16 are integrated . at the optical tomographic measuring system 10 , a living body , such as a nude mouse or the like for example , is the object of measurement . description is given hereinafter with the object of measurement being a mouse 12 ( see fig2 ). note that the object of measurement is not limited to the mouse 12 , and an arbitrary living body can be used as the object of measurement . lesion cells , such as tumor cells or the like for example , are injected or the like into the mouse 12 that is the object of measurement , so as to give rise to ( manifest ) a predetermined lesion . further , a fluorescent labeling agent , that causes a fluorescent substance to be contained in antibodies that adhere uniquely to a specific region such as the lesion or the like for example , is administered to the mouse 12 . at the optical tomographic measuring system 10 , the mouse 12 is loaded into the optical measuring device 14 at the time when , after the fluorescent labeling agent administered to the mouse 12 in which the lesion was generated disperses within the body of the mouse 12 due to blood circulation , the fluorescent labeling agent accumulates at and adheres to the lesion due to the antigen - antibody reaction . the optical measuring device 14 illuminates , toward the mouse 12 , excitation light with respect to the fluorescent labeling agent , and measures the fluorescence intensity emitted from the fluorescent labeling agent within the body of the mouse 12 . at the data processing device 16 , the density distribution of the fluorescence ( the fluorescent labeling agent ) within the mouse 12 is computed on the basis of the measurement data that corresponds to the fluorescence intensity outputted from the optical measuring device 14 , and a tomographic image , that shows the density distribution of the fluorescent labeling agent ( the fluorescent substance ) within the body , is generated ( an optical tomographic image is reconstructed ). the reconstructed optical tomographic image is , for example , displayed on a monitor 18 or the like . as shown in fig2 , in the optical tomographic measuring system 10 , when the mouse 12 is loaded in the optical measuring device 14 , the mouse 12 is accommodated and held in a subject holder 30 . the subject holder 30 is structured by an upper mold block 32 and a lower mold block 34 , and becomes a substantially cylindrical shape of a predetermined outer diameter due to the upper mold block 32 and the lower mold block 34 being superposed one on the other . a recess 32 a , that conforms to the physique ( the outer shape and size ) of the dorsal side of the mouse 12 , is formed in the upper mold block 32 . a recess 34 a , that conforms to the physique of the ventral side of the mouse 12 , is formed in the lower mold block 34 . due to the upper mold block 32 being placed on the lower mold block 34 in the state in which the ventral side of the mouse 12 is accommodated within the recess 34 a of the lower mold block 34 , the mouse 12 is disposed such that the body length direction thereof runs along the axial direction of the subject holder 30 , and is held in the subject holder 30 with the skin thereof closely contacting the inner surface of the subject holder 30 . in the present exemplary embodiment , mainly the torso portion ( from the chest portion to the hip portion ) of the mouse 12 is the measurement region , and the subject holder 30 holds the mouse 12 in a state in which the skin of at least the torso portion of the mouse 12 closely contacts the inner surface of the subject holder 30 . further , at the subject holder 30 , the position of the mouse 12 within the subject holder 30 can be prescribed by the position at which the recess 32 a is formed in the upper mold block 32 and the position at which the recess 34 a is formed in the lower mold block 34 . at the subject holder 30 , for example , the end surface at the head portion side of the mouse 12 is a reference surface 38 . due thereto , when the mouse 12 is accommodated in the subject holder 30 , the position of the measurement region is prescribed in accordance with the physique ( size ). note that , at the subject holder 30 , positioning between the upper mold block 32 and the lower mold block 34 is carried out by , for example , a pair of engaging projections 36 a that are formed at the lower mold block 34 being fit into engaging recesses 36 b that are formed in the upper mold block 32 . further , an arbitrary shape such as a prism or the like can be used for the subject holder 30 provided that it is an external shape that is stipulated in advance . as shown in fig3 , a stand 20 is disposed at the interior of the optical measuring device 14 , which interior is shielded from light by an unillustrated casing . a base plate 24 stands erect on this stand 20 . a measuring head portion 22 is provided at one surface of the base plate 24 . the measuring head portion 22 has a frame 26 that is formed in the shape of a ring for example , and the frame 26 is disposed so as to be coaxial with an unillustrated circular hole that is formed in the base plate 24 . a rotary actuator 28 is mounted to one surface of the base plate 24 . the frame 26 is mounted to the rotary actuator 28 . an unillustrated cavity portion , that corresponds to the circular hole of the base plate 24 , is formed in the rotary actuator 28 , and the cavity portion is mounted to the base plate 24 so as to be coaxial with the circular hole . the frame 26 is mounted so as to be coaxial with the cavity portion of the rotary actuator 28 . due to an unillustrated drive source that uses , for example , a stepping motor , a pulse motor or the like , being operated , the rotary actuator 28 rotates the frame 26 around the axially central portion thereof with respect to the base plate 24 . arms 44 , 46 are provided at the optical measuring device 14 as a pair with the base plate 24 sandwiched therebetween . at the arm 44 , a bracket 50 is mounted to the distal end portion of a support 48 , and the distal end of the bracket 50 passes through the opening of the frame 26 and is directed toward the arm 46 side . further , at the arm 46 , a bracket 54 is mounted to the distal end portion of a support 52 , and the distal end of the bracket 54 passes through the opening of the frame 26 and is directed toward the arm 44 side . an elongated slider 56 and slide base 58 are disposed above the stand 20 . the longitudinal direction of the slider 56 is disposed along the axial direction of the frame 26 . the slider 56 is inserted through an opening portion 24 a that is formed in the lower end portion of the base plate 24 , and is mounted on the base 20 . the slide base 58 is disposed on the slider 56 such that the longitudinal direction of the slide base 58 runs along the longitudinal direction of the slider 56 . the slide base 58 is mounted to the slider 56 via an unillustrated block that is provided at the slider 56 . the support 48 of the arm 44 stands erect at one longitudinal direction end side of the slide base 58 , and the support 52 of the arm 46 stands erect at the other end side . a feed screw mechanism is provided at the interior of the slider 56 . due to the feed screw being driven and rotated , an unillustrated block that is connected to the feed screw is moved . the slider base 58 is mounted to the block that is connected to the feed screw , and is moved along the longitudinal direction ( the left - right direction of the drawing of fig3 ) by the feed screw mechanism . due thereto , at the optical measuring device 14 , the pair of arms 44 , 46 are moved integrally in the axial direction of the frame 26 . note that a general , known structure can be used as the feed screw mechanism , and detailed description thereof is omitted here . further , the structure of moving the pair of arms 44 , 46 integrally is not limited to a feed screw mechanism , and an arbitrary , known structure can be used . moreover , in the present exemplary embodiment , the arms 44 , 46 move , but the present invention is not limited to the same and may be a structure in which the frame 26 ( the measuring head portion 22 ) moves . at the optical measuring device 14 , the subject holder 30 is installed so as to span between the bracket 50 of the arm 44 and the bracket 54 of the arm 46 . at this time , the subject holder 30 is disposed such that the axis thereof overlaps the axis of the frame 26 . further , the mouse 12 within the subject holder 30 is positioned along the body length direction with respect to the optical measuring device 14 due to the reference surface 38 of the subject holder 30 being abutted against a reference surface 50 a that is set at the bracket 50 . at the optical measuring device 14 , a state in which the bracket 50 of the arm 44 is inserted - through an unillustrated through - hole of the base plate 24 and projects - out toward the opposite side of the base plate 24 ( the far back side in the drawing of fig3 ) is the position at which the subject holder 30 is installed at and removed from the brackets 44 , 46 . at the optical measuring device 14 , when the subject holder 30 is installed at this installation / removal position , by driving the slider 56 , the subject holder 30 moves ( in the direction of arrow a ) so as to pass through the axially central portion of the frame 26 . further , at the optical measuring device 14 , removal of the subject holder 30 from the arms 44 , 46 is carried out by the subject holder 30 being moved in the direction opposite to the direction of arrow a and returned to the installation / removal position . on the other hand , as shown in fig1 , a light source unit 40 and plural light - receiving units 42 are mounted to the measuring head portion 22 . the respective optical axes of the light source unit 40 and the light - receiving units 42 are directed toward the axial center of the frame 26 and are in the same plane ( see fig4 , hereinafter called “ measurement plane 92 ”) that intersects the axial direction of the frame 26 . further , as shown in fig1 , the light source unit 40 and the light - receiving units 42 are disposed in a radial form from the axial center of the frame 26 , such that the angles between the optical axes thereof are a predetermined angle θ . note that , in the present exemplary embodiment , as an example , the one light source unit 40 and eleven light - receiving units 42 a , 42 b , 42 c , 42 d , 42 e , 42 f , 42 g , 42 h , 42 i , 42 j , 42 k are provided , and are disposed such that the angle θ is 30 °. on the other hand , as shown in fig5 , a control section 60 is provided at the optical measuring device 14 . the control section 60 has a controller 62 that is equipped with an unillustrated microcomputer . a driving circuit 64 that drives the rotary actuator 28 , and a driving circuit 66 that drives the slider 56 , are provided at the control section 60 , and are connected to the controller 62 . the movement of the subject holder 30 and the rotation of the measuring head portion 22 are controlled by the controller 62 at the optical measuring device 14 . further , the light source unit 40 has a light - emitting head 68 that , by a light - emitting element such as a semiconductor laser or the like , emits light of a predetermined wavelength that is the excitation light with respect to the fluorescent labeling agent . each of the light - receiving units 42 has a light - receiving head 72 that , by a light - receiving element , receives fluorescence emitted by the fluorescent labeling agent . the control section 60 has a light emission driving circuit 70 that drives the light - emitting head 68 provided at the light source unit 40 , amplifiers ( amp ) 74 that amplify electric signals outputted from the light - receiving heads 72 provided at the respective light - receiving units 42 , and an a / d converter 76 that carries out a / d conversion on the electric signals ( analog signals ) outputted from the amplifiers 74 . due thereto , at the control section 60 , the measurement data , that is detected by the light - receiving heads 72 of the respective light - receiving units 42 , is outputted as digital signals while the emission of light by the light - emitting head 68 of the light source unit 40 is controlled . note that an unillustrated display panel is provided at the optical measuring device 14 , and the operating state of the device and the like are displayed by the controller 62 . a computer of a general structure in which a cpu 78 , a rom 80 , a ram 82 , an hdd 84 that is a storage component , an input device 86 such as a keyboard or a mouse ( a pointing device ) or the like , the monitor 18 , and the like are connected to a bus 88 , is formed at the data processing device 16 . an input / output interface ( i / o if ) 90 a is provided at the data processing device 16 . the input / output interface 90 a is connected to an input / output interface 90 b that is provided at the control section 60 of the optical measuring device 14 . note that a known , arbitrary standard , such as a usb interface or the like , can be applied to the connection between the optical measuring device 14 and the data processing device 16 . the data processing device 16 controls the operations of the optical measuring device 14 due to the cpu 78 executing programs stored in the rom 80 or the hdd 84 by using the ram 82 as a work memory . due thereto , at the optical measuring device 14 , in a state in which the subject holder 30 installed at the arms 44 , 46 is moved in the axial direction and a predetermined position of the subject holder 30 ( a predetermined region of the mouse 12 ) is disposed at the axially central portion ( the measurement plane 92 ) of the frame 26 , excitation light is illuminated from the light source unit 40 toward the subject holder 30 . the fluorescence , that is emitted from the fluorescent labeling agent within the mouse 12 in accordance with this excitation light and exits from the periphery of the subject holder 30 , is received at the respective light - receiving units 42 . data corresponding to the received light amounts is outputted as measurement data to the data processing device 16 . the data processing device 16 carries out reconstruction of the density distribution of the fluorescence on the basis of the measurement data outputted from the optical measuring device 14 . note that description is given of a case in which , in the optical tomographic measuring system 10 , the data processing device 16 controls the operations of the optical measuring device 14 . however , the present invention is not limited to the same , and may be a structure in which the optical measuring device 14 operates independently , and outputs the measurement data . as shown in fig4 , in the optical tomographic measuring system 10 , the subject holder 30 is installed in the optical measuring device 14 with the reference surface 38 of the subject holder 30 being made to abut the reference surface 50 a of the bracket 50 . due thereto , at the optical measuring device 14 , the reference surface 50 a of the bracket 50 is origin xs , and the subject holder 30 is relatively moved in the direction of arrow x such that a predetermined position of the subject holder 30 faces the measuring head portion 22 . note that , in the following explanation , description is given with the body length direction of the mouse 12 within the subject holder 30 ( the axial direction of the frame 26 ) being the x - axis , and the coordinate , on the x - axis , of the position of relative movement of the measurement plane 92 from the origin xs with respect to the subject holder 30 being measurement position x . in the optical measuring device 14 , a position that is set in advance is an initial position for measurement ( measurement position x 1 ), and measurement of fluorescence is carried out at each measurement position xn to which the subject holder 30 is moved relatively , at a predetermined interval δx ( e . g ., δx = 3 mm ) each time from the measurement position x 1 . at this time , in the optical measuring device 14 , at each of the measurement positions xn , the light source unit 40 is rotated from a preset original position by a predetermined angle θ each time ( e . g ., from an original position θ 1 to rotational positions θ 2 , θ 3 , . . . θ 12 ( see fig1 )). at each rotational position θ p ( here , p = 1 through 12 ), excitation light is illuminated from the light source unit 40 toward the subject holder 30 , and measurement data m ( m ), that are output signals of the light - receiving units 42 a through 42 k , are read - in . note that m = 1 through 11 , and m is a variable that specifies the light - receiving unit 42 a through 42 k . due thereto , in the optical measuring device 14 , measurement data m ( xn , θp , m ) is obtained as measurement data m ( x , θ , m ). at this time , if the measurement position x is the same , the measurement data m ( x , θ , m ) are data in the same plane ( the measurement plane 92 ) that intersects the moving direction of the subject holder 30 . on the other hand , the living body such as the mouse 12 or the like is an anisotropic scattering medium with respect to light . at an anisotropic scattering medium , until the incident light reaches the light penetration length ( equivalent scattering length ), there is a region at which forward scattering is dominant , and , in regions past the light penetration length , multiple scattering ( isotropic scattering ) in which the deflection of the light is random occurs , and the scattering of the light becomes isotropic ( isotropic scattering region ). the region in which the forward scattering is dominant is around several mm . therefore , at the region at a depth of around several mm or more from the surface of an anisotropic scattering medium , there can be considered to be isotropic scattering . in the present exemplary embodiment , the mouse is accommodated in the subject holder 30 ( the upper mold block 32 and the lower mold block 34 ) that has a thickness of greater than or equal to the light penetration length , so that the scattering of light within the body of the mouse 12 is considered to substantially be an isotropic scattering region . polyethylene ( pe ), or polyacetal resin ( pom ) whose equivalent scattering coefficient μs ′ of light is 1 . 05 mm − 1 , or the like can be used as the material of the subject holder 30 . note that the material that forms the subject holder 30 is not limited to these , and an arbitrary material , that is such that the interior of the body of the mouse 12 is considered to be an isotropic scattering region , can be used . when light propagates within a highly - dense medium while being scattered , the distribution of the light intensity is expressed by a transport equation of light ( photons ) that is a basic equation describing the flow of energy of photons . however , due to the scattering of the light approximating isotropic scattering , the distribution of the light intensity can be expressed by using a light diffusion equation . this light diffusion equation is expressed by formula ( 1 ). note that φ ( r , t ) represents the light density within the mouse 12 , d ( r ) represents the diffusion coefficient , μa ( r ) represents the absorption coefficient , q ( r , t ) represents the light density of the light source , r represents the coordinate position within the mouse 12 that is the object of measurement ( i . e ., within the subject holder 30 ), and t represents time . here , given that the equivalent scattering coefficient is μs ′( r ), in a general , three - dimensional model , there is the relationship expressed by d ( r )= 3 · μs ′( r )) − 1 between the equivalent scattering coefficient μs ′( r ) and the diffusion coefficient d ( r ). μs ′( r ) is the equivalent scattering coefficient , and , in the present exemplary embodiment , is a value used in reconstructing a two - dimensional tomographic image along the measurement plane 92 . in the case of a two - dimensional model , there is the relationship expressed by d ( r )=( 2 · μs ′( r )) − 1 between the diffusion coefficient d ( r ) and the equivalent scattering coefficient μs ′. the equivalent scattering coefficient μs ′ indicates the scattering coefficient in an isotropic scattering region in a substance ( an anisotropic scattering medium ) that includes an anisotropic scattering region and an isotropic scattering region . in the light diffusion equation , only the isotropic scattering region is the object , and here , the equivalent scattering coefficient μs ′ is used . in a case in which continuous light is used for optical tomographic measurement , the distribution of the light intensity is uniform regardless of time , and therefore , the light diffusion equation of formula ( 1 ) can be expressed by formula ( 2 ). {∇· d ( r )∇− μ a ( r )} φ ( r )= − q ( r ) ( 2 ) when the diffusion coefficient d ( r ) and the absorption coefficient μa ( r ) that are optical characteristic values are already known , computation as a forward problem can be carried out in a case in which the intensity distribution of the light that exits from the mouse 12 ( the subject holder 30 ) is determined by using the light diffusion equation expressed by formula ( 2 ). however , the light intensity distribution is already known . from this , in a case in which an optical characteristic value of the mouse 12 is determined by using the light diffusion equation , there becomes inverse problem computation . here , the diffusion coefficient d ( r ) and the absorption coefficient μa ( r ) of the mouse 18 differ in accordance with the wavelength of the light . given that the diffusion coefficient with respect to wavelength λs of the excitation light is ds ( r ), the absorption coefficient is μas ( r ), and the light density of the light source is qs ( r ), the diffusion equation with respect to the excitation light is expressed by formula ( 3 ). further , given that the diffusion coefficient with respect to wavelength λf of the fluorescence is dm ( r ), the absorption coefficient is μam ( r ), and the light density whose light source is the fluorescence is qm ( r ), the light diffusion equation with respect to the fluorescence is expressed by formula ( 4 ). {∇· d s ( r )∇− μ as ( r )} φ s ( r )=− q s ( r ) ( 3 ) {∇· d m ( r )∇− μ am ( r )} φ m ( r )=− q m ( r ) ( 4 ) further , the light density qm ( r ) of the fluorescence can be expressed by qm ( r )= γ · εn ( r )· φ ( r ), by using the light density φs ( r ) within the mouse 12 , the quantum efficiency γ of the fluorescent labeling agent , and the molar absorption coefficient ε . accordingly , formula ( 4 ) is replaced by formula ( 5 ). {∇· d m ( r )∇− μ am ( r )} φ m ( r )=− γε n ( r ) φ s ( r ) ( 5 ) here , if the absorption coefficient μa ( r ) and the equivalent scattering coefficient μs ′( r ) ( diffusion coefficient d ( r )) that are optical characteristics of the mouse 12 are already known , in formula ( 3 ) and formula ( 5 ), substitutions of ds ( r )= dm ( r )= d ( r ) and μas ( r )= μa ( r )+ ε · n ( r ) and μam ( r )= μa ( r ) can be carried out . from this , formula ( 3 ) and formula ( 5 ) are replaced by formula ( 6 ) and formula ( 7 ). note that ε ·( r ) expresses the absorption by the fluorescent labeling agent . {∇· d ( r )∇− μ a ( r )− ε n ( r )} φ s ( r )=− q s ( r ) ( 6 ) {∇· d ( r )∇− μ a ( r )} φ m ( r )=− γε n ( r ) φ s ( r ) ( 7 ) the intensity of the fluorescence whose light source is the fluorescent labeling agent is based on the intensity φs ( r ) of the excitation light . the intensity qs ( r ) of the light source of the excitation light is already known . due to the equivalent scattering coefficient μs ′( r ) ( diffusion coefficient d ( r )) and the absorption coefficient μa ( r ) being already known , the light intensity φs ( r ) within the mouse 12 can be determined as a forward problem by a numerical analysis method such as the finite element method or the like . on the basis thereof , at the data processing device 16 , forward problem computation , and reverse problem computation of one system , are carried out by using the measurement data m ( x , θ , m ), and the density distribution n ( r ) of the fluorescence emitted from the fluorescent labeling agent of the mouse 12 at the interior of the subject holder 30 is obtained . on the other hand , as shown in fig5 , at the optical measuring device 14 , a stepping motor 56 a for example is provided as the driving source of the slider 56 . at the slider 56 , an unillustrated feed screw is rotated by the stepping motor 56 a , and the slide base 58 is moved ( see fig3 ). the controller 62 controls the driving of the stepping motor 56 a via the driving circuit 66 . due thereto , at the optical measuring device 14 , the relative position of the subject holder 30 with respect to the measurement plane 92 of the measuring head section 22 is grasped on the basis of the driving of the stepping motor 56 a . as shown in fig2 , at the subject holder 30 that is applied to the present exemplary embodiment , the mouse 12 is held by the recess 32 a formed in the upper mold block 32 and the recess 34 a formed in the lower mold block 34 . at this time , at the subject holder 30 , the position of the mouse 12 within the subject holder 30 is prescribed by the positions of the recesses 32 a , 34 a with respect to the reference surface 38 . further , as shown in fig6 a , because the anatomic structure of the internal structures ( the innards ) of the mouse 12 is complete , when the mouse 12 is held in the subject holder 30 , the internal structures that are positioned at the predetermined measurement plane 92 can be thought to be substantially the same due to the physique of the mouse 12 . at this time , measurement positions x 1 through x 15 of the optical measuring device 14 relating to the present exemplary embodiment are positioned at a chest portion 100 , an abdominal portion 102 , and a hip portion 104 of the mouse 12 . note that , hereinafter , in addition to internal organs such as the lungs , heart , stomach , liver , intestines , kidneys and the like , bone tissue , and soft tissue such as muscles , fat and the like , are collectively called internal structures . fig6 b is a cross - sectional view at a position included in the chest portion 100 of the mouse 12 shown in fig6 a . as shown in fig6 b , in the chest portion 100 of the mouse 12 , lungs 108 and a heart 110 are positioned around a bone 106 a , and bones 106 b , muscles 112 , and fat 122 are positioned so as to cover these . fig6 c is a cross - sectional view at a position included in the abdominal portion 102 of the mouse 12 shown in fig6 a . as shown in fig6 c , in the abdominal portion 102 of the mouse 12 , there is the bone 106 a , and the majority of the space is occupied by the stomach 114 and the liver 116 , and the muscles 112 and the fat 122 are positioned so as to cover these . fig6 d is a cross - sectional view at a position included in the hip portion 104 of the mouse 12 shown in fig6 a . as shown in fig6 d , the bone 106 a , and internal organs such as intestines 118 and kidneys 120 and the like , and the muscles 112 and the fat 122 that cover these , are positioned at the hip portion 104 of the mouse 12 . namely , at the optical measuring device 14 relating to the present exemplary embodiment , on the basis of the moved distance ( measurement position xn ) of the measurement plane 92 with respect to the reference surface 38 , the position of the measurement plane 92 in the body length direction of the mouse 12 is grasped , and the distribution of the internal structures of the mouse 12 in the measurement plane 92 can be specified . here , as shown in table 1 , at a living body such as the mouse 12 or the like , the optical characteristics such as the absorption coefficient μa , the equivalent scattering coefficient and the like differ in accordance with the internal structures . thus , the data processing device 16 relating to the present exemplary embodiment specifies the internal structures in the measurement plane 92 on the basis of the measurement position xn , and prepares an optical characteristic distribution from the position of the internal structures and the optical characteristic values ( the absorption coefficient μa , the equivalent scattering coefficient μs ′) that differ per internal structure , and stores the prepared optical characteristic distribution in the rom 80 or the hdd 84 or the like of the data processing device 16 . more concretely , in the present exemplary embodiment , as shown in fig6 a , explanation is given with the center at the reference surface 38 of the subject holder 30 being origin o , the moving direction of the subject holder 30 that passes through the origin o being the x - axis , and the axes on the reference surface 38 that pass through the origin o and are respectively perpendicular to the x - axis being the y - axis and the z - axis . at this time , as shown in fig6 b through fig6 d , the measurement plane 92 that is each cross - section of the mouse 12 is on the z - axis and the y - axis . due thereto , the cross - section of the mouse 12 can be expressed by two - dimensional coordinates with each of the measurement planes 92 being a yz coordinate . namely , the distribution of the internal structures within each cross - section is two - dimensional coordinates on the y - axis and the x - axis with respect to the origin o in the measurement plane 92 , and the optical characteristic values ( the absorption coefficient μa , the equivalent scattering coefficient μs ′) of the main internal structures are stored in advance at the coordinate positions . note that , although the lungs , heart , stomach , liver , intestines , kidneys , bone tissue , muscles , fat and the like are used as the main internal structures ( see table 1 ), the present invention is not limited to the same and other internal structures can be used . in this way , in the optical tomographic measuring system 10 , on the basis of the distribution of the internal structures corresponding to the measurement position xn of the mouse 12 , the absorption coefficient μa ( r ) and the equivalent scattering coefficient μs ′( r ) that are used as the optical characteristic values are set , and an optical characteristic distribution corresponding to the distribution of the internal structures is stored in the rom 80 or the hdd 84 of the data processing device 16 . at the data processing device 16 , the absorption coefficient μa and the equivalent scattering coefficient μs ′ are set to the absorption coefficient μa ( r ) and the equivalent scattering coefficient μs ′( r ), and reconstruction of an optical tomographic image that is based on the measurement data m ( xn , θp , m ) is carried out . note that , although it is actually three - dimensional , the optical characteristic values are set in two dimensions in this way , and can be used in computation . the reconstructing of an optical tomographic image at the optical tomographic measuring system 10 relating to the present exemplary embodiment is described hereinafter . a summary of the measuring processings at the optical measuring device 14 provided at the optical tomographic measuring system 10 is shown in fig7 . this flowchart is implemented when the subject holder 30 that accommodates the mouse 12 is installed in the optical measuring device 14 and the start of measuring processing is instructed . note that , here , the measurement position x is measurement position xn , and measurement is carried out at an interval of δx ( e . g ., δx = 3 mm ) from n = 1 through 15 . at each of the measurement positions xn , the measuring head portion 22 is rotated in order at 30 ° intervals from p = 1 through 12 , with the rotational position θ of the light source unit 40 being rotational position θp , and measurement of the fluorescence is carried out at each of the light - receiving units 42 of m = 1 through 11 . operation of the optical measuring device 14 is controlled by the data processing device 16 . in initial step 200 , initial setting is carried out , and values are set to m = 0 , n = 0 , and p = 0 . in step 202 , n is incremented ( n = n + 1 ). next , in step 204 , by driving the stepping motor 56 a and operating the slider 56 , the initial position ( measurement position x 1 ) of the measurement positions xn of the mouse 12 is moved so as to correspond to the measuring head portion 22 . when the mouse 12 moves to the measurement position xn at which measurement of fluorescence is carried out , in step 214 , p is incremented ( p = p + 1 ). in step 216 , by operating the rotating actuator 28 , the measuring head portion 22 is rotated , and the light source unit 40 moves to the original position θ 1 . thereafter , in step 218 , the light - emitting head 68 of the light source unit 40 is operated and illuminates excitation light toward the subject holder 30 . together therewith , in step 220 , m is incremented ( m = m + 1 ). in step 222 , the light amount of the fluorescence received at the light - receiving unit 42 corresponding to m is read - in as measurement data d ( m ) of measurement position xn and rotational position θp . further , in step 224 , it is confirmed whether or not measurement data has been read - in from all of the light - receiving units 42 ( m ≧ 11 ). if m is not greater than or equal to 11 , the judgment in step 224 is negative , the routine moves on to step 220 , and the next measurement data m ( m ) is read - in . when the measurement data of all of the light - receiving units 42 at the measurement position xn and the measurement angle θp have been read - in , the judgment in step 224 is affirmative . the routine moves on to step 226 where emission of light by the light source unit 40 is stopped , and the read - in measurement data m ( xn , θp , m ) is outputted to the data processing device 16 ( step 228 ). in next step 230 , is it confirmed whether or not the light source unit 40 has moved an entire one circumference ( p ≧ 12 ) at the measurement position xn . if the judgment is negative , m is reset ( m = 0 ) ( step 232 ), and the routine moves on to step 214 . in this way , at measurement position xn , the light source unit 40 is rotated from measurement positions θ 1 through θ 12 , and when measurement of the measurement data m ( xn , θp , m ) is finished , the judgment in step 230 is affirmative , and the routine moves on to step 234 . in step 234 , it is confirmed whether or not measurement at all of the measurement positions xn is finished ( n ≧ 15 ). if the judgment is negative , in step 236 , m and p are set to m = 0 and p = 0 , and the routine moves on to step 202 , and measurement at the next measurement position xn is started . further , when measurement at all of the measurement positions xn ( x 1 through x 15 ) is finished , the judgment in step 234 is affirmative , and the measuring processing ends . note that , when the measuring processing ends , the slider 56 is operated , and the subject holder 30 is returned to the installation / removal position . on the other hand , a summary of the processings at the data processing device 16 that are based on the measurement data m ( xn , θp , m ) of the optical measuring device 14 is shown in fig8 . this flowchart is executed by the measuring processing at the optical measuring device 14 being started . in this flowchart , in step 250 and step 252 , first , setting of the measurement position xn is carried out . note that , here , after n is initialized ( n = 0 ), n is incremented ( n = n + 1 ), and is thereby set to the initial measurement position xn ( measurement position x 1 ). in next step 260 , the measurement data outputted from the optical measuring device 14 is read - in in order . in step 262 , it is confirmed whether or not reading - in of the measurement data m ( xn , θp , m ) of the entire one circumferential rotation of the light source unit 40 ( data from p = 1 through 12 ) at the measurement position xn is finished . here , when the measurement data m ( xn , θp , m ) of the entire one circumferential rotation is read - in , the judgment in step 262 is affirmative , and the routine moves on to step 263 . in step 263 , the absorption coefficient μa ( r ) and the equivalent scattering coefficient μs ′( r ), that are optical characteristic values of the mouse 12 , at the measurement position xn are read - out and set . in the present exemplary embodiment , the position of the measurement plane 92 in the body length direction of the mouse 12 is specified from the relative position of the subject holder 30 with respect to the measurement plane 92 by the driving of the stepping motor 56 a . the optical characteristic distribution of the mouse 12 at this position is grasped by a two - dimensional coordinate . thus , the absorption coefficients μa ( r ) and the equivalent scattering coefficients μs ′( r ) that are set in advance for all of the two - dimensional coordinates of the y - axis and z - axis relating to the measurement plane 92 , i . e ., for each of the coordinate positions ( r ) with respect to the origin o , are read - in . in nest step 264 , fluorescence intensity distribution ( fluorescence intensity distribution φm ( r ) meas ) is computed from the read - in measurement data m ( xn , θp , m ). namely , the fluorescence intensity distribution φm ( r ) meas that is based on the measurement data m ( xn , θp , m ) is acquired . thereafter , in step 266 , the initial value of density distribution n ( r ) of the fluorescence ( fluorescent labeling agent ) within the subject holder 30 that contains the mouse 12 is set . in step 268 , fluorescence intensity distribution φm ( r ) calc that exits from the mouse 12 is computed on the basis of the set density distribution n ( r ) and the absorption coefficients μa ( r ) and the equivalent scattering coefficients μs ′( r ) ( diffusion coefficients d ( r )) that were set previously . namely , the virtual fluorescence intensity distribution φm ( r ) calc is acquired . this fluorescence intensity distribution φm ( r ) calc can be easily computed by making a light diffusion equation , that is a mathematical model , be a known forward problem computation that uses a numerical analysis method such as the finite element method or the like . namely , excitation light intensity distribution φs ( r ) calc is obtained from formula ( 6 ) and formula ( 8 ). light intensity distribution φt ( r ) calc , that combines excitation light and fluorescence , is obtained from formula ( 9 ). the fluorescence intensity distribution φm ( r ) calc is obtained from the excitation light intensity distribution φs ( r ) calc and the light intensity distribution φt ( r ) calc ( refer to formula ( 10 )). {∇· d ( r )∇− μ a ( r )− ε n ( r )} φ s ( r )=− q s ( r ) ( 6 ) {∇· d ( r )∇− μ a ( r )− ε n ( r )} φ s ( r )=− q s ( r ) ( 8 ) {∇· d ( r )∇− μ a ( r )} φ t ( r )=− q s ( r ) ( 9 ) in next step 270 , the fluorescence intensity distribution φm ( r ) meas , that is based on the measurement data , and the fluorescence intensity distribution φm ( r ) calc , that is based on the results of computation , are compared , and in step 272 , it is confirmed whether or not these distributions coincide . this judgment may be carried out by , for example , using the square error y of the fluorescence intensity distribution φm ( r ) meas and the fluorescence intensity distribution φm ( r ) calc , and judging whether or not the square error y is within a prescribed value that is set in advance . here , if the square error y is greater than the prescribed value and it is judged that the fluorescence intensity distribution φm ( r ) meas and the fluorescence intensity distribution φm ( r ) calc do not coincide , the judgment in step 272 is negative , and the routine moves on to step 274 . in step 274 , the change in the light intensity distribution with respect to the change in the optical characteristic value is computed by a known method using a jacobian matrix . in next step 276 , the error ( e . g ., the square error y ) of the fluorescence intensity distribution φm ( r ) meas and the fluorescence intensity distribution φm ( r ) calc is evaluated by using inverse problem computation in accordance with an optimization method such as the levenberg - marquardt method or the like . namely , the square error y is obtained from formula ( 11 ), and this square error y is evaluated . note that γ is the quantum efficiency and ε is the molar absorption coefficient . y =∥ φ m ( r ) measure − φ m ( r ) calc ∥ 2 ( 11 ) further , in this step 276 , absorption εn of the fluorescence at the fluorescent labeling agent that makes this square error y be a minimum , i . e ., the density distribution n ( r ) of the fluorescent labeling agent , is estimated . this can be estimated by carrying out inverse problem computation using formula ( 7 ) or formula ( 12 ) that are light diffusion equations . {∇· d ( r )∇− μ a ( r )} φ m ( r )=− γε n ( r ) φ s ( r ) ( 7 ) {∇· d ( r )∇− μ a ( r )} φ m ( r )=− γε n ( r ) φ s ( r ) ( 12 ) when the density distribution n ( r ) is determined in this way , in step 278 , the density distribution n ( r ) is updated on the basis of these computational results . the data processing device 16 repeats step 268 through step 278 until it is considered that the fluorescence intensity distribution φm ( r ) meas and the fluorescence intensity distribution φm ( r ) calc coincide . due thereto , when it is considered that the fluorescence intensity distribution φm ( r ) meas and the fluorescence intensity distribution φm ( r ) calc coincide , the judgment in step 272 is affirmative . the routine moves on to step 280 where the density distribution n ( r ) at this time is stored as the density distribution n ( r ) obtained from the measurement data m ( xn , θp , m ). a tomographic image of the fluorescence distribution at the measurement position xn is obtained by using this density distribution n ( r ). when the computation with respect to the measurement position xn ends in this way , in step 282 , it is confirmed whether or not processing with respect to all of the measurement positions xn is finished ( n ≧ 15 ). if the judgment is negative , the routine moves on to step 252 , and processing with respect to the next measurement position xn is carried out . in this way , at the data processing device 16 , by setting in advance the absorption coefficient μa ( r ) and the equivalent scattering coefficient μs ′( r ) that are optical characteristics of the mouse 16 , the density distribution ( r ) of the fluorescence can be obtained if there is measurement data of the fluorescence intensity . therefore , measurement can be simplified and the measuring time can be shortened . further , at the data processing device 16 , because it suffices for inverse problem computation of a light diffusion equation to be carried out with respect to the fluorescence , the processing load is reduced . at the optical tomographic measuring system 10 , the absorption coefficient μa ( r ) and the equivalent scattering coefficient μs ′( r ) can be set appropriately for each coordinate ( r ) within the measurement plane 92 . therefore , a highly - accurate density distribution n ( r ) of the fluorescence can be obtained as compared with a case in which the entire body of the mouse 12 is set to the same the absorption coefficient μa ( r ) and equivalent scattering coefficient μs ′( r ). for example , a cross - section of the chest portion 100 of the mouse 12 is shown in fig9 . the bone 106 a , the heart 110 , the muscles 112 that cover these , as well as the lungs 108 to which the fluorescent labeling agent has adhered , exist in the measurement plane 92 of the mouse 12 . results , that are obtained by using the optical tomographic measuring system 10 relating to the present exemplary embodiment at the time of carrying out reconstruction of the density distribution of the fluorescence of this measurement plane 92 , are shown in fig1 , and results that are obtained by not using the optical tomographic measuring system 10 are shown in fig1 . at this time , in fig1 , the average value of the entire body of the mouse 12 is set as the optical characteristic value . therefore , in the reconstructed image , the shape of a fluorescent labeling agent 150 breaks - down as compared with the fluorescent labeling agent 150 in fig9 . further , the number of noises ( artifacts ) 152 b that do not originally exist is large , and the fluorescence density also is high . therefore , it is also difficult to judge whether or not a high density region is noise . on the other hand , in fig1 , because the optical characteristic value is set three - dimensionally , the two fluorescent labeling agents 150 on the measurement plane 92 are expressed accurately ( the fluorescence density is high ). further , even though noises 152 a are displayed , because the density thereof is low , it is clearly understood that such regions are noise . note that the above - described present exemplary embodiment illustrates an example of the present invention , and does not limit the structure of the present invention . the present invention is not limited to the optical tomographic measuring system 10 , and can be applied to an optical tomographic measuring device of an arbitrary structure that illuminates excitation light onto a living body that is an object of measurement , and measures the fluorescence , that exits from the object of measurement due to the excitation light , at plural positions at the periphery of the object of measurement . further , in the present exemplary embodiment , a distribution of internal structures of the mouse 12 that has an average physique is supposed , and the optical characteristic value distribution of each cross - section is set . however , the present invention is not limited to the same . the distribution of the internal structures of each physique of the mouse 12 may be supposed , and the optical characteristic value distribution of each cross - section may be set in plural patterns . in this case , at the data processing device 16 , it suffices for the user to select the optical characteristic value distribution pattern that corresponds to the physique of the mouse 12 that is the object of measurement .

US-97920910-A

a container comprises a storage compartment and a lid . the storage compartment may be formed of plastic , and may include indicia of measuring . the lid may be removably attached to the storage compartment by a latching mechanism . the latching mechanism may be sturdy enough to contain the contents of the storage compartment , even when those contents are substantially heavy . the contents of the storage compartment may pass through an opening in the lid . the opening may be covered by a removably attached closure , and the closure may include indicia of measuring . the closure may thus be removed from the lid , and used as a measuring device . a scoop may be removably attached to the inside of the lid , may include indicia of measuring , and may be used as a measuring device .

the embodiments of the invention and the various features and advantageous details thereof are explained more fully with reference to the non - limiting embodiments and examples that are described and / or illustrated in the accompanying drawings and detailed in the following attached description . it should be noted that the features illustrated in the drawings are not necessarily drawn to scale , and features of one embodiment may be employed with other embodiments as the skilled artisan would recognize , even if not explicitly stated herein . descriptions of well - known components and processing techniques may be omitted so as to not unnecessarily obscure the embodiments of the invention . the examples used herein are intended merely to facilitate an understanding of ways in which the invention may be practiced and to further enable those of skill in the art to practice the embodiments of the invention . accordingly , the examples and embodiments herein should not be construed as limiting the scope of the invention , which is defined solely by the appended claims and applicable law . moreover , it is noted that like reference numerals represent similar parts throughout the several views of the drawings . while the invention has been described in terms of exemplary embodiments , those skilled in the art will recognize that the invention can be practiced with modifications in the spirit and scope of the appended claims . these examples given above are merely illustrative and are not meant to be an exhaustive list of all possible designs , embodiments , applications or modifications of the invention . referring now to fig1 - 5 , in preferred embodiments , the container 10 of the present invention includes a storage compartment 20 and a lid 30 . the storage compartment 20 may include a bottom 40 , a first side panel 50 , a second side panel 60 , a front panel 70 , and a back panel 80 . the bottom 40 may merge with the side panels 50 and 60 , and with the front and back panels 70 and 80 in order to form a compartment suitable for storing food stuff such as flour or sugar and the like . the intersections of the bottom 40 , the side panels 50 and 60 , and the front and back panels 70 and 80 may each form a rounded corner 90 , as shown in fig1 , or may be configured to form any shape , for example a rectangular , circular , or ovoid . the side panels 50 and 60 , and the front and back panels 70 and 80 , terminate in an upper edge 100 , having an outwardly extending lip 110 . the lid 30 may be removably attached to the upper edge 100 , through the use of a latching mechanism 120 . the latching mechanism 120 may include at least one latch 130 that is hingedly attached to an edge 140 of lid 30 , which may extend roughly parallel to the first side panel 50 , passing beyond the outwardly extending lip 110 , and latching thereto . preferably , the latching mechanism 120 attaches the lid 30 to the upper edge 100 in a fashion secure enough to bear substantial weight ( for example , that of a 5 pound bag of flour or sugar ) without becoming unintentionally unlatched . the latching mechanism 120 is preferably also attached to the upper edge 100 in a fashion such that it can be easily opened when intentionally unlatched ( for example , by a user having arthritis ). the latching mechanism 120 may , in a preferred embodiment , include two latches 130 , which may be disposed on opposing sides of the upper edge 100 . the lid 30 may include an opening 150 , through which the contents of the storage compartment 20 may be poured . the opening in the lid 150 may be covered by a closure 160 . the closure 160 may be hingedly attached to the lid 30 , such that it may be placed in an open or a closed position , and may be hingedly attached , such that it may be separated from the lid 30 . the closure 160 may be marked with indicia of measuring , so that for example , the user may remove the closure 160 from the lid , and pour a pre - determined amount of the contents of the storage compartment 20 into the closure 160 , using the closure to measure the pre - determined amount . the lid 30 may include a configurable indicator 180 . the configurable indicator 180 may be configured to indicate the date the contents of the storage compartment 20 were placed therein , or may indicate some other notable information , such as the contents of the storage compartment 20 , or a date by which the contents should be used . the configurable indicator 180 may include a plurality of wheels 190 , each of which may be independently rotated about a wheel post 200 , which in turn may be attached to the lid 30 . the configurable indicator 180 may further include a wheel cover 210 , which may also be attached to the lid 30 . the wheel cover 210 may be configured such that certain indicia , such as numbers , that are marked on the wheels 190 , may be seen through the wheel cover 210 , when the container 10 is in use . in this way , each wheel 190 may be rotated to display a certain indicia , such that upon subsequent use of the container 10 , a user may observe the indicia . for example , at the time of filling the container 10 , the wheels 190 may be set to indicate the date “ sep . 18 , 2009 ,” and upon subsequent use of the container , the configurable indicator 180 may indicate that its contents were placed in the container 10 on the 18th day of september , 2009 . alternatively , the configurable indicator 180 may be a digital indicator . for example , e . g ., at the time of filling the container 10 , the configurable indicator 180 may be set to indicate the date “ sep . 18 , 2009 ” in a digital display , and upon subsequent use of the container , the configurable indicator 180 may indicate that its contents were placed in the container 10 on the 18day of sep . 2009 . alternatively , the configurable indicator 180 may be set to indicate the date “ sep . 18 , 2009 ” whether in analog or digital format , and upon subsequent use of the container , the configurable indicator 180 may indicate the number of remaining days until an expiration date of the contents . in this embodiment , a counter may automatically count down from the set value ( using a drive mechanism ( e . g ., a servo - motor ) for the analog version , or a digital circuit for the digital version ), so that when it reaches 0 or a negative number , the configurable indicator 180 may indicate that the contents may be expired and should be discarded . the storage compartment 20 may include one or more indentations 220 , disposed on the back panel 80 of the storage compartment 20 , for ease of handling . the indentations 220 may be disposed such that the container 10 can be more easily lifted , carried , and the contents poured therefrom ( for example , by a user having arthritis ). the indentations 220 may extend only partially up the height of the storage compartment 20 , as shown in fig1 , or alternately may extend up the entire height of the storage compartment 20 . the storage compartment 20 may include indicia of marking 230 , so that , for example , the user may know the amount of the contents of the container 10 . the storage compartment 20 may include three or more feet 240 disposed on the bottom panel 40 of the storage compartment 20 . the feet 240 may be relatively small plastic or rubber disks , and may prevent the bottom panel 40 of the storage container 20 from coming in contact with a surface upon which it may be placed . the feet 240 may further be a material that prevents slipping along a surface upon which the storage container 20 may be placed . within a cavity 240 created by the storage compartment 20 and the lid 30 , a scoop 170 may be stored . the scoop 170 may be removably attached to the underside of the lid 30 , such that it is not buried by the contents of the storage compartment 20 , and such that it is readily accessible by the user . the scoop 170 may include indicia of measuring , so that for example , the user may remove the scoop 170 from the lid , and pour a pre - determined amount of the contents of the storage compartment 20 into the scoop 170 , using the closure to measure the pre - determined amount . in a preferred embodiment , the width of the cavity formed at the upper edge 100 will be large enough to comfortably accommodate a user &# 39 ; s hand while maneuvering the scoop 170 . as shown in fig5 , scoop 170 may have a shape that prevents it from being passed through opening 150 . in a preferred embodiment , the container 10 , when assembled such that the lid 30 is attached to the storage compartment 20 by the latching mechanism 120 , may be airtight and / or watertight , such that the contents of the storage container 20 do not substantially spill , and such that the contents are unharmed by disturbances such as humidity and pests . the elements of the present invention may be made from any materials , but a preferred embodiment may be made of a suitable plastic , most preferably having sufficient rigidity to withstand normal use . the above - described container may be made in a variety of sizes , i . e . lengths , widths , and depths , but a preferred size would approximate a 5 - pound bag of sugar , or a 5 - pound bag of flour , in order to facilitate everyday use . the improved , simple and inexpensive container described herein provides a reliable sealing and storage system for food stuff . various modifications and combinations will occur to persons skilled in the art without involving any departure from the spirit and scope of the invention as defined in the appended claims .

US-56155209-A

a method and apparatus for automatically controlling heart - synchronized circulating pumps ; which method comprises obtaining the parameters needed for regulation by analyzing the blood pressure beat for beat and continuously regulating the pump by reference to the transient parameters thus obtained . an electrocardiogram is taken and analyzed , the immediate past history of the heart beat is derived from the analysis and a calculation used to determine the control action exerted on a heart pump . the control action is exerted on the pump through the control action calculator . thus the body of the patient is included in a closed regulating cycle .

fig1 shows an arrangement which is suitable for all tandem pumping sets and for every method of counterpulsation . from the pressure time curve , input 1 , phases 4 and 5 and amplitudes 6 and 7 of the parameters &# 34 ; valve closure &# 34 ; and &# 34 ; systolic blood pressure &# 34 ; needed for control are determined by a valve closure analyzer 2 and a systolic peak pressure measuring unit 3 . these events are related to the beginning of the cardiac cycle . consequently , windows 9 and 10 are defined from the beginning of the cardiac cycle 7 input 8 by two monostable multivibrators and the pulse frequency described in detail hereinafter . the desired event can occur only within the phase range defined by the window . the trigger pulse derived from the heart beat at input 8 also drives a logic counting system 11 which at the beginning of control after a few pumping cycles interrupts the pumping action by means of a blocking unit 12 for one or more measuring cycles . hence phase and amplitude of the valve closing pressure -- controlled by the logic counting system 11 -- can be stored , first with and then in the absence of pulsation . according to the invention these 2 × 2 measured values i . e . phase and amplitude of the valve closing pressure with and without pulsation , in two memories 13 and 14 are compared in an amplitude discriminator 15 . pump activation is curtailed by a controller 16 when the pressure amplitude at the time of valve closure , in the absence of pulsation , is greater than or equal to the pressure amplitude in the presence of pulsation . however , if the pressure during pulsation in the the said phase rises then the controller 16 will prolong the activation of the pump . the rhythm of the blood pressure time curve is monitored by a cycle length measuring unit 17 and an arrhythmic pulse analyzer 18 and the functioning of the controller can be stopped by blocking device 19 . fig1 also shows a pumping pulse computer 20 which usually obtains its information in the form of positive or negative pulses from the controllers 16 and 22 . if the controllers are blocked the pumping pulse computer 20 computes the pumping pulse from the pulse frequency . when control begins , an uncritical pumping pulse is defined by a starting adjuster 21 . the end of the pumping pulse is controlled in continuous pulsation . a controller 22 starts by lengthening the pumping pulse under the control of the logic counting system 11 . this lengthening depends upon the tendency of the values obtained by the systolic peak pressure measuring unit 3 . according to the invention this tendency is ascertained by a comparison of the averaged amplitudes in a mean value memory 23 with past values which have been delayed by a delay member 24 . if the tendency ascertained by an amplitude discriminator 25 is constant or falling , then the end of the pumping pulse is further delayed . if after optimum relief of the systolic peak has been achieved the tendency rises as the pumping pulse end continues to be delayed , then the end of the pumping pulse is now advanced . the phase 5 of the systolic peak value 3 is controlled as above by a cycle length measuring unit 17 and an arrhythmic pulse analyzer 18 . this control can also be blocked 19 . as described , according to the invention , the beginning of the pumping pulse is so controlled by reference to an analysis of the blood pressure time curve that the pumping pulse becomes effective directly after valve closure , the end of the pumping pulse being controlled so that the systolic peak pressure is a minimum . it is not always possible to determine valve closure directly , for instance by frequency selection or differentiation of the pressure time curve . in clinical practice the available pressure curves are frequently damped . in such a case the invention proposes to employ what is termed the &# 34 ; 2 / t selection method .&# 34 ; tandem and counter - pulsation pumps generate a pressure curve with two peaks . the fundamental wave of this function does not have the frequency of the cycle length but twice the frequency ( 2 / t ). fig2 shows an arrangement based on this principle : the course of the pressure time curve -- input 26 -- is filtered in a 2 / t filter 27 of which the mean frequency is controlled by a cycle length measuring unit 28 . with reference to the heart rate this signal has two maxima and their phase positions 29 , 30 and amplitudes 31 , 32 are measured by two peak measuring units 33 and 34 . the functions of the systolic peak measuring unit 33 and of the diastolic peak measuring unit 34 are controlled by window pulses 35 controlled by ecg ( input 35 ) ( cf . fig1 ). control is effected either by determining the rising or falling tendency of the systolic and diastolic peaks . in fig2 the reference numerals 37 and 38 denote mean value memories which are controlled by logic system 39 . the reference numerals 40 and 41 denote delay units and the reference numerals 42 and 43 amplitude discriminators for determining the tendency of the systolic and diastolic pressure peaks . analogously to the functioning of the system in fig1 a controller 44 delays the end of the pumping pulse from a preadjusted position 45 when the tendency is constant or falling . a rising tendency causes the end of the pumping pulse to be advanced . similarly the beginning of the pumping pulse is delayed by a controller 46 starting from a preadjusted position until the diastolic pressure peak is a maximum . when the starting adjustment 45 has been made a pumping pulse computer 47 obtains its information from the two controllers 44 and 46 . the rhythm of the phase positions 29 and 30 of the systolic and diastolic peaks is checked by cycle length measuring units 48 and arrhythmic pulse analyzers 49 which cause the controllers to be automatically inactivated by a blocking unit 50 when the pulse trains are arrhythmic . this latter method gives optimum control for high heart rates , but at low rates control is imprecise because the instant of valve closure cannot be accurately determined . the special advantage of the method is the extreme insensitivity to irregularities in the blood pressure curve , particularly with regard to damping . the simplified block diagram of fig3 shows the essential construction groups of a further embodiment of the invention arranged slightly differently from fig1 . as illustrated , the beginning of the heart action of heart 8 is determined by way of amplitude discriminator 51 . the heart cycle is measured pulse by pulse in period duration meter 28 . calculator 20 first of all calculates a non - critical pulse pump sequence . the course of the pressure in the circulation 1 is measured and is analyzed in the pressure analyzer 63 in order to determine characteristic values of the blood pressure . these characteristic values of the blood pressure , such as , for example , systolic peak pressure , amplitude and phase of the valve closure and the diastolic pressure dip are supplied to calculator 20 via the lines 52 , 53 where they are analyzed and stored . the non - critical pumping impulses are fed to a pump 55 by way of a control line 54 . the non - critical and thus ineffective pumping impulses are enlarged successively by the regulators 16 , 22 until the optimum from the technical point of view of regulation has been reached . the regulator processes the characteristic values of the blood pressure carried by the calculator 20 by way of the line 56 . from the point of view of regulating technique , always the characteristic values of the blood pressure in the case of a switched - on - pump are compared with the ( a ) standard and ( b ) theoretical values of blood pressure without the pump . this comparison becomes possible by way of the measuring cycle transmitter 21 , which after switching on by way of the switch 57 will interrupt the pump by way of the line 59 , controlled by the heart pulses by way of the line 58 . the control system 60 checks the electrocardiogram and the characteristic values of the blood pressure and in the case of an occurrence of artefacts it will at first block the regulator by way of the line 61 and if necessary also the pump by way of the line 62 . the construction groups according to fig3 are shown in detail in , i . e . phase and amplitude of the valve closing pressure with and without pulsation , the pressure analyzer 63 contains a detector 3 ( also see fig1 ) for recording of the phase 5 and amplitude 7 of the systolic and / or diastolic peak of the blood pressure as well as a high pass filter or differentiator 2 with series connected amplitude 6 of the valve closure . the differentiator 2 triggers a discriminator 64 which analyzes phase 4 and amplitude 6 of the pressure of the valve closure . for realization of the method described according to fig2 the pressure analyzer 63 furthermore contains an adjustable band - pass filter 27 , preferably a wien filter , a regulator 65 controlled by the pertinent duration meter 28 for adjusting of the selective frequency to precisely double the value of the heart frequency and always two detectors 33 , 34 series connected to the wien filter for determining the phase 29 , 30 and amplitude 31 , 32 of the systolic and diastolic peak of the blood pressure . the measuring cycle transmitter 21 is enabled by way of the on / off switch 57 . it contains a monostable multivibrator 66 preferably with a scanning time of about 2 minutes , an astable multivibrator 67 with about the same duration of the cycle , an electronic counter 11 controlled by the electrocardiogram or blood pressure , an and gate 68 for connecting the outlets of the monostable multivibrator 66 and of the counter 11 , as well as an or gate 69 for connecting the outlets of the astable multivibrator 67 and of the and gate 68 . as a result of that the blocking 12 of the pump function becomes possible by way of line 59 . the changeover switches 70 , 71 located in the calculator 20 are also controlled via this line 59 . the calculator 20 processes the amplitude and phase of the valve closure and / or of the systolic pressure peak . these characteristic values of the blood pressure will reach either the storages 13 , 72 for storing of characteristic values while the pump is switched on , or the storages 14 , 73 for storing of the ( a ) standard and ( b ) theoretical values of blood pressure while the pump is switched off by way of the changeover switches 70 , 71 controlled electronically by way of the measuring cycle transmitter 21 . always two assigned storages will operate always one differential amplifier 74 , 75 with series connected amplitude discriminator 15 , 76 . the amplitude discriminator , depending on the difference of the amplitudes delivers a positive or negative signal on the one hand with the pump and on the other hand without the pump . a positive signal of the amplitude discriminator leads to a successive broadening of the impulse . a negative signal leads to a successive reduction of the pumping impulse . this reduction or enlargement takes place by way of the lines 56 in the regulator 16 , 22 . in order to carry out the method according to fig2 the calculator 20 furthermore always contains a storage 37 , 38 for storing the systolic or diastolic peak of the blood pressure . preferably these values are averaged . the differential amplifiers 77 , 78 now always compare present with past values . the past values are stored by means of intermediate storage in the delaying members 40 , 41 controlled by the amplitude discriminator 51 . an amplitude discriminator 42 or 43 series connected with the pertinent differential amplifiers serves for the differentiation of the amplitude differences used for regulation . uncritical pumping pulses are produced by the calculator 20 as follows : the pulses of the amplitude discriminator 51 operate a monostable multivibrator 79 , the latter operates a further monostable multivibrator 80 connected in series . the scanning time of these multivibrators is varied by amplifiers 81 , 82 for the characteristic curves . the amplifiers for the characteristic curves are controlled by a meter for the duration of the periods 28 . the control is accomplished in such a way , that the uncritical impulses viewed temporally will always lie about in the middle of the diastole . in the case of a reduction of the heart frequency , the scanning time of the two multivibrators is thus successively increased . a line 54 leads from the outlet of the multivibrator 80 to the pump 55 . the regulator 16 , 22 too is operated by the pulses of the amplitude discriminator 51 and contains two monostable multivibrators 83 , 84 connected in series . the scanning time of the multivibrators is influenced by the two regulators 85 , 86 . this influencing takes place as has already been described , by way of lines 56 in such a way , that in case of positive signals , the pumping pulse is broadened , in case of negative signals the pumping pulse is made narrower . electronic switches 19 for blocking the regulating process are located within the line 56 . the control system 60 analyzes the occurrences from the electrocardiogram , low voltage , hum ( buzz ), tachycardia and arrhythmia as follows : the amplitude of the ekg is discriminated by way of the amplitude discriminator 87 . the information by way of &# 34 ; low voltage &# 34 ; develops after a logical negation 88 . furthermore , the ekg reaches the subsequent amplitude discriminator 90 for the detection of external voltages in the ekg , by way of a band - pass filter 89 adapted to the grid frequency . a tachycardia can be registered as a result of discrimination 91 of the amplitude of the period duration meter 28 . arrhythmia of the sequence of the heart beat can be recognized by amplitude fluctuations at the outlet of the period duration meter 28 . preferably these fluctuations can be registered by way of a differential amplifier 92 , at the inlets of which variable rc sections are attached . similarly as in the case of a differentiator , the starting voltage of the differential amplifier is large , viewed absolutely , whenever a great difference of the amplitude of the period duration exists . the amplitude discriminator 93 differentiates a critical measure of arrhythmia from those period duration fluctuations which occur customarily within the scope of the biorhythm . the outlets of the pertinent amplitude discriminators 90 , 87 , 91 , 93 are conducted or an or - gate 94 so that in the case of a positive signal , the pump can be blocked by way of the line 62 . the control system 60 furthermore controls the regularity of the characteristic values of the blood pressure supplied by the pressure analyzer . this regularity is carried out analogously to the method described in the last paragraph by way of period duration meters 17 . every outlet of the period duration meters 17 is always connected with a differential amplifier 18 provided with variable rc sections at the inlet . the measure of the arrhythmia is determined in the series connected amplitude discriminators 95 , 96 . an or gate 97 signals each occurrance at its outlet . such an occurrence blocks the function of the regulator 16 , 22 by way of the line 61 . every characteristic value of the blood pressure is at a certain phase relationship to the heart action . on the basis of this realization the operational safety of the pressure analyzer can be considerably increased . thus the control system 60 contains one or more monostable multivibrators 98 , 99 operated by the pulses of the amplitude discriminator 28 . always additional monostable multivibrators 9 , 10 are connected in series in relation to the first mentioned monostable multivibrators . the last mentioned multivibrators thus form an electronic window for the pertinent characteristic value of the blood pressure . a characteristic value of the blood pressure is conducted on by way of an and gate 100 , 101 lying between the pressure analyzer 63 and the calculator 20 only whenever from a temporal point of view it occurs within the defined window . the pump 55 is operated by way of two series of impulses . the non - critical pumping impulses are delivered by way of the line 54 , the critical pumping impulses by way of the line 102 . first of all these impulses are mixed in the or gate 103 . the pump is blocked in two different ways : 1 a positive signal at the outlet of the pressure cycle transmitter 21 leads by way of the logical combination 104 to a blocking of the pumping impulse at the logical and gate 106 , and 2 . an occurrence at the outlet of the control system leads by way of the line 62 and a logical combination 105 lying in the line likewise to the blocking of the pumping function by way of the and gate 106 . the non - blocked pumping impulse is amplified in the output amplifier 107 and is conducted to the pumping element 108 which can be made preferably in the form of an electromagnetic valve . the invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof . the embodiments are therefore to be considered in all respects as illustrative and not restrictive .

US-62099675-A

a real - ball interactive sports entertainment and training system combines real - time motion sensing of real world sports equipment to create simulated interactions with amateur or professional sports figures on - screen , optionally including in - game advertising . the interactive sports entertainment and training experience extends to the internet , where users can view their statistics and highlights and compare notes and simulated sports stories with other users , or “ cyberjocks .” the system implements methods that include embedding a plurality of three - axis motion sensors within a single piece of user sports equipment , wherein each of the plurality of sensors provides a continuous stream of relative motion data for each axis ; disposing the plurality of three - axis motion sensors so that none of the axes are aligned ; connecting the disposed motion sensors to a processor , and powering the sensors and the processor so that the processor receives the relative motion data ; converting the relative motion data into a six or more axis representation of the motion of the single piece of sports equipment ; and communicating the six or more axis representation to a multimedia facility .

referring to fig1 , tracking and interactive simulation of real sports equipment may be performed by a platform 100 . the platform may include real sports equipment 102 adapted to be wirelessly tracked for all forms of movement . the adapted real sports equipment 102 may include a motion detection and transmission facility 104 that may provide a continuous stream of six or more axis position and motion data . the stream of data may be received by a stream processor 110 that may communicate through two way communication with the adapted sports equipment 102 . the processor 110 may take the received data from one or more adapted sports equipment 102 and configure it to be readily receivable by a visualization facility 112 . the visualization facility may include a console 114 for interacting with the processor 110 , a network , simulation data 118 , and an interactive visualization screen 120 . the visualization facility 112 may include computer processors and software to project real - time simulated images of the adapted sports equipment 102 based on motion information provided from the processor 110 . the visualization facility 112 may also use simulation data , such as images , video , backgrounds , real sports 3d surface models , professional athlete models , physics models , inverse kinematics models , and the like to present a 3d image on the visualization screen 120 of the real sports equipment 102 in an environment configured from the simulation data . users may interact with the visualization facility 112 through physical interface associated with the console 114 , a voice activated interface , a smart card near proximity interface , and wirelessly ( e . g . through a smart phone , pda , or other wireless enabled device ). the visualization facility 112 may be networked to the internet so that an internet user may interact with the facility 112 for configuration , inquiry , setup , data collection , advertising , and the like . simulation data 118 may be accessible locally by the visualization facility 112 or may be accessed remotely , such as through the internet , an intranet , a local wifi network , and the like . the platform 100 may include a web server 122 through which users , a platform facilitator , advertisers , and the like may access the processor 110 , visualization facility 112 , and the like . the web server 122 may have access to local or remote data storage that may be associated with one or more users of the adapted real sports equipment . this user data 124 may be configurable by a user that is authorized to make changes to the user data , such as when a user logs into the web server through the secure user interface . advertisers may access aspects of the platform 100 through a web server 122 interface . alternatively , advertisers may operate an advertisement server that may interact with at least the visualization facility 112 to supply advertisements , product placements , logo replacements , and the like to be incorporated into the visualization . a virtualization facility 130 may be incorporated into the platform for the purpose of facilitating virtual adapted real sports leagues , drafts , players , contracts , venues , promotion , ticket sales , and the like . virtualization may allow a blending of real world sport performance by participants using the adapted real sport equipment position and motion tracking platform 100 with virtual reality environments in which , for example the participants may try - out for a virtual team in a virtual league . based on the tracked real - world sport performance , participants may be drafted to a virtual team that may have virtual sponsors , and the like . the adapted real sports equipment 102 , which is further described elsewhere herein , may include any movable sports equipment that can be measured via motion detection , including baseballs , softballs , footballs , basketballs , hockey pucks , soccer balls , golf balls , boxing gloves , bowling balls , lacrosse balls , tennis balls , cricket balls , rugby balls , track and field equipment ( javelin , pole vault pole , relay baton ) and other projectiles or moving objects that are a natural part of any type of sport . a user may utilize other sports equipment , including without limitation hockey sticks , golf clubs , baseball bats , tennis rackets , lacrosse sticks , cricket bats , along with any other equipment that acts as a natural implement for making contact with the object being measured . the other sports equipment , such as that in the above example list , may also be adapted with a motion sensing facility 104 . the adapted sports equipment 102 may include wireless two way communication with the stream processor 110 . the two way communication may facilitate configuring the adapted sports equipment 102 such as by resetting the equipment , adjusting a transmitter frequency , establishing a standby or hibernation mode , calibrating the adapted sports equipment 102 , and the like . data from the adapted sports equipment 102 may be a raw stream of data , may follow one or more industry standard protocols such as bluetooth , rf , and the like . the data may include a unique identification of the adapted spoils equipment 102 that may be associated with a user account . the stream processor 110 may signal the equipment 102 to be activated based on an event , such as a user paying to use the equipment 102 . the adapted sports equipment 102 may include power saving features such as an ‘ at rest ’ detector that may power down elements of the equipment 102 to conserve power when the equipment is determined to be at rest . the adapted sports equipment 102 may include an initial activation function that reduces power consumption to a bare minimum until the equipment 102 is activated . in an embodiment , the adapted sports equipment 102 may include a user accessible on / off switch that is accessed with a small tool , such as a toothpick . in equipment that includes threads , such as a baseball , the switch may be accessible through a thread hole in the outer shell . in fig2 an embodiment of a compact configuration of an interactive sports equipment tracking and simulation facility , herein referred to as a ‘ stadium ’ is depicted . the stadium 200 may include an enclosed structure 202 that is accessible through a door ( not shown ) or opening in a side of the structure . the stadium 200 may include a console 204 , a projector 208 , cameras 210 , interactive visualization screen 212 , ball return 214 , and multimedia equipment such as speakers , lights , and the like . the structure 202 may be sized to allow for a variety of sports actions such as pitching a baseball ( depicted ), batting , kicking a soccer ball , and the like . in the embodiment of fig2 , the structure is approximately 9 feet high , 12 feet long and 8 feet wide . the console 204 may include a card reader , proximity sensor , touch screen , processor with internet connectivity , stream processor 110 , and the like . the elements of the stadium 200 may be interconnected in a similar way to equivalent elements in fig1 . a projector 208 may be positioned so that a visualization of a sports scene , such as a batter , catcher , umpire , and home plate may be presented to the user on the screen 212 . the console 204 may communicate with the projector 208 to present a scene consistent with the user &# 39 ; s selection of sport , skill level , professional athlete to visualize , and the like . a camera or cameras 210 may be positioned inside each stadium 200 in the upper corners and facing diagonally across the playing area to record action within the stadium 200 . information collected within the stadium 200 by the cameras , 210 , console 204 , stream processor 110 , and the like may be provided over the console 204 internet connections to a web server 122 as depicted in fig1 . referring to fig3 , real - time sensing may be provided by the motion sensing facility 104 and may include a ‘ constellation ’ of substantially identical , very low - cost motion sensors arranged in a unique pattern to generate not only the necessary 6 - axis data but also additional axes that can be used to increase accuracy while reducing cost , complexity , and size . since the devices are substantially identical to one another , the data collected from each is similar , which results in simpler processing , which in turn reduces processor complexity , power budget , and other processor support requirements . the constellation configuration of substantially identical sensors employs a novel approach of separating the sensors in space so that no two axes align . in one embodiment , the sensors would be relatively disposed to ensure that no two axes align but at least one axis of each sensor intersects with at least one axis of at least one other sensor . alternatively , the sensors could be disposed to ensure that all axes are not aligned and all axes of any one sensor do not intersect with any axes of any of the other sensors . each of these configurations may provide benefits while presenting assembly tradeoffs that may be evaluated when determining a particular implementation of the methods and systems herein described . in the simplest case of two 3 - axis acceleration sensors , software can choose any arbitrary real - world axis , such as a z - axis defined by earth &# 39 ; s gravitational force , calculate the acceleration vector for this arbitrary axis from each sensor , and convert the difference between the two sensors &# 39 ; outputs into a real - world 6 - axis motion . this approach provides additional benefits as well . for an object at rest , each sensor would be under fixed 1 - gravity acceleration due to the earth &# 39 ; s gravitational field . this information is easily converted to an absolute tilt , or orientation to the earth &# 39 ; s surface . in addition , a unique benefit to separating the sensors is that they would facilitate sensing the centripetal and / or centrifugal forces of the object as it spins . centripetal and / or centrifugal force data cannot be collected using any previous combination of gyroscope , accelerometer , and magnetometer . centripetal and / or centrifugal force data may be particularly valuable for applications of measuring the motion of sports equipment such as balls , pucks , etc . in an example , if the sensors are equidistant from the center of gravity / center of rotation , then centripetal and / or centrifugal force would result in opposite acceleration data for sensors on opposite sides of the center of gravity . the magnitude of acceleration directly relates to rotational speed . the non - alignment may provide that all axis of spin can be detected , because if two sensor axes are aligned and rotation is around the aligned axis , there will be no differential acceleration between the sensors , and spin force associated with the aligned rotation cannot be isolated from linear acceleration . by separating the axes and collecting the acceleration data from all of the non - aligned axes , calculations can be performed on the relative values of acceleration to determine a multitude of rotation related forces acting on the sports equipment . since sensing motion based on directional changes in two 3 - dimensional coordinate systems that produce x / y / z acceleration and yaw / pitch / roll motion data is referred to as ‘ 6 - axis sensing ’, and the methods and systems described herein collect data in at least two additional coordinate systems ( e . g . absolute x / y / z orientation and x / y / z rotational velocity ), we the methods and systems described herein may be referred to as ‘ 12 or more axis capable ’. three sensors would provide 3 × 3 × 2 = 18 axis capability , and four sensors would provide 3 × 4 × 2 = 24 axis capability . tradeoffs of the number of sensors may be made based on accuracy requirements , power budget , size constraints , cost , computing complexity , and the like . while two sensors with optimal physical placement are theoretically sufficient to collect data on all 12 axes of motion , additional sensors may have the result of significantly reducing quantizing error . with four sensors measuring acceleration in 12 different acceleration vectors , software processing the data may automatically choose an optimum axis measurement for position and motion calculations from the available data streams . the methods and systems described herein may reduce positional and motion data through a process of modeling known real - world constraints on the individual sensors . for an object in flight , such as a thrown ball , a typical 6 - axis capable sensor system would sense this flight as a lack of any input since no external forces , ( other than gravity which is constant and therefore has no measurable input ) are acting on the system . the methods and systems herein would similarly sense an object in flight , but the accelerometers will sense the object &# 39 ; s deceleration due to air resistance , thus determining a reference point for the object direction of travel . similarly , lift generated by the object &# 39 ; s spin would also be sensed , but since the multiple sensors can accurately measure spin via centripetal and / or centrifugal force , the lift data can be measured distinctly from air resistance along the direction of travel . additionally , transient environmental conditions , such as cross wind gusts can be measured because the conditions may be characterized as an acceleration that cannot be attributed to line - of - flight resistance and lift associated with spin . for objects not in flight , those being either at rest or in the process of being thrown , the concept of modeled constraints also applies . the sensor array and thus the object can be known to be at rest and idle when all sensors report one gravity of acceleration from the earth in a consistent direction . therefore , being able to detect when the object is at rest and when it is in free - fall ( in flight ) facilitates knowing that the object is in the throwing process . during the complex motions of throwing , much is understood about the real constraints to this motion ; a wrist , elbow , and shoulder can make limited motions relative to each other . these physiologic limitations can be used to correct small error measurements and greatly reduce accumulated errors by providing constant feedback . the outcome is not necessarily to greatly increase positional accuracy , but to prevent runaway accumulation of error that would normally result in wildly inaccurate positional data after a few seconds of complex motion . although an example of throwing a ball is used in this disclosure , the methods and systems are not limited to this example . the methods and systems described here may be applied to any other type of sport equipment that can be moved , such as a basketball , javelin , hockey puck , and the like . the motion sensing facility 104 depicted in fig3 may include two or more 3 - axis acceleration sensors 302 separated in space as herein described . the sensors may be placed on two printed circuit boards 312 that are disposed to facilitate the sensors forming a regular tetrahedron with a sensor 302 attached at each of the 4 vertices . as a result each sensing axis is a multiple of 60 degrees out of alignment with every other axis . alternatively , the facility 104 may be composed of one printed circuit board that is creased to form the tetrahedron . representative sensors 302 may include accelerometer mma7260qt by freescale semiconductor . a processor 304 suitable for interfacing with the sensors 302 and a communication device may include the microchip pic18f24k10 processor . power may be provided by a battery 308 , such as the crf2450 lithium coin cell . wireless communication may be facilitated by a radio device 310 such as linx txm - 916 - es 916 mhz transmitter , however higher frequency burst transmitters in the 2 . 4 ghz or higher range may provide lower power consumption . although sensors , such as gyroscopes , accelerometers and compasses have been available in various forms for many years , recent developments in micromachined microelectromechanical systems ( mems ) technology have resulted in a new generation of sensors that are relatively low cost , accurate , fast , and can measure a very wide range of inputs . it is noteworthy that gyroscopes required by traditional 6 - axis sensing systems remain roughly ten times as expensive as an accelerometer of the same class . while the trend to smaller and cheaper sensor devices can be expected to continue , the complexity of manufacturing a gyroscope sensor shall remain far greater than that of an accelerometer . the same can be said for solid state compasses , which require complex magnetic field sensors and still suffer from very limited accuracy . the methods and systems herein benefit from eliminating the gyroscope and not depending on a compass for an external reference . motion sensing may be particularly effective when the motion data can be read by a subscriber in real - time over a wireless connection , such as a radio or infrared link . both methods place a high demand on power consumption , imposing limitations on the amount of data that can be sent and thus the amount of sensor data that can be processed and transmitted . the invention is particularly suited to overcome these limitations , since using substantially identical sensors may mean that equivalent sensors &# 39 ; data streams can be integrated to a compact set of data with relatively modest processing . referring to fig4 , a flow chart of potential steps associated with the methods and systems herein described , data from the plurality of sensors may be sampled 402 . the sample frequency may be arbitrary , but an exemplary sample frequency facilitates acquiring sixteen samples from each axis of the plurality of sensors each second . the sampled axis sensor data may be processed 404 to adjust for any phase shift associated with the acquisition or transmission of the data from the physical sensors to a processing facility such as a stream processor 110 that is depicted in fig1 . the data may be analyzed to detect a relevant start of motion 408 data set . this may be detected by identifying that the object is at rest or that the object has transitioned from one type of motion ( e . g . a baseball being manipulated by a pitcher to position the ball for throwing ) to another type ( e . g . pitcher going into a windup motion ). this may alternatively be detected by the adapted sport equipment 102 being detected as in a known position ( e . g . a golf ball being placed on a tee ). once a start of motion sequence is detected in step 408 , the motion of the adapted sport equipment 102 may be tracked 410 by collecting motion samples from the sensing facility 104 . the tracked data may be analyzed 412 to generate motion related vectors , moments , torque , and other forces and movements as may be determined from the plurality of sensors 302 in the motion sensing facility 104 . data representing the motion of the object generated in step 412 may be provided to a visualization engine to start visualization 414 of the sport equipment in motion . the visualization engine may use a predetermined physics or inverse kinematics model of the adapted sports equipment 102 to provide a highly accurate visualization that is true to the motion of real sport equipment . a trajectory of the adapted sport equipment 102 is modeled 418 and the object is presented in a visualization following the trajectory . the visualization may include simulation of objects , people , animals , vehicles , other sports equipment , and the like and the interactions between these simulation elements and the visualized sport equipment following the determined trajectory may be simulated 420 and visualized . data related to these interactions and the determined trajectory may be collected and analyzed to generate a rating 422 for the sensed and visualized event . the data and ratings may be associated 424 with a user id and the data may be provided to display process 428 for local display . additionally the data and ratings associated with the user may be stored 430 in a web server so that the user can access the data through a client interface , such as a web browser . simulation of the visualization of the moving sports equipment , virtual participants ( e . g . professional athletes ), and other visualized aspects disclosed herein , may be modeled and controlled , for example , using equations of motion , such as inverse kinematics ( ik ) equations that describe the motion of a feature , such as a professional athlete , in a coordinate system . generally , a set of equations may be established that describe each sub - part of the athlete , based on the athlete &# 39 ; s measurements and estimated degrees of freedom , such as the athlete &# 39 ; s ability to react to the simulated sports object . ik equations may be used , for example , to predict the impact of a simulated baseball bat with a visualized projection of a pitched baseball . an external programming environment that may be associated with the methods and systems herein described may include , for example , a . net object layer for users with microsoft &# 39 ; s . net software development platform . the . net framework offers a development environment for microsoft windows and web applications , as well as more atomic components and web services . while the . net framework is one useful programming paradigm for deploying services and various internet and intranet applications , it will be appreciated that other environments may also , or instead , be usefully employed with the systems described herein . for example , a distributed computing environment may be supported by java ee from sun or component object model (“ com ”), microsoft &# 39 ; s precursor to . net . similarly , the simulation models of the professional athletes may be packaged as libraries or subroutines for a standalone application , or may be deployed as a service , such as a web service ( such as in a services oriented architecture ), or through a web - accessible interface . all such software implementations , as well as variations and combinations thereof , are intended to fall within the scope of this disclosure . an application programming interface (“ api ”) that is associated with the methods and system herein described may communicate with other software aspects of the platform 100 using , for example data messages , a tcp packet stream , or any other message - oriented , connection - oriented , serial , or other communications protocol . in one embodiment , the api exchanges data messages with the . net object layer of the external programming environment . more generally , the api may include any set of definitions of the ways an external computer system communicates with the internal functional modules of the platform 100 . thus , any predefined programmatic interface may be used as the api of the platform 100 , provided the api may be suitably adapted to the external programming environment . in one aspect , the api may accommodate explicit access to each of the facilities of the platform 100 , so that a programmer may , for example , configure , refine , load , customize , analyze , or otherwise manipulate the simulation features . in embodiments , a simulation module may take as inputs three - dimensional models from one or more three - dimensional visualization modules , such as commercially available modules . referring to fig5 , a cut away exploded view of a baseball embodiment of the present invention , the exterior appearance of the baseball 502 may provide the look and feel of a real baseball . the adapted baseball 502 may include a cowhide cover 504 , may weigh between five and five and one quarter ounces , may include a regulation one - hundred eight stitches 508 , the circumference may be between nine and nine and one quarter inches , and the cover 504 may include a brand name , such as a brand name of a real baseball manufacturer 510 . internally , the baseball 502 may be made up of substantially similar materials in a similar construction technique as a baseball with the exception that the motion sensing facility 104 may be enclosed in the baseball 502 . as described herein , the sensing facility 104 may include electronics for multi - axis sensing 512 , processing and wireless communication electronics 514 , and optionally may include an access point to service or configure the motion sensing facility 104 . in this way , a traditional baseball may be adapted to include the innovative methods and systems of multi - axis motion sensing herein described . fig6 depicts the adapted real sport equipment of fig5 replacing the common input structures such as a joystick or a wireless remote ( e . g . wiimote ). the adapted baseball 502 that includes motions sensors 512 and control / communication electronics 514 interface through a wireless connection with game console receivers 602 that receive and convert the data to 3d rendering data to facilitate integrating the received data with game console display 604 . in this way a thrown hall may send sensor data via a bluetooth or rf link to a receiver of a game console that integrates with the game software to show real - time interaction of the sensed baseball 502 and on - screen participants 608 in real - time . fig7 depicts a variety of real sports equipment that may be adapted with the embedded motion sensing facility 104 . fig7 is an exemplary depiction of a subset of the potentially relevant sports equipment and it includes baseball , billiards , softball , volleyball , soccer , basketball , football as represented by element 702 . other exemplary equipment and sports include hockey 704 , boxing 708 , bowling 710 , baseball batting 712 , golf 714 , tennis racket and ball 718 , lacrosse 720 , cricket 722 , rugby 724 , and others depicted here and not depicted here . the methods and system herein facilitate interacting with simulated sports and entertainment activities that go beyond traditional simulated golf or the rudimentary tracking of popular video game controllers . the net result is multiple sports with world - wide appeal . fig8 represents key elements in an embodiment of the methods and systems herein that provide a complete experience for participants . users of a real - sports equipment tracking and interactive simulation system may gain access to the system through a smart card 802 as herein described . in embodiments , the smart card may be a branded smart card provided through or on behalf of a facilitator of the complete experience system . the participant may also interact with the system through a touchscreen 804 that may be associated with or may represent a user interface of a console as herein described . the participant may select sport , configuration , and recording options , among others using the touch - screen . participants may get actively immersed 808 in real - sport games . the participant immersion may be captured by digital cameras 810 to record a video of each game . the system may also include a database system 812 that may include player statistics and rankings . the video , statistics , rankings , payment options , and the like may be accessible through a website 814 associated with the system . in embodiments , promotional contests may be offered to participants and participants who participate in the promotional contests 818 may have an opportunity to receive sponsored prizes 820 . referring to fig9 , an exemplary personal participant web page 900 of the invention , the user may configure demographic information 902 . personal highlight videos 904 of interactive simulation games may be accessible through hyperlinks and displayed in a video window 914 . personal statistics 908 of the participant may be listed along with rank 910 , and comparative data 912 . optionally a user may include an image , such as a photograph of the user 918 to be displayed on the personal participant web page 900 . fig1 depicts a public forum web page 1000 of the invention . a public forum page 1000 may be configured for each sport , such as soccer as depicted in fig1 . the public forum page 1000 may include a list of leaders 1002 in various age - gender categories . the list may be changed to show a specific category by selecting a category . daily high scores 1004 may be displayed and updated throughout the day as scores and rankings for each participant use of the system is automatically uploaded to the web server responsible for the public forum page 1000 . additionally , a viewer of the public forum web page 1000 may view highlights 1008 and may vote for the play of the day 1010 . the methods and systems for real sport equipment motion detection and interactive simulation may have applications in a wide variety of sports and sports entertainment as well as many other fields . below are exemplary descriptions of the utility , benefit , advantages , and applications of the methods and systems herein for some sports related markets . the following descriptions are for pedagogical purposes and not meant to be limiting . as an interface for real - ball simulation games programmed to show virtual baseballs that continue the flight of pitched or batted baseballs , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cybersports (“ cs ”) baseball simulation games , in which the following data is captured : speed read - outs of thrown or batted balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of pitches and throws , graphically recreated and depicted in relation to targets , in particular a virtual catcher &# 39 ; s mitt , strike zone , cut - off man , first baseman &# 39 ; s mitt or advertisers &# 39 ; logos and the like , typically shown on a virtual baseball field as well as other settings ; distance analysis of thrown or batted balls , graphically depicted in the context of various reference points on a virtual baseball field and other settings ; tracking the arm motion and hand path of a pitcher or fielder ( i . e . the ball &# 39 ; s path prior to its release point ) and graphically recreating and depicting that motion on - screen ; for each pitch or throw , a player &# 39 ; s arm motion and hand path may be compared to the arm motion and hand path of select professional players as an ideal frame of reference ; tracking the flight of thrown balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the pitch or throw on - screen ; for each pitch , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a pitcher &# 39 ; s spin and trajectory for various pitches ( fastball , changeup , curveball , slider , split - finger , cut fastball , sinker and the like ) may be compared alongside spin and trajectory calculations of pitches thrown by select professional pitchers as an ideal frame of reference ; tracking the path of a swung bat by embedding multi - axis sensors in two places , the bat : handle and barrel , then translating the data relative to virtual or real pitches and graphically recreating and depicting each swing path on - screen ; for each swing , a player &# 39 ; s swing path may be compared to the swing path of select professional players as an ideal frame of reference ; and , in the context of utilizing cs &# 39 ; baseball simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball baseball simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual baseball gloves and mitts , in branded “ hit it here !” animations beyond the outfield wall and as part of any other types of branding images in various virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy baseball league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as a minor league system , player showcases , contests and tournaments , player drafts , personalized baseball cards , contracts , salaries , stadium and team owners , general managers , team managers , pitching and batting coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously as hitters competing in home run derby contests , as pitchers throwing to cyber - athlete hitters or as pitchers and field players competing in accuracy and distance throwing contests and the like . cs &# 39 ; real - ball object - tracking interface may make the baseball game - play completely realistic due to its ability to generate motion data from inside actual baseballs , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations for throwing , pitching and hitting may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their pitching / throwing form and technique in a graphical way and recognize nuances in their throwing motion compared to professional standards ; ball path and rotation feedback may allow players to see their pitching / throwing performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with arm and hand path feedback , players may be shown the cause and effect between pitching / throwing technique and performance , including how finger placement and pressure on the ball , arm and wrist angle and other mechanics affect the outcome of the throw or pitch ; bat path feedback may allow players to see their hitting form and technique in a graphical way and compare it to professional standards ; combined with speed , direction and distance feedback on the player &# 39 ; s hits , the player may be shown the cause and effect between hitting technique and performance , including how timing and rotation of the wrists , direction and angle of the bat head through point of contact and other factors collectively affect the outcome of the swing ; and , in the context of cs &# 39 ; baseball simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., beer ads in sports bars and sports equipment and apparel ads in sporting goods stores ). nintendo wii — uses a mounted optical sensor and an embedded 3 - axis motion sensor in its handheld remote control , called a wiimote ( with an optional wii motion plus extension for measuring rotation ), which players move around for both pitching and hitting in order to interact with videogame images on - screen ; visual sports systems (“ vss ”)— uses a pair of line - scan cameras that track the trajectory and speed of moving pitches and then shows video images of amateur batters &# 39 ; reactions in real time ; power alley &# 39 ; s power pitcher — uses a radar gun and slitted screen to detect speed and pitch location and then shows slightly - delayed video images of major league batters &# 39 ; responses ; revfire — uses sensors and magnetic radiation to determine speed and rotation of pitches , which register on a digital display ; 3d4life — uses an accelerometer in a disc , called a “ speed ring ”, that goes around the barrel of a bat to measure and display bat speed ; and rawlings &# 39 ; speed ball — uses an accelerometer and digital display inside a baseball to measure and display a player &# 39 ; s throwing speed . how cs &# 39 ; tracking system adds unique value compared to its competitors unlike nintendo &# 39 ; s wii , cs &# 39 ; smart baseballs & amp ; bats may allow players to pitch and make infield and outfield throws using regulation - size base - balls and swing using regulation - size bats within first - person , life - size baseball stadium environments ; cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real baseballs , or close facsimiles , may make the interface and game - play completely realistic , much more so than the interaction offered by nintendo &# 39 ; s wiimote , vss &# 39 ; cameras or power alley &# 39 ; s interactive video screen ; nintendo wii does not use real sports equipment , so it is incapable of providing useful training feedback based on actual athletic performance ; vss and power alley &# 39 ; s power pitcher only measure speed and direction , so they miss out on the rotation of the ball as well as the more nuanced analysis of a pitcher &# 39 ; s arm , hand and finger motions ; cs &# 39 ; performance data and in - depth analysis provides much more comprehensive feedback than revfire and 3d4life , which only offer digital read - outs rather than full video simulations ; revfire measures speed and rotation , but doesn &# 39 ; t provide overall analysis of the trajectory and accuracy of pitches and throws ; 3d4life measures bat speed , but does not take into account bat angle , wrist rotation and other factors associated with successful hitting technique and batting results ; and none of the other real - ball baseball simulation systems feature any type of in - game advertising opportunities , much less interactive promotional tie - ins and targeted , venue - specific advertising strategies . entertainment market — sports bars , entertainment : centers , museums , halls of frame , stadiums , cruise ships , casinos , resorts , movie theaters , military bases , retail stores , malls , retirement communities , fan - fests , college campuses , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - bat , real - ball virtual baseball ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their baseball skills . as an interface for real - ball soccer simulation games programmed to show virtual soccer balls that continue the flight : of kicked , kneed or headed soccer balls , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs soccer simulation games , in which the following data is captured : speed read - outs of kicked balls , linked to a computer , digital display and any other similar electronic device ; accuracy analysis of passes and shots , graphically recreated and depicted in relation to targets , in particular virtual teammates in motion , a virtual soccer net or advertisers &# 39 ; logos and the like , typically shown on a virtual soccer field as well as other settings ; distance analysis of kicked balls , graphically recreated and depicted in the context of various reference points on a virtual soccer field and other settings ; tracking the flight of kicked balls , particularly their acceleration , rotation and the like , specifically in the context of trying to bend them around a wall of defenders and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the kick on - screen ; for each pass or shot , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory may be compared alongside spin and trajectory calculations of bended shots by select professional players as an ideal frame of reference ; showing defensive and goalie reactions to a player &# 39 ; s ball - handling with the on - screen image set in motion as if the player is advancing on the opposing team &# 39 ; s goal ; and , in the context of utilizing cs &# 39 ; soccer simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball soccer simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of the four corners of a virtual soccer goal and as part of any other types of branding images in various virtual locations , and awarding promotional prizes whenever players success - fully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy soccer league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as player showcases , contests and tournaments , player drafts , personalized soccer cards , contracts , salaries , stadium and team owners , general managers , team managers , coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously as shooters competing in goal - scoring contests or passers competing in accuracy and distance kicking contests and the like . cs &# 39 ; real - ball object - tracking interface may make the soccer game - play completely realistic due to its ability to generate motion data from inside actual soccer balls , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations for shooting and passing may provide players with a clear and quantifiable picture of their performances ; ball path and rotation feedback may allow players to see their shooting and passing performances in an in - depth , three - dimensional way and compare them against professional standards ; and , in the context of utilizing cs &# 39 ; soccer simulations for experiential marketing , out - of - home advertising and promotional opportunities that are integrated , customizable , interactive and experiential may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., sports drink ads in fitness centers and videogame ads in malls ). visual sports systems ( vss )— uses a pair of line - scan cameras that track the trajectory and speed of moving shots and then show an amateur goalie &# 39 ; s reactions in real time ; a smaller version uses one set of line - scan cameras with results shown on a mounted video console . how cs &# 39 ; tracking system adds unique value compared to its competitors cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real soccer balls , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than the interaction offered by vss &# 39 ; camera technology ; cs &# 39 ; rotational data and in - depth analysis of each facet of a player &# 39 ; s passes and shots may provide more comprehensive feedback on player performance than vss , which only measures ball speed and direction ; and no other real - ball soccer simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual soccer ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their soccer skills . as an interface for real - ball golf simulation games programmed to show virtual golf balls that continue the flight of impacted golf balls , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs golf simulation games , in which the following data is captured : speed read - outs of impacted balls linked to a computer , digital display and any other similar electronic device , accuracy analysis of shots , graphically recreated and depicted in relation to targets , in particular greens , flags , holes , advertiser &# 39 ; s logos and the like , typically shown on a virtual golf course as well as other settings , distance analysis of impacted golf balls , or close facsimiles , graphically recreated and depicted in the context of various reference points on a virtual golf course , driving range , pitch & amp ; putt , putting green and the like ; tracking the flight of impacted balls , particularly their acceleration , rotation and the like , specifically to measure hook , slice , backspin and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the shot on - screen ; for each shot , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory for various shots ( straight drives , dog - legs left and right , iron shots with forward and back - spin , trap shots and the like ) may be compared alongside spin and trajectory calculations of shots by select professional players as an ideal frame of reference ; demonstrating possible causes of the ball &# 39 ; s trajectory based on extrapolating the player &# 39 ; s club - face angle upon impact as well as an estimation of the player &# 39 ; s swing path , or , for greater precision , tracking the actual path of a swung golf club by embedding multi - axis sensors in two places , the handle and club - head , then translating the data and graphically recreating and depicting each swing path on - screen ; comparisons may be made by graphically depicting the player &# 39 ; s club - face angle and proposed or actual swing path alongside club - face angles and swing paths of professional players &# 39 ; shots as an ideal frame of reference ; and , in the context of utilizing cs &# 39 ; golf simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball golf simulation games and skills training activities , such as integrating advertisers &# 39 ; logos into various situations ( e . g ., to indicate where the 250 - foot marker is on a virtual driving range , to highlight the cup at the end of a 25 - foot putt , or to show the most desirable area to aim for on a par - 3 green as players tee off , and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes when - ever players successfully hit it past , into or onto these targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy golf league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as player showcases , contests and tournaments , purses , caddies , individual statistics , video highlights , “ cybersports center ” broadcasts , trophies , awards ceremonies and the like ; and as part of live promotional events and the like , during which real professional golfers and celebrities appear live via cs &# 39 ; online gaming portal to compete against various golfers , or “ cyber - athletes ”, simultaneously in various types of contests including stroke play , closest - to - the - pin , farthest drive and the like . cs &# 39 ; real - ball object - tracking interface may make the golf game - play completely realistic due to its ability to generate motion data from inside actual golf balls , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations of a variety of shots may provide players with a clear and quantifiable picture of their performances ; ball path and rotation feedback may allow players to see their shooting performances in an in - depth , three - dimensional way and then compare them against professional standards ; club path feedback may allow players to see their golf swing form and technique in a graphical way and compare it to professional standards ; combined with speed , direction and distance feedback on the player &# 39 ; s shots , the player may be shown the cause and effect between swinging technique and performance , including how timing and rotation of the wrists , direction and angle of the club face through point of contact and other factors collectively affect the outcome of the swing ; and , in the context of cs &# 39 ; golf simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., cable / phone service ads in luxury condominiums and foot - wear and apparel ads in golf retail stores ). nintendo wii — uses a mounted optical sensor and an embedded 3 - axis motion sensor in its handheld remote control , called a wiimote ( with an optional wii motion plus extension for measuring rotation ), which players swing in order to interact with videogame images on - screen ; visual sports systems ( vss )— uses a pair of line - scan cameras that track the speed and trajectory of golf shots and show the result of each shot in real time ; full swing golf — uses a pair of infrared sensor arrays that track the speed and trajectory of golf shots and show the result of each shot in real time ; about golf — uses a device placed behind the projection screen that gives off microwave emissions which track the speed and trajectory of golf shots and show the result of each shot in real time ; and deadsolid golf — uses a hitting mat with three parallel sensor strips that detect the speed and angle of the club - head through impact with the ball , which , by extension , tracks speed and trajectory of each golf shot and shows the result of the shot in real time . how cs &# 39 ; tracking system adds unique value compared to its competitors unlike nintendo &# 39 ; s wii , cs &# 39 ; smart golf balls may allow players to hit regulation - size balls and swing regulation - size clubs within first - person , life - size golf course environments ; cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into golf balls , or close facsimiles , may make the interface between the object - tracking and game - play completely realistic , much more so than the interaction offered by nintendo &# 39 ; s wiimote , vss &# 39 ; cameras , full swing golf and deadsolid golf &# 39 ; s infrared sensors , and about , golf &# 39 ; s microwave - emitting pad ; nintendo wii does not use real sports equipment , so it is incapable of providing useful training feedback based on actual athletic performance ; cs &# 39 ; rotational data and in - depth analysis of each facet of a player &# 39 ; s shots may provide more comprehensive feedback on player performance than its competitors &# 39 ; products , which typically only measure the speed and linear direction of the ball ; and none of the other real - ball golf simulation systems feature any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual golf ; and fitness & amp ; training market — athletic training facilities , fitness centers , golf courses , golf academies , hospitals , schools , colleges , sporting goods stores , luxury condominiums , the in - home market and any other place where people may elect to exercise , compete and seek to improve their golf skills . as an interface for real - glove simulation boxing games programmed to show virtual boxing gloves that continue the movements of real boxing gloves , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs boxing simulation games , in which the following data is captured : speed read - outs of punches thrown , linked to a computer , digital display and any other similar electronic device ; accuracy analysis of punches , graphically recreated and depicted in relation to targets , in particular a virtual trainer &# 39 ; s practice gloves , a punching bag , advertisers &# 39 ; logos , sparring partners or competitive boxers in motion and the like ; punch combination analysis , graphically recreated and depicted to show speed of delivery and accuracy of multiple punches thrown in quick succession ; tracking the flight of a punch or series of punches , particularly the acceleration and rotation of a boxer &# 39 ; s jab , cross , hook and uppercut , and graphically recreating and depicting the paths of each type of punch on - screen ; calculating the direction and force of these punches , and graphically manifesting these calculations on - screen ; comparisons may be made by graphically depicting the boxer &# 39 ; s punch trajectories compared with select professional boxers &# 39 ; punches as an ideal frame of reference , and in the context of utilizing cs &# 39 ; boxing simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - glove boxing simulation games and skills training activities , such as integrating advertisers &# 39 ; logos into various situations ( e . g ., practicing with moving logos as targets , having logos as virtual boxers &# 39 ; tattoos which light up when the player punches them , and the like ), and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy boxing league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as contests and tournaments , team matches , contracts , salaries , managers , coaches , individual statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship belts , awards ceremonies , titles by weight class and the like ; and as part of live promotional events and the like , during which real professional boxers and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , in various contests including accuracy of combinations , speed punching , power punching and the like . cs &# 39 ; real - ball object - tracking interface may make the boxing game - play completely realistic due to its ability to generate motion data from inside actual boxing gloves , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and power feedback with graphical representations of each may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their punching form and technique in a graphical way and recognize nuances in their punching motion compared to professional standards ; and , in the context of cs &# 39 ; boxing simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., beer ads in sports bars and sports equipment and apparel ads in sporting goods stores ). konami &# 39 ; s mocap boxing — uses an overhead infrared sensor array that recognizes the timing and linear direction of a player &# 39 ; s punch in relation to an on - screen opponent that reacts in real time ; nintendo wii — uses a mounted optical sensor and an embedded 3 - axis motion sensor in its handheld remote control , called a wiimote ( with an optional wii motion plus extension for measuring rotation ), which players move around to throw punches in order to interact with video - game images on - screen ; how cs &# 39 ; tracking system adds unique value compared to its competitors unlike konami &# 39 ; s mocap boxing and nintendo &# 39 ; s wii , cs &# 39 ; smart gloves may allow boxers to use regulation - size boxing gloves within first - person , life - size boxing ring environments ; cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into boxing gloves , or close facsimiles , may make the interface between the object - tracking and game - play completely realistic , much more so than the interaction offered by konami &# 39 ; s single infrared sensor array and rubber grips and nintendo &# 39 ; s wiimote ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s various punches may provide more comprehensive feedback on player performance than its competitors &# 39 ; products , which typically only register the linear direction of a punch in the context of a videogame ; and no other real - glove boxing simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by participating in real - glove , virtual boxing ; and fitness & amp ; training market — athletic training facilities , fitness centers , hospitals , schools , colleges , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and improve their boxing skills . as an interface for real - ball simulation games programmed to show virtual footballs that continue the flight of thrown or kicked footballs , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs football simulation games , in which the following data is captured : speed read - outs of thrown or kicked balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of passes , field goal attempts and punts , graphically recreated and depicted in relation to targets , in particular virtual receivers in motion , virtual uprights , a virtual football field featuring a color - coded grid overlay between the 20 yard line and end zone , advertisers &# 39 ; logos and the like , typically shown on a virtual football field as well as other settings ; distance analysis of thrown or kicked balls , graphically recreated and depicted in the context of various reference points on a virtual football field and other settings ; tracking the arm motion and hand path of the player as quarterback ( i . e . the ball &# 39 ; s path prior to its release point ) and graphically recreating and depicting that motion on - screen ; for each throw , a player &# 39 ; s arm motion and hand path may be compared to the arm motion and hand path of select professional players as an ideal frame of reference ; tracking the flight of thrown or kicked balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the throw on - screen ; for each throw or kick , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory for various throws or kicks may be compared alongside spin and trajectory calculations of throws or kicks by select professional players as an ideal frame of reference ; showing defensive players &# 39 ; reactions to a player &# 39 ; s ball - carrying skills with the on - screen image set in motion as if the player is advancing on the opposing team &# 39 ; s end zone ; and in the context of utilizing cs &# 39 ; football simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball football simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual receivers and or as branded “ kick it here !” animations beyond the goal - posts and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy football league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as player showcases called “ combines ”, contests and tournaments , player drafts , personalized football cards , contracts , salaries , stadium and team owners , general managers , team managers , coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams , title or “ cyber - bowl champions ” and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously as quarterbacks in accuracy and distance throwing contests and as kickers in field - goal and punting contests and the like ; and cs &# 39 ; real - ball object - tracking interface may make the football game - play completely realistic due to its ability to generate motion data from inside actual footballs , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations for throwing and kicking may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their throwing form and technique in a graphical way and recognize nuances in their throwing motion compared to professional standards ; ball path and rotation feedback may allow players to see their throwing and kicking performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with arm and hand path feedback , players may be shown the cause and effect between throwing technique and performance , including how arm and wrist angle and other mechanics affect the outcome of the throw ; and , in the context of cs &# 39 ; football simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., beer ads in sports bars and sports equipment and apparel ads in sporting goods stores ). nintendo wii — uses a mounted optical sensor and an embedded 3 - axis motion sensor in its handheld remote control , called a wiimote ( with an optional wii motion plus extension for measuring rotation ), which players move around in order to throw passes and interact with video - game images on - screen ; and visual sports systems (“ vss ”)— uses a pair of line - scan cameras that track the trajectory and speed of passes and kicks and then shows video images reacting in real time . how cs &# 39 ; tracking system adds unique value compared to its competitors unlike nintendo &# 39 ; s wii , cs &# 39 ; smart footballs may allow players to throw and kick using regulation - size footballs within first - person , life - size football stadium environments ; cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real footballs , or close facsimiles , may make the interface and game - play completely realistic , much more so than the interaction offered by nintendo &# 39 ; s wiimote or vss &# 39 ; cameras ; nintendo wii does not use real sports equipment , so it is incapable of providing useful training feedback based on actual athletic performance ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s passes and kicks may provide more comprehensive feedback on player performance than vss , which only measures ball speed and direction ; and no other real - ball football simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual football ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their football skills . as an interface for real - ball simulation games programmed to show virtual basketballs that continue the flight of thrown ( by way of passing or shooting ) basketballs , or close facsimiles , and interact with video - game images in real time ; as an interface for skills training activities , separate or combined with the cs basketball simulation games , in which the following data is captured : speed read - outs of thrown balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of passes , free throws and two - & amp ; three - point attempts , graphically recreated and depicted in relation to targets , in particular virtual teammates in motion , a virtual backboard , rim and basket , advertisers &# 39 ; logos and the like , typically shown on a virtual basketball court as well as other settings ; distance analysis of thrown balls , graphically depicted in the context of various reference points on a virtual basketball court and other settings to determine the best passing and shooting techniques from various distances ; tracking the arm motion and hand path of a player in the act of shooting ( i . e . the ball &# 39 ; s path prior to its release point ) and graphically recreating and depicting that motion on - screen ; for each shot , a player &# 39 ; s arm motion and hand path may be compared to the arm motion and hand path of select professional players as an ideal frame of reference ; tracking the flight of balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the pass or shot : on - screen ; for each pass or shot , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory for various passing and shooting situations may be compared alongside spin and trajectory calculations of passes and shots by select professional players as an ideal frame of reference ; showing a defensive player &# 39 ; s reactions to the player &# 39 ; s ball - handling skills with the on - screen image set : in motion as if the player is advancing the ball clown the court ; and in the context of utilizing cs &# 39 ; basketball simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball basketball simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual baskets and teammates , and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy basketball league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as a development league system , player showcases , contests and tournaments , player drafts , personalized basketball cards , con - tracts , salaries , arena and team owners , general managers , team managers , coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , as shooters competing in three - point shooting contests or as passers competing in accuracy contests and the like ; and cs &# 39 ; real - ball object - tracking interface may make the basketball game - play completely realistic due to its ability to generate motion data from inside actual basketballs , or close facsimiles , and process all 6 degrees of freedom in real time ; accuracy feedback with graphical representations for passing and shooting may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their passing and shooting form and technique in a graphical way and recognize nuances in their motion compared to professional standards ; ball path and rotation feedback may allow players to see their passing and shooting performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with arm and hand path feedback , players may be shown the cause and effect between passing and shooting technique and performance , including how arm and wrist angle and other mechanics affect the outcome of the pass or shot ; and , in the context of cs &# 39 ; basketball simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist , sports marketers in reaching their target audiences in venue - specific ways ( e . g ., soda ads in basketball arenas and sports equipment and apparel ads in sporting goods stores ). nintendo wii — uses a mounted optical sensor and an embedded 3 - axis sensor in its handheld remote control , called a wiimote ( with an optional wii motion plus extension for measuring rotation ), which players move around in order to interact with videogame images on - screen ; and visual sports systems (“ vss ”)— uses a pair of line - scan cameras that track the trajectory and speed of shots and passes and then shows video images reacting in real time . how cs &# 39 ; tracking system adds unique value compared to its competitors unlike nintendo &# 39 ; s wii , cs &# 39 ; smart basketballs may allow players to pass and shoot using regulation - size basketballs within first - person , life - size basketball arena environments ; cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real basketballs , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than the interaction offered by nintendo &# 39 ; s wiimote and vss &# 39 ; cameras ; nintendo wii does not use real sports equipment , so it is incapable of providing useful training feedback based on actual athletic performance ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s passes and shots may provide more comprehensive feedback on player performance than vss , which only measures speed and direction ; and no other real - ball basketball simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual basketball ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their basketball skills . as an interface for real - ball simulation games programmed to show virtual hockey pucks that continue the flight of impacted hockey pucks , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs hockey simulation games , in which the following data is captured : speed read - outs of an impacted puck linked to a computer , digital display and any other similar electronic device ; accuracy analysis of passes and shots , graphically recreated and depicted in relation to targets , in particular in particular virtual team - mates in motion , a virtual hockey net , advertisers &# 39 ; logos and the like , typically shown on a virtual hockey rink as well as other settings ; distance analysis of impacted hockey pucks , graphically depicted in the context of various reference points on a virtual hockey rink and other settings ; tracking the movement of impacted pucks , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the pass or shot on - screen ; for or each pass or shot , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory for various passing and shooting situations may be compared alongside spin and trajectory calculations of passes and shots by select professional players as an ideal frame of reference ; tracking the path of a swung hockey stick by embedding multi - axis sensors in two places , in the top ( the handle ) and bottom of the shaft , then translating the data and graphically recreating and depicting each swing path on - screen ; for each swing , a player &# 39 ; s swing path may be compared to the swing path of select professional players as an ideal frame of reference ; showing defensive and goalie reactions to a player &# 39 ; s stick - handling skills with the on - screen image set in motion as if the player is advancing toward the opposing team &# 39 ; s goal ; and in the context of utilizing cs &# 39 ; hockey simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball hockey simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual hockey sticks or the 1 , 2 , 3 , 4 and 5 holes of a hockey net , and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes when - ever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy hockey league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as a minor league system , player showcases , contests and tournaments , player drafts , personalized hockey cards , contracts , salaries , arenas and team owners , general managers , coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , as shooters competing in goal - scoring contests or as passers competing in accuracy contests and the like ; and cs &# 39 ; real - ball object - tracking interface may make the hockey game - play completely realistic due to its ability to generate motion data from inside actual hockey pucks , or close facsimiles , and process all 6 degrees of freedom in real time ; speed and accuracy feedback with graphical representations for passing and shooting may provide players with a clear and quantifiable picture of their performances ; stick path feedback may allow players to see their passing and shooting form and technique in a graphical way and recognize nuances in their stick motion compared to professional standards ; ball path and rotation feedback may allow players to see their passing and shooting performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with stick path feedback , players may be shown the cause and effect between passing and shooting technique and performance , including how swing mechanics affect the outcome of the pass or shot ; and , in the context of cs &# 39 ; hockey simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., soda ads in hockey arenas and sports equipment and apparel ads in sporting goods stores ). visual sports systems (“ vss ”)— uses a pair of line - scan cameras that track the trajectory and speed of shots and then shows video images of goalies &# 39 ; reactions in real time . how cs &# 39 ; tracking system adds unique value compared to its competitors cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real hockey pucks , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than the interaction offered by vss &# 39 ; cameras ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s passes and shots may provide more comprehensive feedback on player performance than vss , which only measures speed and direction ; and no other real - puck hockey simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual hockey ; and fitness & amp ; training market — athletic training facilities , fitness centers , hockey links , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their hockey skills . as an interface for real - ball simulation games programmed to show virtual tennis balls that continue the flight of impacted tennis balls , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs tennis simulation games , in which the following data is captured : speed read - outs of impacted balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of tennis shots , graphically recreated and depicted in relation to targets , in particular color - coded grid overlays on the service box and receiving side of the court for diverse shots as well as various types of match situations and the like , typically shown on a virtual tennis court as well as other settings ; distance analysis of tennis serves and ground strokes , graphically recreated and depicted in the context of a close - up view of the service box , sidelines and end line being targeted ; tracking the flight of impacted balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the serve or shot on - screen ; for each serve or shot , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory for various serves and shots ( first serve , second serve , kick - serve , topspin , slice , drop shot , overhead and the like ) may be compared alongside spin and trajectory calculations of serves and shots by select professional players as an ideal frame of reference ; tracking the path of a swung tennis racket by embedding multi - axis sensors in two places , one at each end of the handle , then translating the data relative to virtual or real balls in motion and graphically recreating and depicting each swing path on - screen ; for each swing , a player &# 39 ; s swing path may be compared to the swing path of select professional players as an ideal frame of reference ; and , in the context of utilizing cs &# 39 ; tennis simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball tennis simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual baselines and service boxes or as branded “ hit it here !” animations placed randomly on the court and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy tennis league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as player showcases , contests and tournaments , purses , coaches , individual statistics , video highlights , “ cybersports center ” broadcasts , trophies , awards ceremonies , rankings and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , in serving accuracy and speed contests as well as ground stroke power and accuracy and the like ; and cs &# 39 ; real - ball object - tracking interface may make the tennis game - play completely realistic due to its ability to generate motion data from inside actual tennis balls , or close facsimiles , and process all 6 degrees of freedom in real time ; speed and accuracy feedback with graphical representations of each may provide players with a clear and quantifiable picture of their performances ; racket path feedback may allow players to see their swinging form and technique in a graphical way and recognize nuances in their swing motion compared to professional standards ; ball path and rotation feedback may allow players to see their serve and ground stroke performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with racket path feedback , players may be shown the cause and effect between swing technique and performance , including how arm and wrist angle and other mechanics affect the outcome of the swing ; and , in the context of cs &# 39 ; tennis simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., credit cards in resorts and sports equipment and apparel ads in sporting goods stores ). nintendo wii — uses a mounted optical sensor and an embedded 3 - axis sensor in its handheld remote control , called a wiimote ( with an optional wii motion plus extension for measuring rotation ), which players move around for both serves and ground strokes in order to inter - act with videogame images on - screen . how cs &# 39 ; tracking system adds unique value compared to its competitors unlike nintendo &# 39 ; s wii , cs &# 39 ; smart tennis balls may allow players to hit serves and ground strokes using regulation - size tennis balls within first - person , life - size tennis court environments ; cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real tennis balls , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than the interaction offered by nintendo &# 39 ; s wiimote ; nintendo wii does not use real sports equipment , so it is incapable of providing useful training feedback based on actual athletic performance ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s shots may provide more comprehensive feedback on player performance than its competitors ; and no other real - ball tennis simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual tennis ; and fitness & amp ; training market — athletic training facilities , fitness centers , country clubs , tennis centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their tennis skills . as an interface for real - ball simulation games programmed to show virtual bowling balls that continue the path of bowled bowling balls , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs bowling simulation games , in which the following data is captured : speed read - outs of bowled balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of bowls , graphically recreated and depicted in relation to targets , in particular virtual bowling pins , advertisers &# 39 ; logos and the like , typically shown in a virtual bowling lane as well as other settings ; tracking the arm motion and hand path of a bowler ( i . e . the ball &# 39 ; s path prior to its release point ) and graphically recreating and depicting that motion on - screen ; for each bowl , a player &# 39 ; s arm motion and hand path may be compared to the arm motion and hand path of select professional players as an ideal frame of reference ; demonstrating the cause and effect of the bowler &# 39 ; s ball movement based on analyzing the angle and rotation of the ball at the bowler &# 39 ; s release point . tracking the movement of bowled balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the bowl on - screen ; for each bowl , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a bowler &# 39 ; s spin and trajectory for various bowling situations ( i . e . pin formations ) may be compared alongside spin and trajectory calculations of bowls thrown by select professional bowlers as an ideal frame of reference ; and in the context of utilizing cs &# 39 ; bowling simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball bowling simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual bowling pins or as branded “ bowl it here !” animations and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy bowling league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as player showcases , contests and tournaments , purses , coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional bowlers and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously in a round of bowling , a series of “ difficult shot ” contests and the like ; and cs &# 39 ; real - ball object - tracking interface may make the bowling game - play completely realistic due to its ability to generate motion data from inside actual bowling balls , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations of each may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their bowling form and technique in a graphical way and recognize nuances in their bowling motion compared to professional standards ; ball path and rotation feedback may allow players to see their bowling performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with arm and hand path feedback , players may be shown the cause and effect between bowling technique and performance , including how arm and wrist angle and other mechanics affect the outcome of the bowl ; and , in the context of cs &# 39 ; bowling simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., beer ads in sports bars and home electronics ads in malls ). nintendo wii — uses a mounted optical sensor and an embedded 3 - axis sensor in its handheld remote control , called a wiimote ( with an optional wii motion plus extension for measuring rotation ), which players move to bowl a virtual ball that interacts with a videogame image on - screen ; brunswick &# 39 ; s virtual bowling — uses sensors at the end of a shortened bowling lane to measure speed and direction of a bowled ball that interacts with videogame images showing the ball &# 39 ; s impact with virtual bowling pins . how cs &# 39 ; tracking system adds unique value compared to its competitors unlike nintendo &# 39 ; s wii , cs &# 39 ; smart bowling balls may allow players to bowl using regulation - size bowling balls within first - person , life - size bowling alley environments ; cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real bowling balls , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than the interaction offered by nintendo &# 39 ; s wiimote and brunswick &# 39 ; s infrared sensors ; nintendo wii does not use real sports equipment , so it is incapable of providing useful training feedback based on actual athletic performance ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s shots may provide more comprehensive feedback on player performance than brunswick , which only measures speed and direction ; and no other real - ball bowling simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , bowling alleys , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement , communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual bowling ; and fitness & amp ; training market — athletic training facilities , bowling alleys , fitness centers , spoils camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their bowling skills . as an interface for real - ball simulation games programmed to show virtual lacrosse balls that continue the flight of thrown lacrosse balls , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs lacrosse simulation games , in which the following data is captured : speed read - outs of thrown balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of passes and shots , graphically recreated and depicted in relation to targets , in particular virtual teammates in motion , a virtual lacrosse net , advertisers &# 39 ; logos and the like , typically shown on a virtual lacrosse field as well as other settings ; distance analysis of thrown balls , graphically depicted in the context of various reference points on a virtual lacrosse field and other set - tings ; tracking the flight of thrown balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the pass or shot on - screen ; for each pass or shot , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory for various passing and shooting situations may be compared alongside spin and trajectory calculations of passes or shots by select professional players as an ideal frame of reference ; tracking the stick path of a player ( i . e . the ball &# 39 ; s path prior to its release point ) by embedding multi - axis sensors in the stick handle , then translating the data relative to the ball in the pocket and graphically recreating and depicting this stick motion on - screen ; for each throw , a player &# 39 ; s stick motion may be compared to the motion of select professional players as an ideal frame of reference ; showing defensive and goalie reactions to a player &# 39 ; s stick - handling skills with the on - screen image set in motion as if the player is advancing toward the opposing team &# 39 ; s goal ; and in the context of utilizing cs &# 39 ; lacrosse simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball lacrosse simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual lacrosse sticks and goals and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy lacrosse league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as a minor league system , player showcases , contests and tournaments , player drafts , personalized lacrosse cards , contracts , salaries , arena and team owners , general managers , team managers , coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , as shooters competing in goal - scoring contests and passers competing in accuracy and distance throwing contests and the like ; and cs &# 39 ; real - ball object - tracking interface may make the lacrosse game - play completely realistic due to its ability to generate motion data from inside actual lacrosse balls , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations for shooting and passing may provide players with a clear and quantifiable picture of their performances ; stick path feedback may allow players to see their throwing form and technique in a graphical way and recognize nuances in their throwing motion compared to professional standards ; ball path and rotation feedback may allow players to see their throwing performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with stick path feedback , players may be shown the cause and effect between throwing technique and performance , including how mechanics affect the outcome of the pass or shot ; in the context of cs &# 39 ; lacrosse simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., beer ads in sports bars and sports equipment and apparel ads in sporting goods stores ). how cs &# 39 ; tracking system adds unique value compared to its competitors cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real lacrosse balls , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than its competitors ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s passes and shots may provide more comprehensive feedback on player performance than its competitors ; and no other real - ball lacrosse simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual lacrosse ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their lacrosse skills . as an interface for real - ball simulation games programmed to show virtual cricket balls that continue the flight of bowled or batted cricket balls , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs cricket simulation games , in which the following data is captured : speed read - outs of thrown or batted balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of bowls , throws and batted balls , graphically recreated and depicted in relation to targets , in particular a virtual catcher &# 39 ; s mitt , wickets , advertisers &# 39 ; logos , highlighted areas of the field for practicing different bat swing techniques and the like , typically shown on a virtual cricket field as well as other settings ; distance analysis of thrown or batted balls , graphically depicted in the context of various reference points on a virtual cricket : ground , in particular the pitch , close - infield , infield , outfield and boundary , as well as other settings ; tracking the arm motion and hand path of a bowler or fielder ( i . e . the ball &# 39 ; s path prior to its release point ) and graphically recreating and depicting that motion on - screen ; for each bowl or throw , a player &# 39 ; s arm motion and hand path may be compared to the arm motion and hand path of select professional players as an ideal frame of reference ; tracking the flight of thrown balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the bowl or throw on - screen ; for each bowl or throw , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a bowler &# 39 ; s spin and trajectory for various types of bowls may be compared alongside spin and trajectory calculations of bowls thrown by select professional bowlers as an ideal frame of reference ; tracking the path of a swung bat by embedding multi - axis sensors in two places , the bat handle and barrel , then translating the data relative to virtual or real bowls and graphically recreating and depicting each swing path on - screen ; for each swing , a player &# 39 ; s swing path may be compared to the swing path of select professional players as an ideal frame of reference ; and , in the context of utilizing cs &# 39 ; cricket simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball cricket simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual cricket gloves and wickets or as branded “ hit it here !” animations beyond the boundary wall and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy cricket league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as player showcases , contests and tournaments , player drafts , contracts , salaries , stadium and team owners , general managers , team managers , bowling and batting coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , as batsmen competing in distance hitting contests , as bowlers bowling to cyber - athlete batsmen , or as bowlers and field players competing in accuracy and distance throwing contests and the like . cs &# 39 ; real - ball object - tracking interface may make the cricket game - play completely realistic due to its ability to generate motion data from inside actual cricket balls , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations for throwing , bowling and batting may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their bowling / throwing form and technique in a graphical way and recognize nuances in their throwing motion compared to professional standards ; ball path and rotation feedback may allow players to see their bowling / throwing performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with arm and hand path feedback , players may be shown the cause and effect between bowling / throwing technique and performance , including how finger placement and pressure on the ball , arm and wrist angle and other mechanics affect : the outcome of the throw or pitch ; bat path feedback may allow players to see their hitting form and technique in a graphical way and compare it to professional standards ; combined with speed , direction and distance feedback on the player &# 39 ; s hits , the player may be shown the cause and effect between hitting technique and performance , including how timing and rotation of the wrists , direction and angle of the bat head through point of contact and other factors collectively affect the outcome of the swing ; and , in the context of cs &# 39 ; cricket simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., beer ads in sports bars and sports equipment and apparel ads in sporting goods stores ). edh sport (“ edh ”)— uses a microwave - emitting pad to detect the motion and speed of bowls as well as ball flight characteristics . how cs &# 39 ; tracking system adds unique value compared to its competitors cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real cricket balls , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , more so than the interaction offered by edh sport &# 39 ; s microwave technology ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s bowls , throws and hits may provide more comprehensive feedback on player performance than edh ; and no other real - ball cricket simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , cricket grounds , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual cricket ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their cricket skills . as an interface for real - ball simulation games programmed to show virtual rugby balls that continue the flight of thrown or kicked rugby balls , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs rugby simulation games , in which the following data is captured : speed read - outs of thrown or kicked balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of passes , kick - offs , attacking kicks , field goals , penalty goals and conversion goal attempts , graphically recreated and depicted in relation to targets , in particular virtual teammates in motion , uprights , advertisers &# 39 ; logos , a rugby field with color - coded grid overlays designed for diverse attacking kick situations , as well as other types of situations and settings distance analysis of thrown or kicked balls , graphically depicted in the context of various reference points on a virtual rugby field and other settings ; and tracking the arm motions and hand paths of a player ( i . e . the ball &# 39 ; s path prior to its release point ) and graphically recreating and depicting that motion on - screen ; for each pass , a player &# 39 ; s arm motions and hand paths may be compared to the arm motions and hand paths of select professional players as an ideal frame of reference ; tracking the flight of thrown or kicked balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the throw or kick on - screen ; for each throw or kick , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a player &# 39 ; s spin and trajectory for various passing and kicking situations may be compared alongside spin and trajectory calculations of passes or kicks by select professional players as an ideal frame of reference ; showing defensive players &# 39 ; reactions to a player &# 39 ; s ball - carrying skills with the on - screen image set in motion as if the player is advancing on the opposing team &# 39 ; s in - goal area ; and in the context of utilizing cs &# 39 ; rugby simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball rugby simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual players &# 39 ; hands or as branded “ kick it here !” animations beyond the uprights and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy rugby league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as player showcases , contests and tournaments , player drafts , contracts , salaries , stadium and team owners , general managers , team managers , coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which real professional athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , as kickers competing in contests that include field goal , penalty goal and conversion goal attempts and the like . cs &# 39 ; real - ball object - tracking interface may make the rugby game - play completely realistic due to its ability to generate motion data from inside actual rugby balls , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations for passing and kicking may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their passing form and technique in a graphical way and recognize nuances in their passing motion compared to professional standards ; ball path and rotation feedback may allow players to see their passing and kicking performances in an in - depth , three - dimensional way and then compare them against professional standards ; combined with arm and hand path feedback , players may be shown the cause and effect between passing technique and performance , including how arm and wrist angle and other mechanics affect the outcome of the pass ; and , in the context of cs &# 39 ; rugby simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., beer ads in spoils bars and sports equipment and apparel ads in sporting goods stores ). how cs &# 39 ; tracking system adds unique value compared to its competitors cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real rugby balls , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than the its competitors ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s passes and kicks may provide more comprehensive feedback on player performance than its competitors ; and no other real - ball rugby simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual rugby ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their rugby skills . as an interface for real - ball simulation games programmed to show virtual softballs that continue the flight of pitched or batted softballs , or close facsimiles , and interact with videogame images in real time ; as an interface for skills training activities , separate or combined with the cs softball simulation games , in which the following data is captured : speed read - outs of thrown or batted balls linked to a computer , digital display and any other similar electronic device ; accuracy analysis of pitches and throws , graphically recreated and depicted in relation to targets , in particular a virtual catcher &# 39 ; s mitt , strike zone , cut - off man , first baseman &# 39 ; s mitt or advertisers &# 39 ; logos and the like , typically shown on a virtual softball field as well as other settings ; distance analysis of thrown or batted balls , graphically depicted in the context of various reference points on a virtual softball field and other settings ; tracking the arm motion and hand path of a pitcher or fielder ( i . e . the ball &# 39 ; s path prior to its release point ) and graphically recreating and depicting that motion on - screen ; for each pitch or throw , a player &# 39 ; s arm motion and hand path may be compared to the arm motion and hand path of select college and olympic players as an ideal frame of reference ; tracking the flight of thrown balls , particularly their acceleration , rotation and the like , and graphically recreating and depicting this acceleration and rotational movement in correlation with the trajectory of the pitch or throw on - screen ; for each pitch , making spin and trajectory calculations and graphically manifesting those calculations on - screen ; the calculations of a pitcher &# 39 ; s spin and trajectory for various pitches ( fastball , changeup , drop pitch and the like ) may be compared alongside spin and trajectory calculations of pitches thrown by select college and olympic pitchers as an ideal frame of reference ; tracking the path of a swung bat by embedding multi - axis sensors in two places , the bat handle and barrel , then translating the data relative to virtual or real pitches and graphically recreating and depicting each swing path on - screen ; for each swing , a player &# 39 ; s swing path may be compared to the swing path of select college and olympic players as an ideal frame of reference ; and , in the context of utilizing cs &# 39 ; softball simulations for purposes of marketing , advertising and promoting third - party products and services , the cs object - tracking system may be applied : as a means to facilitate experiential marketing interactions between brands and players &# 39 ; interactive experiences by seamlessly placing branding elements into cs &# 39 ; real - ball softball simulation games and skills training activities , such as having advertisers &# 39 ; logos appear as targets in front of virtual softball gloves and mitts or as branded “ hit it here !” animations beyond the outfield wall and as part of any other types of branding images in various other virtual locations , and awarding promotional prizes whenever players successfully hit the targets , in addition to many other promotional marketing strategies that may be implemented using this experiential sports simulation platform ; and as part of a real - ball , virtual fantasy softball league in which players actually compete via online gaming experiences , all tied together by an avatar - based community that offers social networking features , such as a minor league system , player showcases , contests and tournaments , player drafts , personalized softball cards , contracts , salaries , stadium and team owners , general managers , team managers , pitching and batting coaches , individual and team statistics , video highlights , “ cybersports center ” broadcasts , trophies , championship rings , awards ceremonies , all - star teams and the like ; and as part of live promotional events and the like , during which top athletes and celebrities appear live via cs &# 39 ; online gaming portal to compete against various players , or “ cyber - athletes ”, simultaneously , as hitters competing in home run derby contests , as pitchers throwing to cyber - athlete hitters , or as pitchers and field players competing in accuracy and distance throwing contests and the like . cs &# 39 ; real - ball object - tracking interface may make the softball game - play completely realistic due to its ability to generate motion data from inside actual softballs , or close facsimiles , and process all 6 degrees of freedom in real time ; speed , accuracy and distance feedback with graphical representations for throwing , pitching and hitting may provide players with a clear and quantifiable picture of their performances ; arm & amp ; hand path feedback may allow players to see their pitching / throwing form and technique in a graphical way and recognize nuances in their throwing motion compared to professional standards ; ball path and rotation feedback may allow players to see their pitching / throwing performances in an in - depth , three - dimensional way and compare them against professional standards ; combined with arm and hand path feedback , players may be shown the cause and effect between pitching / throwing technique and performance , including how finger placement and pressure on the ball , arm and wrist angle and other mechanics affect the outcome of the throw or pitch ; bat path feedback may allow players to see their hitting form and technique in a graphical way and compare it to professional standards ; combined with speed , direction and distance feedback on the player &# 39 ; s hits , the player may be shown the cause and effect between hitting technique and performance , including how timing and rotation of the wrists , direction and angle of the bat head through point of contact and other factors collectively affect the outcome of the swing ; and , in the context of cs &# 39 ; softball simulations being utilized for experiential marketing , out - of - home advertising and promotional opportunities that are fully integrated , customizable , experiential and interactive may assist sports marketers in reaching their target audiences in venue - specific ways ( e . g ., sports drink ads in fitness centers and sports equipment and apparel ads in sporting goods stores ). how cs &# 39 ; tracking system adds unique value compared to its competitors cs &# 39 ; multi - axis sensors ( 6 axes or more ) embedded into real softballs , or close facsimiles , may make the interface between object - tracking and game - play completely realistic , much more so than its competitors ; cs &# 39 ; performance data and in - depth analysis of each facet of a player &# 39 ; s pitches , throws and hits may provide more comprehensive feedback on player performance than its competitors ; and no other real - ball softball simulation system features any type of in - game advertising opportunities , much less interactive promotional tie - ins and venue - specific targeted advertising strategies . entertainment market — sports bars , entertainment centers , museums , halls of fame , stadiums , arenas , cruise ships , casinos , resorts , movie theaters , malls , retail stores , military bases , retirement communities , college campuses , fan - fests , trade shows , corporate events , promotional events , luxury condominiums , the in - home market and any other place where people may choose to be entertained by playing real - ball virtual softball ; and fitness & amp ; training market — athletic training facilities , fitness centers , sports camps , hospitals , schools , colleges , pro teams , sporting goods stores , luxury condominiums , the in - home market and any other place where people may choose to exercise , compete and seek to improve their softball skills . the elements depicted in flow charts and block diagrams throughout the figures imply logical boundaries between the elements . however , according to software or hardware engineering practices , the depicted elements and the functions thereof may be implemented as parts of a monolithic software structure , as standalone software modules , or as modules that employ external routines , code , services , and so forth , or any combination of these , and all such implementations are within the scope of the present disclosure . thus , while the foregoing drawings and description set forth functional aspects of the disclosed systems , no particular arrangement of software for implementing these functional aspects should be inferred from these descriptions unless explicitly stated or otherwise clear from the context . similarly , it will be appreciated that the various steps identified and described above may be varied , and that the order of steps may be adapted to particular applications of the techniques disclosed herein . all such variations and modifications are intended to fall within the scope of this disclosure . as such , the depiction and / or description of an order for various steps should not be understood to require a particular order of execution for those steps , unless required by a particular application , or explicitly stated or otherwise clear from the context . the methods or processes described above , and steps thereof , may be realized in hardware , software , or any combination of these suitable for a particular application . the hardware may include a general - purpose computer and / or dedicated computing device . the processes may be realized in one or more microprocessors , microcontrollers , embedded microcontrollers , programmable digital signal processors or other programmable device , along with internal and / or external memory . the processes may also , or instead , be embodied in an application - specific integrated circuit , a programmable gate array , programmable array logic , or any other device or combination of devices that may be configured to process electronic signals . it will further be appreciated that one or more of the processes may be realized as computer executable code created using a structured programming language such as c , an object oriented programming language such as c ++, or any other high - level or low - level programming language ( including assembly languages , hardware description languages , and database programming languages and technologies ) that may be stored , compiled or interpreted to run on one of the above devices , as well as heterogeneous combinations of processors , processor architectures , or combinations of different hardware and software . thus , in one aspect , each method described above and combinations thereof may be embodied in computer executable code that , when executing on one or more computing devices , performs the steps thereof . in another aspect , the methods may be embodied in systems that perform the steps thereof , and may be distributed across devices in a number of ways , or all of the functionality may be integrated into a dedicated , standalone device or other hardware . in another aspect , means for performing the steps associated with the processes described above may include any of the hardware and / or software described above . all such permutations and combinations are intended to fall within the scope of the present disclosure . while the invention has been disclosed in connection with the preferred embodiments shown and described in detail , various modifications and improvements thereon will become readily apparent to those skilled in the art . accordingly , the spirit and scope of the present invention is not to be limited by the foregoing examples , but is to be understood in the broadest sense allowable by law .

US-17854508-A

a wall of a uterus is ablated by expanding a structure in the uterus and applying energy across the wall of the structure into the uterine wall . an exterior surface of the structure conforms to an inner wall of the uterus , and the energy may cause vapor to collect between the wall and the structure . the vapor is released by providing a barrier to release which is inflated at a pressure above which the barrier at least partially collapses to allow the vapor to leave the uterus .

in the following description , various embodiments of the present invention will be described . for purposes of explanation , specific configurations and details are set forth in order to provide a thorough understanding of the embodiments . however , it will also be apparent to one skilled in the art that the present invention may be practiced without the specific details . furthermore , well - known features may be omitted or simplified in order not to obscure the embodiment being described . in general , an electrosurgical ablation system is described herein that comprises an elongated introducer member for accessing a patient &# 39 ; s uterine cavity with a working end that deploys an expandable thin - wall dielectric structure containing an electrically non - conductive gas as a dielectric . in one embodiment , an interior chamber of the thin - wall dielectric structure contains a circulating neutral gas such as argon . an rf power source provides current that is coupled to the neutral gas flow by a first polarity electrode disposed within the interior chamber and a second polarity electrode at an exterior of the working end . the gas flow , which is converted to a conductive plasma by an electrode arrangement , functions as a switching mechanism that permits current flow to engaged endometrial tissue only when the voltage across the combination of the gas , the thin - wall dielectric structure and the engaged tissue reaches a threshold that causes capacitive coupling across the thin - wall dielectric material . by capacitively coupling current to tissue in this manner , the system provides a substantially uniform tissue effect within all tissue in contact with the expanded dielectric structure . further , the invention allows the neutral gas to be created contemporaneously with the capacitive coupling of current to tissue . in general , this disclosure may use the terms “ plasma ”, “ conductive gas ” and “ ionized gas ” interchangeably . a plasma consists of a state of matter in which electrons in a neutral gas are stripped or “ ionized ” from their molecules or atoms . such plasmas can be formed by application of an electric field or by high temperatures . in a neutral gas , electrical conductivity is non - existent or very low . neutral gases act as a dielectric or insulator until the electric field reaches a breakdown value , freeing the electrons from the atoms in an avalanche process thus forming a plasma . such a plasma provides mobile electrons and positive ions , and acts as a conductor which supports electric currents and can form spark or arc . due to their lower mass , the electrons in a plasma accelerate more quickly in response to an electric field than the heavier positive ions , and hence carry the bulk of the current . fig1 depicts one embodiment of an electrosurgical ablation system 100 configured for endometrial ablation . the system 100 includes a hand - held apparatus 105 with a proximal handle 106 shaped for grasping with a human hand that is coupled to an elongated introducer sleeve 110 having axis 111 that extends to a distal end 112 . the introducer sleeve 110 can be fabricated of a thin - wall plastic , composite , ceramic or metal in a round or oval cross - section having a diameter or major axis ranging from about 4 mm to 8 mm in at least a distal portion of the sleeve that accesses the uterine cavity . the handle 106 is fabricated of an electrically insulative material such as a molded plastic with a pistol - grip having first and second portions , 114 a and 114 b , that can be squeezed toward one another to translate an elongated translatable sleeve 115 which is housed in a bore 120 in the elongated introducer sleeve 110 . by actuating the first and second handle portions , 114 a and 114 b , a working end 122 can be deployed from a first retracted position ( fig1 ) in the distal portion of bore 120 in introducer sleeve 110 to an extended position as shown in fig2 . in fig2 , it can be seen that the first and second handle portions , 114 a and 114 b , are in a second actuated position with the working end 122 deployed from the bore 120 in introducer sleeve 110 . fig2 and 3 shows that ablation system 100 includes an rf energy source 130 a and rf controller 130 b in a control unit 135 . the rf energy source 130 a is connected to the hand - held device 105 by a flexible conduit 136 with a plug - in connector 137 configured with a gas inflow channel , a gas outflow channel , and first and second electrical leads for connecting to receiving connector 138 in the control unit 135 . the control unit 135 , as will be described further below in fig3 and 4 , further comprises a neutral gas inflow source 140 a , gas flow controller 140 b and optional vacuum or negative pressure source 145 to provide controlled gas inflows and gas outflows to and from the working end 122 . the control unit 135 further includes a balloon inflation source 148 for inflating an expandable sealing balloon 225 carried on introducer sleeve 110 as described further below . referring to fig2 , the working end 122 includes a flexible , thin - wall member or structure 150 of a dielectric material that when expanded has a triangular shape configured for contacting the patient &# 39 ; s endometrial lining that is targeted for ablation . in one embodiment as shown in fig2 and 6 , the dielectric structure 150 comprises a thin - wall material such as silicone with a fluid - tight interior chamber 152 . in an embodiment , an expandable - collapsible frame assembly 155 is disposed in the interior chamber . alternatively , the dielectric structure may be expanded by a neutral gas without a frame , but using a frame offers a number of advantages . first , the uterine cavity is flattened with the opposing walls in contact with one another . expanding a balloon - type member may cause undesirable pain or spasms . for this reason , a flat structure that is expanded by a frame is better suited for deployment in the uterine cavity . second , in embodiments herein , the neutral gas is converted to a conductive plasma at a very low pressure controlled by gas inflows and gas outflows — so that any pressurization of a balloon - type member with the neutral gas may exceed a desired pressure range and would require complex controls of gas inflows and gas outflows . third , as described below , the frame provides an electrode for contact with the neutral gas in the interior chamber 152 of the dielectric structure 150 , and the frame 155 extends into all regions of the interior chamber to insure electrode exposure to all regions of the neutral gas and plasma . the frame 155 can be constructed of any flexible material with at least portions of the frame functioning as spring elements to move the thin - wall structure 150 from a collapsed configuration ( fig1 ) to an expanded , deployed configuration ( fig2 ) in a patient &# 39 ; s uterine cavity . in one embodiment , the frame 155 comprises stainless steel elements 158 a , 158 b and 160 a and 160 b that function akin to leaf springs . the frame can be a stainless steel such as 316 ss , 17a ss , 420 ss , 440 ss or the frame can be a niti material . the frame preferably extends along a single plane , yet remains thin transverse to the plane , so that the frame may expand into the uterine cavity . the frame elements can have a thickness ranging from about 0 . 005 ″ to 0 . 025 ″. as can be seen in fig5 and 6 , the proximal ends 162 a and 162 b of spring elements 158 a , 158 b are fixed ( e . g ., by welds 164 ) to the distal end 165 of sleeve member 115 . the proximal ends 166 a and 166 b of spring elements 160 a , 160 b are welded to distal portion 168 of a secondary translatable sleeve 170 that can be extended from bore 175 in translatable sleeve 115 . the secondary translatable sleeve 170 is dimensioned for a loose fit in bore 175 to allow gas flows within bore 175 . fig5 and 6 further illustrate the distal ends 176 a and 176 b of spring elements 158 a , 158 b are welded to distal ends 178 a and 178 b of spring elements 160 a and 160 b to thus provide a frame 155 that can be moved from a linear shape ( see fig1 ) to an expanded triangular shape ( fig5 and 6 ). as will be described further below , the bore 175 in sleeve 115 and bore 180 in secondary translatable sleeve 170 function as gas outflow and gas inflow lumens , respectively . it should be appreciated that the gas inflow lumen can comprise any single lumen or plurality of lumens in either sleeve 115 or sleeve 170 or another sleeve , or other parts of the frame 155 or the at least one gas flow lumen can be formed into a wall of dielectric structure 150 . in fig5 and 7 it can be seen that gas inflows are provided through bore 180 in sleeve 170 , and gas outflows are provided in bore 175 of sleeve 115 . however , the inflows and outflows can be also be reversed between bores 175 and 180 of the various sleeves . fig5 and 6 further show that a rounded bumper element 185 is provided at the distal end of sleeve 170 to insure that no sharp edges of the distal end of sleeve 170 can contact the inside of the thin dielectric wall 150 . in one embodiment , the bumper element 185 is silicone , but it could also comprise a rounded metal element . fig5 and 6 also show that a plurality of gas inflow ports 188 can be provided along a length of in sleeve 170 in chamber 152 , as well as a port 190 in the distal end of sleeve 170 and bumper element 185 . the sectional view of fig7 also shows the gas flow passageways within the interior of introducer sleeve 110 . it can be understood from fig1 , 5 and 6 that actuation of first and second handle portions , 114 a and 114 b , ( i ) initially causes movement of the assembly of sleeves 115 and 170 relative to bore 120 of introducer sleeve 110 , and ( ii ) secondarily causes extension of sleeve 170 from bore 175 in sleeve 115 to expand the frame 155 into the triangular shape of fig5 . the dimensions of the triangular shape are suited for a patient uterine cavity , and for example can have an axial length a ranging from 4 to 10 cm and a maximum width b at the distal end ranging from about 2 to 5 cm . in one embodiment , the thickness c of the thin - wall structure 150 can be from 1 to 4 mm as determined by the dimensions of spring elements 158 a , 158 b , 160 a and 160 b of frame assembly 155 . it should be appreciated that the frame assembly 155 can comprise round wire elements , flat spring elements , of any suitable metal or polymer that can provide opening forces to move thin - wall structure 150 from a collapsed configuration to an expanded configuration within the patient uterus . alternatively , some elements of the frame 155 can be spring elements and some elements can be flexible without inherent spring characteristics . as will be described below , the working end embodiment of fig2 and 6 has a thin - wall structure 150 that is formed of a dielectric material such as silicone that permits capacitive coupling of current to engaged tissue while the frame assembly 155 provides structural support to position the thin - wall structure 150 against tissue . further , gas inflows into the interior chamber 152 of the thin - wall structure can assist in supporting the dielectric wall so as to contact endometrial tissue . the dielectric thin - wall structure 150 can be free from fixation to the frame assembly 155 , or can be bonded to an outward - facing portion or portions of frame elements 158 a and 158 b . the proximal end 182 of thin - wall structure 150 is bonded to the exterior of the distal end of sleeve 115 to thus provide a sealed , fluid - tight interior chamber 152 ( fig5 ). in one embodiment , the gas inflow source 140 a comprises one or more compressed gas cartridges that communicate with flexible conduit 136 through plug - in connector 137 and receiving connector 138 in the control unit 135 ( fig1 - 2 ). as can be seen in fig5 - 6 , the gas inflows from source 140 a flow through bore 180 in sleeve 170 to open terminations 188 and 190 therein to flow into interior chamber 152 . a vacuum source 145 is connected through conduit 136 and connector 137 to allow circulation of gas flow through the interior chamber 152 of the thin - wall dielectric structure 150 . in fig5 and 6 , it can be seen that gas outflows communicate with vacuum source 145 through open end 200 of bore 175 in sleeve 115 . referring to fig5 , it can be seen that frame elements 158 a and 158 b are configured with a plurality of apertures 202 to allow for gas flows through all interior portions of the frame elements , and thus gas inflows from open terminations 188 , 190 in bore 180 are free to circulated through interior chamber 152 to return to an outflow path through open end 200 of bore 175 of sleeve 115 . as will be described below ( see fig3 - 4 ), the gas inflow source 140 a is connected to a gas flow or circulation controller 140 b which controls a pressure regulator 205 and also controls vacuum source 145 which is adapted for assisting in circulation of the gas . it should be appreciated that the frame elements can be configured with apertures , notched edges or any other configurations that allow for effective circulation of a gas through interior chamber 152 of the thin - wall structure 150 between the inflow and outflow passageways . now turning to the electrosurgical aspects of the invention , fig5 and 6 illustrate opposing polarity electrodes of the system 100 that are configured to convert a flow of neutral gas in chamber 152 into a plasma 208 ( fig6 ) and to allow capacitive coupling of current through a wall 210 of the thin - wall dielectric structure 150 to endometrial tissue in contact with the wall 210 . the electrosurgical methods of capacitively coupling rf current across a plasma 208 and dielectric wall 210 are described in u . s . patent application ser . no . 12 / 541 , 043 ; filed aug . 13 , 2009 and u . s . application ser . no . 12 / 541 , 050 , referenced above . in fig5 and 6 , the first polarity electrode 215 is within interior chamber 152 to contact the neutral gas flow and comprises the frame assembly 155 that is fabricated of an electrically conductive stainless steel . in another embodiment , the first polarity electrode can be any element disposed within the interior chamber 152 , or extendable into interior chamber 152 . the first polarity electrode 215 is electrically coupled to sleeves 115 and 170 which extends through the introducer sleeve 110 to handle 106 and conduit 136 and is connected to a first pole of the rf source energy source 130 a and controller 130 b . a second polarity electrode 220 is external of the internal chamber 152 and in one embodiment the electrode is spaced apart from wall 210 of the thin - wall dielectric structure 150 . in one embodiment as depicted in fig5 and 6 , the second polarity electrode 220 comprises a surface element of an expandable balloon member 225 carried by introducer sleeve 110 . the second polarity electrode 220 is coupled by a lead ( not shown ) that extends through the introducer sleeve 110 and conduit 136 to a second pole of the rf source 130 a . it should be appreciated that second polarity electrode 220 can be positioned on sleeve 110 or can be attached to surface portions of the expandable thin - wall dielectric structure 150 , as will be described below , to provide suitable contact with body tissue to allow the electrosurgical ablation of the method of the invention . the second polarity electrode 220 can comprise a thin conductive metallic film , thin metal wires , a conductive flexible polymer or a polymeric positive temperature coefficient material . in one embodiment depicted in fig5 and 6 , the expandable member 225 comprises a thin - wall compliant balloon having a length of about 1 cm to 6 cm that can be expanded to seal the cervical canal . the balloon 225 can be inflated with a gas or liquid by any inflation source 148 , and can comprise a syringe mechanism controlled manually or by control unit 135 . the balloon inflation source 148 is in fluid communication with an inflation lumen 228 in introducer sleeve 110 that extends to an inflation chamber of balloon 225 ( see fig7 ). referring back to fig1 , the control unit 135 can include a display 230 and touch screen or other controls 232 for setting and controlling operational parameters such as treatment time intervals , treatment algorithms , gas flows , power levels and the like . suitable gases for use in the system include argon , other noble gases and mixtures thereof . in one embodiment , a footswitch 235 is coupled to the control unit 135 for actuating the system . the box diagrams of fig3 and 4 schematically depict the system 100 , subsystems and components that are configured for an endometrial ablation system . in the box diagram of fig3 , it can be seen that rf energy source 130 a and circuitry is controlled by a controller 130 b . the system can include feedback control systems that include signals relating to operating parameters of the plasma in interior chamber 152 of the dielectric structure 150 . for example , feedback signals can be provided from at least one temperature sensor 240 in the interior chamber 152 of the dielectric structure 150 , from a pressure sensor within , or in communication , with interior chamber 152 , and / or from a gas flow rate sensor in an inflow or outflow channel of the system . fig4 is a schematic block diagram of the flow control components relating to the flow of gas media through the system 100 and hand - held device 105 . it can be seen that a pressurized gas source 140 a is linked to a downstream pressure regulator 205 , an inflow proportional valve 246 , flow meter 248 and normally closed solenoid valve 250 . the valve 250 is actuated by the system operator which then allows a flow of a neutral gas from gas source 140 a to circulate through flexible conduit 136 and the device 105 . the gas outflow side of the system includes a normally open solenoid valve 260 , outflow proportional valve 262 and flow meter 264 that communicate with vacuum pump or source 145 . the gas can be exhausted into the environment or into a containment system . a temperature sensor 270 ( e . g ., thermocouple ) is shown in fig4 that is configured for monitoring the temperature of outflow gases . fig4 further depicts an optional subsystem 275 which comprises a vacuum source 280 and solenoid valve 285 coupled to the controller 140 b for suctioning steam from a uterine cavity 302 at an exterior of the dielectric structure 150 during a treatment interval . as can be understood from fig4 , the flow passageway from the uterine cavity 302 can be through bore 120 in sleeve 110 ( see fig2 and 7 ) or another lumen in a wall of sleeve 110 can be provided . fig8 a - 8d schematically illustrate a method of the invention wherein ( i ) the thin - wall dielectric structure 150 is deployed within a patient uterus and ( ii ) rf current is applied to a contained neutral gas volume in the interior chamber 152 to contemporaneously create a plasma 208 in the chamber and capacitively couple current through the thin dielectric wall 210 to apply ablative energy to the endometrial lining to accomplish global endometrial ablation . more in particular , fig8 a illustrates a patient uterus 300 with uterine cavity 302 surrounded by endometrium 306 and myometrium 310 . the external cervical os 312 is the opening of the cervix 314 into the vagina 316 . the internal os or opening 320 is a region of the cervical canal that opens to the uterine cavity 302 . fig8 a depicts a first step of a method of the invention wherein the physician has introduced a distal portion of sleeve 110 into the uterine cavity 302 . the physician gently can advance the sleeve 110 until its distal tip contacts the fundus 324 of the uterus . prior to insertion of the device , the physician can optionally introduce a sounding instrument into the uterine cavity to determine uterine dimensions , for example from the internal os 320 to fundus 324 . fig8 b illustrates a subsequent step of a method of the invention wherein the physician begins to actuate the first and second handle portions , 114 a and 114 b , and the introducer sleeve 110 retracts in the proximal direction to expose the collapsed frame 155 and thin - wall structure 150 within the uterine cavity 302 . the sleeve 110 can be retracted to expose a selected axial length of thin - wall dielectric structure 150 , which can be determined by markings 330 on sleeve 115 ( see fig1 ) which indicate the axial travel of sleeve 115 relative to sleeve 170 and thus directly related to the length of deployed thin - wall structure 150 . fig2 depicts the handle portions 114 a and 114 b fully approximated thus deploying the thin - wall structure to its maximum length . fig8 c illustrates several subsequent steps of a method of the invention . fig8 c first depicts the physician continuing to actuate the first and second handle portions , 114 a and 114 b , which further actuates the frame 155 ( see fig5 - 6 ) to expand the frame 155 and thin - wall structure 150 to a deployed triangular shape to contact the patient &# 39 ; s endometrial lining 306 . the physician can slightly rotate and move the expanding dielectric structure 150 back and forth as the structure is opened to insure it is opened to the desired extent . in performing this step , the physician can actuate handle portions , 114 a and 114 b , a selected degree which causes a select length of travel of sleeve 170 relative to sleeve 115 which in turn opens the frame 155 to a selected degree . the selected actuation of sleeve 170 relative to sleeve 115 also controls the length of dielectric structure deployed from sleeve 110 into the uterine cavity . thus , the thin - wall structure 150 can be deployed in the uterine cavity with a selected length , and the spring force of the elements of frame 155 will open the structure 150 to a selected triangular shape to contact or engage the endometrium 306 . in one embodiment , the expandable thin - wall structure 150 is urged toward and maintained in an open position by the spring force of elements of the frame 155 . in the embodiment depicted in fig1 and 2 , the handle 106 includes a locking mechanism with finger - actuated sliders 332 on either side of the handle that engage a grip - lock element against a notch in housing 333 coupled to introducer sleeve 110 ( fig2 ) to lock sleeves 115 and 170 relative to introducer sleeve 110 to maintain the thin - wall dielectric structure 150 in the selected open position . fig8 c further illustrates the physician expanding the expandable balloon structure 225 from inflation source 148 to thus provide an elongated sealing member to seal the cervix 314 outward from the internal os 320 . following deployment of the thin - wall structure 150 and balloon 225 in the cervix 314 , the system 100 is ready for the application of rf energy to ablate endometrial tissue 306 . fig8 c next depicts the actuation of the system 100 , for example , by actuating footswitch 235 , which commences a flow of neutral gas from source 140 a into the interior chamber 152 of the thin - wall dielectric structure 150 . contemporaneous with , or after a selected delay , the system &# 39 ; s actuation delivers rf energy to the electrode arrangement which includes first polarity electrode 215 (+) of frame 155 and the second polarity electrode 220 (−) which is carried on the surface of expandable balloon member 225 . the delivery of rf energy delivery will instantly convert the neutral gas in interior chamber 152 into conductive plasma 208 which in turn results in capacitive coupling of current through the dielectric wall 210 of the thin - wall structure 150 resulting in ohmic heating of the engaged tissue . fig8 c schematically illustrates the multiplicity of rf current paths 350 between the plasma 208 and the second polarity electrode 220 through the dielectric wall 210 . by this method , it has been found that ablation depths of three mm to six mm or more can be accomplished very rapidly , for example in 60 seconds to 120 seconds dependent upon the selected voltage and other operating parameters . in operation , the voltage at which the neutral gas inflow , such as argon , becomes conductive ( i . e ., converted in part into a plasma ) is dependent upon a number of factors controlled by the controllers 130 b and 140 b , including the pressure of the neutral gas , the volume of interior chamber 152 , the flow rate of the gas through the chamber 152 , the distance between electrode 210 and interior surfaces of the dielectric wall 210 , the dielectric constant of the dielectric wall 210 and the selected voltage applied by the rf source 130 , all of which can be optimized by experimentation . in one embodiment , the gas flow rate can be in the range of 5 ml / sec to 50 ml / sec . the dielectric wall 210 can comprise a silicone material having a thickness ranging from a 0 . 005 ″ to 0 . 015 and having a relative permittivity in the range of 3 to 4 . the gas can be argon supplied in a pressurized cartridge which is commercially available . pressure in the interior chamber 152 of dielectric structure 150 can be maintained between 14 psia and 15 psia with zero or negative differential pressure between gas inflow source 140 a and negative pressure or vacuum source 145 . the controller is configured to maintain the pressure in interior chamber in a range that varies by less than 10 % or less than 5 % from a target pressure . the rf power source 130 a can have a frequency of 450 to 550 khz , and electrical power can be provided within the range of 600 vrms to about 1200 vrms and about 0 . 2 amps to 0 . 4 amps and an effective power of 40 w to 100 w . in one method , the control unit 135 can be programmed to delivery rf energy for a preselected time interval , for example , between 60 seconds and 120 seconds . one aspect of a treatment method corresponding to the invention consists of ablating endometrial tissue with rf energy to elevate endometrial tissue to a temperature greater than 45 degrees celsius for a time interval sufficient to ablate tissue to a depth of at least 1 mm . another aspect of the method of endometrial ablation of consists of applying radiofrequency energy to elevate endometrial tissue to a temperature greater than 45 degrees celsius without damaging the myometrium . fig8 d illustrates a final step of the method wherein the physician deflates the expandable balloon member 225 and then extends sleeve 110 distally by actuating the handles 114 a and 114 b to collapse frame 155 and then retracting the assembly from the uterine cavity 302 . alternatively , the deployed working end 122 as shown in fig8 c can be withdrawn in the proximal direction from the uterine cavity wherein the frame 155 and thin - wall structure 150 will collapse as it is pulled through the cervix . fig8 d shows the completed ablation with the ablated endometrial tissue indicated at 360 . in another embodiment , the system can include an electrode arrangement in the handle 106 or within the gas inflow channel to pre - ionize the neutral gas flow before it reaches the interior chamber 152 . for example , the gas inflow channel can be configured with axially or radially spaced apart opposing polarity electrodes configured to ionize the gas inflow . such electrodes would be connected in separate circuitry to an rf source . the first and second electrodes 215 (+) and 220 (−) described above would operate as described above to provide the current that is capacitively coupled to tissue through the walls of the dielectric structure 150 . in all other respects , the system and method would function as described above . now turning to fig9 and 10 , an alternate working end 122 with thin - wall dielectric structure 150 is shown . in this embodiment , the thin - wall dielectric structure 150 is similar to that of fig5 and 6 except that the second polarity electrode 220 ′ that is exterior of the internal chamber 152 is disposed on a surface portion 370 of the thin - wall dielectric structure 150 . in this embodiment , the second polarity electrode 220 ′ comprises a thin - film conductive material , such as gold , that is bonded to the exterior of thin - wall material 210 along two lateral sides 354 of dielectric structure 150 . it should be appreciated that the second polarity electrode can comprise one or more conductive elements disposed on the exterior of wall material 210 , and can extend axially , or transversely to axis 111 and can be singular or multiple elements . in one embodiment shown in more detail in fig1 , the second polarity electrode 220 ′ can be fixed on another lubricious layer 360 , such as a polyimide film , for example kapton ®. the polyimide tape extends about the lateral sides 354 of the dielectric structure 150 and provides protection to the wall 210 when it is advanced from or withdrawn into bore 120 in sleeve 110 . in operation , the rf delivery method using the embodiment of fig9 and 10 is the same as described above , with rf current being capacitively coupled from the plasma 208 through the wall 210 and endometrial tissue to the second polarity electrode 220 ′ to cause the ablation . fig9 further shows an optional temperature sensor 390 , such as a thermocouple , carried at an exterior of the dielectric structure 150 . in one method of use , the control unit 135 can acquire temperature feedback signals from at least one temperature sensor 390 to modulate or terminate rf energy delivery , or to modulate gas flows within the system . in a related method of the invention , the control unit 135 can acquire temperature feedback signals from temperature sensor 240 in interior chamber 152 ( fig6 to modulate or terminate rf energy delivery or to modulate gas flows within the system . in another embodiment of the invention , fig1 - 14 depict systems and methods for evaluating the integrity of the uterine cavity which may be perforated or otherwise damaged by the transcervical introduction of probes and instruments into a uterine cavity . if the uterine wall is perforated , it would be preferable to defer any ablation treatment until the uterine wall is healed . a method of the invention comprises introducing transcervically a probe into a patient &# 39 ; s uterine cavity , providing a flow of a fluid ( e . g ., co 2 ) through the probe into the uterine cavity and monitoring the rate of the flow to characterize the uterine cavity as perforated or non - perforated based on a change in the flow rate . if the flow rate drops to zero or close to zero , this indicates that the uterine cavity is intact and not perforated . if the flow rate does not drop to zero or close to zero , this indicates that a fluid flow is leaking through a perforation in the uterine cavity 302 into the uterine cavity or escaping around an occlusion balloon that occludes the cervical canal . in fig1 , it can be seen how a pressurized fluid source 405 and controller 410 for controlling and monitoring flows is in fluid communication with lumen 120 of introducer sleeve 110 ( see fig7 ). in one embodiment , the fluid source can be a pressurized cartridge containing co 2 or another biocompatible gas . in fig1 , it can be seen that fluid source 405 communicates with a flexible conduit 412 that is connected to a “ pig - tail ” tubing connector 414 extending outward from handle 106 of the hand - held probe . a tubing in the interior of handle component 114 a provides a flow passageway 415 to the lumen 120 in the introducer sleeve . in another embodiment , the fluid source 405 and flexible conduit 408 can be integrated into conduit 136 of fig1 . in fig1 , it can be seen that the flow of fluid is introduced into the uterine cavity 302 after the balloon 225 in the cervical canal has been inflated and after the working end and dielectric structure 150 has been expanded into its triangular shape to occupy the uterine cavity . thus , the co 2 gas flows around the exterior surfaces of expanded dielectric structure 150 to fill the uterine cavity . alternatively , the flow of co 2 can be provided after the balloon 225 in the cervical canal is inflated but before the dielectric structure 150 is expanded . fig1 is a block diagram that schematically depicts the components of subsystem 420 that provides the flow of co 2 to and through the hand - held probe 105 . it can be seen that pressurized fluid source 405 communicates with a downstream pressure regulator 422 , a proportional valve 424 , flow meter 440 , normally closed solenoid valve 450 and one - way valve 452 . the valve 450 upon actuation by the system operator allows a flow of co 2 gas from source 405 at a predetermined flow rate and pressure through the subsystem and into the uterine cavity 302 . in one embodiment of the method of operation , the physician actuates the system and electronically opens valve 450 which can provide a co 2 flow through the system . the controller 410 monitors the flow meter or sensor 440 over an interval that can range from 1 second to 60 seconds , or 5 second to 30 seconds to determine the change in the rate of flow and / or a change in the rate of flow . in an embodiment , the flow sensor comprises a honeywell awm5000 series mass airflow sensor , for example model awm5101 , that measure flows in units of mass flow . in one embodiment , the initial flow rate is between 0 . 05 slpm ( standard liters per minute ) and 2 . 0 slpm , or between 0 . 1 slpm and 0 . 2 slpm . the controller 410 includes a microprocessor or programmable logic device that provides a feedback signal from the flow sensors indicating either ( i ) that the flow rate has dropped to zero or close to zero to thus characterize the uterine cavity as non - perforated , or ( ii ) that the flow rate has not dropped to a predetermined threshold level within a predetermined time interval to thus characterize the uterine cavity as perforated or that there is a failure in occlusion balloon 225 or its deployment so that the cervical canal is not occluded . in one embodiment , the threshold level is 0 . 05 slpm for characterizing the uterine cavity as non - perforated . in this embodiment , the controller provides a signal indicating a non - perforated uterine cavity if the flow drops below 0 . 05 slpm between the fifth second of the flow and the flow time - out , which can be , for example , 30 seconds . fig1 depicts aspects of an algorithm used by controller 410 to accomplish a uterine cavity integrity check , with the first step comprising actuating a footswitch or hand switch . upon actuation , a timer is initialized for 1 to 5 seconds to determine that a fluid source 405 is capable of providing a fluid flow , which can be checked by a pressure sensor between the source 405 and pressure regulator 422 . if no flow is detected , an error signal is provided , such as a visual display signal on the control unit 135 ( fig1 ). as can be understood from fig1 , after the fluid source 405 is checked , the controller opens the supply solenoid valve 450 and a timer is initialized for a 1 to 5 second test interval to insure fluid flows through the subsystem 420 of fig1 , with either or both a flow meter 440 or a pressure sensor . at the same time as valve 450 is opened , a timer is initialized for cavity integrity test interval of 30 seconds . the controller 410 monitors the flow meter 440 and provides a signal characterizing the uterine cavity as non - perforated if , at any time after the initial 5 second check interval and before the end of the timed - out period ( e . g ., the 30 second time - out ), the flow rate drops below a threshold minimum rate , in one embodiment , to below 0 . 05 slpm . if the interval times out after 30 seconds and the flow rate does not drop below this threshold , then a signal is generated that characterizes that the uterine cavity is perforated . this signal also can indicate a failure of the occlusion balloon 225 . referring to fig1 , in one embodiment , in response or otherwise as a result of the signal that the uterine cavity is not perforated , the controller 410 can automatically enable and activate the rf ablation system described above to perform an ablation procedure . the controller 410 can provide a time interval from 1 to 15 seconds to allow co 2 gas to vent from the uterine cavity 302 before activating rf energy delivery . in another embodiment , the endometrial ablation system may include the optional subsystem 275 for exhausting fluids or gas from the uterine cavity during an ablation treatment ( see fig4 and accompanying text ). this subsystem 275 can be actuated to exhaust co 2 from the uterine cavity 302 which include opening solenoid valve 285 shown in fig4 . the system can further include an override to repeat the cavity integrity check , for example , after evaluation and re - deployment of the occlusion balloon 225 . fig1 and 16 represent another system and method for characterizing the uterine cavity as being non - perforated so as to safely permit an ablation procedure . this system and method utilizes variations in the algorithms that introduce a gas media fluid into the uterine cavity and thereafter measure the changes in flow rates in the gas media . the system again is configured to introduce a gas into the uterine cavity after deployment and expansion of an ablation device in the cavity . if the flow rate of the gas drops to approximately zero , this indicates that the uterine cavity is intact and not perforated . in the event the flow rate of the gas does not drop , there is likely a gas escaping from the uterine cavity 302 through a perforation in the uterine wall . thus , the gas flow failing to drop may be an indication of a perforation . fig1 schematically illustrates three different conditions that may occur when operating the system , which indicate whether the system is functioning properly , and whether the uterine wall is non - perforated or perforated . in fig1 , the vertical axis indicates a gas flow rate measure in slpm ( standard liters per minute ), and the horizontal axis represents time in seconds . in one system variation , a gas source 405 such as a pressurized cartridge containing co 2 is controlled by a controller 410 , and the gas is introduced into the uterine cavity through a passageway in the device introducer sleeve 110 as described above ( fig1 - 13 ). the controller 410 and flowmeter monitor flows from the device into the uterine cavity ( fig1 ). the initial flow rate can be in the range of 0 . 010 splm to 0 . 20 splm . in one aspect of the invention , a minimum flow rate has been found to be important as a system diagnostic check to insure gas flow is reaching the uterine cavity . thus , fig1 illustrates gas flow rate curve in a “ condition 1 ” that may occur when the system fails in delivering gas through the passageways of the system . in one variation , the “ condition 1 ” will be represented by a flow rate over time wherein the flow rate does not achieve a minimum threshold flow rate , which can be from 0 . 010 splm to 0 . 050 splm over a predetermined time interval . in one variation , the minimum flow rate is 0 . 035 splm . the time interval can be from 1 second to 15 seconds . this “ condition 1 ” as in fig1 could occur , for example , if the gas supply tubing within the device were kinked or pinched which would then prevent gas flow through the system and into the uterine cavity . in a related variation that indicates system failure , a controller algorithm can calculate the volume of gas delivered , and if the volume is less than a threshold volume , then a system failure or fault can be determined . the gas volume v 1 is represented by the “ area under the curve ” in fig1 , which is a function of flow rate and time . fig1 further illustrates a flow rate curve in a “ condition 2 ” which corresponds to an intact , non - perforated uterine cavity . as can be understood from a practical perspective , a gas flow into an intact uterine cavity at a set pressure from a low pressure source , for example within a range of 0 . 025 psi to 1 . 0 psi , would provide an increasing flow rate into the cavity until the cavity was filled with gas , and thereafter the flow rate would diminish to a very low or zero flow rate . such a “ condition 2 ” flow rate curve as in fig1 further assumes that there is an adequate sealing mechanism in the cervical canal . thus , if controller obtains flow rate data from the flowmeter indicating “ condition 2 ”, then the patient &# 39 ; s uterus is non - perforated and is suitable for an ablation . in operation , the controller can look at various specific aspects and parameters of the flow rate curve of “ condition 2 ” in fig1 to determine that the uterine cavity integrity test has passed , wherein such parameters can comprise any single parameter or a combination of the following parameters : ( i ) the flow rate falling below a threshold rate , for example between 0 . 010 - 0 . 10 splm ; ( ii ) a change in rate of flow ; ( iii ) a peak flow rate ; ( iii ) the total gas volume v 2 delivered ; ( iv ) an actual flow rate at a point in time compared to a peak flow rate ; ( v ) a derivative of flow rate at a point in time , and ( vi ) any of the preceding parameters combined with a predetermined time interval . in one embodiment , a constant pressure ( 0 . 85 psi ) gas is introduced and a minimum threshold flow is set at 0 . 035 splm . a peak flow is calculated after a time interval of 2 to 15 seconds , and thereafter it is determined if the flow rate diminished by at least 10 %, 20 %, 30 %, 40 % or 50 % over a time interval of less than 30 seconds . fig1 next illustrates a flow rate curve in “ condition 3 ” which represents a gas flow when there is a perforated wall in a uterine cavity , which would allow the gas to escape into the abdominal cavity . in fig1 , a gas flow at a constant pressure is shown ramping up in flow rate until it levels off and may decline but not the rate of decline to may not go below a threshold value or may not decline a significant amount relative to a peak flow rate . such a flow rate curve over time would indicate that the gas is leaking from the uterine cavity . now turning to fig1 , an algorithm diagram is shown that describe one variation in a method of operating a uterine cavity integrity test based on measuring gas flow rates over a selected time interval . at the top of the diagram , the physician actuates the system in which a valve 450 is opened to provide a co 2 flow through the system ( fig1 ). the controller 410 provides a flow at a pressure , for example 0 . 85 psi . the actuation of the system also starts a timer wherein a first interval is 30 seconds or less . over this 30 - second interval , the controller records the peak flow rate which typically can occur within 2 to 10 seconds , then monitors the flow rate over the remainder of the 30 second interval and determined whether the flow rate drops 20 % or more from the peak flow rate . then , the controller additionally monitors whether the flow rate falls below a threshold value , for example 0 . 035 splm . if these two conditions are met , the test indicates that there is no leakage of gas media from the uterine cavity . if the flow rates does not drop 20 % from its peak with 30 seconds together with flow being below threshold value , then the test fails indicating a leak of gas from the uterine cavity . thereafter , the diagram in fig1 , indicates one additional test which consists of calculating the volume of gas delivered and comparing the volume to the maximum volume within a kinked gas delivery line . if the delivered gas volume is less than the capacity of the gas delivery line , then the test fails and the signal on the controller can indicate this type of test failure . if the delivered gas volume is greater than the capacity of a gas delivery line , then the test passes . in one variation of the controller algorithm can then automatically actuate the delivery of rf energy in an ablation cycle . alternatively , the controller can provide a signal that the test has passed , and the physician can manually actuate the rf ablation system . fig1 schematically illustrates another system and method for characterizing integrity of the walls of a uterine cavity . as can be seen in fig1 . an introducer sleeve 510 carrying an expandable working end 520 is deployed in the uterine cavity 302 . the working end includes a balloon - like member 522 with a fluid - tight interior chamber 524 . in one embodiment , the working end 510 is expanded laterally by frame elements 526 a and 526 b , which is similar to previously described embodiments . in addition , a pressurized gas source 540 is actuated to provide an inflation gas through interior sleeve 542 and ports 544 therein that further expands and opens the working end 520 transverse to opening forces applied by frame elements 526 a and 526 b . the inflation gas can comprise an argon gas that later is converted to a plasma as described previously . the inflation gas can pressurize the working end to a selected pressure ranging from 0 . 10 psi to 10 psi . in one variation , the pressure can be 0 . 50 psi . as can be seen in fig1 , an expandable member 548 or balloon is expanded to prevent any gas flow outwardly through the bore 550 in introducer sleeve 510 . thereafter , a gas inflow system 410 similar to that of fig1 is utilized to flow a gas source , such as co 2 into the uterine cavity 302 ( fig1 ). in fig1 , the gas inflow is indicated by arrows 555 which can comprise an inflow at a predetermined pressure through passageway 558 as described above , and in one variation can be 0 . 85 psi . the test for uterine cavity integrity then can monitor one or more gas leakage parameters relating to the inflation gas in the interior chamber 524 of the working end 520 . for example , the flow into the uterine cavity 302 will cause an outflow of gas from the interior chamber 524 through passageway 558 which can be measure by a flow meter , or the volume of gas outflow can be measured or the change in gas pressure can be measured . if there is no leak in the uterine cavity , the parameter of the inflation can in the interior chamber 524 will reach an equilibrium in relation to the co 2 inflow into the cavity . if the inflation gas parameter does not reach an equilibrium , then the change in parameter ( flow , volume or pressure ) will indicate a leakage of gas from the uterine cavity through a perforation . in general , a method of characterizing the integrity of a patient &# 39 ; s uterus comprises positioning a probe working end is a patient &# 39 ; s uterine cavity , the working end comprising an inflated resilient structure , introducing a flow of a gas through the probe into a uterine cavity exterior about the exterior of the working end , and measuring a gas flow , gas volume or gas pressure parameter of the inflation media in the inflated resilient structure in response to the gas flow into the uterine cavity . fig1 and 19a - 19b schematically illustrates another embodiment of working end 600 and a method of use . fig1 is a plan view of an expandable dielectric member or membrane 605 carried at distal end of introducer 610 that extend along longitudinal axis 615 . the working end 600 is similar to previously described embodiments , which includes an expandable - collapsible frame of a spring material within a fluid - tight interior chamber 616 of an elastic dielectric member 605 . in one embodiment the frame comprises flexible outward frame elements 618 a and 618 b that can bowed outwardly from shape have width w to a shape with width w ′ to fully expanded width w ″ as shown in fig1 . the outward frame elements 618 a and 618 b are flexed by distal movement of inner frame elements 620 a and 620 b that are coupled at proximal ends 622 a and 622 b to slidable inner sleeve 624 . it can be understood from fig1 that the distal tips of inner frame elements 620 a and 602 b are welded to distal tips of outward frame elements 618 a and 618 b , respectively as indicated by welds 628 a and 628 b . the frame elements are thus configured to provide lateral expansion forces to expand the dielectric member 605 and its ablation surface 630 ( fig1 a ) laterally relative to axis 615 . fig1 a - 19b illustrates another aspect of the invention wherein the working end 600 and more particularly the dielectric member 605 can be expanded in a second direction relative to axis 615 that is transverse to the plane p of the frame expansion . fig1 a shows the dielectric membrane 605 stretched and expanded laterally by the frame elements as in fig1 . fig1 b shows the dielectric membrane 605 further expanded by inflation of the interior chamber 616 by means of a pressurized inflow of gas from a gas inflow source 635 that is in communication with the interior chamber . in one embodiment , the gas flow into the dielectric member 605 comprises the argon gas inflow that is ionized as described previously to enable the electrosurgical energy delivery aspects of the invention . referring to fig1 b , it has been found that positive pressure in the interior chamber 616 during operation is useful in ablating tissue since the positive pressure can help in maintaining the ablation surface 630 in contact with tissue , which in turn permits more effective capacitive coupling through the dielectric membrane 605 and passive heating from the membrane when heated by ion bombardment . in one embodiment , the pressure in the balloon is at least 20 mm hg , at least 30 mm hg , at least 40 mm hg or at least 50 mm hg . since the argon gas is circulating as described above , the gas inflow rate and gas outflow rate can be modulated with valve assemblies to provide a net positive pressure in the interior chamber . it also has been found that positive pressure in the interior chamber 616 can be useful in causing plasma filaments to be more uniform and more widely dispersed since the dielectric membrane is spaces away from the frame elements 620 a and 620 b in the central region of the interior chamber . in another aspect of the invention , the gas pressure in the interior chamber 616 of the dielectric membrane 605 can be modulated during the initiation and duration of a treatment cycle . in one variation , the pressure in the interior chamber prior to actuating rf delivery can be lowered to less than ambient pressure . at the time of rf actuation , the lower argon pressure will permit more instantaneous ignition of the plasma due to such lowered pressure . since the argon gas is circulating , the gas inflow and outflow rates can be modulated with the valve subsystems to provide a negative pressure in interior chamber 616 . the pressure can be at least 5 % below ambient pressure , at least 10 % below ambient pressure , at least 15 % below ambient pressure , or at least 20 % below ambient pressure . after ignition of plasma in the interior chamber 616 , the pressure can be regulated to a higher pressure as described above to expand the dielectric membrane away from the frame elements 620 a and 620 b . fig2 illustrates another embodiment of an endometrial ablation system 800 with an elongated sleeve 810 having axis 812 and carrying expandable dielectric structure 815 that is expanded by a frame 818 in an interior chamber 820 of the dielectric . the system operates to apply ablative energy to endometrial tissue as described previously with a first polarity electrode 825 in the interior chamber 820 of the dielectric and second polarity electrodes 828 a , 828 b on the exterior of the dielectric 815 . plasma is formed in the interior chamber 820 which allows capacitive coupling of rf current across dielectric wall 832 which thus causes tissue heating as described previously . the embodiment of working end depicted in fig2 is configured to allow steam and / or fluid media to escape from the uterine cavity 830 during a treatment cycle if pressure exceeds a predetermined level . it has been found that the surface of silicone wall 832 can intermittently generate steam within the cavity 830 which will locally push the uterine wall out of contact with the dielectric structure 815 . fig2 depicts the dielectric structure 815 expanded in the uterine cavity during an ablation cycle wherein pockets or regions 836 are created by steam expansion around the cavity ( see arrows in regions 836 ). in fig2 , an inflatable balloon 840 is disposed in the distal end of sleeve 810 to function as a relief valve . the balloon 840 has an annular configuration and surrounds the axial - extending member 842 that carries the frame 818 and the dielectric structure 815 . the balloon 840 can have any suitable axial length ranging from about 5 mm to 5 cm . the inflatable valve balloon 840 is in communication with an inflation source 845 and controller 848 for expanding the balloon in lumen 846 of sleeve 810 . the balloon 840 is controlled at a pressure ranging from 10 mmhg to 100 mmhg in the interior chamber of the valve balloon 840 . in one variation , the balloon 840 is inflated to a pressure of between 25 to 50 mmhg , and during a treatment cycle , transient steam pockets 836 may form and the increase in uterine cavity pressure compresses the balloon 840 and permits fluid media to escape around the balloon into lumen 846 as indicated by arrows 850 ( fig2 ). the lumen 846 in sleeve 810 is configured to direct any escaped fluid media in the proximal direction to vent or collect such fluid . the fluid pathway can further include an aspiration or negative pressure source coupled to lumen 846 ( fig2 ). in this embodiment , the valve balloon 840 is independent of the fluid - tight dielectric structure 815 which also can be characterized as a balloon . the surface of balloon 840 and the surface of lumen 846 can be designed to cooperate in sealing the lumen 846 at low pressure and then functioning at a relief valve at a predetermined higher pressure . for example , the interior surface of the lumen 846 can be configured with annular or axial ridges that cooperate with the modulus and wall thickness of the valve balloon 840 . also , the sleeve lumen 846 can have a hydrophilic or hydrophobic surface to provide a releasable sealing effect against the balloon 840 . likewise , the surface of balloon 840 can be configured with annular or axial ridges that cooperate a smooth lumen wall or a grooved lumen wall . also , the balloon can have a hydrophilic or hydrophobic surface to provide the desired releasable sealing effect . as can be seen in fig2 , the system provides positive and negative pressure sources , 855 and 860 , to circulate a neutral gas such as argon through the interior chamber 820 of the dielectric 815 as described previously . the rf source 870 and controller 848 also operate as described previously to generate plasma within the dielectric 815 and to apply energy to tissue through the dielectric . fig2 illustrates another system embodiment 800 ′ for endometrial ablation in which elongated sleeve 810 carries an expandable dielectric structure 815 ′ that again is expanded laterally by frame 818 in interior chamber 820 of the dielectric . the system utilizes an rf electrode 825 in interior chamber 820 and opposing polarity electrodes 828 a , 828 b on the exterior of the dielectric 815 as described previously to allow capacitive coupling of rf current across dielectric wall 832 . the embodiment of fig2 uses positive and negative pressure sources 855 and 860 to circulate a neutral gas through interior chamber 820 and control pressure in the fluid - tight interior chamber 820 of the dielectric 815 ′ during a treatment cycle . as can be seen in fig2 , the proximal portion 872 of the inflatable dielectric 815 ′ extends into lumen 875 of sleeve 810 . thus , the proximal portion 872 of dielectric 815 ′ can function as a balloon valve as described in the embodiment of fig2 to allow steam and / or fluid media to escape from the uterine cavity 830 during a treatment cycle if pressure exceeds a predetermined level . in the embodiment of fig2 , the system parameters for plasma generation are adapted to provide a pre - determined pressure ( e . g ., 50 mmhg ) for releasing pressure from the uterine cavity . fig2 depicts vapor / fluid escape from the uterine cavity along arrows 850 from transient vapor pockets 836 . in all other respects , the embodiment of fig2 functions as the embodiment of fig2 . the advantage of the system embodiment 800 ′ of fig2 is that a single expandable member 815 ′ functions the ablation structure and the balloon valve . this aspect of the invention reduces complexity and eliminates the need for independent inflation source 845 for inflating an independent balloon valve . fig2 and 23 illustrates another system embodiment 800 ″ for endometrial ablation . in this embodiment , the distal end portion 880 of sleeve 810 includes a plurality of slots 882 which allow the end portion 880 to flex outward to provide a larger cross section when the expandable dielectric structure 815 ″ is expanded . the slots 882 can extend axially and have a length of from about 5 mm to 25 mm . the flexibility of the distal end portion 880 reduces the risk of the distal edge 884 cutting the elastomeric wall 832 of the dielectric structure after its expansion . the slots 882 can range in number from one to 10 or more and can be symmetric or asymmetric around the sleeve . fig2 shows one variation in which the slots 882 are asymmetric and are configured to cooperate with the height dimension h of the laterally - expandable frame 818 . it can be seen that radial angle r 1 is less than radial angle r 2 and in use the lateral elements 886 a and 886 b would flex outward upon expansion of the frame 818 and dielectric structure 815 ″. in one embodiment , the height h of the frame is about 2 . 5 to 3 . 0 mm and the diameter of the sleeve 810 is from 6 mm to 8 mm . the distal end portion 880 of the sleeve 810 also can be covered with a thin wall elastomer to cover the slots 882 ( not shown ) which permits outward flexing under expansion of the dielectric to provide further protection of the dielectric structure . referring to fig2 , the dielectric structure 815 ″ can extend proximally a distance of 5 to 20 mm proximal from the slots 882 to permit the dielectric to function as a valve as in the embodiment of fig2 . in fig2 , vapor or fluid media is indicated at 850 escaping around the inflated dielectric 815 ″. although particular embodiments of the present invention have been described above in detail , it will be understood that this description is merely for purposes of illustration and the above description of the invention is not exhaustive . specific features of the invention are shown in some drawings and not in others , and this is for convenience only and any feature may be combined with another in accordance with the invention . a number of variations and alternatives will be apparent to one having ordinary skills in the art . such alternatives and variations are intended to be included within the scope of the claims . particular features that are presented in dependent claims can be combined and fall within the scope of the invention . the invention also encompasses embodiments as if dependent claims were alternatively written in a multiple dependent claim format with reference to other independent claims . other variations are within the spirit of the present invention . thus , while the invention is susceptible to various modifications and alternative constructions , certain illustrated embodiments thereof are shown in the drawings and have been described above in detail . it should be understood , however , that there is no intention to limit the invention to the specific form or forms disclosed , but on the contrary , the intention is to cover all modifications , alternative constructions , and equivalents falling within the spirit and scope of the invention , as defined in the appended claims . the use of the terms “ a ” and “ an ” and “ the ” and similar referents in the context of describing the invention ( especially in the context of the following claims ) are to be construed to cover both the singular and the plural , unless otherwise indicated herein or clearly contradicted by context . the terms “ comprising ,” “ having ,” “ including ,” and “ containing ” are to be construed as open - ended terms ( i . e ., meaning “ including , but not limited to ,”) unless otherwise noted . the term “ connected ” is to be construed as partly or wholly contained within , attached to , or joined together , even if there is something intervening . recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range , unless otherwise indicated herein , and each separate value is incorporated into the specification as if it were individually recited herein . all methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context . the use of any and all examples , or exemplary language ( e . g ., “ such as ”) provided herein , is intended merely to better illuminate embodiments of the invention and does not pose a limitation on the scope of the invention unless otherwise claimed . no language in the specification should be construed as indicating any non - claimed element as essential to the practice of the invention . preferred embodiments of this invention are described herein , including the best mode known to the inventors for carrying out the invention . variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description . the inventors expect skilled artisans to employ such variations as appropriate , and the inventors intend for the invention to be practiced otherwise than as specifically described herein . accordingly , this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law . moreover , any combination of the above - described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context . all references , including publications , patent applications , and patents , cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein .

US-201514705224-A

a method of data management for optimizing the patient outcome from the provision of external counterpulsation therapy is described . this method describes a process by which sets of dynamic cardiopulmonary dependent variables are measured during steady - state conditions , displayed , and translated into quantitative and qualitative measurements while the independent variables of ecp , cuff inflation duration and cuff inflation pressure settings of ecp systems , are altered by a physician . in combination with visual observation and computer - assisted ranking of the dependent variables , a physician can utilize the resulting information to render decisions on the optimal choice of the independent variables . the method will enable physicians to collect , view , track and manage complicated data using well - understood visualization techniques to better understand the consequences , acutely and chronically , of their therapeutic actions in general , and of their provision of ecp therapy in particular .

the following detailed description with respect to patient data is intended to be exemplary of a preferred method of utilizing the concepts of the present invention and is not intended to be exhaustive or limiting in any manner with respect to similar methods and additional or other steps which might occur to those skilled in the art . the following description further utilizes illustrative examples , which are believed sufficient to convey an adequate understanding of the broader concepts to those skilled in the art , and exhaustive examples are believed unnecessary . general considerations — the present invention is not intended to make decisions , but rather to provide information to guide the decision making process by the physician . in doing so , decisions regarding cuff inflation pressure and cuff inflation duration can be made . in some cases , the answer to these questions may be no — there is no clear reason to use one choice over another . even in this case , the decision making process described in the present invention is an improvement over a process devoid of specific , sensitive data . in the present invention , specificity is provided by a quantitative analysis of response variables that are based upon well known , proven measurements of human physiology . sensitivity is supported by qualitative assessments of the measurements themselves . the present invention also provides information that can be used to make decisions acutely ( is the new cuff inflation pressure better than the last pressure ?) and chronically ( has patient mortality been improved as a result of the therapy ?). in the latter case , factors such as chronic adaptation to exercise and therapies other than ecp may influence changes in the patient &# 39 ; s condition . since the general objective of all patient therapy is to improve patient outcome , the decision - making tools described in the present invention increase the likelihood that ecp will contribute to improved patient outcome . the general class of data utilized in the present invention , dynamic - cardiopulmonary ( dcp ), is obtained at rest during the ecp session . such data can be viewed as an “ acute ” evaluation of the primary “ endpoint ” to gauge the effect of ecp on hemodynamic and pulmonary performance and on left ventricular stroke volume . the physiologic changes are measured using a cardiopulmonary exercise testing system ( cpx ) to measure selected variables associated with expired oxygen , carbon dioxide , ventilation , and heart rate . in theory , certain benefits derived from the present invention could be implemented using only a carbon dioxide analyzer equipped with a means for displaying the expired co 2 waveform . however , because of the requirement for measuring “ forward ” pump function , both heart rate and oxygen consumption , per breath , are needed to measure o 2 pulse . consequently , a carbon dioxide analyzer alone is insufficient . during the acute phase of evaluation , the dependent variables , etco 2 , eqco 2 , o 2 pulse , and the ventilatory efficiency slope , are measured during steady - state conditions at rest . in the present invention , the independent variables are 1 ) cuff inflation pressure ( cip ), and 2 ) the cuff inflation duration ( cid ) values . thus , changes made by the physician to an independent variable have the effect of changing the ventricular filling and stroke output of the heart that , in turn , alters the ventilation - perfusion coupling . as the local autoregulatory mechanisms seek to restore the synchronization of alveolar and pulmonary perfusion , the dependent variables rapidly change , are measured , and the measured values are automatically scaled and displayed to provide visual feedback to the physician during cuff inflation pressure and duration selection . in doing so , a physician is provided with a true , physiologic assessment of the patient &# 39 ; s condition resulting from changes made to an independent variable at any point in time during the procedure . the data gathering aspect of the invention involves known techniques and analyses and it is the aspects of processing , combining , and presenting the data in which the invention enables an observer to gain new and valuable insight into the present condition and condition trends in patents . thus , in accordance with the preferred method , a dynamic cardiopulmonary analysis is displayed for each data set . the performance of such a test is well understood by individuals skilled in the art , and no further explanation of this , except for the cuff inflation pressure / duration optimization protocol , is believed necessary . equipment — with this in mind typical hardware is shown in fig1 which illustrates typical equipment whereby a cardiopulmonary exercise test ( cpx ) may be conducted and the results displayed in accordance with the method of the present invention . the system is seen to include a data processing device , here shown as a personal computer of pc 12 , which comprises a video display terminal 14 with associated mouse 16 , report printer 17 and a keyboard 18 . the system further has a floppy disc handler 20 with associated floppy disc 22 . as is well known in the art , the floppy - disc handler 20 input / output interfaces comprise read / write devices for reading prerecorded information stored , deleting , adding or changing recorded information , on a machine - readable medium , i . e ., a floppy disc , and for providing signals which can be considered as data or operands to be manipulated in accordance with a software program loaded into the ram or rom memory ( not shown ) included in the computing module 12 . the equipment used in the exercise protocol for the chronic assessment includes either a bicycle ergometer or treadmill designed for use in a cardiopulmonary stress testing system ( cpx ) as is represented at 28 together with a subject 30 operating a pedal crank input device 32 of the ergometer . a graphic display device 34 interfaces with the subject during operation of the cpx device the physiological variables may be selected from heart rate ( hr ), ventilation ( ve ), rate of oxygen uptake or consumption ( vo 2 ) and carbon dioxide production ( vco 2 ) or other variables derived from these basic measurements . physiological data collected is fed into the computing module 12 via a conductor 31 , or other communication device . the equipment used in providing ecp therapy is schematically illustrated in fig2 . the equipment includes a compressor system including parallel units 40 , 42 , 44 and 46 , which supply an air tank 48 which , in turn , supplies air to a valve assembly 50 . the valve assembly 50 supplies air to hoses which are used to inflate the cuffs in accordance with the testing procedure of the invention at 52 . pressure relief is provided for the air tank by a relief valve 54 and to the valve assembly via pressure relief valve 56 . the cuffs are exhausted to the room when deflated by an exhaust valve depicted by the box 58 . an electronic control system as shown including connected software monitoring and alarm system 57 and electronic valve control 59 . it should be noted that either a pc ( 12 ) or the ecp microcontroller ( 50 ) could be used to acquire the measurements and process those measurements to implement the present invention . therefore , the further detailed description of the present invention will be made independent of the type and characteristics of the data processing means . the present invention provides a feedback mechanism to gauge the effectiveness of the choices for cuff inflation pressure and duration settings . since the main objective of ecp therapy itself is improved hemodynamic and pulmonary performance , the present invention provides a direct measurement of hemodynamic and pulmonary performance that can be used in real - time to evaluate if the choices are optimally reached . this can be determined on a relative basis for different inflation pressures and duration factors using a display of these variables as shown in fig3 variable display . the present invention further provides a computer assisted optimizing process for optimizing cuff inflation pressures and duration of pressurization of the cuffs located on the patient . an “ acute assessment ” of any combination of cuff inflation pressure and duration that can be programmed is obtained by monitoring of parameters indicative of the patient &# 39 ; s forward pump function or stroke volume output , as well as retrograde effects on filling pressures , pulmonary venous flow , and gas exchange at the alveolar / capillary membrane interface . the best choices are o 2 pulse for “ forward ” pump function and eqco 2 for “ retrograde ” effects . however , in order to further refine the selection process , additional measurements such as the linear ventilatory efficiency slope [ minute ventilation ( ve ) to expired carbon dioxide ( vco 2 ) slope ] and etco 2 can be included . the most optimally programmed cuff inflation pressure and duration will result in the highest expired etco 2 and o 2 pulse values and the best ventilation efficiency ( lowest linear slope ) and lowest eqco 2 during ecp therapy . these parameters are measured at pre - determined values for cuff inflation pressure and duration , as defined in the table identified in fig4 as boundary conditions . a unique table of boundary conditions is established for each manufacturer of ecp systems , and the size of the table , in terms of number of rows and number of columns , can be adjusted to accommodate many different such devices . in the example provided in fig4 three values of cuff inflation pressure ( cip ) are stored that correspond to minimum ( 60 ), average ( 62 ), and maximum ( 64 ) pressure values allowable by the ecp system . similarly , three values of cuff inflation duration ( cid ) are stored that correspond to the minimum ( 66 ), average ( 68 ), and maximum ( 70 ) duration values allowable by the ecp system . to expedite the procedure , the data collection phase is divided into two sessions of 4 . 5 - 6 minute sessions while the patient is undergoing ecp therapy ( fig5 — optimization protocol ). in the example provided in fig5 during the first 4 . 5 minutes , the three values of cuff inflation duration are sequentially programmed into the ecp controller every 1 . 5 minutes . this programming can be accomplished manually or automatically . after zeroing all entries , all measured data for each breath during the 1 . 5 - minute collection period associated with each of the three cuff inflation duration values is stored into the tables at 82 in fig6 . upon completion of each of the 1 . 5 - minute data collection periods , the central tendency and deviation percentage of each measured variable is computed and , after zeroing all entries , stored in an intermediate table as described in fig7 . only data for breaths recorded during the last one minute of each collection period is used in the calculations . such computations of central tendency can include , but is not limited to , the simple arithmetic average , as at 102 in fig7 for example . the deviation % as in 104 is first calculated by summing , for each breath in the one - minute calculation period , the absolute value of the difference between the average value 102 and the recorded value . this total is then divided by the product of the number of breaths in the calculation period times the average value 102 . multiplying this calculation by 100 yields the deviation % 104 . the deviation % is intended to provide a qualitative assessment of the “ tightness ” of the data sets . in other words , a small deviation % is indicative of low variability of the data in each set , hence a high quality test . a large value of deviation % would indicate unwanted patient events ( coughing , for example ) or unwanted physiologic consequences ( cheyne - stoke breathing patterns , for example ). upon completion of the first 4 . 5 minutes of data collection , further processing of the data stored in the intermediate table is performed . the decision matrix as in the example shown in fig8 is first zeroed , and the following steps are taken to calculate the values for each row and column . step 1 — assign rank — the rank value is intended to provide a qualitative assessment of the optimal choice for either cuff inflation pressure or cuff inflation duration . first , the highest average value for o 2 pulse and etco 2 and the lowest average value for eqco 2 and v . e . slope are identified . a rank value of 100 is assigned to the corresponding position in the decision matrix for each such determination . for example , if the highest value found in column 2 , rows 3 - 5 , in fig7 was at row 4 , or cid ave , then 100 is assigned in fig8 to column 2 in the row defined as cid ave . the associated value for deviation % found in fig7 is also stored in the next column in the same row of fig8 . next , the lowest average value for o 2 pulse and etco 2 and the highest average value for eqco 2 and v . e . slope are identified . a rank value of 50 is assigned to the corresponding position in the decision matrix for each such determination . for example , if the lowest - value found in column 2 , rows 3 - 5 , in fig7 was at row 5 , or cid max , then 50 is assigned in fig8 to column 2 in the row defined as cid max . the associated value for deviation % found in fig7 is also stored in the next column in the same row of fig8 . a rank value of 75 is then assigned to the rank column in the row for which no entry has been previously made , and the associated value for deviation % found in fig7 is also stored in the next column is the same row of fig8 . in this manner entries will have been made in all columns for the rows identified as cid min , cid ave , and cid max except the s % column and the average of the totals . the next step is to compute , for each row in fig8 identified as cid min , cid ave , and cid max , the average total rank . this is done by summing the individually assigned rank values for each of the variables in the same row and dividing by 4 . the “ perfect ” average rank , then , is 100 , which indicates that each variable for that particular setting is in theoretical conformance — the two that should be the highest are the highest and the two that should be the lowest are the lowest . step 2 define deviation — similarly , the average deviation percentage is calculated for each such row and stored in the column of that row identified in fig8 as d %. step 3 — define separation — the next step is to compute the values for separation % for each of the rows in fig8 identified as cid min , cid ave , and cid max . the separation % value provides a qualitative assessment of the difference , or separation , between the components of rank ( in this example , average value of the variable data set at each cid setting ). a small value of s % indicates that there is little measured difference between the average values of data sets at each duration setting ; hence the test may prove inconclusive . the higher the value of s %, the more conclusive the test results . for each of the columns for each of the variables , a value of 0 is assigned to the s % column in the row having the maximum average rank . for example , in fig8 the row with the highest average rank , 93 . 75 , is the row cid ave , consequently , each column identified as s % is set to 0 . the values for s % for each column of the remaining , unassigned rows is first computed by subtracting the average value from fig7 for the associated row from the average value from fig7 for the row that has been assigned a value of 0 for s %. the absolute value of this operation is then divided by the average value from fig7 for the row that has been assigned a value of 0 for s %. multiplying this operation by 100 yields s % for each of the remaining 2 rows , in this example , for each variable . in a similar fashion described to compute average rank and d %, average s % is computed for each row and stored in the s % column under average of totals . the physician then prints the final report for review at 90 in fig5 . the final report consists of a printed version of the decision matrix fig8 and a report summary , fig9 summarizing the calculations stored in the decision matrix in the form of a histogram in this case ( any other choice for graphical display is suitable ). the rank bar for each cid setting is placed on a scale with a maximum value of 100 . the height of the bar for each setting is then the value of average rank from the decision matrix for that setting . to match the “ bigger is better ” assumption for rank value , the height of the d % bar in fig9 is scaled to a value equal to 100 minus the average d % for each setting . the average s % for the settings with lower average rank values is printed below their associated setting columns . thus , the optimal setting is quantified as the setting with the highest average rank , and this , in turn , can be assessed qualitatively by the relative heights of the rank columns ( equal heights indicate poor quality ), average deviation % ( large values indicates poor quality ), and separation % ( low value indicates poor quality ). during a one - minute ( or optionally , longer ) period , the physician selects and programs the cid value at 92 in fig5 after first inspecting the decision matrix fig8 and the report summary fig9 . the second 4 . 5 minute data collection phase is started . similarly , each of the cip values defined in the boundary conditions table fig4 are programmed every 1 . 5 minutes and each of the measured values for each breath is stored into the stored data sets ( 84 ) identified in fig6 . the entire process described above for selecting cid is repeated in detail for selecting cip , using instead those rows identified in fig6 , and 8 for cip data storage . after inspecting the decision matrix fig8 and the report summary fig9 ( in this case , showing cip min , cip ave , and cip max ), the physician then selects and programs the cip value at 96 in fig5 . upon completion of the acute phase of evaluation , the patient is ready for the chronic assessment phase , which may be performed immediately after the acute assessment or at a later time . the invention has been described in considerable detail in order to comply with the patent statutes and to provide those skilled in the art with the information needed to apply the novel principles and to construct and use such specialized components as are required . however , it is to be understood that the invention can be carried out by specifically different equipment and devices , and that various modifications , both as the equipment details and operating procedures can be accomplished without departing from the scope of the invention itself .

US-88959504-A

the present invention is an improved putter that assists a player in perfecting a putt stroke during practice and repeating it with the same club during play . the shaft is attached to the clubhead such that it can swivel from a practice configuration to a play configuration . the putter also comprises a hosel with an attached alignment cap has lobes which matingly engage a series of recesses on the clubhead to secure the clubhead to the shaft . the putter conforms to the rules of golf so that the player does not have to change clubs between practice and play . the club may be used for either a right or left - handed stroke .

the present invention comprises a putter having a shaft 12 attached to a clubhead 11 with a hosel 13 . see fig1 - 7 . the present device may be used with shafts of any length . the hosel 13 includes an alignment cap 18 that firmly secures clubhead 11 to shaft 12 to form a unit that is not conveniently taken apart . the clubhead 11 has two faces , a practice face 14 and a play face 15 . only the play face is used as a striking surface during play , thereby conforming with a usga rule that a clubhead have only one striking face . the shaft is attached to the clubhead in such a way that the clubhead can rotate from a practice position to a play position , keeping the shaft in the same position relative to the golfer . see fig1 which shows the practice face 14 of a clubhead 11 in the play position for a right handed golfer . fig2 shows the play face 15 of the same putter . fig8 shows a right - handed golfer 80 making a putt stroke with the practice face 14 and fig9 shows the same golfer 80 making a putt with a play face 15 . the shaft 12 is attached to the hosel 13 as shown in fig4 . in turn , the hosel 13 is attached to the alignment cap 18 , which cooperates with one or more mated structures in the clubhead 11 to align the shaft 12 and the clubhead . as used herein , “ attached ” means that the parts are integral with each other or are separate components that have been connected to each other . in the preferred embodiment , the alignment cap 18 includes three lobes 24 a , 24 b , and 24 c which engage three mated recesses 26 a , 26 b , and 26 c which are defined by the clubhead 11 . see fig4 . in this preferred embodiment , the recesses 26 are connected to each other , but non - connected recesses 26 could be used and fall within the scope of the present invention . in alternative embodiments , the number of mated lobes and recesses can be increased or decreased , and the shape of the lobes and recesses can be changed , for example from circular to square , ovoid , triangular or other shape . additionally , instead of lobes and recesses , pins , pegs or other types of protrusions could be placed on the alignment cap 18 to engage apertures , holes or any other type of recess located on the clubhead 11 . alternatively , the clubhead could have protrusions that mate with apertures in the alignment cap . when three lobes 24 are used , a center lobe 24 b is designed to fit within a center recess 26 b defined by the clubhead 11 . see fig4 and 5 a . the remaining two side lobes , 24 a and 24 c in turn engage corresponding recesses 26 a and 26 c . the mated structures ensure that the shaft 12 and the clubhead 11 are aligned and tightly secured to each other . several components cooperate to fix the shaft 12 to the clubhead . see fig6 . a first attachment structure causes the alignment cap 18 to be rotatably retained to the clubhead 11 and the second attachment structure causes the alignment cap 18 to be fixed securely to the clubhead 11 . in the first attachment structure , a retention screw 40 is aligned through a mated retention aperture 41 that extends through the clubhead 11 and into the alignment cap 18 . the retention aperture 41 has smooth sidewalls where it goes through the clubhead 11 but the retention aperture is matedly threaded in the alignment cap 18 to securely receive the retention screw 40 . see fig6 . as a result , when the retention screw 40 is in place , the alignment cap 18 can be separated from the clubhead 11 distance “ a ” while still being retained thereto , so that it swivels freely . the retention screw may take the form of a regular screw , a chicago screw , rivet , detent and socket pair , or other device that allows the alignment cap 18 to be rotatably retained to the clubhead . the distance “ a ” that the alignment cap 18 can be separated from the clubhead 11 is greater than or equal to the thickness “ b ” of the alignment cap 18 . this facilitates the rotation of the shaft from a practice position to a play position . in the second attachment structure , a set screw 42 is aligned through one of two mated set apertures 43 that extend through the alignment cap 18 and into the clubhead 11 . the clubhead portion of the set aperture 43 is matedly threaded to securely receive the set screw 42 . see fig6 . the portion of the set aperture 43 in the alignment cap 18 can be smooth - walled or threaded . as a result , when the set screw 42 is in place , the alignment cap 18 cannot be separated from the clubhead 11 . this prevents the rotation of the shaft 12 and fixes the shaft 12 and the clubhead 11 together to form essentially one unit . preferably the set screw 42 is a hex screw or some other screw with a head that would be difficult or time - consuming to remove while on a golf course . the clubhead 11 is switched from a practice position to a play position by removing set screw 42 so that the shaft 12 may be pulled away from the clubhead 11 . once the hosel 13 and alignment cap 18 are free of their seated position in the clubhead 11 , the clubhead 11 is rotated approximately 180 degrees relative to the shaft 12 . the hosel 13 is guided to its seated position by placing lobes 24 a , 24 b , 24 c within recesses 26 a , 26 b , 26 c and the play face 15 is now facing the ball . the process is completed by re - inserting and tightening set screw 42 into the other set aperture 43 . in the preferred embodiment , the clubhead 11 has recesses 46 to hold removable weights . see fig5 a and 5 b . the recesses are referred to herein as weight cavities 46 . one or more weights 38 may be inserted into each weight cavity 46 to adjust the weight of clubhead 11 to the golfer &# 39 ; s liking . see fig5 b . preferably the weights 38 fit snugly in the weight cavities 46 . a golfer can vary the weight of clubhead 11 by using equally - sized weights 38 made of different materials that have different densities . for example , aluminum weights would cause the club to weigh less than brass weights , which would weigh less than lead weights . preferably only a single weight 38 is placed within each of the cavities , which complies with usga rules , but alternatively several weights 38 can be placed in cavities . preferably the weight cavities 46 are aligned with the recesses 26 such that the weights are retained within the weight cavity by the alignment cap . aligning the weight cavities will also make it easier to load the weights and to manufacture the clubhead . further , in the preferred embodiment , the clubhead 11 has one or more apertures on the practice face 14 that allow the golfer to see the weight 38 in the weight cavity 46 without having to remove the alignment cap 18 . by using weights of different colors , whether painted or simply by the nature of the material used , the golfer can quickly determine which weights are in the clubhead and therefore the weight . these apertures are referred to herein as weight windows 51 . as described in the related applications and patent , the practice face 14 has a substantially circular insert , referred to as a practice insert 16 . the practice insert 16 is convex relative to the practice face 14 , and the practice face 14 shape ranges from elliptical to spherical . the curved shape limits the number of points at which the practice face 14 can strike a golf ball in order for the golf ball to move in a straight line perpendicular to the practice face 14 , referred to as the line of putt . hitting the center of the golf ball with the center of the practice face 14 will cause the golf ball to move on the perpendicular line . however , if the golfer hits the golf ball with any part of the practice face 14 other than the center of the practice insert 16 , the golf ball will veer off the perpendicular line . the farther away from the center of the practice insert 16 , the worse the veer angle will be . preferably the practice insert 16 is an ellipse . with an elliptically practice insert 16 , the veer is relatively small at short radii from its center , thereby being somewhat forgiving to a less - than - perfect stroke . this approximates the amount of forgiveness of putts in play , because slight deviations for a perfect line of putt will not prevent the golf ball from falling in the hole . however , as the veer angle grows increasingly larger farther away from the center of the practice face 14 , the “ penalty ” for a bad stroke increases as the strokes become increasingly off - center . a spherical practice insert may also be used ; it provides a less forgiving center , but a more forgiving perimeter , as the veer angle changes relatively less than at the perimeter of an elliptical practice insert . the “ penalty ” for a bad stroke is constant regardless of how off - center the stroke is . it is likely that a better golfer will use the spherical practice insert to fine tune his putt stroke . in addition to the curvature of the practice insert 16 , the present invention includes a number of alignment apertures 50 for assisting the golfer in visualizing a straight line to the ball or other desired point . each alignment aperture is made in the clubhead 11 to receive a lightweight post that extends substantially perpendicularly from the practice face 14 . a conventional drinking straw is suitable for the post , as is it extremely lightweight and most convenient to obtain at a golf course . preferably , the diameter of each aperture is made to enable a drinking straw to be inserted and held in place snugly simply by friction . a post can be inserted in any one or more of the alignment apertures , in whichever placement the golfer finds it assists his alignment the best . in the preferred embodiment , the practice face 14 has two alignment apertures , however more are acceptable . the play face 15 also has a substantially circular insert , referred to as a play insert 17 . the play insert 17 is inwardly parabolic relative to the play face 15 , ranging from flat to concave . a flat striking face is required under usga rules , so a flat play insert should be used when playing a round of golf . see fig1 . a parabolic - shaped play insert is self - correcting to some degree , because the curve of the insert will urge the golf ball to the center of the parabola before redirecting the ball away from the play face . a parabola is the set of all points in a plane equidistant from a fixed point ( called the focus ) and a fixed line ( called the directrix ). the formula for a parabola is generally : thus , when p is large , the curvature of the play insert 17 is great and the ball is strongly urged to the center of the parabola . as the parabola flattens out , that is , as p becomes small , the play insert 17 provides less assistance in getting the ball to travel on the putt line perpendicular to the play face . when the parabola is flat , that is , when y is constant , the striking face is flat , and the putter 10 provides no self - correcting assistance to the golfer . preferably , the play insert 17 is flat so that the putter 10 conforms to usga rules . fig1 - 3 illustrates a preferred embodiment of the clubhead 11 having a curved practice insert 16 and flat play insert 17 . as shown in fig7 , the clubhead 11 includes a base plate 62 that is attached to the clubhead 11 , preferably by friction fit , although , glue , another adhesive or any other attachment mechanism may suffice . the base plate 62 is preferably has a cross section to minimize the amount of head surface that comes into contact with green . the base plate 62 may be smooth or , preferably , include a series of ridges 66 creating grooves aligned along the line of putt that allow grass to pass through them thereby reducing the amount of friction between clubhead 11 and the ground . the grooves aid in combing the green thus aiding the golfer in holding the head perpendicular to the intended line while the stroke is in the critical phase of moving across the green . the clubhead is made of any durable material , and preferably metal such as aluminum , brass or steel . the practice insert 16 is also made of a durable material , but preferably a hard composite material such as a polymer that provides for a satisfying “ thunk ,” such as surlyn ® thermoplastic resin sold by the e . i . dupont denemours and company , which was the first and most durable cover material that revolutionized the construction of the golf ball when it was introduced in the 1980s . the play insert 17 is made of durable materials , metal or composite , and preferably the same material as the practice insert 16 so that the feel of the practice stroke is the same as the stroke during play . one usga rule requires that the projection of the straight part of the shaft 12 onto the vertical plane through the toe and heel shall diverge from the vertical by at least 10 degrees . in other words , the angle between the shaft 12 and the sole of the club must be less than 80 degrees . fig8 and 9 illustrate a golfer 80 practicing a right - handed putt stroke into hole 83 . the golfer uses the practice face 14 to hit the ball and improve his aim . by rotating the putter approximately 180 degrees in his hands , the golfer can use the same putter 10 and the same stance to putt in play . fig9 illustrates the same golfer putting in play , using the play face 15 as the striking face . while there has been illustrated and described what is at present considered to be the preferred embodiment of the present invention , it will be understood by those skilled in the art that various changes and modifications may be made and equivalents may be substituted for elements thereof without departing from the true scope of the invention . therefore , it is intended that this invention not be limited to the particular embodiment disclosed , but that the invention will include all embodiments falling within the scope of the appended claims .

US-22907205-A

the present invention is directed to a method for treating individuals having inflammation or preventing inflammation in individuals at risk for inflammation , more specifically individuals with chronic inflammation as evidenced by elevated c - reactive protein , serum fibrinogen , elevated platelet count and platelet activity , elevated blood glucose , any component or combination of components of the metabolic syndrome by using the selected immunoregulators . the present invention also includes a method for preventing the development of inflammation in individuals at risk for inflammation by using the selected immunoregulators , and for deferring progression of the inflammatory state to the more specific outcomes of the metabolic syndrome including diabetes mellitus , coronary heart disease , and cancer .

the “ selected immunoregulators ” (“ selected immunormodulators ” “ selected immunoamplifiers ”) include the purified leukocyte dialysate subfraction ( lds ) described by dr . a . arthur gottlieb patents ( u . s . pat . nos . 5 , 100 , 663 , 4 , 616 , 079 , 4 , 699 , 898 , 4 , 710 , 380 , 4 , 778 , 750 , 4 , 874 , 608 , 5 , 013 , 546 , 5 , 081 , 108 , 5 , 093 , 321 which are incorporated herein by references ) which is naturally derived from healthy human leukocytes , as well as purified immunologically active components of the naturally derived immunoregulators including the dipeptide tyrosylglycine ( yg ) and the tripeptide tyrosylglycylglycine ( ygg ), as well as synthetically produced yg and ygg . these regulators also include covalently modified yg and ygg , such modifications designed to stabilize or to enhance the biological activity of said regulators , as well as pharmaceutically acceptable salts , suitable for human use , of yg , ygg , and related molecules including covalently modified yg , and covalently modified ygg . yg - material ( or yg - product ) means a member of a group consisting of a set of molecular species wherein each molecule contains a tyr - gly amino acid residue sequence , and no other amino acid residues . the molecule may be in the form of a simple tyr - gly sequence , or the molecule may be methylated , amidified , esterified , acetylated , etc . yg - material does not include tripeptides or higher polypeptides . however , two yg - materials ( e . g ., two molecules of tyr - gly ) may be complexed together in the form : ( tyr - gly ) zn ++( tyr - gly ), or they may be dimerized as described in a . arthur gottlieb u . s . pat . no . 5 , 100 , 663 . such a complex or dimer is not considered a tetrapeptide , but merely two dipeptides complexed together or dimerized . ygg - material means a member of a group consisting of a set of molecular species wherein each molecule contains a tyr - gly - gly amino acid residue sequence , and no other amino acid residues . the molecule may be in the form of a simple tyr - gly - gly sequence , or the molecule may be methylated , amidified , esterified , acetylated , etc . ygg - material does not include dipeptides , tetrapeptides , or higher polypeptides . however , two ygg - materials ( e . g ., two molecules of tyr - gly - gly ), or yg - material and ygg - material , may be complexed together or dimerized . such a complex or dimer is not considered a pentapeptide or hexapeptide . inhibited yg - material means yg - material that has been mixed , complexed , bound , linked , or otherwise combined with a means for inhibiting cleavage of the tyr - gly bond of the molecule by endogenous enzymes ; however , the material must still contain a tyr - gly amino acid residue sequence and no other amino acid residue sequence . puromycin and bacitracin are examples of inhibitors that may be mixed with yg - material . it is also known to n - methylate the tyr residue to inhibit enzymatic action . it is also known to esterify or amidify the c - terminal carboxyl group to inhibit enzymatic cleavage . the products of such expedients are hereinafter termed inhibited yg - material . inhibited yg - material does not include expanded yg - material , as defined below ; the two terms are mutually exclusive . also , the term “ inhibited yg - material ” falls within the scope of the term “ yg - material .” expanded yg - material means a molecule of the form tyr - x - gly , where x is a d - amino acid , such as d - ala . the term includes amides , esters , salts , etc ., as in the case of yg - material . it is known that the insertion of a d - amino acid into tyr - gly tends to inhibit cleavage of the tyr - gly bond by endogenous enzymes . the terms yg - material and expanded yg - material are mutually exclusive , since the former is a dipeptide and the latter is a tripeptide ; also the former has a tyr - gly bond and the latter does not . yg product includes yg , yg material , inhibited yg material , expanded yg material , and endogenous yg material . ygg product includes ygg material , endogenous ygg material , and any covalent or other modification to said ygg , and any salt of any of these . extraneous - peptide amino acid residue sequences means any and all amino acid residue sequences except tyr - gly and tyr - gly - gly . as used herein , “ sequence ” refers to a plurality of residues , and the terms excludes a molecule with only a single amino acid residue , such as glycine . the metabolic syndrome is a constellation of characteristics which may include obesity , hypertension , insulin resistance , hyperinsulinemia , impaired glucose tolerance , atherogenic dyslipidemia , including elevated serum triglycerides and low serum hdl cholesterol levels , and elevated fibrinogen and c - reactive protein , coagulation disorders , acanthosis nigricans and polycystic ovary syndrome . the most prevalent current hypothesis regarding causation is that the metabolic syndrome , which is present in 25 % of the population is secondary to overeating and lack of physical exercise , characteristic of the modern lifestyle . it is possible that the metabolic syndrome is initiated by chronic antigenic stimulation and then the adipose tissue becomes a depot for further antigenic substance accumulation such as occurs with exposure to fine particle air pollution , dioxin from burning of plastics , or from tobacco smoke and the cycle reinforces itself since adipose tissue secretes increased levels of cytokines , causing dyslipidemia and other effects associated with the metabolic syndrome . the process then becomes self - perpetuating with obesity leading to insulin resistance , elevated triglycerides , impaired glucose tolerance , etc . the presence of the acute phase reactants fibrinogen and c - reactive protein , markers for that inflammation , draws one &# 39 ; s attention to look for the cause of the inflammation , and to postulate that the underlying pathology may be caused by a chronic inflammatory state , whether it is induced by antigens associated with environmental factors or by chronic infection which overwhelms the ability of the innate immune system to remove them . moreover , the association of coronary heart disease with elevated cholesterol levels , as causative , is now brought into question , given the observation that elevated c - reactive protein is a better predictor of coronary heart disease than elevated cholesterol ( r idker , p m , et al . circulation 107 : 391 - 7 ( 2003 ). cholesterol is a necessary component of intact cell membranes . therefore , elevated serum cholesterol levels may be markers of cellular membrane disruption secondary to inflammation from either infectious or non - infectious antigenic stimulation , which then secondarily contribute to endothelial plaque and thrombus formation . it has been recognized that the hmg - coa reductase inhibitors (“ statin ” drugs ) lower cholesterol levels and decrease coronary heart disease mortality . these drugs are also anti - inflammatory . regular use of aspirin has been reported to decrease coronary heart disease mortality . this reduction has been attributed to the anticoagulant effect of aspirin . however , aspirin is an anti - inflammatory agent , as well , and has been recently been desribed as facilitating blood glucose control in diabetes mellitus ( for example , hundal , rs , et al . journal of clinical investigation . 109 : 1321 - 6 ( 2002 ). “ stress ,” ( either physiological or psychological , i . e ., type “ a ” personality ) which decreases immune function may also contribute to coronary heart disease by enabling antigenic stimulation to proceed due to reduced ability to clear the “ foreign ” agent . stress is known to increase production of corticosteroids , which , in turn , reduce functional immunity . if chronic antigenic stimulation resulting from immune dysfunction is causal of the metabolic syndrome , then correction of immune dysfunction could reduce the symptoms and characteristics of the metabolic syndrome , and thus the factors leading to diabetes mellitus and coronary heart disease . the instant application describes the use of the selected immunoregulators to affect metabolic aspects of certain disease conditions , including the “ type 2 diabetes mellitus ” and other conditions found in association with or as a result of the metabolic syndrome , also known as syndrome x , or caused by the same physiological basis as the metabolic syndrome ( for example , hiv lipodystrophy ). the instant application will further describe the control of inflammatory effects of chronic antigenic stimulation . such stimulation and inflammation may be caused by factors including but not limited to infectious pathogens and environmental pollutants such as particulates , organic materials , and cigarette smoke . the effects of the immunomodulators have been demonstrated in both clinical and laboratory studies and include , but are not limited to the findings described below : the metabolic syndrome , or syndrome “ x ”, is a recently described illness which is characterized by obesity , insulin resistance , hypertension , dyslipidemia , decreased serum hdl - l , elevated serum triglycerides , impaired glucose tolerance , polycystic ovary syndrome , increased acute phase proteins , including c - reactive protein and fibrinogen , and leads to diabetes mellitus , coronary artery disease , and cancer . coronary heart disease and diabetes mellitus have been reported to be increased in populations chronically exposed to air pollution and to dioxins . people who are long - term survivors with aids develop a lipodystrophy with features very similar to the metabolic syndrome . both of these populations are subject to chronic antigenic stimulation . there are data from a clinical trial in patients with hiv disease , using the leukocyte - derived immunoregulator which has yg and ygg as the active components ( g ottlieb , m s . a nnals of i nternal m edicine . 115 : 84 ( 1991 )), which were not examined with regard to evaluation of the immunoregulator , that are useful with regard to the current thinking concerning the metabolic syndrome . re - examination of some of the toxicity evaluation data collected during the clinical trial showed that during the course of the trial , mean serum glucose increased in those who received placebo ( p & lt ; 0 . 015 ) and became significantly higher than in those treated with the immunoregulator ( p & lt ; 0 . 043 ), which either declined if all subjects were included or rose slightly if only those subjects with normal values at baseline were included ( table 1 ). similarly , blood platelets which contribute to the coagulopathy associated with the metabolic syndrome , were “ reduced ” in treated patients and significantly increased in those receiving placebo ( p = 0 . 038 ). the between group difference was significant ( p = 0 . 032 ) ( table 1 ). a the value at baseline is that at the start of treatment . d p - values correspond to the mann - whitney ( stratified wilcoxon rank sum ) test statistic . these findings support an hypothesis that uncontrolled and chronic antigenic stimulation due to infection ( hiv is present in many tissues and cells once infection has occurred ) or environmental pollutants , and the relative immunologic deficiency and failure to effectively remove such foreign material due to an overwhelming antigen and / or reduced immune function load may be contribute to the metabolic syndrome and insulin resistance which is a result of interference with insulin activity and the activity of enzymes related to glucose metabolism . correction of such immune deficiency or dysregulation with the unique immunoregulators described herein appears to correct key components of the metabolic syndrome and lipoatrophic diabetes mellitus associated with hiv disease . based on these findings , it is possible , then to treat patients who have or who are at risk for the metabolic syndrome with one or more of the immunoregulators described herein , and thus to prevent the diabetes mellitus , coronary heart disease , cancer , and other outcomes associated with the metabolic syndrome which is seen in increasing frequency worldwide , and more so in areas of increased pollution , and in populations with high prevalence of and at high risk for chronic infections , e . g . tuberculosis and malaria , by improving the individual &# 39 ; s immune function . the further application of the instant invention is illustrated by the following forward looking examples . a group of employees in an industrial plant are repeatedly exposed to organic solvents and other reagents . the company physician realizes that prolonged exposure , even at low levels , may diminish immune function . the physician tests a number of employees and finds reduced dh responsiveness and increased c - reactive protein . he prescribes doses of an effective dose of yg product ( for example , 10 μg of yg to be taken at periodic intervals as determined by the physician , depending upon the patient &# 39 ; s condition ). the physician follows the employees &# 39 ; dh responsiveness and notes improvement . the physician also follows the employees &# 39 ; immune function using standard laboratory proliferative assays , testing the ability of peripheral blood mononuclear cells to respond to stimulation with certain antigens or mitogens . he also notes a decline in employee illness - related absence , elevated blood pressure and dyslipidemia . a military air wing is preparing for deployment to a combat zone . it is known that exposure to jet fuel suppresses immune function . the wing physician , knowing that the psychological stress of deployment also reduces immune function orders an effective dosage of ygg material to be taken periodically by each member of the group . he reasons that maintaining normal immune balance will avoid illnesses and infections commonly seen in military personnel under these conditions , thereby maintaining a higher level of troop readiness . he also knows that the immunosuppressive effects of exposure to jet fuel linger well beyond the initial period of exposure . he therefore orders continuation of ygg material upon return to the home base until he confirms the return of normal immune function . by doing so , he prevents sequelae of chronic inflammation such as the metabolic syndrome . a patient is treated for hiv disease . his viral load decreases , however he begins to show signs of lipodystrophy and other indications of the metabolic syndrome . his physician is particularly concerned that the patient &# 39 ; s glucose tolerance is abnormal , indicating possible onset of the “ type 2 ” diabetes mellitus and the other abnormalities associated with the metabolic syndrome , which lead to coronary heart disease . also , recognizing that the patient &# 39 ; s immune function is compromised and that chronic antigenic stimulation , and the resulting metabolic syndrome which could lead to insulin resistance , the physician prescribes 10 μg of yg product to be taken at periodic intervals , depending upon the patient &# 39 ; s status , for the remainder of the patient &# 39 ; s life , as hiv is known to incorporate itself into many different cells and tissues such that it cannot be totally eliminated . hiv disease remains under control and the patient &# 39 ; s glucose tolerance returns to normal . a young woman presents to her physician , on annual physical examination , with a weight gain of 50 pounds , is found to have high blood pressure , and reports vaginal pruritis . over the past few years , she has lived in an area of major traffic congestion ( near an oil refinery ). the physician does a physical examination and discovers unusual black pigmented areas in her neck creases ( acanthosis nigricans ) and orders laboratory tests , including fasting and 2 - hour blood glucose , serum triglycerides , serum insulin , a cholesterol profile , c - reactive protein , serum fibrinogen , and a vaginal smear for candidiasis . she is found to have impaired glucose tolerance , elevated serum triglycerides , low hdl and high ldl receptors and high c - reactive protein and fibrinogen levels . her vaginal smear is positive for candida albicans . the physician knows that he is seeing a case of the metabolic syndrome which progresses to diabetes mellitus and coronary heart disease . he prescribes a weight reduction diabetic diet , physical exercise , an ace inhibitor , and fluconazole . the patient reports losing weight and gaining it back . since the physician knows of the patient &# 39 ; s prolonged and constant exposure to environmental antigens , and since refractory infection with candida albicans is a hallmark of immune dysfunction , he prescribes yg ( sublingual ) to be taken once every two weeks , in addition to continuation of the other recommendations . the physician monitors her blood glucose , c - reactive protein , serum triglycerides , serum cholesterol , and weight , periodically . over the course of a year , her blood glucose changes toward normal , her c - reactive protein is reduced ( indicating reduced inflammatory processes ) and her cholesterol level is reduced . she continues her diet and physical exercise and loses weight . she requires less high blood pressure medication . the physician continues to monitor her cell - mediated immune function , blood glucose levels , lipid profile , and measures of inflammation , and adjusts her medications appropriately . the patient continues to lose weight to reach her target weight , blood pressure is controlled , blood glucose is normalized , and her risk of diabetes mellitus and coronary heart disease is reduced . as the preceding examples and discussion show , the invention can be practiced with a genus of products characterized by the presence of tyr ( y ) and gly ( g ) amino acid residues , specifically di - and tripeptides containing y and g amino acid residues , with optional admixture with other products and with optional modification of certain parts of the structure . while the invention has been described in connection with specific and preferred embodiments thereof , it is capable of further modifications without departing from the spirit and scope of the invention . this application is intended to cover all variations , uses , or adaptations of the invention , following , in general , the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains , or as are obvious to persons skilled in the art , at the time the departure is made . it should be appreciated that the scope of this invention is not limited to the detailed description of the invention hereinabove , which is intended merely to be illustrative , but rather comprehends the subject matter defined by the following claims .

US-80495404-A

device and method for puncturing blood vessels while using fluoroscopy . the disclosed device enables improved needle orientation control and avoids direct exposure of the clinician &# 39 ; s hand to x - ray during the puncturing procedure .

reference is now made to fig1 , which illustrates a needle holder 10 , constructed and operative in accordance with an embodiment of the present invention . needle holder 10 is an elongate stiff member 13 that includes a needle connector 14 , such as but not limited to , a male luer connector , at a distal end 15 thereof . connector 14 connects to a needle 11 , such as by means of connecting with a female luer connector affixed to the proximal end of the needle 11 . needle holder 10 may be supplied without the needle 11 and the user connects the holder to the needle . alternatively , needle holder 10 may be supplied with needle 11 already assembled therewith . without limitation , needle holder 10 preferably has a length of at least 12 cm , most preferably in the range of 20 - 25 cm ; holder 10 is preferably longer than the needle 11 . the elongate stiff member 13 may be a hollow tube with a lumen 16 , which may be made , without limitation , from a stiff , clear polymeric material , e . g ., polycarbonate . lumen 16 is big enough for easy blood flow therethrough , preferably , but not necessarily , having a diameter of equal to or more than 1 . 0 mm . the long and stiff holder 10 reduces the clinician &# 39 ; s hand exposure to x - rays during insertion of needle 11 , and provides better control of the needle orientation , trajectory , and puncture . needle holder 10 includes a vent 12 at a proximal end thereof for blood flow to verify that the needle tip is properly located inside the blood vessel . vent 12 preferably , but not necessarily , has a standard female luer shape . reference is now made to fig2 , which illustrates a needle holder 10 and guidewire holder 17 , constructed and operative in accordance with an embodiment of the present invention . guidewire holder 17 may be used to hold the distal portion of a guidewire 25 inside the needle holder lumen before and during blood vessel puncturing . the option to hold the guidewire distal section inside the needle holder lumen may be useful for the operator , because it eliminates the need to look for the guidewire at the operation table , while holding the needle and needle holder steady . it reduces the amount of blood coming out of the needle , and spillage near the patient , by shortening the time needed to insert the guidewire through the needle . guidewire holder 17 includes a guidewire locking element 18 , which may be made of a flexible material , such as but not limited to , silicone . a sliding knob 19 is arranged to slide over guidewire locking element 18 , which forces element 18 through a small hole 41 in elongate stiff member 13 into lumen 16 , thereby pressing the distal end of guidewire 25 against the inner wall of lumen 16 and holding guidewire 25 in place . to release guidewire 25 , the user slides sliding knob 19 to release guidewire locking element 18 from lumen 16 . a vent hole 20 may be added to elongate stiff member 13 distal to guidewire holder 17 to allow free blood flow outwards from the needle , even if lumen 16 is blocked by guidewire holder closing element 18 . guidewire locking element 18 and / or other locking elements can be alternatively assembled to vent 12 . in accordance with an embodiment of the present invention , the procedure steps are : b . optionally insert and lock the distal portion of guidewire 25 inside needle holder lumen 16 . c . using x - ray angiography , insert and adjust the needle and needle tip until entering the blood vessel . d . confirm needle tip is inside the blood vessel by looking at blood coming up into lumen 16 of elongate stiff member 13 . e . insert guidewire 25 through vent 12 ( e . g ., female luer ) and lumen 16 ( if not inserted and locked before ), through connector 14 and needle 11 , and into the blood vessel . f . extract needle holder 10 together with needle 11 from the patient , and remove proximally from guidewire 25 .

US-201113390143-A

an assembly for coupling a first portion of an anatomy to a second portion of the anatomy includes an anchor having an anchor body and a first and second bores through the anchor body . a first adjustable suture construct having a body portion passes through the first bore of the anchor and includes first and second adjustable loops slidable relative to a passage portion defined in the body portion of the first adjustable suture construct . a similar second adjustable suture construct passes through the second bore of the anchor .

the following description is merely exemplary in nature and is not intended to limit the present disclosure , application , or uses . it should be understood that throughout the drawings , corresponding reference numerals indicate like or corresponding parts and features . fig2 a represents a suture construction 20 according to the present teachings . shown is a suture 22 having a first end 24 and a second end 26 . the suture 22 is formed of a braided body 28 that defines a longitudinally formed hollow passage 30 therein . first and second apertures 32 and 34 are defined in the braided body 28 at first and second locations of the longitudinally formed passage 30 . briefly referring to fig3 , a first end 24 of the suture 22 is passed through the first aperture 32 and through longitudinal passage 30 formed by a passage portion and out the second aperture 34 . the second end 26 is passed through the second aperture 34 , through the passage 30 and out the first aperture 32 . this forms two loops 46 and 46 ′. as seen in fig2 b , the relationship of the first and second apertures 32 and 34 with respect to the first and second ends 24 and 26 can be modified so as to allow a bow - tie suture construction 36 . as described below , the longitudinal and parallel placement of first and second suture portions 38 and 40 of the suture 22 within the longitudinal passage 30 resists the reverse relative movement of the first and second portions 38 and 40 of the suture 22 once it is tightened . the first and second apertures are formed during the braiding process as loose portions between pairs of fibers defining the suture 22 . as further described below , the first and second ends 24 and 26 can be passed through the longitudinal passage 30 multiple times . it is envisioned that either a single or multiple apertures can be formed at the ends of the longitudinally formed passage . as best seen in fig4 a and 4b , a portion of the braided body 28 of the suture 22 defining the longitudinal passage 30 can be braided so as to have a diameter larger than the diameter of the first and second ends 24 and 26 . additionally shown are first through fourth apertures 32 , 34 , 42 , and 44 . these apertures can be formed in the braiding process or can be formed during the construction process . in this regard , the apertures 32 , 34 , 42 , and 44 are defined between adjacent fibers in the braided body 28 . as shown in fig4 b , and described below , it is envisioned the sutures can be passed through other biomedically compatible structures . fig5 - 7 represent alternate constructions wherein a plurality of loops 46 a - d are formed by passing the first and second ends 24 and 26 through the longitudinal passage 30 multiple times . the first and second ends 24 and 26 can be passed through multiple or single apertures defined at the ends of the longitudinal passage 30 . the tensioning of the ends 24 and 26 cause relative translation of the sides of the suture 22 with respect to each other . upon applying tension to the first and second ends 24 and 26 of the suture 22 , the size of the loops 46 a - d is reduced to a desired size or load . at this point , additional tension causes the body of the suture 22 defining the longitudinal passage 30 to constrict about the parallel portions of the suture 22 within the longitudinal passage 30 . this constriction reduces the diameter of the longitudinal passage 30 , thus forming a mechanical interface between the exterior surfaces of the first and second parallel portions as well as the interior surface of the longitudinal passage 30 . as seen in fig8 - 10 and 11 a - 11 b , the suture construction can be coupled to various biocompatible hardware . in this regard , the suture construction 20 can be coupled to an aperture 52 of the bone engaging fastener 54 . additionally , it is envisioned that soft tissue or bone engaging members 56 can be fastened to one or two loops 46 . after fixing the bone engaging fastener 54 , the members 56 can be used to repair , for instance , a meniscal tear . the first and second ends 24 , 26 are then pulled , setting the tension on the loops 46 , thus pulling the meniscus into place . additionally , upon application of tension , the longitudinal passage 30 is constricted , thus preventing the relaxation of the tension caused by relative movement of the first and second parallel portions 38 , 40 , within the longitudinal passage 30 . as seen in fig9 - 10 and 11 a - 11 b , the loops 46 can be used to fasten the suture construction 20 to multiple types of prosthetic devices . as described further below , the suture 22 can further be used to repair and couple soft tissues in an anatomically desired position . further , retraction of the first and second ends allows a physician to adjust the tension on the loops between the prosthetic devices . fig1 b represents the coupling of the suture construction according to fig2 b with a bone fastening member . coupled to a pair of loops 46 and 46 ′ is tissue fastening members 56 . the application of tension to either the first or second end 24 or 26 will tighten the loops 46 or 46 ′ separately . fig1 a - 12e represent potential uses of the suture constructions 20 in fig2 a - 7 in an acl repair . as can be seen in fig1 a , the longitudinal passage portion 30 of suture construction 20 can be first coupled to a fixation member 60 . the member 60 can have a first profile which allows insertion of the member 60 through the tunnel and a second profile which allows engagement with a positive locking surface upon rotation . the longitudinal passage portion 30 of the suture construction 20 , member 60 , loops 46 and ends 24 , 26 can then be passed through a femoral and tibial tunnel 62 . the fixation member 60 is positioned or coupled to the femur . at this point , a natural or artificial acl 64 can be passed through a loop or loops 46 formed in the suture construction 20 . tensioning of the first and second ends 24 and 26 applies tension to the loops 46 , thus pulling the acl 64 into the tunnel . in this regard , the first and second ends are pulled through the femoral and tibial tunnel , thus constricting the loops 46 about the acl 64 ( see fig1 b ). as shown , the suture construction 20 allows for the application of force along an axis 61 defining the femoral tunnel . specifically , the orientation of the suture construction 20 and , more specifically , the orientation of the longitudinal passage portion 30 , the loops 46 , and ends 24 , 26 allow for tension to be applied to the construction 20 without applying non - seating forces to the fixation member 60 . as an example , should the loops 24 , 26 be positioned at the member 60 , application of forces to the ends 24 , 26 may reduce the seating force applied by the member 60 onto the bone . as best seen in fig1 c , the body portion 28 and parallel portions 38 , 40 of the suture construction 20 remain disposed within to the fixation member 60 . further tension of the first ends draws the acl 64 up through the tibial component into the femoral component . in this way , suture ends can be used to apply appropriate tension onto the acl 64 component . the acl 64 would be fixed to the tibial component using a plug or screw as is known . after feeding the acl 64 through the loops 46 , tensioning of the ends allows engagement of the acl with bearing surfaces defined on the loops . the tensioning pulls the acl 64 through a femoral and tibial tunnel . the acl 64 could be further coupled to the femur using a transverse pin or plug . as shown in fig1 e , once the acl is fastened to the tibia , further tensioning can be applied to the first and second ends 24 , 26 placing a desired predetermined load on the acl . this tension can be measured using a force gauge . this load is maintained by the suture configuration . it is equally envisioned that the fixation member 60 can be placed on the tibial component 66 and the acl pulled into the tunnel through the femur . further , it is envisioned that bone cement or biological materials may be inserted into the tunnel 62 . fig1 a - 13d represent a close - up of a portion of the suture 20 . as can be seen , the portion of the suture defining the longitudinal passage 30 has a diameter d 1 which is larger than the diameter d 2 of the ends 24 and 26 . the first aperture 32 is formed between a pair of fiber members . as can be seen , the apertures 32 , 34 can be formed between two adjacent fiber pairs 68 , 70 . further , various shapes can be braided onto a surface of the longitudinal passage 30 . the sutures are typically braided of from 8 to 16 fibers . these fibers are made of nylon or other biocompatible material . it is envisioned that the suture 22 can be formed of multiple type of biocompatible fibers having multiple coefficients of friction or size . further , the braiding can be accomplished so that different portions of the exterior surface of the suture can have different coefficients of friction or mechanical properties . the placement of a carrier fiber having a particular surface property can be modified along the length of the suture so as to place it at varying locations within the braided constructions . fig1 a - 14c , 15 a - 15 c , 16 a - 16 c , 17 a - 17 c , and 18 a - 18 c represent various fasteners which can be used with the suture constructions of fig1 - 7 . fig1 a - 14c represent an elongated anchor 70 defining a suture accepting bore 72 . as described below , the anchor 70 has a first profile 79 which allows the anchor 70 to be passed through a bore defined in a bone . the anchor 70 can be rotated so as to have a second profile 74 to allow engagement with a patient . the fastener 70 has a tissue engaging surface 76 which is configured to engage either soft tissue or bone . examples of this can be found in the form of a toggle lock in co - assigned and co - pending u . s . patent application ser . no . 10 / 864 , 900 , incorporated herein by reference . as shown in fig1 a - 15c and 16 a - 16 c , the fasteners 78 and 80 can have a generally cylindrical body 82 defining a through bore 84 . disposed across the through bore 84 is a transverse pin 86 which is configured to slidably bear the suture construction . optionally , the fastener can have an outer engagement rib or flange 83 which is configured to engage the periphery of an aperture formed in the bone . the cylindrical body 82 can have an outside diameter which is less than the diameter of the bore in the bone . as shown in fig1 a - 17c and 18 a - 18 c , the fasteners 90 and 92 can have a general planar button configuration having a plurality of suture accepting through bores 93 . these bores 93 can slidably or fixably accept the suture 22 . the button can have a diameter greater than the diameter of the tunnel formed in the bone . it is envisioned the fasteners 90 and 92 can have flat or curved bearing surfaces . in this regard , the bearing surface of the fasteners 90 and 92 can have a convex bearing shape . fig1 - 21 and 22 a - 22 b represent the use of the suture construction to couple a bone - tendon - bone graft construction 100 within a femoral / tibial tunnel 102 . as shown in fig1 , the tunnel 99 can have a first portion 103 with a first diameter 107 and a second portion 109 having second smaller diameter 108 within the femur . as described below , the second diameter 108 can be used to couple the bone - tendon - bone construction 100 to the tunnel . as shown in fig2 and 21 , a loop of suture 96 is passed through a collapsible tube 98 . the collapsible tube or a pair of loops formed by a suture 22 is positioned within the bore 72 of a first fastener 70 . as described above , the collapsible tube 98 can be a portion of the suture 22 , or can be a separate member . as seen in fig2 , to form the suture construction 73 , the suture 22 is passed through the first bore 72 defined by the first fastener 70 . the suture 22 can then be passed through a second bore defined by a second fastener 70 or a suture loop 77 . in any of the embodiments , the collapsible tube 98 can be a portion of the suture . a first end 26 of the suture 22 is passed through a first aperture 34 defined by the collapsible tube 98 into a passage portion 30 defined by the collapsible tube 98 and out a second aperture 36 defined by the collapsible tube 98 so as to place the first end outside of the passage portion 30 and form a first loop . a second end 26 of the suture 22 is passed through the second aperture 36 into the passage portion 30 and out the first aperture 34 so as to place the second end 26 outside of the passage portion 30 and form a second loop 47 . at this point , the passage portion 30 can optionally be positioned within the first bore 72 of the fastener 70 or the loop of the suture 22 . as seen in fig2 a and 22b , the construction 73 is coupled to a bone - tendon - bone construction 100 using the loop of suture 77 or a fastener . the bone - tendon - bone implant 100 can be formed of an allograph - tendon construction or artificial bone - tendon or bone - tendon - bone prosthetic assembly . it is envisioned the physician can intraoperatively determine the desired graft or graft assembly length and appropriate graft tension . after fixing the suture construction to the bone - tendon - bone construction 100 by for example a through pin 111 , the bone - tendon - bone construction 100 is installed into the tunnel 102 formed in a femur and tibia 104 , 105 . as described above with respect to fig1 a , the suture construction 73 of fig2 can be fed through the femoral tunnel 102 . the bone - tendon - bone construction 100 is then put into the tunnel 102 . a first portion 106 of the bone - tendon - bone construction 100 is coupled to a tibial tunnel using a fastener 101 positioned within the tunnel . a second portion of the bone - tendon - bone construction 100 is pulled taught into the femoral tunnel by tensioning the ends 24 and 26 of the suture construction 73 . the portion 113 of the bone - tendon - bone construction 100 can be coupled to the femur using a transverse or parallel bone engaging screw 101 . as seen in fig2 c and 22d , a pair of suture constructions 22 and 22 ′ are coupled to a pair of soft tissue replacements 64 and 64 ′ using the loops of suture 77 , 77 ′ or a fastener . the pair of soft tissue replacements 64 and 64 ′ can be formed of artificial of harvested tendon material . it is envisioned the physician can intraoperatively determine the desired graft or graft assembly length and appropriate graft tension . after fixing the suture constructions 22 and 22 ′ to a toggle lock ( see fig2 d ) and the pair of soft tissue replacements 64 and 64 ′ are implant into the tunnel 102 formed in a femur and tibia 104 , 105 . as described above with respect to fig1 a , the suture constructions 22 and 22 ′ of fig2 can be fed through the femoral tunnel 104 . the pair of soft tissue replacements 64 and 64 ′ are then pulled into the tunnel 104 by applying tension onto the ends 24 - 26 ′ of the suture constructions . a first portion 106 of the pair of soft tissue replacements 64 and 64 ′ is coupled to a tibial tunnel 105 using a fastener 101 such as a washerlok ™ tibial fixation as provided by biomet sports medicine positioned within the tunnel . a second portion of the pair of soft tissue replacements 64 and 64 ′ is pulled taught into the femoral tunnel by tensioning the ends 24 and 26 of the suture construction 73 . the portion 113 of the pair of soft tissue replacements 64 and 64 ′ can be coupled to the femur using a transverse or parallel bone engaging screw 101 . it is envisioned the suture ends 24 and 26 can be passed though a medial portal 25 to facilitate the tensioning of the pair of soft tissue replacements 64 and 64 . alternatively , after insertion into the femoral tunnel 102 , as seen in fig1 b , an appropriate amount of tension is applied to the pair of soft tissue replacements 64 and 64 ′ by applying tension to the ends 24 and 26 of the suture construction . a fastener 101 is engageably driven between the ends of pair of soft tissue replacements 64 and 64 ′ and the internal surface of the bore formed in the tibia . this locks the pair of soft tissue replacements 64 and 64 ′ to the bone . fig2 represents the coupling of a flexor tendon 110 to the humerus . shown is the ulna 112 having a through bore 114 . the through bore 114 can accept the suture construction 73 shown in fig2 . as described above with respect to the acl replacement shown in fig1 a , the suture construction 73 is fed through the tunnel 114 formed in the ulna 112 . a soft tissue graft 110 is fed through the pair of loops 46 , 47 formed by the suture construction 73 . the ends 24 , 26 of the suture 22 are then pulled so as to pull the soft tissue graft 110 to or into the tunnel 114 . a second end of the soft tissue graft 118 can be coupled to a bore 120 formed in a lateral epicondyle 122 of the humerus . a soft tissue engaging fastener 101 can be used to couple a soft tissue 110 to the bore 120 . after engagement of the soft tissue fastener 101 , the tension of the soft tissue 110 can be adjusted by the tensioning of the suture construction 73 . similarly , as shown in fig2 , the bicep brachii tendon 130 can be coupled to the ulna 112 using the suture construction 73 shown in fig2 . in this regard , a bore 114 is formed in the ulna . the fixation member 70 is then positioned or coupled to the ulna 112 . at this point , a natural or artificial bicep brachii tendon 130 can be passed through a loop or second fastener 70 or the loops 46 , 47 formed in the suture construction 73 . tensioning of the first and second ends 24 and 26 applies tension to the loops 46 , 47 , thus pulling the tendon 64 to or into the bore 114 . the constricting the loops 46 , 47 then fasten the bicep brachii tendon 130 to the ulna 112 . it is envisioned a bone coupling fastener 101 can be used to fix the soft tissue 130 to the ulna . fig2 shows the coupling of soft tissue 140 to the head of the humerus . defined in the humerus is a bore 114 configured to support the suture construction 73 . this bore can further have a transverse passage 134 . the transverse passage 134 can have at least one loop of the suture construction 73 disposed therethrough so as to allow the coupling of soft tissue to or through the transverse passage 134 . the longitudinal passage portion 30 of suture construction 73 can be first coupled to a fixation member 70 . the member 70 has a first profile which allows insertion of the member 70 through the tunnel and a second profile which allows engagement with a positive locking surface upon rotation . the longitudinal passage portion 30 of the suture construction 73 , member 70 , loops 46 and ends 24 , 26 can then be passed through the tunnel . the fixation member 70 is positioned or coupled to the humeral head . at this point , a natural or artificial bicep tendon 140 can be passed through a loop or loops formed in the suture construction 73 . tensioning of the first and second ends 24 and 26 applies tension to the loops , thus pulling the tendon 140 to or into the transverse passage 134 . in this regard , the first and second ends are pulled through the tunnel 114 , thus constricting the loops about the tendon 140 and pulling the tendon 140 or soft tissue to the transverse tunnel 134 . optionally , a soft tissue fastening screw can be used to fix the tendon 140 to the transverse passage 134 . as shown in fig2 - 28 , the suture construction 73 as shown in fig1 - 7 can be used to couple and position bony elements of a patient . fig2 shows the coupling of a coracoid process 137 to the spine of scapula 139 . in this regard , a pair of coaxial bores 138 and 140 are formed within the coracoid process 137 and spine of scapula 139 . a pair of anchors 70 , such as those shown in fig1 a - 14c , 15 a - 15 c , 16 a - 16 c , 17 a - 17 c , and 18 a - 18 c , are coupled to a suture construction 73 such as the one shown in fig2 a or 4 a . a first fastener 70 is fed through the aperture formed in the spine of scapula while the second fastener 70 ′ is fed through the bore 140 formed in the coracoid process 137 . tension is applied to the ends 24 and 26 of the suture construction 73 , pulling the bony structures into proper position . the suture construction of fig1 - 7 allow for the alignment compression and / or positioning of the bone elements without the need to form knots . similarly , as shown in fig2 , the lunate 142 and scaphoid 144 can be drawn together using the construction 73 shown in fig2 . in this regard , it is envisioned that both the lunate 142 and scaphoid 144 can have appropriate bores 138 and 140 formed therein . these bores accept the suture construction 73 as shown in 26 to allow stabilization of the patient &# 39 ; s anatomy . as shown in fig2 , the radius 146 and ulna 148 can be coupled together by the use of a pair of axial suture accepting passages 138 and 140 . in this configuration , the suture construction uses a first fastener 70 which is configured to pass through the passages 138 and 140 . additionally , the fastener 92 shown in fig1 a - 18c can be used as a load bearing member and bear against the ulna 148 and the application of tension to the ends 24 and 26 of the suture construction 73 tightens the suture construction and stabilizes the bones of the joint . the description of the invention is merely exemplary in nature and , thus , variations that do not depart from the gist of the invention are intended to be within the scope of the invention . for example , any of the above mentioned surgical procedures is applicable to repair of other body portions . for example , the procedures can be equally applied to the repair of wrists , elbows , ankles , and meniscal repair . the suture loops can be passed through bores formed in soft or hard tissue . it is equally envisioned that the loops can be passed through or formed around an aperture or apertures formed in prosthetic devices e . g . humeral , femoral or tibial stems . such variations are not to be regarded as a departure from the spirit and scope of the invention .

US-201414275548-A

an impact emulator that provides impact effects to a player of a video game system is provided . the video game system has a magnetic field generator that is able to produce magnetic field to generate a force on a magnet on a remote controller . the amount of magnetic field to be produced is depending on the relative movement of the remote controller and a target element .

fig1 shows a top view of major components of one exemplary video game system 10 of the present invention . fig2 shows a front view of major components in the embodiment of fig1 . referring to fig1 and 2 , the video game system 10 has a console 20 , a remote controller 30 , a sensor bar 40 , a video display 50 , a plurality of electrical wires 60 , 70 , and a current generator 80 . the console 20 has a built - in microprocessor to execute software programs . the software program can be stored in a disk and can be read by the microprocessor of the console 20 . the console 20 is electronically coupled to the sensor bar 40 . the sensor bar 40 contains a plurality of leds . the console 20 is also electronically coupled to the video display 50 . when there is a movement in the remote controller 30 , the video game system 10 detects and reflects the movement by showing movements of two objects on the video display 50 . one object represents the player who moves the controller 30 while the other object represents an opponent who can be another player of the video game system , sometimes also called the computer . the video game system 10 also makes a reaction on the opponent object based on the algorithm stored in the console 20 or just to reflect the reaction from another player and shows that on the display 50 accordingly . the remote controller 30 is the primary controller for the console 20 . the remote controller 30 has built - in accelerometers and gyroscopes . when the remote controller 30 is moving relatively to the leds within the sensor bar 40 , the infra - red detection is able to sense its position in 3d space on the remote controller 30 . this enables users to control the game by moving physically as well as pressing buttons . as shown in fig1 , the remote controller 30 is swing by a player ( not shown ) in a desired direction 32 from a first position 30 b ( shown in dashed box ) to a second position 30 a ( shown in dashed box ) and to the current position 30 . the remote controller 30 is able to sense its motions including : tilting and rotation up and down , tilting and rotation left and right , rotation along the main axis ( as with a screwdriver ), acceleration up and down , acceleration left and right , and acceleration toward and away from the sensor bar 40 , or the video display 50 if the sensor bar 40 is placed near the display 50 . the information of motions is sent to the console 20 for displaying on the display 50 and for calculating possible hit of an object . in the embodiment of fig1 and 2 , two wires 60 , 70 are set up around the playing environment with a first wire 60 set up on the front side and a second wire 70 set up on the rear side . in other words , the first wire 60 is located between the video display 50 and the remote controller 30 while the remote controller 30 is located between the first wire 60 and the second wire 70 . the first wire 60 can have four segments that a first segment 62 is generally extended vertically from the ground to a position that is higher than the height of the player &# 39 ; s hand when his or her arm is raised . a second segment 64 is generally extended horizontally from the top - right side of the player to the top - left side of the player . the second segment 64 can be fixed on its position by hangers . alternatively , the second segment 64 can be fixed to the ceiling of the room where the video game system 10 is set up . a third segment 66 is extended generally vertically from where the second segment 64 ends to the ground . a fourth segment 68 goes horizontally and can be placed on the ground . the second wire 70 can have a similar setting as the first wire 60 . the second wire 70 also has four segments 72 , 74 , 76 , 78 that placed around the playing environment . the second wire 70 is placed in parallel with the first wire 60 so that the distance between the first wire 60 and the second wire 70 is about the same between each corresponding segments . for demonstration purpose , the wires 60 , 70 in fig2 are shown in skewed positions . they are preferred to be placed at the same level for each segment . especially , the fourth segments 68 , 78 can both be placed on the ground . the way it shows that segment 68 is higher than wire 78 is just for demonstration purpose . in the embodiment of fig1 - 2 , the wires 60 , 70 are set up as a square and the distance between the two wires is about one half of the side length of the square . for example , assuming that the height of the first segments 62 is two meters , it is preferred that all other segments 64 , 66 , 68 , 72 , 74 , 76 , 78 are also about two meters long and the distance between the first wire 60 and the second wire 70 is about one meter . in another embodiment , the first wire 60 and the second wire 70 can each be shaped as a circle . in that case , it is preferred that the first wire 60 and the second wire 70 have the same radius and the distance between the first wire 60 and the second wire 70 is about the same as the radius of the circles . the current generator 80 has input ports and output ports . the first segment 62 of the first wire 60 is electrically coupled to one of the output ports of the current generator 80 and the fourth segment 68 of the first wire 60 is electrically coupled to one of the input ports of the current generator 80 . similarly , the first segment 72 of the second wire 70 is electrically coupled to one of the output ports of the current generator 80 and the fourth segment 78 of the second wire 70 is electrically coupled to one of the input ports of the current generator 80 . fig3 shows a magnetic field distribution of fig1 when impulse electrical current is applied to wires 60 , 70 by the current generator 80 . fig4 shows a magnetic field distribution of fig2 when impulse electrical current is applied . the direction of impulse electrical current flow is shown by arrows on wires 60 , 70 . in the first wire 60 , the impulse electrical current is flow out from the current generator 80 to the first segment 62 , the second segment 64 , the third segment 66 , the fourth segment 68 , and finally flow back to the current generator 80 . similarly , in the second wire 70 , the impulse electrical current is flow out from the current generator 80 to the first segment 72 , the second segment 74 , the third segment 76 , the fourth segment 78 , and flow back to the current generator 80 . based on the ampère - maxwell equation , induced magnetic field can be produced by the change of electrical field , which can be produced by an electrical current , as shown in the second term on the right hand side of the following equation : where curl ( b ) is the curl of the magnetic field in teslas , μ 0 is the permeability constant ( 4π × 10 − 7 tm / a ), ε 0 is the vacuum permittivity , and e is the electric field . arrows in fig3 represent magnetic field vectors in a plane bisecting the wires 60 , 70 . note that the magnetic field is approximately uniform between the wires 60 , 70 . in fig4 , the magnetic field vectors pointing out of the page are denoted by double circles when they are within the loop of wires . the magnetic field vectors pointing into the page are denoted by an x in circle when they are outside the loop of wires . therefore , once the current is turned on , a temporarily magnetic field will be generated by the impulse electrical current . the timing of when and how much magnetic field needed to be generated will be described below with the interaction of the remote controller 30 . fig5 shows an enlarged perspective view of the remote controller 30 of fig1 - 4 . the remote controller 30 has a handle 31 with a first permanent magnets 32 and a second permanent magnets 36 attached thereto . the second permanent magnet 36 longitudinally perpendicular to the first permanent magnet 32 . the handle 31 has a front face 42 , a rear face 44 , a left face 46 , and a right face ( not shown ). the first permanent magnet 32 has a first pole 33 and a second pole 34 while the second permanent magnet 36 has a first pole 37 and a second pole 38 . the face of the first pole 33 of the first permanent magnet 32 is parallel to the front face 42 of the handle 31 . the face of the second pole 34 of the first permanent magnet 32 is parallel to the rear face 44 of the handle 31 . the face of the first pole 37 of the second permanent magnet 36 is parallel to the left face 46 . the face of the second pole 38 of the second permanent magnet 36 is parallel to the right face 48 of the handle 31 . the orientation as well as the strength of the permanent magnets 32 , 36 are calibrated and stored in the console 20 by , for example , the manufacturing . when a user turns on the video game system 10 , the system 10 detects the position of the wires 60 , 70 . this detection can be made by placing sensor tabs on the four corners of each wire 60 , 70 . based on the placement of the wires 60 , 70 , the magnitude of induced magnetic field at each point in space between the loop of wires 60 , 70 can be calculated when a known impulse electrical currents are applied to wires 60 , 70 by the current generator 80 . therefore , when a user is playing , the system 10 detects the relative acceleration and direction of the movement between the remote controller 30 and a target . the position of both the remote controller 30 and the target are shown on the display 50 as they move . the system 10 predicts the timing and location a strike or a hit will occur . the system 10 then utilizes vector arithmetic to calculate the amount and direction of an impact reaction force that will be occurred by such a hit based on the speed , acceleration , and direction of the remote controller 30 and also the target . once the desired impact reaction force is known , the current generator 80 generates a suitable impulse currents to both wires 60 , 70 . the impulse currents then generate a desired induced magnetic field as shown in fig3 and 4 . the calculation of magnetic field is briefly described below . a pair of two identical cylindrical wires are placed side - by - side one on each side of the environment as shown in fig1 - 4 and 6 - 7 , and separated by a distance h equal to one half of the side or radius r of the wire . each wire carries an equal electrical current flowing in the same direction . setting h = r , minimizes the non - uniformity of the magnetic field at the center of the wires , in the sense of setting d 2 b / dx 2 = 0 , but leaves a small amount of variation in field strength between the center and the planes of the wires . a slightly larger value of h reduces the difference in field between the center and the planes of the wires , at the expense of decreasing the field &# 39 ; s uniformity in the region near the center , as measured by d 2 b / dx 2 . the calculation of the magnetic field at central point along the axis of the pair of wires is described below . it is convenient to think about the taylor series expansion of the field strength as a function of x , the distance from the central point of the wire - pair along the axis . by symmetry the odd order terms in the expansion are zero . by separating the wires so that x = 0 is an inflection point for each wire separately , it can be expected that the order x 2 term is also zero , and hence the leading non - uniform term is of order x 4 . the inflection point for a simple wire is r / 2 from the wire center along the axis . as a result , the location of each wire at x =± r / 2 . if the current flowing through the wires is i , then the magnetic flux density , b at the midpoint between the wires will be given by b equals to ( ⅘ ) 3 / 2 μ 0 i / r , where μ 0 is the permeability constant ( 1 . 26 × 10 − 6 tm / a ), and r is in meters . the calculation of the exact magnetic field at any point in space is more complicate since it involves bessel functions . the mathematical functions can be programmed into software form and stored in a memory that can be accessed by the microprocessor of the console 20 . alternatively , the mathematical functions can be implemented in hardware so the exact magnetic field at any point in space can be calculated in a “ real - time ” fashion . the generated induced magnetic field thus generates a force on the permanent magnets 32 , 36 of the remote controller 30 . the system 10 emulates the impact reaction force by creating a magnetic field that generates a force in a direction against the direction of the movement of the remote controller 30 . the magnetic field that can be changed dynamically according to the movement of the remote controller 30 . the timing , direction and magnitude of the magnetic field are determined by the microcontroller embedded in the console 20 based on the information about the relative movement between the player and an object , the way the player holds the remote controller , and the setting of the pair of wires 60 , 70 . the player therefore senses the impact reaction force when he or she strikes a ball . the remote controller 30 connects to the console 20 using bluetooth and features rumble as well as an internal speaker . when there is a hit between objects such as a baseball bat and a baseball , the system 10 produces a “ pop ” sound and makes an impact reaction force on the remote controller 30 . the synchronized sound and the impact reaction force make the video game system 10 “ real ” to a player by emulating the real - life experiences . following is an example of a tennis game played by a right - handed player on the video game system 10 . the player holds the remote controller 30 use the right hand as if he or she is holding a tennis racquet . video display 50 displays a player holding a tennis racquet that represents the player while the opponent can be another human player or the computer . for a right - handed player , to play a forehand , the player moves the racquet from the right side of the player &# 39 ; s body , continues across the body as contact is made with the ball , and ends on the left side of the body . to play a backhand , the player moves the racquet from the left side of the body , continues across the body as contact is made with the ball , and ends on the right side of the body . when the player plays a forehand , the face of the first pole 33 of the permanent magnet 32 will first face the display 50 and then the face of the second pole 38 will face the display 50 . the system 10 detects the acceleration and direction of the relative movement between the remote controller 30 and the target tennis ball served by the opponent . the position of both the remote controller 30 and the target tennis ball are shown on the display 50 as they move . the system 10 predicts the timing and location of a strike or a collision between the tennis racquet and the target tennis ball will occur . the system 10 then calculates the amount and direction of an impact force and its reaction force that will be produced by such a hit based on the speed , acceleration , and direction of the remote controller 30 and the target tennis ball . just before the face of the first pole 33 is going to face the display 50 , the system 10 creates an impulse current that induces a suitable magnetic field in a direction as shown of fig3 and 4 based on the desired impact reaction force . the magnetic field therefore creates a magnetic force emulating the impact reaction force on the permanent magnet 32 and the player can feel it . the system 10 keeps on monitoring the direction and position of the remote controller 30 . when the motion continues for a 90 ° turn and just before the face of the second pole 38 of the permanent magnet 36 is facing the display 50 , the system 10 turns off the current from the current generator 80 . this current change in wires 60 , 70 then generates a magnetic field in the opposite direction as shown in fig3 and 4 . since the face of the second pole 38 is now facing the display 50 , the magnetic force emulating the impact reaction force is also acting on the permanent magnet 36 and the player will be able to feel it . thus , when the hand of a player is moving around his or her body , the system 10 detects the swing and generates magnetic force two times within a 90 ° turn of the remote controller 30 . these two consecutive forces happened in a short period of time that the player may “ feel ” just like one hit of a tennis ball with an elastic tennis racquet . when the player plays a backhand , the face of the second pole 34 of the permanent magnet 32 will first face the display 50 and then the face of the first pole 37 will face the display 50 . just before the face of the second pole 34 is going to face the display 50 , the system 10 generates an impulse current that generates a suitable magnetic field in a direction opposite to the arrows shown of fig3 and 4 . the magnetic field therefore creates a magnetic force emulating the impact reaction force on the permanent magnet 32 of the remote controller 30 and also the player &# 39 ; s hand . when the motion continues for a 90 ° turn and just before the face of the first pole 37 of the permanent magnet 36 is facing the display 50 , the system 10 turns off the current from the current generator 80 . this current change is then generates a magnetic field that is in the same direction as shown in fig3 and 4 . since the face of the first pole 37 is now facing the display 50 , the magnetic force emulating the impact reaction force is also acting on the permanent magnet 36 of the remote controller 30 and also the player &# 39 ; s hand . fig6 shows a top view of major components and magnetic field distribution in a second exemplary video game system 110 of the present invention . fig7 shows a front view of major components and magnetic field distribution in the embodiment of fig6 . for purpose of demonstration , not all components in fig6 are shown in fig7 . the main difference between fig6 and fig3 is that in fig6 , a steady dc current is generated by the current generator 180 so that there is a steady magnetic field within the wire loops 160 , 170 . referring to fig6 and 7 , the video game system 110 has a console 120 , a remote controller 130 , a sensor bar 140 , a video display 150 , a plurality of electrical wires 160 , 170 , and a dc current generator 180 . the console 120 has a built - in microprocessor to execute software programs that stored in a disk and can be read by a disk drive of the console 120 . the console 120 is electronically coupled to the sensor bar 140 which contains a plurality of leds . the console 120 is also electronically coupled to the video display 150 . typically , the sensor bar 140 is placed on top of the display without movement . when there is a movement between the remote controller 130 and the sensor bar 140 , the video game system 110 detects and reflects the movement by showing that movement on the video display 150 . the video game system 110 also makes a reaction based on the algorithm stored in the console 120 and shows that on the display 150 accordingly . the remote controller 130 is the primary controller for the console 120 . the remote controller 130 has built - in accelerometers and gyroscopes . when the remote controller 130 is using with the leds within the sensor bar 140 , the infrared detection is able to sense its position in 3d space . users control the game by using physical gestures as well as pressing buttons . the remote controller 130 is able to sense its motions including : tilting and rotation up and down , tilting and rotation left and right , rotation along the main axis ( as with a screwdriver ), acceleration up and down , acceleration left and right , and acceleration toward and away from the sensor bar 140 , or the video display 150 if the sensor bar 140 is placed near the display 150 . in the embodiment of fig6 and 7 , two wires 160 , 170 are set up around the playing environment with a first wire 160 set up on the front side and a second wire 170 set up on the rear side . in other words , the first wire 160 is located between the video display 150 and the remote controller 130 while the remote controller 130 is located between the first wire 160 and the second wire 170 . the first wire 160 can have four segments that a first segment 162 is generally extended vertically from the ground to a position that is higher than the height of the player &# 39 ; s hand when his or her arm is raised . a second segment 164 is generally extended horizontally from the top - right side of the player to the top - left side of the player . the second segment 164 can be fixed on its position by hangers . alternatively , the second segment 164 can be fixed to the ceiling of the room where the video game system 110 is set up . a third segment 166 is extended generally vertically from where the second segment 164 ends to the ground . a fourth segment 168 goes horizontally and can be placed on the ground . the second wire 170 can have a similar setting as the first wire 160 . the second wire 170 also has four segments 172 , 174 , 176 , 178 that placed around the playing environment . the second wire 170 is placed in parallel with the first wire 160 so that the distance between the first wire 160 and the second wire 170 is about the same between each corresponding segments . although fig7 is a front view and the wires 160 , 170 are shown in skew . especially , the fourth segments 168 , 178 can be both placed on the ground . the way it shows that segment 168 is higher than wire 178 is just for demonstration purpose . in the embodiment of fig6 - 7 , the wires 160 , 170 are set up as a square and the distance between the two wires is about one half of the side of the square . for example , assuming that the height of the first segments 162 is two meters , it is preferred that all other segments 164 , 166 , 168 , 172 , 174 , 176 , 178 are also about two meters and the distance between the first wire 160 and the second wire 170 is about one meter . in another embodiment , the first wire 160 and the second wire 170 can each be shaped as a circle . in that case , it is preferred that the first wire 160 and the second wire 170 have the same radius and the distance between the first wire 160 and the second wire 170 is about the same as the radius of the circles . the current generator 180 has input ports and output ports . the first segment 162 of the first wire 160 is electrically coupled to one of the output ports of the current generator 180 and the fourth segment 168 of the first wire 160 is electrically coupled to one of the input ports of the current generator 180 . similarly , the first segment 172 of the second wire 170 is electrically coupled to one of the output ports of the current generator 180 and the fourth segment 178 of the second wire 170 is electrically coupled to one of the input ports of the current generator 180 . fig6 also shows a magnetic field distribution when steady dc electrical currents are applied to wires 160 , 170 by the current generator 180 while fig7 shows the front view . the direction of dc electrical current flow is shown by arrows on wires 160 , 170 . in the first wire 160 , the steady electrical current is flow out from the current generator 180 to the first segment 162 , the second segment 164 , the third segment 166 , the fourth segment 168 , and then flow back to the current generator 180 . similarly , in the second wire 170 , the impulse electrical current is flow out from the current generator 180 to the first segment 172 , the second segment 174 , the third segment 176 , the fourth segment 178 , and flow back to the current generator 180 . based on the ampère - maxwell equation , magnetic field can be produced by the steady electrical current as shown in the first term on the right hand side of the following equation : where j is the current density in amperes per square meter . arrows in fig6 represent magnetic field vectors in a plane bisecting the wires 160 , 170 . note that the magnetic field is approximately uniform in between the wires 160 , 170 . in fig7 , the magnetic field vectors are point out from the page and denoted by double circles when they are within the loop of wires . the magnetic field vectors are point into the page and denoted by an x in circle when they are outside the loop of wires . therefore , a steady magnetic field is generated by dc electrical currents . fig8 shows an enlarged perspective view of the remote controller 130 of fig6 - 7 . the remote controller 130 has a handle 131 with two electromagnets 132 , 136 attached . the handle 131 has a front face 142 , a rear face 144 , a left face 146 and a right face 148 ( not shown ). the first electromagnet 132 has a first end 133 and a second end 134 while the second electromagnet 136 has a first end 137 and a second end 138 . the face of the first end 133 is parallel to the front face 142 . the face of the second end 134 is parallel to the rear face 144 . the face of the first end 137 is parallel to the left face 146 . the face of the second end 138 is parallel to the right face 148 . the orientation as well as the strength of the electromagnets 132 , 136 are stored in the console 120 by manufacturing . when a user turns on the video game system 110 , the system 110 detects the position of the wires 160 , 170 . this detection can be made by placing tabs on the four corners of each wire 160 , 170 . based on the placement of the wires 160 , 170 , the magnitude of magnetic field within the loop of wires 160 , 170 can be calculated when electrical currents are applied to wires 160 , 170 by the current generator 180 . therefore , when a user is playing , the system 110 uses the acceleration and direction of the movement of the remote controller 130 to calculate the amount of force required and the timing to produce the impact reaction force . once the desired impact reaction force is known , the system 110 creates a temporary magnet on the electromagnets 132 , 136 . the steady magnetic field thus generates a magnetic force emulating the impact reaction force on the electromagnets 132 , 136 of the remote controller 130 . the user therefore senses the impact reaction force when he or she strikes a ball . following is an example of a tennis game played by a right - handed player with the system 110 . when the player plays a forehand , the face of the first end 133 of the electromagnet 132 will first face the display 150 and then the face of the second end 138 will face the display 150 . just before the face of the first end 133 is going to face the display 150 , the controller 130 set the first end 133 as the north pole with a desired magnitude based on the calculation previously described . the magnetic field generated by the wires 160 , 170 creates a magnetic force on the electromagnet 132 of the remote controller 130 to emulate the calculated impact reaction force . when the motion continues for a 90 ° turn and just before the face of the second end 138 of the electromagnet 136 is facing the display 150 , the controller 130 set the second end 138 of the electromagnet 136 as the north pole with a desired magnitude . the magnetic force created by magnetic field generated by the wires 160 , 170 acting on the electromagnet 136 of the remote controller 130 to emulate the calculated impact reaction force . therefore , when the hand of a player is moving around his or her body , the system 110 detects the swing and generates magnetic force two times within a 90 ° turn of the controller 130 . these two consecutive forces happened in a short period of time that the player may “ feel ” just like one hit of a tennis ball with an elastic tennis racquet . when the player plays a backhand , the face of the second end 134 of the electromagnet 132 will first face the display 150 and then the face of the first end 137 of the electromagnet 136 will face the display 150 . just before the face of the second end 134 is going to face the display 50 , the controller 130 set the second end 134 of the electromagnet 132 as the north pole with a desired magnitude based on a calculation described previously . the magnetic field generated by the wires 160 , 170 creates a magnetic force on the electromagnet 132 of the remote controller 130 to emulate the impact reaction force . when the motion continues for a 90 ° turn and just before the face of the first end 137 of the electromagnet 136 is facing the display 150 , the controller 130 set the first end 137 of the electromagnet 136 as the north pole with a desired magnitude so that a magnetic force is also applied on the electromagnet 136 of the remote controller 130 to emulate the impact reaction force . in the exemplary embodiments described previously , although tennis is used as example , it is understandable that the exemplary embodiments also applied to other games such baseball , golf , or boxing . although the remote controller 30 , 130 shown previously is in a shape like a traditional tv remote control , it can be embedded in any shape as desired . for example , the remote controller 30 , 130 can be embedded in a boxer glove so that when a player is playing a box game with the system 10 , 110 , he or she can feel the impact reaction force when he or she strikes the opponent shown on the display 50 , 150 . various modifications and alternative embodiments such as would ordinarily occur to one skilled in the art to which the invention relates are also contemplated and included within the scopes of the invention described and claimed herein .

US-7798108-A

a beverage preparation device is disclosed which comprises an insert that is inserted into a receptacle and can be interlocked with the receptacle . the beverage preparation device comprises a receptacle , a receptacle holder , and an insert , e . g . a lid or a holding element . the receptacle holder has at least one element which protrudes from the receptacle and on which at least one engaging structure is provided that cooperates with a second engaging structure on the insert in such a way that the insert is releasably interlocked with the receptacle . preferably , the two engaging structures represent a bayonet joint .

fig1 to 3 show different illustrations of a first exemplary embodiment of a beverage maker according to the invention . the beverage maker has a cylindrical , upwardly open glass receptacle 1 with a circumferential side wall 13 and a substantially flat , but slightly upwardly curved bottom 12 , a receptacle holder 2 and a lid 3 . in the present illustrations , the glass receptacle is shown in non - transparent ( opaque ) form but it may also be transparent or translucent . a filter plunger 4 is arranged in the glass receptacle , the filter plunger comprising a plunger rod 41 , a knob - shaped actuating element 42 fitted to the upper end of said plunger rod , and a plunger filter 43 of a type known per se which is fitted to the lower end of the plunger rod . the plunger rod is arranged vertically and passes through the lid 3 . the plunger filter 43 comprises an upper perforated plate 431 which is raised at its outer border and is provided with a multiplicity of small openings . a toroidal wire coil 433 is threaded through said openings . a fine wire mesh 432 rests on the lower side of the perforated plate 431 and is drawn upward beyond the wire coil 433 . the wire mesh 432 is downwardly fixed by a star - like or perforated - plate - like fixing plate 434 mounted parallel to the perforated plate below the wire mesh . the perforated plate 431 , the wire mesh 432 and the fixing plate 434 are secured on the plunger rod by a common fixing screw 435 which engages in a counternut 436 . the lid 3 projects partially by a skirt - like section 391 into the glass receptacle 1 . a lower covering wall substantially covers the opening in the glass receptacle 1 and , together with the glass receptacle , bounds the receptacle interior 11 . a pouring opening 38 is formed in the lower covering wall 39 . starting from the lower covering wall 39 , a cylindrical side wall 392 extends upward at the outer border of said covering wall , said side wall being interrupted by a spout 31 and by a recess for a lever 32 . also starting from the lower covering wall 39 , a circumferential , cylindrical skirt 391 of somewhat smaller diameter extends downward into the receptacle . a pair of annular , spaced - apart webs extends outward from the skirt , forming a receptacle for a circumferential , annular seal 33 having a radially outwardly protruding sealing lip . by this means , after the lid 3 has been inserted , a seal is formed between the receptacle 1 and the lid , the seal preventing liquid from being able to escape between the receptacle and lid . an elongate lever 32 which extends above the lower covering wall 39 transversely with respect to the plunger rod 41 is fitted to the lid 3 in a manner such that it can pivot about a horizontal axis . in the region of its front end , the lever comprises a closure body 321 in order to close the pouring opening 38 . at its rear end facing away from the spout 31 , the lever 32 protrudes radially with an actuating region out of the lid 3 and , by pressure being applied by the user &# 39 ; s thumb , can pivot downwards slightly about its horizontal pivot axis such that the closure body 321 is raised from the pouring opening 38 and opens up the pouring opening . in the direction of its first position , the lever is spring - loaded by a helical spring 322 in order to ensure that the pouring opening is closed if the lever is not being consciously actuated . the helical spring 322 , which is preloaded into the closing position , is formed in the rear lever region facing away from the spout 31 , still within the lid 3 . in order to guide the plunger rod 41 through the lid 3 , the lever has a passage opening , but may also be guided laterally around the plunger rod . an upwardly curved , double - walled upper dome , consisting of an inner covering wall 36 and an outer covering wall 35 , extends from the upper edge of the cylindrical side wall of the lid 3 . the double - walled configuration of the upper dome minimizes the heat loss through the lid . in addition , this design makes it possible to form the outer covering wall in an aesthetically attractive manner , for example from thin sheet metal , irrespective of any stability requirements . a vertical guide sleeve 351 in which the plunger rod 41 of the filter plunger 4 is guided is inserted into a central opening in the inner covering wall 35 . the lever 32 and the lower covering wall 39 each have a passage opening through which the plunger rod is likewise guided . a further guide sleeve 393 is formed as a single piece with the lower covering wall 39 and extends downward from the latter . the receptacle holder 2 comprises a retaining ring 21 which embraces the side wall 13 of the glass receptacle 1 in the upper region of the receptacle , and struts 22 extending in the longitudinal direction of the vessel . in the region where the side wall 13 of the glass receptacle 1 meets the bottom 12 , said longitudinal struts form feet which project outward and downward and permit the beverage maker to be placed onto a flat underlying surface without the glass receptacle 1 which is heated by the beverage coming into contact with the underlying surface . the longitudinal struts 22 are connected to one another below the bottom 12 of the glass receptacle . the upper end of a handle 23 is connected to the retaining ring 21 and the lower end of said handle is connected to the receptacle holder 2 via a transverse strut 27 connecting two longitudinal struts 22 . a bow - like element 24 which protrudes over the glass receptacle 1 and has two limbs and a connecting region connecting the latter is fastened to the handle 23 by means of a fixing screw 25 . the element projects beyond the retaining ring 21 and the upper edge of the glass receptacle 1 . a recess which forms a radial groove 26 is formed in the region of one of the limbs of the bow on the part projecting over the glass receptacle . said radial groove is designed to receive a lug 34 which is fitted to the exterior of the side wall 392 of the lid 3 below the closure lever 32 . by means of a rotational movement over a small angular range and the latching of the lug 34 into the radial groove 26 , a bayonet joint is formed , by means of which the lid 3 can be locked releasably to the glass receptacle 1 . a marking 37 on the exterior of the upper , outer covering wall 35 of the lid 3 indicates the correct positioning for latching and locking the lid 3 to the glass receptacle 1 . a further exemplary embodiment is illustrated in fig4 to 7 in which identical parts are provided with the same reference numbers as in fig1 to 3 . in contrast to the first embodiment , in this embodiment , the beverage maker additionally has a filter insert 6 and an annular retaining element 5 therefor . the filter insert 6 has a circumferential side wall and a bottom ( not illustrated ) which is adjacent to the side wall at the bottom . the cylindrical side wall has a multiplicity of small openings or holes through which liquid can pass but which are smaller than the solid beverage constituents which are intended to be filtered out when preparing the beverage . a circumferential , radially outwardly protruding flange 61 is provided on the upper edge of the filter insert 6 . the flange is used to enable the filter insert to rest on the retaining element 5 into which the filter insert is pushed . the filter insert 6 serves to separate solid constituents of the beverage from liquid constituents while the filter plunger 4 is being pressed down . the use of the filter insert enables the plunger filter 43 to be pressed downwards more rapidly and with less application of force because liquid beverage constituents can be displaced not only through the plunger filter itself but also through the side wall of the filter insert 6 . furthermore , because of the filter insert , the glass receptacle is subjected to a less severe loading when the filter plunger is pressed down , thus reducing the risk of the glass breaking . finally , the filter insert permits greater design freedom with respect to the shape of the glass receptacle 1 ′. the retaining element 5 rests on the upper rim of the glass receptacle 1 ′, the retaining element having for this purpose a radially protruding supporting structure in the form of a circumferential , radial supporting flange 55 . the retaining element extends with an annular , circular - cylindrical side wall ( skirt ) from above into the glass receptacle 1 ′ to an extent such that said retaining element protrudes downward over the spout 14 ′ which , in this exemplary embodiment , is formed on the glass receptacle 1 ′. a radially outwardly pointing , circumferential sealing lip 52 is formed in the region of the lower end of the retaining element 5 , said sealing lip bearing against the interior of the side wall 13 ′ of the glass receptacle below the spout 14 ′ and thereby producing a seal between the retaining element 5 and the glass receptacle 1 ′. a multiplicity of slot - shaped apertures 53 serving as pouring openings are provided over a small angular range in the side wall of the retaining element . the presence of the sealing lip 52 means that liquid can only pass through said apertures 53 to the spout 14 ′ when the liquid is intended to be poured out of the receptacle . the plunger rod 41 is guided through a central opening in a lid 3 ′. the open , lower end of the lid 3 ′ can be pushed into the retaining element 5 and fixed releasably thereto . for this purpose , the retaining element 5 has an upwardly extending annular flange 54 which serves as a receiving ring and extends upward from the radially outer border of the supporting flange 55 . the lid 3 ′ is locked releasably to the retaining element 5 by means of a bayonet joint which is not visible in the drawings . for this purpose , a lug fitted to the radial exterior on the lower border of the lid 3 ′ can be inserted from above into a vertical inlet groove which is formed on the radial interior of the annular flange 54 and which is adjoined by a horizontal radial groove extending over a small angular range of , for example 5 °- 15 ° of the flange circumference . by means of a rotational movement of the lid 3 ′, the lug engages in the radial groove , as a result of which the lid 3 ′ is locked releasably to the retaining element 5 . the lid 3 ′ can thereby be fixed releasably in the retaining element 5 . instead , however , there may also be a simple latching connection . the lid 3 ′ is of double - walled design with an outer covering wall 35 ′ and an inner covering wall 36 ′ which upwardly bounds the receptacle interior 11 ′. in order to lock the retaining element 5 releasably to the glass receptacle 1 ′, the retaining element 5 on the radial exterior of the annular flange 54 has a bayonet lug 51 which is fitted to the diametrically opposite side with respect to the apertures 53 . as in the first exemplary embodiment , a bow - like , protruding element 24 ′ is fitted to the receptacle holder and , in this embodiment , is designed to be somewhat longer than in the first exemplary embodiment . the protruding element 24 ′ is fitted to the handle 23 of the receptacle holder 2 ′ by means of the fixing screw 25 and extends upward along the side wall 13 ′ beyond the upper rim of the glass receptacle 1 ′. said bow - shaped , protruding element 24 ′ also has in the region of one of the limbs thereof a recess which forms a radial groove 26 ′. by means of a rotational movement , the lug 51 of the retaining element 5 can be introduced into the radial groove 26 ′ and can be locked to the latter in the manner of a bayonet joint . by means of the releasably locked connection between the retaining element 5 and the glass receptacle 1 ′, the apertures 53 are directed toward the spout 14 ′ in a well defined position in the locked state , as a result of which the beverage can be poured out through the apertures 53 and via the spout 14 ′. the retaining element 5 or the lid 3 ′ is prevented from slipping by the locking of the two engagement structures 51 and 26 . a further exemplary embodiment is depicted in fig8 . the functional features of this embodiment , with the exception of the latching connection between the lid 3 ″ and the receptacle holder 2 ″, are analogous to the features described in the first exemplary embodiment ( fig1 to 3 ). the receptacle holder 2 ″ protrudes upward with a ring 21 ″, which embraces the glass receptacle , over the side wall 13 of the glass receptacle and along the entire circumference of the side wall 13 . in the protruding part of the ring 21 ″, a first cutout is formed at the upper edge , the cutout leaving space for the spout 31 ″ of the lid 3 ″ and leaving additional space in order to allow a rotational movement of the lid 3 ″ in the ring 21 ″ over a small angular range . on the diametrically opposite side of the first cutout , a second cutout is formed on the upper edge of the ring 21 ″ in order to enable the closure lever 32 ″ to be pressed downward in the locked state . in the interior of its circumferential surface area , the ring 21 ″ of the receptacle holder 2 ″ has two identical engagement structures 26 ″ which lie diametrically opposite each other . the engagement structures 26 ″ each consist of a vertically formed , upwardly open inlet groove and a horizontally extending radial groove which is adjacent to the inlet groove in the lower region . the two lugs 34 ″ which are formed on the exterior of the lid 3 ″ and are each arranged at half the angle between the spout 31 ″ and closure lever 32 ″ are configured in such a manner that they can be introduced into the vertical inlet grooves of the engagement structures 26 ″ upon correct insertion of the lid 3 ″. by means of a rotational movement over a small angular range , the lugs 34 ″ are introduced into the radial grooves of the engagement structures 26 ″ and latch therein when the rotational movement is fully executed . as a result , the lid 3 ″ is locked releasably to the receptacle holder 2 ″. of course , the invention is not restricted to the above examples , and a multiplicity of modifications is possible . in particular the two engagement structures 26 , 26 ′, 26 ″ and 34 , 34 ″ may also be formed differently , in each case matching each other . instead of rectangular lugs , for example cylindrical bayonet studs may be present . instead of the receptacle holder illustrated in the drawings , any other holder may also be used if said holder has an element protruding over the glass receptacle . a differently designed lid with or without a spout and with or without a closure mechanism may also be used . a multiplicity of further applications is possible .

US-200913060865-A

balloon dilation addresses the dangers of blunt instrument dilation or surgical dissection by placing a balloon within soft tissue and inflating the balloon to displace the soft tissue in a manner to create a cavity or space for receipt of an implantable device . a prosthesis balloon dilation catheter set facilitates a surgical procedure to implant semi - rigid and / or inflatable prostheses .

balloon dilation in this specification refers to the inflation of a balloon in soft tissue to create , or to complete the creation of a cavity in the soft tissue where none formerly existed , wherein the cavity is created to receive a medical implant . preferably , the cavity is created with a shape corresponding to the shape of an implant which is disposed and retained in the cavity . a balloon dilation set is a set of one or more instruments that enable the insertion of a balloon into soft tissue for the purpose of creating , or completing the creation of a cavity in the soft tissue where none existed before , wherein the cavity is created to receive a medical implant . the embodiments described in this specification are directed toward implantation of prosthesis devices or elements thereof , but this is not intended to , and does not exclude the application of the illustrated principles to creation of cavities in soft tissues for other medical implants such as therapeutic and measurement devices . in one embodiment , balloon dilation is used in creating at least one cavity in a corpus cavernosum for implantation of a penile prosthesis , either semi - rigid or inflatable . an instrument set for balloon dilation of soft tissue (“ a balloon dilation set ”) to receive a penile prosthesis apparatus includes elements illustrated in fig1 a , 1 b , and 2 - 5 . preferably , although not necessarily , this balloon dilation set includes at least one dilator ( fig1 a and 1b ), at least one sheath introducer ( fig2 ), at least one glide wire ( fig3 ), at least one distal balloon instrument ( fig4 ), and at least one inflation syringe ( fig5 ). in some aspects , this balloon dilation set further includes at least one proximal balloon catheter ( fig6 ). the set supports methods that allow for both creation of new spaces in at least one corpus cavernosum as well as dilation of scarred spaces therein to allow implantation of a penile prosthesis . with reference to fig1 a and 1b , a dilator 12 may be , for example , an elongate , rigid , hollow point , 7 french , plastic or steel dilator that is tapered on both ends 14 . the dilator 12 may be straight or slightly curved like a hager dilator . the length of the dilator 12 should be sufficient to reach through a corpus cavernosum , from a penoscrotal ( or infrapubic ) entry point to a point near the glans ; for example , the dilator may be at least 20 cm in length . preferably , the dilator 12 is hollow , having a central bore 15 , with a small diameter . for example , the diameter of the bore 15 may be about 5 mm . as seen in fig2 , a needle sheath introducer 20 may be , for example , a hollow , 20 gauge , 20 cm long , stainless steel or plastic needle sheath introducer with sharp , beveled distal end 22 and proximal bulbous blunt end 24 . as illustrated in fig3 , a glide wire ( also called a guide wire ) 30 may be a 0 . 888 mm ( 0 . 035 in ) diameter , relatively stiff , wire of a length sufficient to reach through the introducer 20 , with excess length left outside ; for example , the glide wire 30 may be 75 cm in length . preferably , the glide wire 30 has a lubricous coating , a straight distal end 31 , and a proximal end 32 in which a small loop or eye is formed . as per fig4 , a distal balloon dilation instrument may include an instrument with the construction of a distal balloon catheter , such as the distal balloon catheter 40 illustrated in fig4 , preferably , two such distal balloon instruments are provided . preferably , the catheter 40 has a balloon 41 mounted distally on a tube 42 with a distal tip 43 . preferably , the tube 42 is a double - walled tube which includes an air supply path for inflating the balloon 41 and a bore extending to the distal tip 43 . a connector 45 on the proximal end of the tube 42 includes a first port 46 in communication with the bore and a second port 47 in fluid communication with the air supply path . the balloon 41 has a length and a diameter appropriate to the size of a patient receiving a penile prosthesis . for example , the balloon may be about 20 cm long with either a 10 f or a 14 f diameter . in some aspects , the balloon 41 , or , if the balloon is transparent , the surface of the tube 42 within the balloon , may have a series of uniformly - spaced marks 48 disposed longitudinally of the tube 42 as an aid to making measurements as described below . the distal balloon instrument is of sufficient stiffness that , with a lubricous coating , allows for smooth advancement within the corpora of the penis . fig5 illustrates a source of pressurized air which may be connected to a distal balloon instrument for inflating a balloon thereon . for inflation of catheter - mounted balloons such as the balloon 41 illustrated in fig4 , the source of pressurized air may be constituted , for example , of a leveen inflation syringe 50 with a plunger 51 and a tip 52 which connects to the port 47 of the distal balloon catheter 40 . at least one proximal balloon instrument , such as the proximal balloon catheter 60 illustrated in fig6 , is provided ; preferably , two such proximal balloon instruments are provided . the catheter 60 has a balloon 61 mounted proximally on a tube 62 with a distal tip 63 . preferably , the tube 62 is a double - walled tube which includes an air supply path for inflating the balloon 61 and a bore extending to the distal tip 63 . a connector 65 on the proximal end of the tube 62 includes a first port 66 in communication with the bore and a second port 67 in fluid communication with the air supply path . the balloon 61 has a length and a diameter appropriate to the size of a patient receiving a penile prosthesis . for example , the balloon may be about 10 cm long with either a 10 f ( for smaller anatomic corpora ) or a 14 f diameter . in some aspects , the balloon 61 , or , if the balloon is transparent , the surface of the tube 62 within the balloon , may have a series of uniformly - spaced marks 68 disposed longitudinally of the tube 62 as an aid to making measurements as described below one example of a balloon dilation set for use in creating parallel cavities in corpora cavernosa includes distal balloon catheters having a lubricous coating . each distal balloon catheter is hollow so as to slide over a 20 gauge needle sheath introducer ( 18 gauge ). each distal balloon catheter has a sharply tapered tip so as to slide along a needle introducer and out the glans penis . marks spaced at , for example , 1 cm , are labeled on the distal balloon catheters . the distal balloon catheters are 20 cm in length , each with a distal port and balloon port . the proximal balloon catheters are 10 cm in length . all of the distal and proximal balloon catheters may come in 2 or more balloon sizes , for example , 10 and 14 french . with reference to fig7 a , in using a penile prosthesis balloon dilation set such as one including distal and proximal balloon catheters in the example above , a surgeon makes a traditional penoscrotal or infra - pubic incision , and then makes the traditional respective corporotomies in the corpora . for example , the locations of respective coporotomies via penoscrotal incisions are indicated by 70 . the surgeon may then create an initial opening in a corpus cavernosum 72 by advancing a small ( 7 french ) hollow point dilator through an incision 70 and into the corpus distally ( in the direction 73 ) until the end of the dilator is palpated within the glans penis 74 in the traditional fashion . a 20 gauge needle sheath introducer is then advanced through the dilator , which is held in position within the respective corpus 72 , until the distal end of the introducer is pushed out through the glans 74 . a 0 . 888 mm glide wire is threaded through the needle sheath introducer in the dilator until the distal end of the wire emerges through the distal end of the introducer and is clamped outside of the glans 74 . the dilator is then pulled proximally , out through the incision 70 , and removed , leaving the needle sheath introducer and the wire positioned within the corpus 72 . a first distal balloon catheter is advanced , distal end first , toward the glans 74 , over the proximal portion of the wire , and then over the needle introducer and the wire ( the lubricious coating of the balloon catheter facilitates advancement forward ) until the distal tip of the catheter tube is detected at the glans 74 . the needle introducer sheath is then retracted from the corpus , leaving the distal balloon catheter with the glide wire extending through the bore thereof in the corpus . with reference to fig7 a and 7b , a leveen inflation syringe is attached to the balloon port of the catheter and is activated . the inflation syringe has a pressure gauge to accurately confirm proper inflation . the first balloon is held secure manually as full inflation occurs . as it inflates , the balloon expands circumferentially and compresses the soft tissue of the corpus , creating generally cylindrical space therein for implantation of a prosthesis cylinder . see fig7 b in this regard . the syringe is locked on full inflation and the distal measurements are made by observing the marks on the balloon . if desired , this balloon may be left intact and inflated within one corpus while attention is then turned to the other corpus . the same technique is then performed for the other corpus cavernosum with an identical set of elements to place a second distal balloon catheter . the second balloon is inflated with a second inflation syringe and the second inflation syringe is locked . with both balloons inflated the effect of an inflatable penile prosthetic is mimicked and an immediate assessment of the dilated corpora can be made . in this regard , inflation of the distal balloons erects the penis in much the same manner as an inflatable penile prosthesis . the penis is inspected while erected by the first and second balloons to assess the quality of dilation in the corpora cavernosa , and to gauge the proposed positions of the penile prosthetic cylinders to be placed . then , the first and second balloons are deflated . the two distal catheters and the two needle introducers may be retracted along the glide wires , out of the corpora cavernosa through the incisions 70 , and off of the glide wires . next , a hollow 7 french dilator may used to traditionally dilate the proximal end 76 of each corpus . the blunt bulbous end of a hollow spinal needle may be inserted through the dilator until the bone of the inferior rami is encountered . the dilator is removed and a proximal balloon catheter with no tip extending from the tip of the balloon is advanced over the needle . the needle is removed and the proximal catheter balloon is inflated using an inflation syringe . immediate measurements are made proximally and this is repeated for the other proximal corpus end 76 . with the proximal portions of the corpora cavernosa thus dilated and evaluated , the needles and proximal catheters are removed , and the cylinders of the implants are placed in the traditional manner and the remaining part of the penile implantation is completed . with reference to fig8 , a complete inflatable penile prosthesis apparatus is shown , implanted in a male patient . the prosthesis apparatus includes inflatable stiffening cylinders 80 . in some aspects , once the cavities for the cylinders 80 have been formed by the exemplary method described above , the balloon catheters may be removed by sliding them proximally over the and off of the glide wires . the glide wires may be left in the distal portions of the corpora cavernosa in order to assist in placement of the stiffening cylinders . in this regard , it is known to provide an eyelet 82 in a solid portion at the end of each stiffening cylinder 80 , to which a suture 84 is threaded to provide a line to grip and pull the cylinder home in the cavity created by inflation of a balloon . in this regard , each suture 84 may be tied or secured to the proximal end 32 of a respective glide wire 30 , after removal of the balloon catheter therefrom . pulling the distal end of the glide wire 30 out through the glans 74 will pull the prosthesis cylinder coupled to its proximal end into place in the cavity created in the corpus . when the cylinder is seated , the suture is cut and , with the glide wire 30 , pulled out of the corpus through the glans . in another embodiment , balloon dilation is used in creating a circumferential cavity around the urethra for implantation of the inflatable cuff of an artificial sphincter therein . an artificial urethral sphincter apparatus includes an elastic reservoir to store an inflating fluid , an inflatable cuff , and a control pump to control the flow of inflating fluid between the reservoir and the cuff . these elements are connected by tubing , and all elements are implanted in the body . the urethral cuff is implanted around the bulbous urethra to keep the urethra closed . squeezing the pump implanted in the soft tissue of the scrotum or labium empties fluid from the cuff into the elastic reservoir , and opens the urethra for urination . afterwards the fluid slowly refills the cuff , closing the urethra . for an understanding of the operation and implantation of an artificial urethral sphincter , see the article by d . s . elliott and d . m . barrett entitled “ the artificial genitourinary sphincter ” in digital urology journal , downloaded jul . 11 , 2007 . implantation of an artificial urethral sphincter apparatus requires creation of one or more cavities in soft tissue where elements of the apparatus are implanted . one such cavity must be formed around the urethra in order to implant the cuff . a balloon dilation set for dilation of the soft tissue around the urethra includes elements illustrated in fig9 and 10 . preferably , although not necessarily , the instrument set includes a curved needle ( fig9 ), a distal balloon catheter ( fig1 ), and an inflation syringe ( fig5 ) as seen in fig9 , a curved needle 90 has a distal end 91 with a blunt tip and an end 92 with an eyelet 93 . in fig1 , a distal balloon catheter 100 includes a hollow tube 101 with a balloon 102 mounted thereon . the balloon has a length and an inflation width appropriate to the dimensions of the patient . typically , for an adult male , the balloon may be about 10 cm long and 10 french when inflated . the distal end 103 of the tube 101 extends beyond the balloon 102 , preferably for about 2 cm . the distal end includes an eyelet 104 and ends in a sharpened tip . a connector 105 with a balloon port 106 is coupled to the proximal end of the tube 101 . placement of a cuff for an artificial sphincter requires opening a circumferential cavity posteriorly around the bulbous urethra . see the article by d . s . elliott and d . m . barrett cited previously . with reference to fig9 and 11 , the bulbocavernous muscle 110 is opened along the front of the bulbous urethra 112 of a patient in the lithotomy position . in order to seat the cuff , a suture 114 is threaded through the eyelet 93 of the curved needle 90 and through the eyelet 104 in the distal end of the balloon sphincter 100 . the needle 90 is oriented such that its concave side faces the bulbous urethra 112 , and , in this orientation , is passed , blunt distal end 91 first through the undissected soft tissue , along one side , around the rear , and back along and out the other side of the bulbous urethra 112 , pulling the suture 114 through the soft tissue . as the suture 114 is pulled , the balloon catheter 100 follows , distal end 103 first , along the path traveled by the needle 90 around the back of the bulbous urethra , until it is in the position seen in fig1 . at this position , the suture 114 is removed from the eyelet 105 the balloon 102 is inflated , dilating the soft tissue to create the circumferential cavity around the bulbous urethra 112 . again , with the balloon 102 inflated , the effect of an inflatable sphincter prosthetic is mimicked and an immediate assessment of the dilated corpora can be made . the balloon catheter 100 may have markings as described above to enable measurement of the circumferential cavity . the balloon 102 is then deflated , and pulled back out of the circumferential cavity by the coupler 105 . the inflatable cuff 120 of the artificial sphincter is passed through the circumferential cavity thus created around the back of the bulbous urethra 112 , and its ends are joined around the front of the bulbous urethra as seen in fig1 . other balloon instruments may be provided to create cavities by balloon dilation in soft tissue for other elements of the artificial urethral sphincter . in another embodiment , balloon dilation is used in creating a circumferential cavity around the anal canal for implantation of the inflatable cuff of an artificial sphincter therein . with reference to fig1 , an artificial anal sphincter is a surgically implanted device constituted of an inflatable cuff 130 , a pressure regulating elastic reservoir 131 and a control pump 132 . the rectal cuff 130 is implanted around the anal canal to keep the canal closed . squeezing the pump 132 implanted in the soft tissue of the labium ( or scrotum ) empties fluid from the cuff 130 into the elastic reservoir 131 , and opens the anal canal for defecation . afterwards the fluid slowly refills the cuff 130 , closing the anal canal . surgical implantation of the cuff is accomplished via a perineal incision under the vagina ( or scrotum ), isolating the rectal sphincter circumferentially in a similar fashion to that of the aforementioned urethra . the posterior aspect of the rectum is a risky dissection similar to the dorsal urethra whereas using the proposed balloon catheter safely and efficiently allows a circumferential empty space to be developed for the anal cuff . placement of a cuff for an artificial anal sphincter requires opening a circumferential cavity posteriorly around the anal canal . see the article by j . christiansen and b . sparso entitled “ treatment of anal incontinence by an implantable prosthetic anal sphincter ” in annals of surgery , april 1992 , pp . 383 - 386 . in this regard , either a single incision is made along the perineum or two are made on either side of the anus of a patient in the lithotomy position , and an opening is made in the soft tissue along the anal canal . in order to seat the cuff , a circumferential opening is created posteriorly around the anus using an instrument set such as is illustrated in fig9 and 10 . that is to say , a blunt needle tethered thereto by a suture to the sharp tip of a balloon catheter . then , working through the opening , the needle is passed circumferentially under and around the rectum far enough below the bowel to avoid injury thereto , and is pulled out of the soft tissue . the movement of the blunt needle as just described causes the balloon catheter to be pulled circumferentially under and around the rectum to a position where the balloon catheter is untethered from the needle and the balloon is inflated to create the circumferential cavity posteriorly to the rectum . the balloon catheter may have markings as described above to enable measurement of the circumferential cavity . the balloon is then deflated , and pulled back out of the circumferential cavity by the coupler mounted to its proximal end . the inflatable cuff of the artificial sphincter is passed through the circumferential cavity thus created around the back of the rectum , and its ends are joined around the front of the rectum as seen in fig1 . other balloon instruments may be provided to create cavities by balloon dilation in soft tissue for other elements of the artificial anal sphincter , which are shown in fig1 . the novel tools and methods disclosed and illustrated herein may suitably be practiced in the absence of any element or step which is not specifically disclosed in the specification , illustrated in the drawings , and / or exemplified in the embodiments of this application . furthermore , although the balloon dilation instruments and methods have been described with reference to presently preferred embodiments , it should be understood that various modifications can be made without departing from the spirit of the principles set forth herein . accordingly , my invention is limited only by the following claims .

US-37366707-A

a skinning machine having a height adjustment assembly to raise and lower a primary cabinet in relation to the supporting legs .

fig1 shows a meat skinning machine 10 mounted on a pair of legs 12 that are connected to a pair of elongated support members 14 . while an open top skinning machine is shown , understood is that any type of skinning machine may be used including automatic skinning machines for conveyor systems . the skinning machine has a primary cabinet 16 that houses the skinning assembly ( not shown ). extending below the primary cabinet is a sub cabinet 18 that contains the height adjustment assembly 20 and receives the legs 12 through openings in the bottom of the sub cabinet . one skilled in the art could appreciate that the primary cabinet 16 and the subcabinet 18 could be combined to form a single housing for the skinning assembly and the height adjustment assembly 20 . while the height adjustment assembly 20 can take many forms , preferred is an elongated pinion 22 that is mounted to the interior of the sub cabinet 18 and engages racks 24 mounted on the legs 12 . mounted on the pinion 22 is a radially extending gear 26 . the gear 26 is positioned to engage a shaft 28 that extends outwardly through the sub cabinet 18 and is connected to a crank shaft 30 . in operation , the height of the skinning machine 10 is adjusted by rotating the crank shaft 30 in a first direction which in turn rotates the shaft 28 in the same direction . the shaft 28 engages and rotates the worm gear 26 which in turn rotates the pinion 22 . as the pinion 22 rotates and engages the rack 24 , the sub cabinet 18 and in turn the primary cabinet of the skinning machine 10 is raised . by rotating the crank shaft 30 in an opposite direction , the skinning machine is lowered in a similar manner . in the alternative , the skinning machine can be raised and lowered with a powered source ( not shown ). accordingly , disclosed is a height adjusting assembly for a skinning machine that easily raises and lowers the skinning machine to adjust to the height of the operator or other compatible devices . thus , at least the stated objectives have been met .

US-5322405-A

embodiments of the present invention relate to an injection devices that inject a specified reagent with cells into lesions and other areas of body tissue . particular embodiments comprise a main tube with a projection hole on its exterior , an axially - moveable needle tube with a needle at its tip , a reagent supplier configured to supply a specified reagent into the needle tube , and axially - moveable guide wires .

the structures of reagent injection devices embodied by the present invention are explained below in detail by referring to the drawings , in order to further elaborate on the present invention . [ 0039 ] fig1 and 2 show a front and cross sectional view , respectively , of a preferred embodiment of a reagent injection device of the present invention . fig1 and 2 , show a catheter body ( 10 ), or main tube , comprising a long tubular body . there is provided a needle tube ( 12 ) comprising a needle ( 11 ) at its tip , a first guide wire ( 14 ) and a second guide wire ( 16 ), each of which are inserted into the catheter body and movable in their respective axial directions . the catheter body ( 10 ) preferably has a thickness ( approximately 2 . 0 mm in diameter ) and length that allows the catheter to be preferably inserted into the blood vessels extending from the thighs or wrists to the heart in the human body at any point over their entire lengths . the catheter body ( 10 ) preferably comprises flexible , tubular inner and outer layers comprising a specific resin , which in some preferred embodiments comprises sandwiching stainless wires . this construction ensures both appropriate stiffness and flexibility to enable smooth insertion into a winding blood vessel . other preferred embodiments comprise various materials with desired elasticity known to those skilled in the art that could be used to construct such a catheter body ( 10 ), such as polyamide and other composite resin materials , ni — ti alloy and other ultra - elastic alloy materials , and stainless steel and other metals . the catheter body ( 10 ) preferably further contains four independent lumens , from first through fourth ( 18 a through 18 d ), which preferably have different diameters and extend continuously in the longitudinal direction . of the four lumens ( 18 a through 18 d ), the first and second lumens ( 18 a , 18 b ) preferably have the same diameter , which is smaller than the third lumen ( 18 c ) but larger than the fourth lumen ( 18 d ). the third lumen ( 18 c ) preferably has the largest diameter , and the fourth lumen ( 18 d ) has the smallest diameter . the first and second lumens ( 18 a , 18 b ) are preferably arranged in such a way that the center axis ( p 0 ) of the catheter body ( 10 ) is positioned in the plane ( α ) ( indicated by the two - dot chain line in fig2 ) that includes the center axes ( p 1 , p 2 ) of the first and second lumens ( 18 a , 18 b ). in accordance with preferred embodiments , the third lumen ( 18 c ) is arranged in such a way that its center axis ( p 3 ) corresponds to the center axis ( p 0 ) of the catheter body ( 10 ) and is positioned at the center between the first lumen ( 18 a ) and second lumen ( 18 b ). furthermore , the fourth lumen ( 18 d ) is preferably arranged in such a way that the plane ( β ) ( indicated by the two - dot chain line in fig2 ) that includes its center axis ( p 4 ) and the center axis ( p 3 ) of the third lumen ( 18 c ) lies orthogonal to the plane ( α ) that includes the center axes ( p 1 , p 2 ) of the first and second lumens ( 18 a , 18 b ). the catheter body ( 10 ) containing these four lumens ( 18 a through 18 d ) preferably comprises a tip aperture ( 20 ) that opens in the axial direction at the tip of the front end ( right side in fig1 ) as viewed in the insertion direction into the blood vessel . in addition , a projection hole ( 22 ) that opens to the side through the tubular wall is preferably formed in the catheter body ( 10 ) at a position slightly to the rear of the tip of its front end . furthermore , a side hole ( 24 ) that penetrates through the tubular wall is preferably provided at a position further to the rear of the projection hole ( 22 ), at the front end of the catheter body ( 10 ). as shown in fig2 and 3 , of the above three holes ( 20 , 22 , 24 ) provided at the front end of the catheter body ( 10 ), the tip aperture ( 20 ) and side hole ( 24 ) are preferably arranged in such a way that their centers ( o 1 , o 2 ) are positioned in the plane ( α ) that includes the center axes ( p 1 , p 2 ) of the first lumen ( 18 a ) and second lumen ( 18 b ). in accordance with preferred embodiments , the projection hole ( 22 ) is arranged in such a way that its center ( o 3 ) is positioned in the aforementioned plane ( β ) that includes the center axis ( p 0 ) of the catheter body ( 10 ) and that lies orthogonal to the plane ( α ). this preferably allows the side hole ( 24 ) to open perpendicularly to the opening direction of the tip aperture ( 20 ) and to that of the projection hole ( 22 ). in one preferred embodiment , the tip aperture ( 20 ) provided at the front end of the catheter body ( 10 ) connects to the first lumen ( 18 a ), the side hole ( 24 ) connects to the second lumen ( 18 b ), and the projection hole ( 22 ) connects to the third lumen ( 18 c ). this preferred configuration allows the first lumen ( 18 a ) to open in the forward axial direction ( right direction in fig1 ) through the tip aperture ( 20 ) at the front end of the catheter body ( 10 ). the second lumen ( 18 b ) preferably opens sideways through the side hole ( 24 ) perpendicularly to the opening direction of the first lumen ( 18 a ), while the third lumen ( 18 c ) opens through the projection hole ( 22 ) perpendicularly to both the opening directions of the first lumen ( 18 a ) and the second lumen ( 18 b ) ( downward direction in fig1 ). in accordance with preferred embodiments of the present invention , three connectors ( 28 , 30 , 32 ) are attached to the catheter body ( 10 ) at its rear end as viewed in the insertion direction into the blood vessel ( left side in fig1 ). the connectors ( 28 , 30 , 32 ) are preferably attached via a branching socket ( 26 ), which branches the catheter body ( 10 ) into three parts . in addition , an insertion hole ( 34 ) that penetrates through the tubular wall of the catheter body ( 10 ) is preferably provided at a specified distance from the front of the installation position of the branching socket ( 26 ) at the rear end of the catheter body ( 10 ). the insertion hole preferably opens in the direction opposite to the opening direction of the aforementioned side hole ( 24 ), along the direction of the diameter of the catheter body ( 10 ). the three connectors ( 28 , 30 , 32 ) each preferably connect to the second through fourth lumens ( 18 b - 18 d ) provided inside of the catheter . body ( 10 ). the insertion hole ( 34 ) also preferably connects to the first lumen ( 18 a ). this configuration preferably allows the first lumen ( 18 a ) to open outward through the insertion hole ( 34 ) at the rear end of the catheter body ( 10 ) as viewed in the insertion direction into the blood vessel , while allowing the second , third and fourth lumen ( 18 b through 18 d ) to open outward through the three connectors ( 28 , 30 , 32 ). in accordance with preferred embodiments , the needle tube ( 12 ) and first and second guide wires ( 14 , 16 ) are inserted into the catheter body ( 10 ) to allow movement in their respective axial directions . the first guide wire ( 14 ) is preferably inserted into the first lumen ( 18 a ) provided in the catheter body ( 10 ) through the insertion hole ( 34 ) provided in the tubular wall at the rear end of the catheter body ( 10 ). the second guide wire ( 16 ) is preferably inserted into the second lumen ( 18 b ) provided in the catheter body ( 10 ) through the rear - end aperture opening in the connector ( 28 ) attached at the rear end of the catheter body ( 10 ). further , the needle tube ( 12 ) is preferably inserted into the third lumen ( 18 c ) provided in the catheter body ( 10 ) through the opening in the connector ( 30 ) attached at the rear end of the catheter body ( 10 ). as illustrated in fig1 and 3 , which show the center axis positions of the needle tube ( 12 ) and guide wires ( 14 , 16 ), the first guide wire ( 14 ) preferably moves in the forward axial direction inside of the first lumen ( 18 a ) and extends out of the first lumen ( 18 a ) in the forward axial direction within the aforementioned plane ( α ) and through the tip aperture ( 20 ) at the front end of the catheter body ( 10 ). the second guide wire ( 16 ) preferably moves in the forward axial direction inside of the second lumen ( 18 b ), and extends out of the second lumen ( 18 b ) sideways within the aforementioned plane ( α ) and through the side hole ( 24 ) at the front end of the catheter body ( 10 ). in accordance with preferred embodiments , the needle tube ( 12 ) moves in the forward axial direction inside of the third lumen ( 18 c ) and the tip of the needle ( 11 ) extends out of the third lumen ( 18 c ) perpendicular to both the extension direction of the first ( 14 ) and second guide wires ( 16 ), inside of the plane ( β ) orthogonal to the aforementioned plane ( α ) and through the projection hole ( 22 ) at the front end of the catheter body ( 10 ). the needle tube ( 12 ) which is inserted into the third lumen ( 18 c ) preferably comprises a flexible tube . a part of the needle tube ( 12 ), excluding the needle ( 11 ) at its tip , comprises a reagent flow channel ( 36 ) comprising a thin tube which is preferably longer than the catheter body ( 10 ) and which preferably comprises a diameter of approx 0 . 4 mm . in preferred embodiments , the needle tube ( 12 ) is continuous with the needle ( 11 ) and reagent flow channel ( 36 ). the reagent flow channel ( 36 ) of the needle tube ( 12 ) preferably comprises a flexible composite resin material such as polytetrafluoroethylene or polyimide . the needle ( 11 ) preferably comprises an elastic alloy material such as ni — ti alloy , stainless steel , or other material known to those skilled in the art . the reagent flow channel ( 36 ), of the needle tube ( 12 ) is preferably connected to a syringe ( 38 ), which is attached to the connector ( 30 ) at the rear end of the catheter body ( 10 ) and which provides a reagent supplier for supplying a specified reagent . preferred structures of the needle tube ( 12 ) allows smooth insertion axial movement inside of the third lumen ( 18 c ) of the catheter body ( 10 ), which preferably has sufficient flexibility and / or elasticity for insertion into the winding blood vessel . the forward axial movement inside of the third lumeri ( 18 c ) causes the needle ( 11 ) to project out of the projection hole ( 22 ) of the catheter body ( 10 ) and pierce the myocardium . in particularly preferred embodiments , a reagent containing osteoblasts and / or growth factor for regenerating nearly or substantially dead cells of the myocardium , such as bfgf ( basic fibroblast growth factor ), vegf ( vascular endothelial - cell growth factor ) or hgf ( hepatic growth factor ), can be introduced into the reagent flow channel ( 36 ) and discharged through the opening in the needle ( 11 ) by means of the syringe ( 38 ). as illustrated in fig4 the interior surface of the front end of the third lumen ( 18 c ), which includes the peripheral edge of the opening of the projection hole ( 22 ), preferably provides a guide surface ( 40 ) consisting of a convex curved surface curving in the forward axial direction toward the opening direction of the projection hole ( 22 ). in addition , the needle ( 11 ) of the needle tube ( 12 ) comprises a curved shape corresponding to the curved structure of the guide surface ( 40 ). this allows the needle ( 11 ) to be guided smoothly toward the projection hole ( 22 ) by the guide surface ( 40 ), through sliding contact with the guide surface ( 40 ), as the needle tube ( 12 ) moves in the forward axial direction . appropriate curved shapes of the guide surface ( 40 ) and needle ( 11 ) can preferably be determined by considering the stiffness of the needle ( 11 ). while the radius of curvature and other properties of the curved sections of the guide surface ( 40 ) and needle ( 11 ) are not specified herein , it is desirable that the projection angle ( θ ), which is formed at the contact point of the two sections when the curved pattern of the guide surface ( 40 ) is combined with the curved shape of the needle ( 11 ) when the needle ( 11 ) is projected out of the projection hole ( 22 ), is about forty - five degrees . in other preferred embodiments , the projection angle ( θ ) is more than forty - five degrees . as shown in fig4 the curved shapes of the guide surface ( 40 ) and needle ( 11 ) preferably allow the tip of the needle ( 11 ) to be positioned close to the projection hole ( 22 ) when the needle ( 11 ) is projected sufficiently out of the projection hole ( 22 ), thereby allowing the projecting position of the needle ( 11 ) to be easily identified . in addition , the tangential line ( m ) of the needle ( 11 ) can be caused to cross orthogonally , at a position closer to the projection hole ( 22 ), the center axis ( p 0 ) of the catheter body ( 10 ) and the center axis ( p 3 ) of the third lumen ( 18 c ) into which the needle tube ( 12 ) is inserted . as a result , the component force in the progressing direction of the needle tube ( 12 ) into the myocardium ( of the two vectors vv and vh shown in fig3 this component force corresponds to vv , which is the vector perpendicular to the center axis ( p 3 ) of the third lumen ( 18 c )) will increase , thereby enabling the needle tube ( 12 ) to be inserted more smoothly into the myocardium . furthermore , the tip surface of the needle ( 11 ), namely the opening end face ( 41 ) of the opening in the needle ( 11 ), preferably provides an inclined surface facing the opening of the projection hole ( 22 ) when the needle ( 11 ) is projecting from the catheter body ( 10 ) ( namely , the downward inclined surface shown in fig4 ). in preferred embodiments , a balloon ( 42 ) is provided between where the projection hole ( 22 ) and side hole ( 24 ) are formed at the front end of the catheter body ( 10 ). this balloon ( 42 ) preferably comprises a soft composite resin material and has a known structure that allows it to expand in the opening direction of the projection hole ( 22 ) when saline solution or other liquid is injected inside of the balloon . the balloon preferably shrinks from an extended state when such liquid is discharged . the fourth lumen ( 18 d ) preferably opens toward the inside of the balloon ( 42 ). as shown in fig1 when being connected to the fourth lumen ( 18 d ), the connector ( 32 ) attached at the rear end of the catheter body ( 10 ) preferably has a syringe ( 44 ) connected thereto . the syringe ( 44 ) provides a means for supplying fluid to expand the balloon ( 42 ). in the preferred embodiments of fig1 and 4 a , a marker tube ( 46 ) can be made of a radio - opaque material such as gold , platinum or platinum - rhodium alloy . preferred embodiments of the marker tube ( 46 ) have an inclined opening end face on one side of the axial direction , with the longest and shortest sections ( 46 b , 46 a ) in the axial direction formed along the cylinder wall . this marker tube ( 46 ) is preferably inserted over the front end of the catheter body ( 10 ) and is preferably fixed at a position where either the longest or shortest sections ( 46 b , 46 a ) of the cylinder wall corresponds to the position of the projection hole ( 22 ) at the front end of the catheter body ( 10 ). the tip of the marker tube ( 46 ) preferably corresponds to the tangential line ( m ) of the needle tube ( 12 ) ( needle ( 11 )) when the needle tube ( 12 ) is projected . this allows the position of the projection hole ( 22 ) and that of the tip of the needle tube ( 12 ), in a condition where the catheter body ( 10 ) is inserted into the blood vessel , to be identified easily through an x - ray fluoroscopy of the tip , the longest section ( 46 b ), and the shortest section ( 46 a ) of the cylinder wall of the marker tube ( 46 ). in the preferred embodiment shown in fig4 the shortest section ( 46 a ) of the cylinder wall of the marker tube ( 46 ) is preferably positioned on the side which comprises the projection hole ( 22 ). embodiments of the present invention further comprise methods of injecting a specified reagent into tissue , such as a nearly or substantially necrosis tissue or other lesion in the myocardium , using a reagent injection catheter of the present invention . when implementing a reagent injection therapy using such a reagent injection catheter , the first guide wire ( 14 ) is preferably inserted into the main blood vessel ( 50 ) at the surface of the myocardium ( 48 ), as shown in fig5 . the second guide wire ( 16 ) is preferably inserted into the branch blood vessel ( 52 ) at the surface of the myocardium ( 48 ), which is branching from the main blood vessel ( 50 ) in which the first guide wire ( 14 ) is inserted . in some preferred embodiments , the insertion operations of the first and second guide wires ( 14 , 16 ) into the main blood vessel ( 50 ) and branch blood vessel ( 52 ) can be performed manually . the catheter body ( 10 ) is then preferably inserted into the main blood vessel ( 50 ) at the surface of the myocardium ( 48 ), along the first guide wire ( 14 ). this insertion operation of the catheter body ( 10 ) into the main blood vessel ( 50 ) is preferably performed while checking , using x - ray fluoroscopy and a monitor or other means known to those skilled in the art , the position of the marker tube ( 46 ) inserted over the front end of the catheter body ( 10 ) as viewed in the insertion direction . when the marker tube ( 46 ) reaches a specified position in the main blood vessel ( 50 ), as the catheter body ( 10 ) progresses into the main blood vessel ( 50 ), the insertion operation of the catheter body ( 10 ) can be temporarily stopped . the positions of the shortest section ( 46 a ) and longest section ( 46 b ) of the marker tube ( 46 ) are then preferably checked , and the catheter body ( 10 ) rotated around its axis so that the projection hole ( 22 ) opens toward the specified position in the lesion in the myocardium ( 48 ) into which the reagent will be injected . the axial - direction position of the catheter body in the blood vessel ( 50 ) can be simultaneously adjusted . when the catheter body ( 10 ) reaches the aforementioned specified position in the main blood vessel ( 50 ), as shown in fig6 saline solution or other liquid can be introduced from the syringe ( 44 ) into the fourth lumen ( 18 d ) inside the catheter body ( 10 ) to expand the balloon ( 42 ) toward the opening direction of the projection hole ( 22 ). this preferably fixes the catheter body ( 10 ) inside the main blood vessel ( 50 ) over the lesion in the myocardium ( 48 ) into which the reagent will be injected . next , the needle tube ( 12 ) is preferably inserted into the third lumen ( 18 c ) in the catheter body ( 10 ) through the connector ( 30 ), and is moved forward in the insertion direction of the catheter body ( 10 ) into the main blood vessel ( 50 ). once the needle ( 11 ) at the tip of the needle tube ( 12 ) reaches the front end of the third lumen ( 18 c ), the needle ( 11 ) can progress forward smoothly toward the projection hole ( 22 ) by means of sliding contact with the guide surface ( 40 ) provided on the interior surface of the third lumen ( 18 c ) at the front end , as shown by the two - dot chain line in fig6 . by this further forward movement of the needle tube ( 12 ), the needle ( 11 ) is preferably caused to project out of the projection hole ( 22 ), as shown by the solid line in fig6 . this projection operation of the needle ( 11 ), by means of the movement of the needle tube ( 12 ), can preferably be performed manually or by using a known screw mechanism known by those skilled in the art . preferred embodiments of the reagent injection catheter allow the needle ( 11 ) of the needle tube ( 12 ) to be projected out of the projection hole ( 22 ) in a direction virtually perpendicular to the extension direction of the first guide wire ( 14 ), which extends out of the tip aperture ( 20 ) in the catheter body ( 10 ). preferred embodiments of the reagent injection catheter also allow the needle ( 11 ) of the needle tube ( 12 ) to be projected out of the projection hole ( 22 ) in a direction virtually perpendicular to the extension direction of the second guide wire ( 16 ), which extends out of the side hole ( 24 ) in the catheter body ( 10 ). the first guide wire ( 14 ) is inserted into the main blood vessel running at the surface of the myocardium ( 48 ), and the second guide wire ( 16 ) is inserted into the branch blood vessel ( 52 ) which also runs at the surface of the myocardium ( 48 ). thus , the surface formed by the first and second guide wires ( 14 , 16 ) virtually approximates the surface of the myocardium ( 48 ). the needle ( 11 ) of the needle tube ( 12 ) projecting out of the projection hole ( 22 ) in the catheter body ( 10 ) via the aforementioned operation will preferably project in the direction virtually perpendicular to the surface of the myocardium ( 48 ). furthermore , the curved shape of the needle ( 11 ), which is curved in the projection direction out of the projection hole ( 22 ) in the moving direction of the needle tube ( 12 ), preferably allows the tangential line ( m ) at the tip to cross orthogonally the center axis ( p 0 ) of the catheter body ( 10 ) when the needle is projecting out of the projection hole ( 22 ). the term “ virtually perpendicular ” is used here because , since the myocardium ( 48 ) actually has a complex shape , in the strict sense the needle ( 11 ) may not always project perpendicularly to the surface of the myocardium ( 48 ). in preferred embodiments , the needle ( 11 ) of the needle tube ( 12 ) projecting out of the projection hole ( 22 ) in the catheter body ( 10 ) will pierce through the vascular wall ( 54 ) of the main blood vessel ( 50 ) to reach the specified position in the lesion in the myocardium ( 48 ). as the needle tube ( 12 ) moves forward in the catheter body ( 10 ), the needle ( 11 ) will progress in a direction virtually perpendicular to the surface of the myocardium ( 48 ) to reach the specified depth in the lesion . when the needle ( 11 ) progresses into the lesion , a majority of the reactive force generated in response to the progress of the needle ( 11 ) into the myocardium ( 48 ) will act on the catheter body ( 10 ) in the direction opposite to the progressing direction of the needle ( 11 ), or , the direction perpendicular to the surface of the myocardium ( 48 ). however , the first guide wire ( 14 ) and second guide wire ( 16 ) can be inserted into the main blood vessel ( 50 ) and branch blood vessel ( 52 ), respectively , at the surface of the myocardium ( 48 ). therefore , such reactive force can be divided and each component force can be sufficiently and reliably supported by the first and second guide wires . this operation preferably allows the needle to progress to a specified depth in the lesion in the myocardium ( 48 ) in a smooth and reliable manner . in accordance with preferred embodiments , when the needle ( 11 ) reaches the desired depth in the lesion in the myocardium ( 48 ), the movement of the needle tube ( 12 ) will be terminated . thereafter , a reagent containing osteoblast and / or growth factor , or other reagent known to those skilled in the art , to regenerate the myocardium ( 48 ) can be introduced into the internal hole of the needle tube ( 12 ) via the syringe ( 44 ) connected to the connector ( 32 ) at the basal position of the needle tube ( 12 ). such a reagent is preferably discharged from the tip aperture of the needle ( 11 ) and injected into the lesion in the myocardium ( 48 ). thereafter , when the reagent is injected into one location of lesion in the myocardium ( 48 ), the needle tube ( 12 ) can be preferably retracted within the catheter body ( 10 ), and the needle ( 11 ) pulled into the catheter body ( 10 ). this reagent injection operation at a lesion in the myocardium ( 48 ) can preferably be repeated multiple times , thereby allowing the reagent to be injected into multiple lesions in the myocardium ( 48 ). the needle ( 11 ) projecting out of the projection hole ( 22 ) in the catheter body ( 10 ) preferably pierces a specified position in the lesion in the myocardium ( 48 ) in a reliable manner . in addition , a majority of the reactive force generated by such piercing of the myocardium ( 48 ) by the needle ( 11 ) can be sufficiently and reliably supported by the first guide wire ( 14 ) and second guide wire ( 16 ) inserted into the main blood vessel ( 50 ) and branch blood vessel ( 52 ), respectively , at the surface of the myocardium ( 48 ). this allows the needle ( 11 ) to preferably progress into a specified depth at the lesion in the myocardium ( 48 ) in a very smooth and reliable manner . thus , by using such a reagent injection catheter of this example , the needle ( 11 ) will preferably pierce through to a desired depth at a specified position in the lesion in the myocardium ( 48 ), even when the lesion has been hardened . this further and sufficiently increases the effect of the treatment or procedure to inject into the lesion in the myocardium ( 48 ) a reagent for regenerating the myocardium ( 48 ). in preferred embodiments , the first through fourth lumens ( 18 a through 18 d ) are provided independently inside the catheter body ( 10 ) in a manner extending continuously in the longitudinal direction of the catheter body ( 10 ). the first , second and third lumens ( 18 a through 18 c ) preferably contain the first and second guide wires ( 14 , 16 ) and needle tube ( 12 ), respectively , in a manner which allows movement in the axial direction . this configuration allows the first and second guide wires ( 14 , 16 ) and needle tube ( 12 ) to smoothly move in the axial direction inside the catheter body ( 10 ). consequently , a smoother implementation of the applicable medical technique becomes possible . furthermore , in embodiments of the present invention , the first guide wire ( 14 ) is inserted into the first lumen ( 18 a ) through an insertion hole ( 34 ) that opens to the side at the rear end of the catheter body ( 10 ), and extends straight in the forward axial direction via the tip aperture ( 20 ) in the catheter body ( 10 ). additionally , the second guide wire ( 16 ) is inserted straight into the second lumen ( 18 b ) through the opening in the connector ( 26 ) attached at the rear end of the catheter body ( 10 ), and extends sideways via the side hole ( 24 ) that opens to the side at the front end of the catheter body ( 10 ). in preferred reagent injection catheters both the first guide wire ( 14 ) and second guide wire ( 16 ) preferably pass through the catheter body ( 10 ) in a condition that is bent or curved at only one location . therefore , when the catheter body ( 10 ) is inserted into the main blood vessel ( 50 ) at the surface of the myocardium ( 48 ) along the first and second guide wires ( 14 , 16 ), the guide wires ( 14 , 16 ) will experience relatively small slide resistance , thus allowing for a smoother insertion of the catheter body ( 10 ) into the main blood vessel ( 50 ). the third lumen ( 18 c ), into which the needle tube ( 12 ) is inserted , can be preferably arranged so that its center axis ( p 3 ) corresponds to the center axis ( p 0 ) of the catheter body ( 10 ). this ensures a good overall balance of the reagent injection catheter and enables the applicable medical technique for injecting a reagent into a lesion in the myocardium ( 48 ) to be performed in a more stable manner . in preferred embodiments of the reagent injection catheter the projection hole ( 22 ) is arranged so that the center ( o 3 ) of the projection hole ( 22 ), through which the needle ( 11 ) of the needle tube ( 12 ) projects , is positioned in the plane ( β ) lying orthogonal to the plane ( α ) that includes the center axis ( p 3 ) of the third lumen ( 18 c ) into which the needle tube ( 12 ) is inserted , the corresponding center axis ( p 0 ) of the catheter body ( 10 ), and the center axes ( p 1 , p 2 ) of the first and second lumens ( 18 a , 18 b ) into which the first and second guide wires ( 14 , 16 ) are inserted . this allows a preferable layout balance of the needle tube ( 12 ) inside of the catheter body ( 10 ), and a good balance when the needle ( 11 ) is projected out of the projection hole ( 22 ). as a result , the applicable medical technique to inject a reagent into a lesion in the myocardium ( 48 ) can be performed in a more stable and smoother manner . in preferred embodiments the center axes ( p 1 , p 2 ) of the first and second lumens ( 18 a , 18 b ), into which the first and second guide wires ( 14 , 16 ) are inserted , are positioned in the aforementioned single plane ( α ) together with the center axis ( p 0 ) of the catheter body ( 10 ) and the center axis ( p 3 ) of the third lumen ( 18 c ) into which the needle tube ( 12 ) is inserted . moreover , the first and second lumens ( 18 a , 18 b ) can be preferably located on both sides of the third lumen ( 18 c ). this configuration preferably maximizes the distance between the first lumen ( 18 a ) and second lumen ( 18 b ), thereby increasing the distance between the first guide wire ( 14 ) and second guide wire ( 16 ) extending out form these two lumens ( 18 a , 18 b ) through the tip aperture ( 20 ) and side hole ( 24 ) in the catheter body ( 10 ), respectively . as a result , a majority of the reactive force generated as the needle ( 11 ) progresses into the lesion in the myocardium ( 48 ) can be supported by the first guide wire ( 14 ) and second guide wire ( 16 ). in accordance with preferred embodiments , the fourth lumen ( 18 d ) that supplies the liquid for expanding the balloon ( 42 ) is positioned in such a way that its center axis ( p 4 ) is positioned in the aforementioned plane ( β ) that includes the center axis ( p 3 ) of the third lumen ( 18 c ) into which the needle tube ( 12 ) is inserted , the center axis ( p 0 ) of the catheter body , and the center ( o 3 ) of the projection hole ( 22 ). this configuration preferably ensures a good overall balance of the reagent injection catheter , thus allowing the applicable medical technique for injecting a reagent into a lesion in the myocardium ( 48 ) to be performed in a more stable manner . the interior surface at the front end of the third lumen ( 18 c ), into which the needle tube ( 12 ) is inserted , preferably provides a guide surface ( 40 ) consisting of a convex curved surface curving in the opening direction of the projection hole ( 22 ) in the forward axial direction . additionally , the needle ( 11 ) of the needle tube ( 12 ) is also preferably formed with a curved shape corresponding to the guide surface ( 40 ). therefore , as the needle tube ( 12 ) moves forward inside the catheter body ( 10 ), the needle ( 11 ) will preferably project out of the projection hole ( 22 ) in a direction perpendicular to the surface of the myocardium ( 48 ). this structure also allows the applicable medical technique for injecting a reagent into a lesion in the myocardium ( 48 ) to be performed in a more stable and reliable manner . preferred embodiments provide various possible configurations of the positions of the first through fourth lumens ( 18 a through 18 d ) provided within the catheter body ( 10 ). for example , as shown in fig7 the third lumen ( 18 c ) can be preferably arranged so that its center axis ( p 3 ) deviates from the center axis ( p 0 ) of the catheter body ( 10 ) toward the projection hole ( 22 ) along the diameter direction of the catheter body ( 10 ), while the first and second lumens ( 18 a , 18 b ) can be arranged in such a way that the plane ( α ) including their respective center axes ( p 1 , p 2 ) deviates from the center axis ( p 0 ) of the catheter body ( 10 ) toward the opposite direction of the projection hole ( 22 ) along the diameter direction of the catheter body ( 10 ). moreover , as shown in fig8 the third lumen ( 18 c ) can preferably be arranged in such a way that its center axis ( p 3 ) deviates from the center axis ( p 0 ) of the catheter body ( 10 ) toward the opposite direction of the projection hole ( 22 ) along the diameter direction of the catheter body ( 10 ). the first and second lumens ( 18 a , 18 b ) can simultaneously be arranged in such a way that the plane ( α ), including their respective center axes ( p 1 , p 2 ), deviates from the center axis ( p 0 ) of the catheter body ( 10 ) toward the projection hole ( 22 ) along the diameter direction of the catheter body ( 10 ). in the two embodiments shown in fig7 and 8 , the needle ( 11 ) of the needle tube ( 12 ) is projected in a direction perpendicular to the extension directions of the first and second guide wires ( 14 , 16 ). therefore , these second and third examples can function similarly to the previously described embodiments . as shown in fig9 the third lumen ( l 8 c ) can preferably be arranged coaxially to the catheter body ( 10 ), while the first lumen ( 18 a ) can be arranged in such a way that its center axis ( p 1 ) is positioned on the opposite side of the center ( o 3 ) of the projection hole ( 22 ) across the center axis ( p 3 ) of the third lumen ( 18 c ) inside the plane ( β ) that includes the center axis ( p 3 ) of the third lumen ( 18 c ), the center axis ( p 0 ) of the catheter body ( 10 ) and the center ( o 3 ) of the projection hole ( 22 ). the second lumen ( 18 b ) can then preferably be arranged in such a way that its center axis ( p 2 ) is positioned in the plane ( α ) that lies orthogonally to the above plane ( β ), and includes the center axis ( p 3 ) of the third lumen ( 18 c ), and the center axis ( p 0 ) of the catheter body ( 10 ). furthermore , as shown in fig1 , the first , second and third lumens ( 18 a through 18 c ) can be arranged in such a way that their center axes ( p 1 through p 3 ) are positioned in the aforementioned plane ( β ) that includes the center axis ( p 0 ) of the catheter body ( 10 ) and the center ( o 3 ) of the projection hole ( 22 ). the fourth lumen ( 18 d ) can also be arranged in a position different from those in the first through third examples explained above . in the embodiments shown in fig9 and 10 , the first lumen ( 18 a ) and second lumen ( 18 b ) are displaced and parallel with each other , and the positions of their respective center axes ( p 1 , p 2 ) have a deviation ( d ) in the diameter direction of the catheter body ( 10 ). however , such deviation ( d ) is minute , and is preferably smaller than the diameter of the catheter body ( 10 ). therefore , the extension - direction vectors of the first and second guide wires ( 14 , 16 ), which are inserted into these first and second lumens ( 18 a , 18 b ), still preferably cross each other , and thus the needle tube ( 12 ) can virtually project onto the plane that includes these vectors . thus , in preferred embodiments little impact is caused by the minute deviation ( d ). in accordance with preferred embodiments of fig9 and 10 , the needle ( 11 ) of the needle tube ( 12 ) preferably projects in a direction virtually perpendicular to the extension directions of the first and second guide wires ( 14 , 16 ). further preferred embodiments of the reagent injection catheter of the present invention provide numerous structural variations . for example , the balloon ( 42 ) provided externally to the catheter body ( 10 ), and the fourth lumen ( 18 d ) provided in the catheter body ( 10 ) to supply the liquid for expanding such a balloon ( 42 ), can be omitted from some embodiments . of course , in the event that the balloon ( 42 ) and fourth lumen ( 18 d ) are to be provided , their positions and quantities should not be limited to those in the aforementioned examples . other preferred embodiments comprise a guide surface ( 40 ) comprising a convex curved surface on the interior surface at the front end of the third lumen ( 18 c ), and comprise a needle ( 11 ) having a straight shape . furthermore , while in the aforementioned examples the opening end face ( 41 ) of the needle ( 11 ) provides an inclined surface ( downward inclined surface in fig1 ) that slopes in the projection direction of the needle ( 11 ), toward the moving direction of the needle tube ( 12 ) when the needle ( 11 ) projects out of the projection hole ( 22 ), preferred embodiments can alternatively comprise an opening end face ( 41 ) that can be provided as an inclined surface ( upward inclined surface in fig1 ) that slopes in the projection direction of the needle ( 11 ) toward the opposite direction to the moving direction of the needle tube ( 12 ) when the needle ( 11 ) projects out of the projection hole ( 22 ). in certain embodiments , an opening end face ( 41 ) which comprises a downward inclined surface ( see fig1 ) can preferably prevent the interior surface of the third lumen ( 18 c ) from being scratched or damaged due to contact with the needle ( 11 ), which might otherwise occur as the needle ( 11 ) moves inside the third lumen ( 18 c ). preferred embodiments of the present invention , including but not limited to the aforementioned embodiments , can also be used for injecting a reagent into tissues other than the myocardium . moreover , preferred embodiments of the present invention can also apply to non - catheter reagent injection devices for injecting a reagent into myocardium lesions or other tissues known to those skilled in the art . the present invention can be embodied with various changes , modifications or improvements added based on the knowledge of those skilled in the art , although specific examples of such changes , modifications and improvements are not listed here . of course , such embodiments are included in the scope of the present invention unless they deviate from the purpose of the present invention .

US-79335104-A

a tack welded joint for a metal casket is covered by a trim strip following the contour of the shell along a length of the joint . an adhesive tape interposed between the strip and the shell overlies the joint in cooperating in releasably coupling the trim strip to the shell and provide a hermetic seal . screws extending through the trim strip and the joint cooperating in strengthening the shell in this location .

in the drawings , casket 10 of selected metal , such as bronze , copper or the various grades of steel or zinc coated steel is shown without conventional , decorative , functional or traditional hardware other than that proposed by the teachings of the present invention . the casket 10 may be of any one of many different styles and variety including the full and half couch designs . towards this end , a typical casket will include a cap or lid 12 , opposed side panels 14 and end panels 16 , as well as a base or bottom ( not shown ). as shown , the side panels 14 may be straight with the end panels 16 provided with rounded corner sections 18 or each end panel 16 may be straight as shown in fig6 with a corner piece 20 employed to connect the panels . the connection between the rounded corner end panels 16 and side panels 14 as well as the connection between the corner piece 20 and the straight end panels 16 &# 39 ; and side panels 14 &# 39 ; may be a butt welded connection as shown in fig4 or it may be an overlapping edge connection which is tack welded together as shown in fig5 . in the normal course of securing and squaring the side panels 14 with the end panels 16 , a number of tack or spot welds 26 are normally applied at strategic stress points . the present invention envisions applying a complete weld along the joint 24a and 24b defined by the top rail 26 and the bottom rail 28 . at these locations the complete weld provides a hermetic connection which is later subjected to a grinding operation followed by buffing and fine finishing to obtain the desired aesthetic appearance . in most instances , there is no visible appearance of a connection or joint at this location , particularly after the casket shell has been primed and painted . after the tack welding and squaring operation , the present invention contemplates the application and installation of trim strips 30 over the joints 22a and 22b intermediate the top rail 26 and bottom rail 28 at anyone of a number of stages of the ensuing manufacturing and assembly procedures . these trim strips 30 may be conveniently injection molded of suitable resinous material and to provide the desired aesthetic and decorative affect and compliment the remaining hardware applied to the casket 10 , may be suitably finished . for example , the finish may be obtained by the application of a metalized surface to the exposed portions of the strip , which in addition conveys the impression of strength and rigidity along that portion of the joint 22a and 22b which the trim strip is applied . each of the trim strips 30 is fabricated to closely follow the contour of the casket shell , particularly the intermediate section 32 and in a majority of instances the adjacent sectors of the top rail 26 and bottom rail 28 that are inaccessible and somewhat difficult to grind and polish . in this connection , each trim strip 30 will include an intermediate part 34 which follows the contour of the intermediate part 32 of the casket shell and an outwardly extending upper rail part 36 and lower rail part 38 , which follows the contours of the adjacent or opposed sectors of the upper rail 26 and bottom rail 28 . the outer face 40 of the trim strip 30 may be molded with and provided with the desired configuration for aesthetic and decorative purposes which together with a metallized finish may contribute to the impression for the viewer of strength and rigidity at this location , while complimenting the remaining hardware applied to the casket 10 . the inner face 42 of the trim strip 30 is recessed to provide a recess 44 defined by an inwardly projecting flange 46 extending around essentially the entire periphery of the inner face of the trim strip 30 . the recess 44 of the trim strips conveniently accommodate the outwardly projecting portions of the tack weld 24 . of course , the trim strips may be of substantially any thickness and width depending upon the nature of the joint to be covered and the desired aesthetic affect to be achieved . the present invention also contemplates the utilization and application of a resilient cushioning layer or material 50 , which is preferably flexible in order to follow the inner contour of and for disposition within the recess 42 of the trim strip 30 . in an at rest position layer 50 may extend beyond the flange 46 , but is adapted to be compressed when applied to the shell as shown in section in fig4 and 5 . the cushioning material may be utilized to dampen and eliminate vibration of the trim strip 30 and / or may be fabricated of a suitable material , as for example , a close cell foam material , to provide an air , moisture and waterproof joint 22a and 22b . material of this type will compress and distort about the outwardly projecting portions of the tack welds 24 . in accordance with a successful specific application of the present invention , the layer 50 formed of a close cell foam material , was supplied in tape form and cut from a web of a roll of such material . each of the opposed side faces 52 and 54 of the tape 50 will preferably have a pressure sensitive adhesive surface or layer applied thereto which may be covered and protected by a release sheet or strip if necessary . be that as it may , the adhesive layer 54 on layer surface 52 will permit the tape or strip 50 to be applied to the inner face 42 of the strip 30 in the recess 42 in order that it may closely follow the inner contour of the strip 30 . the outer adhesive layer 54 performs a number of important functions including permitting the strip 30 to be attached to the shell without danger of it becoming dislodged or disassociated from the shell by falling on the ground or other surface during the ensuing manufacturation and assembly operations . thereafter , a suitable number of screws 56 may be utilized , extending through the strip 30 , layer 50 and the shell , to secure these parts together . in addition , the screw 56 when extending through the overlap connection or joint shown in fig5 will add further securement of these connected parts of the shell and specifically the side panels 14 and the end panels 16 or the overlapped connections shown in fig6 . the adhesive surfaces of the tape 50 serve other useful and important functions including assurance that the strip 30 follows the contour of the outer contour of the shell at the joint 22a and 22b notwithstanding the effects of heat and cold and unequal expansion of the parts . in addition , this tape will reduce any permissible and undesirable flexing and movement of the trim strip 30 by assuring that the strip follows and maintains the contour of the shell . in addition , the presence of the adhesive surfaces contributes to the moisture and waterproof nature , airtightness , and hermetic seal of the joint . in this manner , the damage to the casket interior as a result of these elements will be minimized if not prevented . thus , it will be evident that the extensive grinding , buffing and fine finishing procedures heretofore employed in the industry at the panel joints is most effectively minimized as a result of the provision of the trim strips 30 and accompanying layer of tape 50 . each strip may be suitably contoured and finished to provide the desired aesthetic appearance in arriving at the various casket styles of each manufacturer and supplier . in this connection , trim strips 30 may be prefinished as discussed above or simply receive paint during the spray finishing operation . with the elimination of the grinding , buffing and fine finishing operations at each of the aforenoted joints , there is a corresponding increase in production , decrease in required manual labor , decrease in noise abatement and dust from such procedures . with noise abatement and dust reduction there is a pronounced reduction in health hazards that may otherwise ensue . needless to say , the present invention will decrease the cost in manufacturing and assembling a casket . thus , the aforenoted objects and advantages are most effectively attained . although several somewhat preferred embodiments of the invention have been disclosed and described in detail herein , it should be understood that this invention is in no sense limited thereby and its scope is to be determined by that of the appended claims .

US-13529380-A

a motorized toy vehicle actuated by liquid such as water is provided . the toy vehicle includes a frame having wheels rotatably supported thereon and a motor operatively coupled to the wheels for rotating the wheels . a reservoir having a float disposed therein is supported on the toy vehicle frame . a switch selectively actuated by the float is coupled to the motor . when a predetermined amount of liquid is present in the reservoir , the float will actuate the switch thereby turning on the motor .

reference is made to the drawings wherein a toy vehicle , generally indicated at 10 , constructed in accordance with a preferred embodiment of the present invention , is depicted . toy car 10 includes a chassis 12 having a body 14 depicted in phantom in fig1 disposed thereon . body 14 is secured to chassis 12 by means of screws 16 . chassis 12 and body 14 are preferably formed of a resilient plastic material . a pair of front wheels 20 and 20a are rotatably coupled to front end 12a of chassis 12 by means of an axle 22 . similarly , a pair of rear wheels 24 and 24a are rotatably coupled to rear end 12b of chassis 12 by means of an axle 26 . a conventional dc motor 30 is supported on front end 12a of chassis 12 . motor 30 includes a drive shaft 32 having a gear 34 affixed thereto and rotatable therewith . gear 34 may be a pinion gear . a gear 36 is fixed to front axle 22 adjacent front wheel 20 . gear 36 meshes with gear 34 of motor 30 so that when drive shaft 32 of motor 30 is rotating , gear 34 will cause rotation of front axle 22 thereby resulting in rotation of front wheels 20 and 20a to propel toy vehicle 10 . a float and reservoir assembly , generally indicated at 40 , is supported on rear end 12b of chassis 12 . assembly 40 includes a reservoir 42 having a filling neck 44 with an opening 46 which communicates with reservoir 42 . reservoir 42 also includes an air release port 48 which includes an opening 50 which communicates with reservoir 42 . reservoir 42 includes an opening 52 having a flexible sheet or diaphragm 54 disposed across opening 52 . diaphragm 54 may be a latex or rubber membrane or other deformable material . a plastic float 56 having a buoyant material 57 such as styrofoam or the like coupled thereto is disposed in reservoir 42 . float 56 includes a rigid projection 58 which extends towards opening 52 against diaphragm 54 . a switch mechanism generally indicated at 60 , includes first and second resilient contact leafs 62 and 64 which are respectively coupled to chassis 12 by means of screws 66 and 68 . end 62a of contact leaf 62 is disposed so as to extend over and substantially rest on diaphragm 54 . end 64a of contact leaf 64 extends over and is normally spaced from end 62a of contact 62 . a battery compartment 70 is adapted to receive and support a battery 72 such as a 9 v battery . a removable battery cover 71 is provided to secure battery 72 in battery compartment 70 . a battery cap 74 is provided for coupling to terminals 76 of battery 72 . a first lead 80 is coupled intermediate motor 30 and a first terminal 76 of battery 72 . a second lead 82 is coupled intermediate the second terminal 76 of battery 72 and first contact leaf 62 . a third lead 83 is coupled intermediate motor 30 and second contact leaf 64 . to facilitate coupling of leads 82 and 83 to contact leafs 62 and 64 respectively , friction couplings 84 and 85 may be provided . a drain tank or secondary reservoir 90 is disposed below reservoir 42 . an opening 92 is provided in reservoir 42 which communicates with drain tank 90 . a metering pad 94 for impeding the flow is made of felt , sponge material or the like and is disposed in opening 92 . reservoir 92 includes an opening 96 in which a plug 98 is removably secured . plug 98 is coupled to metering pad 94 by means of a rod 100 . the operation of toy vehicle 10 will now be described . since contact leafs 62 and 64 and specifically terminals 62a and 64a thereof are normally disposed in spaced relation as best depicted in fig1 and 3 , an open circuit is present and no power is supplied to motor 30 . when a liquid 102 is introduced through filler neck 44 into reservoir 42 , the buoyant property of material 57 of float 56 will cause it to rise , as best depicted in fig4 . a simulated plastic fuel tank 104 which is filled with water may be utilized to introduce liquid 102 through opening 46 of filler neck 44 into reservoir 42 . when a sufficient amount of water 102 is introduced into reservoir 42 , projection 58 will cause sufficient deformation of diaphragm 54 to press terminal 62a of contact leaf 62 against terminal 64a of contact leaf 64 . in order to insure proper electrical coupling , terminal 64a may include a conductive projection 65 which faces terminal 62a . when terminal 62a of contact leaf 62 is pressed against terminal 64a of contact leaf 64 as depicted in fig4 a closed circuit is defined between battery 72 and motor 30 and power is supplied to motor 30 thereby causing drive shaft 32 thereof to rotate . the rotation of drive shaft 32 will be transferred to front wheels 20 and 20a through gears 34 and 36 and front axle 22 thereby propelling the car in a forward direction . the proper polarity of battery 72 is selected so that motor 30 drives car 10 in a forward direction . diaphragm 54 serves two purposes . first , it normally biases projection 58 and hence float 56 away from terminal 62a of contact leaf 62 to provide normal spacing between contact leafs 62 and 64 . second , diaphragm 54 prevents liquid in reservoir 42 from wetting contact leafs 62 and 64 which could result in damage thereto or inadvertant closing of the circuit . exhaust tube 48 permits the escape of air as liquid 102 is introduced through filling spout 44 into reservoir 42 . metering pad 94 permits slow draining or filtering of liquid 102 from reservoir 42 into drain tank 90 . as the liquid slowly drains through opening 92 into drain tank 90 , the level of liquid in reservoir 42 will be decreased . eventually , projection 58 of float 56 will drop to a sufficient level so that terminal 62a moves out of contact with terminal 64a thereby opening the circuit and causing the car to stop running . this provides a simulation of an actual gas - powered vehicle which eventually runs out of gas . after several fillings of reservoir 42 and the subsequent draining into drain tank 90 , plug 98 may be removed to drain out water 102 . an opening 105 , best depicted in fig1 and 2 opens drain tank 90 to atmosphere so that as liquid 102 slowly drains into drain tank 90 , air can escape through opening 105 . an override on - off switch for the toy vehicle may be provided to prevent drainage of the battery when the toy vehicle is not being used . the float activated toy vehicle of the present invention provides a toy vehicle which simulates an actual gas - powered vehicle which substantially enhances the play value of the toy vehicle . the vehicle runs on a conventional 9 v battery although it is recognized that other types and sizes of batteries may be utilized . the toy vehicle is easy and inexpensive to manufacture and is safe for use by children since the preferred liquid of water is utilized . it will thus be seen that the objects set forth above , among those made apparent from the preceding description , are efficiently attained and , since certain changes may be made in the above construction without departing from the spirit and scope of the invention , it is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense . it is also to be understood that the following claims are intended to cover all the generic and specific features of the invention herein described and all statements of the scope of the invention which , as a matter of language , might be said to fall therebetween .

US-46374983-A

processes are described for making a cryopreserved composite living construct as well as a corresponding thawed and rinsed cclc , comprised of separated layers of cultured fibroblasts and cultured keratinocytes , wherein the percent of cells that are viable , i . e ., the cell viability , of such cclc is at least about 70 %. the viable cell density in the cclc is at least about 50 % of that before cryopreservation . the storage stability of the cclc is at least about 12 months . additionally , the metabolic activity of thawed and rinsed cclc is at least about 50 % of the composite living construct before cryopreservation . the structural integrity of cclc is substantially the same as the clc before cryopreservation . the process for making the cclc comprises the steps of : providing a collagen substrate comprised of a collagen sponge layer and a nonporous to cells , semipermeable collagen layer ; seeding and culturing , in the presence of a cell growth medium , fibroblasts on and within the collagen sponge layer and keratinocytes on the nonporous to cells , semipermeable collagen layer , thereby providing a clc ; equilibrating the clc , according to a defined equilibration program with a cryoprotectant solution comprising at least chondroitin sulfate and dimethylsulfoxide ; lowering the temperature , according to a programmed rate , to about − 90 ° c . ; and storing the cclc at about − 150 ° c . or lower . the process for preparing the cclc to treat wounds in humans and in animals additionally comprises programmed thawing as well as a rinsing sequence to substantially remove the cryoprotectants .

the process for making the preferred clc , which is to be cryopreserved by the methods of this invention , is herein briefly described with reference to a flow scheme of the process , fig1 . the process has been described in detail in u . s . pat . nos . 5 , 282 , 859 , re 35 , 399 and 6 , 039 , 859 , to eisenberg , which are entirely incorporated herein by reference . the process for making the clc as described more fully therein and used in this invention comprises : treating a skin sample enzymatically to separate epidermis from dermis ; treating the epidermis enzymatically , preferably with trypsin , to release the keratinocyte cells ; treating the dermis enzymatically , preferably with collagenase , to release the fibroblast cells . one surface of a crosslinked collagen sponge is coated with a layer of high purity nonporous - to - cells , semipermeable collagen , to form a layered collagen substrate ; seeding , i . e . inoculating , the porous , crosslinked collagen sponge with fibroblasts ; culturing , i . e ., incubating , the seeded collagen sponge in the presence of growth medium to allow growth of the fibroblast cells on and within the collagen sponge ; seeding the coated side of the collagen sponge with keratinocytes and culturing in presence of growth medium to yield a clc comprising a collagen matrix with fibroblasts and keratinocytes . various media are used in this invention for operations such as culturing the skin - derived fibroblasts and keratinocytes , seeding and culturing the fibroblasts and keratinocytes , respectively , onto the collagen sponge and the nonporous - to - cells , semipermeable layer of the collagen substrate , and for further culturing of the construct to the point at which it is ready for cryopreservation . such media comprise dulbecco &# 39 ; s modified eagle &# 39 ; s medium ( dmem ), well - known to those skilled in the art , and supplements such as growth factors and other nutrient components . the preferred growth medium for the culturing of the clc used in this invention , is “ complete dmem ” ( cdmem ) ( see solution a ) which contains , in addition to dmem , components such as fetal bovine serum , recombinant human epidermal growth factor , hydrocortisone , l - glutamine , cholera toxin , nonessential amino acids ( neaa ), hepes ( a buffer ) and glucose , preferably at a concentration of about 4 g / l . after use , the growth medium ( the conditional or spent medium ) is removed and fresh growth medium is added periodically during culturing . a preferred medium for rinsing at the end of culturing is dmem + 2 ( see solution b ), that is , dmem plus l - glutamine plus non - essential amino acids ( neaa ). the process for making the cclc of this invention comprises : equilibrating the clc according to an equilibration program with a cryoprotectant solution comprising at least chondroitin sulfate and dimethyl sulfoxide as previously noted ; lowering the temperature , according to a temperature lowering program , from about ambient temperature to at least about − 90 ° c . and storing at a temperature below about − 150 ° c . it should be noted that details given in the following discussion are meant to serve as examples of how , in general and in preferred modes , the various steps of the processes are carried out and to describe examples of products that result from such processes and are not meant to exclude alternative methods that may logically be used , and the products resulting therefrom , by those skilled in the art who might practice this invention . the following immediate discussion is given with reference to fig2 a flow scheme of the process for making the cclc of this invention . solution d secondary   cryo   solution primary   cryo   solution + 20  %   v / v   dmso the clc described above is rinsed with a protein - free dmem + 2 ( solution b ) to remove conditioned medium , agitated , and then incubated for a period of time , e . g ., about 30 minutes . the dmem + 2 in contact with the clc is then replaced with fresh dmem + 2 and agitated . this procedure is repeated , preferably at least about two more times . the clc is then incubated in dmem + 2 , preferably for less then eight hours , until it can be placed in a primary package preparatory to cryopreservation . the rinsed clc is removed from incubation and is placed in a liquid permeable tray between layers of medical grade nonadherent polyethylene net or medical grade gauze . the clc , in its support , is placed within a cryogenically compatible package , the package being fitted with fluid access and removal means . the first cryogenically compatible package , now containing the clc within the support , is sealed by means such as heat . two solutions are prepared in low bicarbonate dmem ( lb - dmem ) comprising dmem , folic acid , l - glutamine , sodium bicarbonate , naoh and hepes . the first solution ( solution c ) is the primary cryoprotectant solution comprising chondroitin sulfate at a basal concentration of about 2 . 5 % with a suitable range of about 2 - 3 %. the second cryoprotectant solution ( solution d ) comprising an approximately 4 : 1 mixture of the primary solution and dimethyl sulfoxide . the solutions are preferably prepared and then stored at temperatures below room temperature to help dissipate the heat of solution formed during the preparation . once prepared , the cryoprotectant solutions are preferably used at room temperature . the primary cryoprotectant solution is admitted through the fluid access means to the package , preferably by a pumping means , while the package is being agitated by means such as a shaking platform , to form an initial equilibrated clc . any non - contaminating pumping means may be used such as a peristaltic pump . the temperature of the primary cryoprotectant solution is introduced into the package at between 5 - 20 ° c ., preferably at room temperature . the secondary cryoprotectant solution ( solution d ) then is admitted through the fluid access means to the package with agitation , in a manner similar to that used for the primary cryoprotectant solution , to form the final equilibrated clc , said clc having a chondroitin sulfate concentration of about 2 . 5 % and dimethyl sulfoxide concentration of about 10 %. the secondary cryoprotectant solution admitted to the package is between about 5 - 20 ° c ., preferably at room temperature . residual air and excess cryoprotectant solution is withdrawn from the package by pumping means , preferably by a peristaltic pump . all fluid access means then are closed or otherwise sealed , e . g ., heat sealing and removed . the package containing the ceclc is sealed , e . g ., by thermal or ultrasonic means , and placed within a cryogenically compatible overwrap to provide a double - packaged clc which is then placed in a heat - conducting , e . g . metal , preferably aluminum , canister . the temperature of the double - packaged clc then is lowered preferably using the vapor phase of liquid nitrogen according to a temperature lowering program . the temperature lowering program may be implemented by means of microprocessor - controlled freezing chambers . a temperature probe is employed to monitor the temperature of the freezing chamber and a second probe monitors the surface of the clc . in practice , it is preferred to monitor the temperature in the ambient space around the clc with the vapor phase of the liquid nitrogen as opposed to the temperature of the clc itself . thus , the temperature recited in the freezing programs herein is that in the freezing chamber unless otherwise stated . the preferred temperature lowering program comprises the steps of : lowering the temperature from ambient temperature to about 4 ° c . ; lowering the temperature from about 4 ° c . to about − 20 ° c . at a rate of about 1 ° c ./ minute and holding the temperature at about − 20 ° c . for about 15 minutes ; lowering the temperature from about − 20 ° c . to about − 25 ° c . at a rate of about 0 . 5 ° c ./ minute and holding the temperature at about − 25 ° c . for about 15 minutes ; lowering the temperature from about − 25 ° c . to about − 70 ° c . at a rate of about 1 ° c ./ minute ; and lowering the temperature from about − 70 ° c . to about − 90 ° c . at a rate of about 5 ° c ./ minute . at this point , it is preferred to hold the temperature of the freezing chamber at about − 90 ° c . until the temperature at the clc surface is between about − 85 ° c . to − 90 ° c . the cclc is then stored below about − 150 ° c . and preferably at about − 170 ° c . to − 190 ° c . in the vapor phase of liquid nitrogen . fig3 depicts a flow scheme of the processes for thawing and rinsing the cclc of this invention . the process comprises two steps , the first of which is to allow the frozen cclc to warm up to about − 100 ° c . by allowing it to stand at room temperature . the second step involves thawing the frozen cclc to a temperature above freezing by warming it in room temperature saline or water and thereafter rinsing the cclc substantially free of cryoprotectants . in practice , the double - packaged cclc is removed from vapor phase liquid nitrogen storage in the metal canister and permitted to warm for about four minutes at about ambient temperature , to the first higher temperature usually about − 100 ° c . the double - packaged cclc is further warmed for about five minutes in about ambient temperature water or saline to the second higher temperature , which is in the range from about 4 ° c . to about ambient temperature . the cclc is removed from its outer package and transferred to the sterile or clean field . the cclc is then removed from the primary package while in its liquid permeable support , placed in normal saline at about ambient temperature , with agitation , for about ten minutes , thereby rinsing it to substantially remove the cryoprotectants . alternatively , the rinsing step may be performed in two or more steps by removing the saline rinse solution after five minutes or so of agitation and replacing it with fresh saline and repeating the agitation for another five minutes or less . the following in vitro assays are used to assess the immediate and long - term effects of cryopreservation , thawing and rinsing processes on cclc . the assays include cryoprotectant residuals , cell number , percent cell viability , metabolic activity , histologic examination and cytokine expression . samples for assaying cclc are taken using appropriately sized diameter biopsy punches selected randomly from the cclc device . biopsy punch samples taken from the clc or the cclc are enzymatically digested to release fibroblasts and keratinocytes from the collagen matrix . the percent cell viability and cell number are then determined by a hemocytometer using trypan blue dye exclusion to differentiate living from dead cells . metabolic activity is a measure of the overall physiologic state of viable cells . biopsy punch samples , taken from the clc or the cclc , are incubated with alamar blue dye . the assay measures mitochondrial activity using a non - cytotoxic alamar blue dye which diffuses into the cell mitochondria and undergoes a reduction - oxidation reaction to give a fluorescent product that is read by a fluorescent spectrophotometer . histology provides the following visual assessment of the structure and morphology of both the clc and cclc : 1 . presence and distribution of fibroblasts and keratinocytes within and on the matrix of the collagen substrate . 2 . morphology of the matrix itself , such as the effects of cryopreservation or thawing on the attachment and distribution of keratinocyte cells on the nonporous - to - cells , semipermeable collagen layer , the attachment and distribution of fibroblast cells on and within the collagen sponge layer and 3 . the structural integrity and morphology of the cclc scaffold . the expression of cytokines is a measure of the potential of cclc to stimulate wound healing and tissue regeneration . cytokine expression data is obtained by analyzing spent culture media of the clc prior to cryopreservation and after thawing , rinsing and incubation for about 48 hours in cdmgm - hg . the spent media are assayed for cytokines using appropriate available elisa kits . fig4 a ) and 4 b ) are pictorial representations of cross - sectional histological views of the clc 10 used in this invention before cryopreservation and cclc 100 obtained from clc 10 after cryopreservation . the two pictures show regions of reference before and after cryopreservation according to the invention . the clc of fig4 a ), beginning from the top of the figure has a nonporous - to - cells , semipermeable collagen layer 14 having normal human keratinocytes 12 on the semipermeable collagen layer 14 , a collagen sponge layer 16 in which spaces 20 are open air spaces of the sponge layer some of which contain normal human fibroblasts 18 within the spaces 20 . boundary lines 22 are the collagen structure of the collagen sponge layer 16 while the thinner boundary lines 24 surround thicker areas of the collagen structure . cclc 100 ( fig4 b ) after cryopreservation has the same sequence of layers and cells top to bottom as is shown in fig4 a ). in all instances the comparison between the various components of the clc and the cclc ( i . e ., before and after cryopreservation ) shows that there is little or no difference in morphologies of the collagen sponge layer 16 and the semipermeable collagen layer 14 , the keratinocytes 12 and the presence and distribution of fibroblasts 18 within the matrix of the collagen sponge 16 , attachment and distribution of keratinocytes 12 on the nonporous - to - cells , semipermeable layer of collagen 14 , and the structural integrity of the boundaries 22 and 24 of the cclc 100 and clc 10 . the following procedure was conducted under aseptic and , unless otherwise noted , ambient conditions : clcs measuring approximately 6 cm × 6 cm × 2 - 3 mm , were produced as described in the eisenberg u . s . pat . nos . 6 , 039 , 760 , 5 , 282 , 859 , and reissue no . 35 , 399 with the following exceptions : a high glucose culture medium containing about 4 g / l glucose ( instead of 1 g / l ) was used with a feeding schedule for exchanging spent medium with fresh medium of every 2 - 3 days for up to 11 - 13 days as desired instead of the 14 days described in the patents . during the last 3 days of culture ( maturation period ), spent medium samples were collected and frozen in aliquots and held for testing for expression of various cytokines using commercially available elisa assays . on one of the last three days of culturing , the clcs were rinsed in protein - free , serum - free medium and all but one subjected to the cryopreservation step below . the one saved unit was tested for cell number and viability , metabolic activity , and histology testing to be compared with the same parameters for the cclcs prepared below . each rinsed clc was placed in a liquid permeable tray between two opposing sheets of non - adherent medical grade gauze in such a way that the 6 × 6 cm surfaces of the clc were accessible for subsequent treatment by a cryoprotectant solution . the tray was then placed into and heat - sealed within a cryogenic bag having luer lock connectors . the cryogenic bags were then connected to a peristaltic pump via the luerlock connectors and the pump operated to withdraw air from the bags . a primary cryoprotectant solution of 75 cc volume ( solution c ) at or below room temperature containing 2 . 5 % chondroitin sulfate was then introduced using the pump as the bags were continuously agitated . after 9 - 11 minutes of equilibration at room temperature with cyroprotectant solution c under agitation , 75 cc of a secondary cryoprotectant solution ( solution d ) containing 20 % dmso and 2 . 5 % chondroitin sulfate at or below room temperature was introduced using the pump with constant agitation . after a total of 12 - 13 minutes , the pump was reversed , first to withdraw any excess air and then to withdraw 100 cc of solution . the solution introduction ports then were heat - sealed and excess tubing trimmed . each sealed package was then placed into a separate cryogenic overwrap package which then was vacuum heat - sealed . the double - packaged units were then placed into aluminum canisters and placed into a microprocessor - controlled rate freezing chamber . the units were frozen under a microprocessor controlled schedule using the vapor phase of liquid nitrogen and then stored in the vapor phase of liquid nitrogen at below − 150 ° c . until ready for use . the temperature lowering program comprised the steps of : lowering the chamber temperature from ambient temperature to about 4 ° c . ; lowering the chamber temperature from about 4 ° c . to about − 20 ° c ., at a rate of about 1 ° c ./ minute and holding the chamber temperature at about − 20 ° c . for about 15 minutes ; lowering the chamber temperature from about − 20 ° c . to about − 25 ° c ., at a rate of about 0 . 5 ° c ./ minute and holding the chamber temperature at about − 25 ° c . for about 15 minutes ; lowering the chamber temperature from about − 25 ° c . to about − 70 ° c . at a rate of about 1 ° c ./ minute ; lowering the chamber temperature from about − 70 ° c . to about − 90 ° c . at a rate of about 5 ° c ./ minute ; holding the clc in the freezing chamber until the surface of the clc reached − 85 ° c . to − 90 ° c . ; and storing the cclc below about − 150 ° c . the cryopreserved ( cclc ) units prepared above are suitable for either patient grafting or other studies after subjecting thereto the following procedures . first , the cclc is warmed at room temperature for about four minutes . at the end of the warming time , the overwrapped packaged cclc is placed into 4 liters of room temperature sterile water ( or sterile saline ) bath for thawing in the second stage for about five to seven minutes with periodic manual agitation . the overwrap is cut open , the inner package removed and cut open , and the tray containing the cclc removed . the cclc in the tray is rinsed to remove the cryoprotectant solution by placing it into 3 liters of sterile saline , and agitating for about ten minutes , or alternatively , for five minutes after which the saline is removed and replaced with another 3 liters of saline and agitating for another five minutes . at the end of that time , the cclc can be removed from the tray and applied onto a patient or used for in vitro studies . for in vitro studies , the cclc can be placed back into the high glucose culture medium and incubated and assayed for cytokine expression using commercially available elisa kits . the cclc can also be used immediately for testing , as was done in the pre - cryopreservation step , that is , tested for cell number , viability , metabolic activity , and histology , and testing for comparison with the pre - cryopreservation material . an in vivo grafting study was performed to compare the healing characteristics of full - thickness skin wounds in severe combined immuno - deficient ( scid ) mice grafted with the cclc of example 1 compared to a fresh clc prepared according to the eisenberg u . s . patents referred to in example 1 and used without being subjected to cryopreservation and / or freezing . the study was conducted as two trials of twelve animals each , which were initiated approximately 24 hours apart . a full - thickness wound ( 1 . 7 cm in diameter ) was created using surgical scissors on the dorsum of each mouse just prior to applying a clc or cclc graft of the same size and shape into the wound . six mice in each trial received fresh clc grafts and six mice received cclc grafts . samples of clc and cclc from each of the four groups were assayed in vitro for cell yield , cell viability , and the ability to secrete several wound - healing associated cytokines and growth factors . following placement of the grafts , the wounds were covered with one layer of polyethylene net , then with two layers of paraffin gauze and three circuits of dressing around the trunk of each mouse to secure the grafts . mice were observed and weighed daily . bandages were removed and wounds were examined and photographed macroscopically 8 and 14 days after grafting . the degree of wound contraction was calculated on day 8 and 14 . on day 14 , the mice were sacrificed and the wounds were excised for histological preparation and evaluation . all biopsy samples were placed in fixative , sectioned at 8 um and stained with hematoxylin and eosin , and / or trichrome and / or orcein and methylene blue . the extent of epithelialization , the average dermal and epidermal thickness and the cellularity of the dermis were calculated . other histological features were noted as comments . no significant adverse effects were observed during the course of this study . by day 14 , most of the grafts were not apparent due to the healing processes and resorption of the collagen matrix of the clc and ccls . the fresh clc and cclc grafts produced similar results with respect to macroscopic wound appearance and contraction . microscopically , no significant differences were noted in the healing properties of wounds treated with fresh clc or cclc grafts . by day 14 , 8 / 12 and 7 / 12 of the wounds in the fresh clc and cclc groups , respectively , had undergone complete epithelialization . no difference in epithelialization was observed between fresh clc and cclc grafts and it was concluded , from the results of this study , that cclc grafts of the invention and fresh clc were not substantially different and had similar effects on wound healing parameters when compared in a full - thickness would healing model in scid mice .

US-3292901-A

playthings , such as exercise and entertainment hoops , children &# 39 ; s bats , batons and jump ropes , are provided with an elongated sheath of fabric tightly adhering thereto , the fabric sheath being available in a variety of decorative patterns at a low cost . this enables the base product to be mass produced in an inexpensive way in accordance with conventional practice , but then to provide such products with individualized appearance with the fabric covering .

fig1 shows what is known as a soft bat 10 intended for very young children . as is conventional , it has a hollow plastic handle 12 to which is attached in a suitable and known manner a soft foam ( e . g . polyurethane rubber ) &# 34 ; hitting &# 34 ; portion 14 of larger than normal diameter . all this is conventional . in accordance with the present invention , there is provided a sock - like fabric covering 16 which covers the entire &# 34 ; hitting &# 34 ; portion 14 . the fabric &# 34 ; sock &# 34 ; 16 is desirably closed at the free end 18 and is tucked - in and sealed in a suitable manner such as by the use of adhesive , or even mechanical means such as staples or thread , at the juncture 20 between the handle 12 and the hitting portion 14 . it is a key aspect of the present invention that the &# 34 ; sock &# 34 ; 16 can be simply , easily and inexpensively woven or knitted in a wide variety of patterns and colors , and thereby provides the bat 10 with a very wide range of appearances in an exceedingly inexpensive manner . the sock 16 is of course woven or knitted in the approximately correct size and is then stretched to fit tightly and snugly over the foam core 14 so as to conform to the configuration of the core 14 . while the main advantage is , as pointed out above , the provision of an easily and inexpensively changed decorative pattern so that all the soft bats 10 do not have the same appearance , there are secondary advantages as well . thus , the foam core 14 is protected and is not so easily subjected to shredding and tearing . in addition , the fabric 16 provides a certain degree of roughness , and thereby makes good contact between the bat 10 and any ball hit by it . fig4 - 6 show another embodiment of a bat , also inexpensively formed of plastic , intended for use by a child somewhat older than the child who would use the soft bat of fig1 - 3 . the bat 40 of fig4 - 6 comprises a generally unitary hollow shell 42 formed of relatively rigid plastic , such as a polyolefin or pvc or the like . the shell 42 in turn is provided with a gripping sheath 44 which defines the handle portion , the sheath being formed of an elastomer , e . g . rubber or an elastomeric plastic , as is conventional . in accordance with the present invention , the hollow shell 42 may desirably be filled with a flexible or rigid foam 48 for structural support , density and weight . the bat 40 is covered with a fabric stretch sock 46 of the character of the sock 16 described above , the sock 46 being slipped over the plastic shell 42 and stretched to conform to the exterior of the shell 42 , and then being closed at one end , e . g . the handle end , such as by sewing to fix it to teh bat 40 . the handle sheath 44 is then applied over the stretch fabric sock 46 . the baton 70 of fig7 - 9 is formed of a rigid cylinder 72 , such as one formed of pvc or acrylic plastic or the like , and has two end caps 74 as is conventional . in accordance with the present invention , either a cylindrical sheath of decorative fabric 76 open at both ends or a similar sock closed at one end is stretched tightly over the rigid cylinder 72 with one or both ends being tucked within the cylinder 72 , after which the end caps 74 are applied to frictionally hold the decorative stretch fabric cover 76 in place . fig1 - 12 show a jump rope 100 with a &# 34 ; rope &# 34 ; section 102 , here shown in the form of a flexible plastic tube , and handles 104 at both ends thereof , as is conventional . in accordance with the present invention , the rope portion 102 is covered with a tube or sheath 106 of stretch fabric of the same character as those described above . after being applied over the rope portion 102 , the stretch fabric tube 106 is stretched tight to conform to the exterior of the &# 34 ; rope &# 34 ; 102 , and is sealed at the ends 108 . fig1 - 15 show an exercise and entertainment hoop 130 . the hoop 130 is formed of a semi - rigid plastic such as a polyolefin as is well known . such hoops are conventionally made by bending plastic tubing 132 into a circular form and then bringing the two free ends together and closing same by suitable means well known in the art . in accordance with the present invention , a sock or tube 136 is placed over the bent tube 132 before its ends are joined , and the fabric sheath 136 is stretched tight and its free ends 137 are tucked into the open ends of the tube 132 . a plug 138 , such as one formed of wood or plastic or rubber , is then forced into the two open ends of the tube 132 so as to frictionally hold together the two ends of the tube 132 as well as to fix the decorative , stretched fabric sheath 136 . to insure tightness of the joint , staples may be applied from the outside . the decorative stretch fabric sheath not only has its main function as described above , namely the provision of a great variety of patterns at a very low cost so as to be able to provide a plaything 130 which is still inexpensive but which is variable in appearance , but the roughness of the fabric also improves the ease with which the hoop 130 can be rotated about the user &# 39 ; s body , the fabric providing an enhanced degree of friction between the hoop and the clothing of the user . the foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can , by applying current knowledge , readily modify and / or adapt for various applications such specific embodiments without departing from the generic concept , and , therefore , such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments . it is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation .

US-17566893-A

a fluid pressure generating means for a heart assist device having blood pumping means . the pressure generating means includes a housing , defining an interior volume , and having a substantially rigid first housing portion , a substantially rigid second housing portion , a flexible third housing portion extending between the first and second housing portions and an inlet / outlet port adapted for fluid communication with the blood pumping means . the pressure generating means also includes a fluid filling the housing and a motor disposed within the housing and connected between the first and second housing portions . actuation of the motor moves the first and second housing portions relative to one another to generate fluid pressure changes at the inlet / outlet port . a related heart assist device and method for the treatment of congestive heart failure , myocardial ischemia and like conditions are also disclosed .

referring firstly to fig1 , there is shown a schematic longitudinal sectional view of a first embodiment of a fluid pressure generating means according to the invention , in the form of pump 10 . the pump 10 includes a housing , indicated generally by the reference numeral 11 , comprising a substantially rigid bell - shaped first housing portion 12 , a substantially rigid flat circular second housing portion 14 and a flexible third housing portion or membrane 16 . the first , second and third housing portions 12 , 14 and 16 together define an external boundary of the housing 11 around an interior volume denoted 18 , which is filled with a silicone oil . the second housing portion 12 itself formed from a cone - shaped portion 12 a which is sealingly connected , after assembly of the pump 10 , to a cylindrical portion 12 b . the cone - shaped portion 12 a also includes an inlet / outlet port 15 , which is connected in fluid communication with an aortic compression means or blood pumping means ( not shown ) by a conduit 17 . the membrane 16 is substantially annular in configuration and has enlarged inner and outer edges 16 a and 16 b which are sealingly received in corresponding circumferential recesses 12 c and 14 a provided in the first and second housing portions 12 and 14 respectively . the pump 10 also includes an electric motor , indicated generally by the reference numeral 20 , within the interior volume 18 of the housing 11 . the motor includes a rotor 21 , rotor laminations 22 , magnets 24 , stator 25 , stator laminations 26 , end windings 28 and bearings 30 . the stator 25 is fixed to the housing portion 12 a by a number of screws 30 ( only one shown ). the rotor 21 is fixed to a nut 32 , which is itself threadedly engaged with a threaded shaft 34 through ball bearings ( not shown ). the shaft 34 is fixed to the housing portion 14 by screw 36 . the stator 25 also includes a number of guide journals 38 ( only one shown ) through which are guided a corresponding number of shafts 40 that depend from the housing portion 14 . power and control signals are fed to the motor 20 through lines 42 and 44 respectively . the operation of the pump 10 will now be described . energising the motor 20 to rotate in a first direction rotates the nut 32 relative to the threaded shaft 34 which causes the threaded shaft 34 to move in a direction parallel to its longitudinal axis in a first direction indicated by arrow 46 . fig1 shows the shaft 34 at the end of its travel in this direction and after driving the housing portion 14 away from the housing portion 12 to increase the interior volume 18 and cause a suction or negative pressure at the inlet / outlet port 15 . this suction actively deflates the aortic compression means ( not shown ). energising the motor to rotate in the opposite direction causes the threaded shaft 34 to move parallel to the longitudinal axis in the opposite direction indicated by arrow 48 and draw the portion 14 towards the housing portion 12 . the end limit of travel in this direction is indicated in phantom in fig1 and , with reference to which it should be noted that , the guide shaft 40 abuts the inner surface of the housing portion 12 a at the limit of its travel at recess 50 . drawing the flexible portion 14 towards the housing portion 12 reduces the interior volume 18 which causes a positive pressure at the inlet / outlet port 15 and drives fluid from the interior volume 18 to inflate the aortic compression means . the motor 20 is actuated cyclicly in this manner in counterpulsation with the patient &# 39 ; s heart in response to signals received from an ecg monitor or systemic arterial pressure , as disclosed in the pct application . referring now to fig2 , there is shown a schematic longitudinal sectional view of a second embodiment of a fluid pressure generating means according to the invention , in the form of pump 60 . the pump 60 is similar to the pump 10 shown in fig1 and like features are indicated with like reference numerals . differences between the pumps 10 and 60 are described in detail below . firstly , the housing portion 12 a of the pump 60 includes an opening 62 sealed by a second flexible membrane 64 which forms a compliance chamber 65 . the chamber 65 is in fluid communication with the interior volume 18 . secondly , the inlet / outlet port 15 is provided in a further housing portion 66 which is sealed with respect to the side of the second housing portions 14 and third housing portion 16 that is remote the motor 20 . the housing portion 66 creates , in conjunction with the housing portions 14 and 16 , a second interior volume 68 in fluid communication with the aortic compression means or blood pumping means ( not shown ) via conduit 17 . the operation of the pump 60 is similar to that as described with reference to the pump 10 with the exception that the movement of the housing portion 14 causes volume changes in the second interior volume 68 which in turn inflates and deflates the aortic compression means . the movement of the housing portion 14 also causes fluid movement in the part of the interior volume 18 within the first , second and third housing portions 12 , 14 and 16 and these changes cause an identical volume change in the interior of the compliance chamber 65 , which is shown having a decreased volume in response to the compression means being inflated . the chamber 65 will have an increased volume in response to the compression means being deflated , as is shown in phantom . as the interior volumes 18 and 68 are maintained sealed from one another by the second and third housing portions 14 and 16 , the pump 60 can be configured to use different fluids in each of the interior volumes 18 and 60 , as desired . for example , a saline solution can be used in the interior volume 68 and a lubricating oil can be used in the interior volume 18 which contains the motor 20 . fig3 is a schematic cross sectional side view of a third embodiment of a fluid pressure generating means according to the invention , in the form of pump 80 . the pump 80 is shown connected to an aortic compression means or blood pumping means in the form of cuff 82 . the pump 80 is similar to the pump 60 described in relation to fig2 and like reference numerals will be used to indicate like features . differences between the pumps 60 and 80 are described in detail below . firstly , the pump 80 has a first external substantially rigid cylindrical housing portion 84 , a pair of second internal substantially rigid housing portions 86 a and 86 b and a third substantially flexible housing portion 88 . the latter seals an end of the first housing portion 84 . the pump 80 also includes a second flexible housing portion 90 which seals the other end of the second housing portion 84 and forms a compliance chamber 92 . secondly , the second housing portion 86 and the third flexible housing portion 88 abut , but are not connected , to each other . the operation of the pump 80 is similar to that described with reference to pump 60 in that the motor 20 is energised to reciprocally drive the threaded shaft 34 and thus the second housing portion 86 a in directions 46 and 48 parallel to the longitudinal axis of the threaded shaft 34 . fig3 shows the pump 80 in a position after movement of the second housing portion 86 a in the direction 46 and driving fluid from the second interior volume 68 into the cuff 82 to inflate same . in this position , the second membrane of 64 is drawn into the interior of the second housing portion 84 to maintain the interior volume 18 constant . driving the threaded shaft 34 in the opposite direction 48 results in the housing portion 86 b forcing the membrane 64 to the position shown in phantom which is external the second housing portion 84 . this also results in the third housing portion 88 being drawn to the position also shown in phantom to maintain the interior volume 18 constant . as previously described in relation to pump 60 , when the third housing portion 86 is in this position fluid is drawn into the second interior volume 68 from the cuff 82 to deflate same . fig4 a to 4c show a fourth embodiment of a fluid pressure generating means according to the invention , in the form of pump 100 . the pump 100 is similar to the pump 10 shown in fig1 and like components have been referred to with like reference numerals . however , the pump 100 has been designed to be as thin as possible ( dimensions : 82 mm long ; 60 mm wide ; and 45 mm deep ) in order to allow positioning in a patient &# 39 ; s chest in contact with the mediastinum adjacent the heart . the pump 100 is placed with the planar housing portion 14 lying in a sagittal plane and as with the edge of the housing 100 clear of the inside surface of the chest wall . this orientation is chosen so as to minimise pain and trauma to the patient and also minimise the length of conduit required between the pump 100 and the aortic compression means ( not shown ). this positioning also assists the surgeon in placing the device . referring finally to fig5 to 7 , there is shown a schematic longitudinal sectional view of a fifth embodiment of a fluid pressure generating means according to the invention in the form of pump 120 . the pump 120 is shown connected to an aortic compression means or blood pumping means in the form of cuff 122 . the construction and operation of the pump 120 is similar to die pump 10 shown in fig1 and like features are indicated with like reference numerals . the size of the pump 120 is similar to the pump 100 shown in fig4 a to 4c , except it is more ovate and has flattened sides ( see fig6 ). the ovate form of the pump 120 and the positioning of the cuff 122 nearer one end allows the device to be placed in the plural cavity , medial to the lung , and lying in a sagittal plane within the patient &# 39 ; s body , as is shown in fig7 . the pump 120 does not touch the inside surface of the patient &# 39 ; s chest wall in this position . fig7 also shows an external battery pack 123 which powers the pump 120 . the main differences between the pumps 10 and 120 are as follows . firstly , the flexible third housing portion 16 is sealingly connected about its outer edge 16 b to the substantially rigid ovate cup - shaped first housing portion 12 . the connection and sealing is achieved by a sealing rim 124 on the third portion 16 being snugly received in an annular recess 126 on the first portion 12 . secondly , the substantially rigid flat ovate second housing portion 14 is received within a corresponding recess in the third portion 16 , on the interior side of the third portion 16 , and is thus within the interior volume 18 . fig5 shows the pump 120 in a position after movement of the second housing portion 14 in the direction 46 , which draws fluid into the interior volume 18 from the cuff 122 and deflates same . driving the threaded shaft 34 in the opposite direction 48 forces the second housing portion 14 towards the motor 20 ( see the position of the shaft 34 shown in phantom ). as previously described , when this occurs , fluid is forced from the interior volume 18 into the cuff 82 to inflate same . an advantage of the preferred embodiments of fluid pressure generating means described above is the liquid surrounding the motor is used both as a driving fluid to inflate / deflate the compressions ( either directly as per the embodiments of fig1 and 4 or indirectly as per the embodiments of fig2 and 3 ) and as a cooling / lubricating / heat exchanging fluid . the liquid also dampens sound made by the pump mechanism . this simplifies the construction , and minimises the size , of the fluid pressure generating means . whilst the fluid pressure generating means will normally actively drive both the inflation and deflation of the aortic compression means , the motor is preferably designed so that the cogging torque of the motor is sufficiently low that the natural systolic blood pressure of the patient is sufficient to deflate the cuff . if the motor is inactivated for any reason with the cuff in an inflated condition ( and thus with the aorta partially occluded ), this arrangement means that the natural systolic blood pressure will deflate the cuff by pushing fluid from the cuff into the housing and passively driving the second housing portion away from the motor . it will be appreciated by person skilled in the art that numerous variations and / or modifications can be made to the invention as shown in the specific embodiments without departing from the spirit or scope of invention as broadly described . for example , the embodiments of the invention are not restricted for use with the embodiments of the heart assist device shown in the pct application . the specific embodiments are , therefore , to be considered in all respects as illustrative and not restrictive .

US-38078903-A

a dispenser of boxed articles for retail shops , comprising a plurality of plates , each having a number of vertical , parallel slits , are arranged side by side and are spaced by assembly means ; rigid boards inserted through the vertical slits to define rectangular wells for holding the boxed articles in a stacked arrangement ; and rest ledges arranged at staggered heights below each well , in order to prevent the articles held in the wells from dropping out , while allowing them to be horizontally withdrawn at the bottom one at a time .

with particular reference to fig1 and 2 , the dispenser according to the first preferred embodiment is assembled essentially from a plurality of identical profiled plates such as 10 , which are one of the most peculiar features of the invention . each plate 10 is of metal sheet or other rigid sheet material , which is cut or punched in the shape shown in fig2 , i . e . having a roughly four - sided profile , with three straight sides 12 , 14 , 16 at right angles , and a fourth inclined side , shaped as a sequence of four steps 18 . the four corners of each plate 10 are shaped into respective tabs 20 in which respective holes 22 are made . several plates 10 are arranged side by side , parallel to each other , by rigid tension rods 24 threading the respective holes 22 in corresponding tabs 20 in each plate . between adjacent plates , sleeves 26 borne on the rods act as spacers to maintain a fixed mutual spacing between the plates . clamping nuts 28 are screwed onto the opposite ends of each rod 24 in order to maintain the structure of the dispenser rigidly assembled . each plate 10 is cut with five pairs of aligned vertical slits 30 , 32 , ending at staggered heights at the bottom , substantially aligned with steps 18 . rigid sheets or boards 34 , 36 , of a material such as pvc , are threaded through vertical slits 30 , 32 , which boards , together with adjacent plates 10 , define vertical bays or wells having a rectangular transverse cross section , and arranged in four ranks over the plate width . each plate 10 also has four horizontal slits 38 , which are located near respective steps 18 ( and therefore at staggered heights ). rigid slats 40 are inserted through the horizontal slits , thereby acting as rest ledges for each well , as explained below . it should be understood the pairs of vertical slits 30 , 32 are actually equivalent to respective single slits of equal overall length , in which respective vertical boards of corresponding height are received , and that their splitting into pairs of aligned slits is essentially due to the need of ensuring the structural strength of the plate . similarly , triplets or quadruplets of aligned slits might be used . in the disclosure and the claims , the expression “ vertical slit ” denotes an arbitrary number of aligned slits , which together make it possible , by insertion of boards , to implement partitions that are substantially equivalent to a continuous wall . on opposite sides of the structure two panels 42 are attached , fastened with screws 44 to the ends of the tension rods 24 , which panels retain boards 34 , 36 and slats 40 , preventing them from sliding off the slits . for installation in the appointed place , typically above a sales counter , the above described dispenser can be mounted on supports formed as uprights rising from below , or as supports hanging from the ceiling . for instance , in the solution of fig3 and 4 , two tubular members 50 are affixed to the ceiling by fastening flanges 52 , so that they extend downwardly , and they respectively receive staves 54 which can be adjusted at a desired height by screws 56 engaging in holes 58 made in the staves 54 . respective beams 60 are integral with staves 54 , which are provided with respective saddles 62 at their opposite ends . the ends of the upper assembly rods of the dispenser are removably hooked on said saddles . in the vertical wells defined by the crossings of plates 10 with vertical boards 34 , 36 , stacks of superposed boxes or packets can be received . with reference to fig5 , stacks of boxes such as 46 rest on horizontal slats 40 , which , due to their staggered heights , allow the boxes to be withdrawn horizontally one at a time . it can be seen that the shopkeeper at the counter can quickly pick the required packet , without having to move or turn . when one of the wells is empty , it can be easily reloaded from above with a fresh complete stack of boxes , by stepping on a footstool or ladder , or , alternatively , the boxes can be re - inserted one at a time from the bottom , during idle moments . although the drawings show uniformly spaced plates ( i . e ., uniformly sized sleeves 26 ) as well as uniformly spaced slits in each plate , it will be evident that there is no impediment that sleeves 26 may have different lengths , so that narrower and wider intervals are created between the plates , or that the distance between vertical slits 32 , 34 may be different for one or more pairs of slits ( for instance , an oversized distance may be chosen between the two slits at the back ), provided it is identical for all plates . the dispenser can thereby be adapted to boxes having different , desired widths and lengths , within wide limits . obviously , it is also possible to make the plates with a different number of vertical slits , say larger than four , in order distribute the wells over a larger number of ranks , or , vice verse , smaller than four , in case of special needs in connection with the sizes of the articles or the availability of space . fig6 shows an alternative version of a plate that can be used to obtain a dispenser according to the invention . plate 10 ′ has , again , a four - sided profile similar to plate 10 of fig3 , including steps 18 ′, bored tabs 20 ′ and vertical slits 30 ′, 32 ′, but has no horizontal slits ; in lieu of those , plate 10 ′ has fins 70 which are cut integral with the plate sheet at each step , and bent at right angles . plates 10 ′ are assembled identically as the plates 10 of fig3 , but do not require the horizontal slats 40 of fig1 to 5 , the latter being replaced by right - angled fins 70 , which act as equivalent rest ledges . the manufacture of the dispenser only involves materials that are cheaply available on the market , such as metal plate , metal rods , etc ., and which are processed by simple and inexpensive mechanical operations : with the exception of plate 10 , which requires a simple die or punch , the other operations are simply cutting and boring ; the overall cost of the dispenser is therefore considerably lower than similar dispenser of the prior art . it is also evident that the bulk of the unassembled dispenser is also quite limited , with consequent reduction of the costs of transport . it is understood that changes and modifications can be made to the preferred embodiments as described above . for instance , beside changing the number of vertical slits as disclosed above , the number of box - holding wells could be reduced to three or increased to five or more , by broadening the plates and increasing the number of vertical and horizontal slits . also , the assembly of the plates might be achieved , rather than by rods and sleeves , by means of other known assembly means which are capable of ensuring the proper mutual positioning of the plates . furthermore , although the above disclosed supporting means for the dispenser are preferred at this time , obviously the dispenser could be supported by any other known means that may be convenient , depending on the environment in which the dispenser is to be installed . the scope of the invention should therefore be determined exclusively from the attached claims . the disclosures in italian patent application no . to2009a000587 from which this application claims priority are incorporated herein by reference .

US-80531110-A

a medical device for processing physiological signals such as electrocardiograms . the processing includes : sampling a physiologic signal in a first channel with a first sampling rate , simultaneously sampling the physiologic signal in a second channel with a higher sampling rate to thus generate pairs of sampling values , forming the difference between two sampling values of each pair , comparing said difference with a threshold , and generating a noise detection indicator whenever said threshold is exceeded .

the following description is of the best mode presently contemplated for carrying out the invention . this description is not to be taken in a limiting sense , but is made merely for the purpose of describing the general principles of the invention . the scope of the invention should be determined with reference to the claims . fig1 shows an implantable medical device 10 connected to electrode leads 14 and 16 having electrodes placed in a heart . as will be more apparent from the following description of the implantable medical device 10 , the implantable medical device 10 is capable of making up intracardiac electrograms that represent electrical activity of the myocardium of either a right atrium or a right ventricle of a heart . according to further embodiments not represented in detail within this disclosure , the implantable medical device could also be capable of picking up intracardiac electrograms from the left atrium and / or or the left ventricle . further , the implantable medical device can be made capable of creating a far field electrogram signal from intracardiac electrogram signals picked up via electrodes located at the implantable medical device 10 . in order to be capable to pick up electric potentials of the myocardium , the implantable medical device 10 ( dual chamber pacemaker 10 ) of fig1 is connected to electrode leads 14 and 16 , comprising stimulation and sensing electrodes 18 and 20 and 22 and 24 , respectively . electrodes 18 and 20 are placed in the right atrium 26 of the heart whereas electrodes 22 and 24 are placed in the right ventricle 28 of the art . fig2 shows the schematic block diagram of the implantable medical device 10 . atrial electrode lead 14 is connected to an atrial stimulation unit 60 and an atrial sensing unit 62 . ventricular electrode lead 16 is connected to a ventricular stimulation unit 64 and a ventricular sensing unit 66 . both the atrial stimulation unit 60 and the ventricular stimulation unit 64 are adapted to generate atrial or ventricular stimulation pulses , respectively , for stimulation of the respective heart chamber . the atrial sensing unit 62 and the ventricular sensing unit 66 are adapted to process electric potentials picked up via a pair of atrial electrodes 18 and 20 or the pair of ventricular electrodes 22 and 24 , respectively . atrial electrode 18 and atrial electrode 20 is a right atrial ventricular electrode . similarly , ventricular electrode 22 is a right ventricular tip electrode and electrode 24 is a right ventricular ring electrode . atrial stimulation unit 60 , atrial sensing unit 62 , ventricular stimulation unit 64 and ventricular sensing unit 66 are connected to a control unit 70 of the implantable medical device 10 . control unit 70 is further connected to an activity sensor 72 which , for example , can be an accelerometer . further , control unit 70 is connected to a timer 78 providing a time signal . control unit 70 is also connected to a memory 74 that can serve for storing data , such as data representing electrograms or programs controlling control unit 70 . finally , control unit 70 is connected to a telemetry unit 76 that is adapted to allow wireless data communication between implantable medical device 10 and the external device 30 ( see fig1 ). the ventricular sensing unit 66 features two processing channels 66 . 1 and 66 . 2 . the first processing channel comprises sampling stage 80 that is adapted to sample a picked up myocardial electric signal at a fixed sampling rate that has been determined from the frequency content of the cardiac signal , e . g . 256 hz . the first processing channel is further adapted to process picked - up electric potentials , so as to generate an electrogram signal in a conventional manner . this signal is fed to control unit 70 . the second processing channel comprises a high frequency sampling stage 82 for sampling the picked - up myocardial electric signals with a second sampling rate , e . g . 4 - 30 khz , that is higher than the first sampling rate . in particular , for each sampled myocardial electric signal value sampled by the first channel , a pair of sampled myocardial electric signal values are sampled by the high frequency sampling stage with an interval of 30 - 240 microseconds , corresponding to a sampling rate of 4 - 30 khz . the second channel further comprises a differential stage 84 connected to the high frequency sampling stage and being adapted to generate a high frequency sampling output signal , representing the difference between the two values of each pair of sampled myocardial electric signal values . a comparator 86 is connected to the differential stage and is adapted to compare the high frequency sampled signal with a threshold and to generate a noise detection indicator whenever the threshold is exceeded . this signal is fed to control unit 70 in addition to the output signal of the first channel representing an ecg . it should be appreciated that no continuous sampling of the picked - up myocardial electric signal by the high frequency sampling stage 82 is required for performing the invention . it is sufficient if the high frequency sampling stage 82 generates a pair of high frequency sampled signal values . control unit 70 provides a timer ( not shown ) that is started whenever control unit 70 receives a noise detection indicator from the second channel 66 . 2 of ventricular sensing unit 66 . the timer times a noise detection period . during such noise detection period , the ecg signal received from the first channel 66 . 1 of ventricular sensing unit 66 is considered to be affected by noise and , thus , treated differently by control 70 than an ecg signal considered being free of noise . the timer and further means for evaluating the ecg signal could also be part of ventricular sensing unit 66 instead of control unit 70 . thus the ventricular sensing unit 66 itself would be capable to generate marker signals for each detected ventricular event based on a comparison of the noise - free portions of the ecg signal with a detection threshold . portions of the ecg signal falling into a noise detection period would be excluded from event detection . the implantable medical device 10 is a hermetically sealed electronic device that can be implanted under the patient &# 39 ; s skin to act as a subcutaneous ecg monitor . the ecg is detected using a pair of sensing electrodes , e . g . electrodes 22 and 24 , which — in the disclosed example — are intracardiac electrodes . the invention , however , is also applicable to heart monitoring implants that do require electrode leads and that has electrodes , which have no direct contact to the myocardium . in such devices the invention would be particularly beneficial since it allows reliable processing of signals having a low amplitude in environment exhibiting high noise levels . the latter is usually not the case in intracardiac signals . the picked up myocardial electric signal is fed to the first channel 66 . 1 and the second channel 66 . 2 of the ventricular sensing stage 66 simultaneously . in the second channel , measurements are made from the same pair of electrodes but with a different electronic circuit ( including sampling stage 82 , differential stage 84 and comparator 86 ), providing what is called the “ high frequency sampling output ”. these measurements ( samplings ) are made at a repetition rate that is comparable to or less than the sampling rate of the ecg measurements in the first channel . the measurement is carried out using a pair of sampling points with a short interval between them , such as 30 - 240 microseconds and renders a pair of sampled values . the difference between these values corresponding to a pair of sampling points may then be calculated in order to measure the change of the sensor potential ( myocardial potential ) over the short interval . in this way , rapidly changing potentials result in a higher number at the output of the high frequency sampling output . the high frequency sampling output signal is used to determine whether noise is present by assessing whether its value surpasses a pre - defined threshold or not . if the absolute value of the output exceeds the threshold , noise is considered present and a timer is started , which must expire before the noise detection is reset . based on the value of this noise detection signal quality metric , the subcutaneous ecg data is classified as valid or invalid . sensed events in valid data are then used to classify arrhythmias without the interference commonly encountered in data that has not been properly validated . the results of the preceding analyses are accurate measurements of brady / tachycardia episodes , asystolic episodes , periods of invalid data , and episodes of ventricular instability resulting , for instance , from atrial fibrillation . these data are stored in the device &# 39 ; s memory 74 and transmitted wirelessly via telemetry unit 76 at programmed intervals to a data collection station for patient monitoring by the physician . thus , the physician is provided with a regularly scheduled set of data with which to make an accurate assessment of cardiac activity and arrhythmias . these data may be used to schedule office visits for the patient or to change pharmacologic therapies . one example of a processed picked - up myocardial signal is illustrated in fig3 . the numbers indicated in this example are provided in order to provide a comparative illustration only . in the first row of fig3 , cardiac cycles are denoted with a , b , c , d , e and f . in the second line , sampling points are indicated . sampling points are points in time , where sampling of the input signal — the myocardial electric signal — is performed in the first channel . the third row of fig3 represents an intracardiac electrogram ( ecg ) that is acquired by the first channel 66 . 1 of the sensing unit 66 . the fourth line of fig3 depicts the high - frequency sampling output signal generated in the second channel 66 . 2 of ventricular sensing unit 66 . the signal depicted in line 4 of fig3 represents the difference between two sampling values for each sampling point of line 2 of fig3 . these two sampling values forming a pair of high - frequency sampled myocardial electric signal values are sampled in an interval of 30 to 240 μs duration . these pairs of sampling values are taken at a frequency comparable to the first sampling rate , corresponding to the sampling points in line 2 fig3 . the detailed illustration at the bottom of fig3 illustrates that the sampling points in line 2 of fig3 are spaced apart in time by 4 ms ( corresponding to a sampling rate of 256 hz ). the detail given at the bottom of fig3 further shows that for each of the sampling points in line 1 corresponding to the sampling rate of the first channel , two sampling points corresponding to a much higher sampling rate of 4 to 30 khz are provided in the second channel . the fifth line of fig3 illustrates time windows corresponding to noise detection . in the example given in fig3 , cardiac cycles a , b , and c are of sufficient amplitude to be detected easily , using only ecg data , and there is no noise present in the signal . however , the ecg signal corresponding to cycle d is corrupted by noise that could be due to myopotentials or transient and intermittent loss of contact with the sensing electrodes of the implanted device . this could result in over - sensing of the ecg signal and classification as tachycardia or arrhythmia . however , the high frequency sampling output signal ( line 4 of fig3 ) captures this noise , and when it crosses a programmed threshold , it provides a noise detection indicator . when this noise detection occurs , subsequent interpretation of qrs complexes within the ecg is either suspended or is subject to increased scrutiny until noise is no longer detected and a preset timer ( noise detection period ) has expired . after the noise episode , small amplitude qrs complexes ( e and f ) could be detected with a low programmed threshold and without fear of incorrectly sensing noise . although an exemplary embodiment of the present invention has been shown and described , it should be apparent to those of ordinary skill that a number of changes and modifications to the invention may be made without departing from the spirit and scope of the invention . in particular , it is possible to apply the concept of noise detection to other signals than ventricular signal or myocardial signal in general . this invention can readily be adapted to a number of different kinds of medical devices by following the present teachings . all such changes , modifications and alterations should therefore be recognized as falling within the scope of the present invention .

US-39120809-A

deoxyuridine derivatives of the formula where r 1 is h or various substituents ; d is — nhco —, — conh —, - 0 -, — c —, — ch ═ ch , — c ≡ c —, — nr 5 —; r 4 is hydrogen or various substituents ; r 5 is h , c 1 - c 4 alkyl , c 1 - c 4 alkanoyl ; e is si or c ; r 6 , r 7 and r 8 are independently selected from c 1 - c 8 alkyl , c 2 - c 8 alkenyl , c 2 - c 8 alkynyl or a stable monocyclic , bicyclic or tricyclic ring system ; g is — o —, — s —, — chr 10 —, — c —; j is — ch 2 —, or when g is chr 10 may also be — o — or — nh —; r 10 is h , f , — ch 3 , — ch 2 nh 2 , — ch 2 oh ; — ohr 11 is h , f , — ch 3 , — ch 2 nh 2 , — ch 2 oh , — chch 3 , chch 3 ; or r 10 and r 11 together define an olefinic bond , or together form a — ch 2 - group , thereby defining a cis or trans cyclopropyl group ; have utility in the prophylaxis or treatment of protozoal diseases such as malaria .

various aspects of the invention will now be described by way of illustration only with reference to the following non - limiting examples , showing compounds of the invention and intermediates therefor . note that the exemplified intermediates , such as the acyclic side chain building blocks are readily reacted with alternative bases to form additional compounds of the invention . trityl chloride ( 557 mg ; 2 mmol ) et 3 n ( 0 . 306 ml ; 2 . 2 mmol ) and dmap ( 10 mg ; 0 . 08 mmol ) were added to an emulsion of cis - 2 - buten - 1 , 4 - diol ( 1 . 76 g ; 20 mmol ) in dcm ( 10 ml ). the mixture was stirred at room temperature under atmosphere of nitrogen for 24 hours . after such period of time the complete disappearance of trityl chloride was observed by tlc ( etoac / hexane 50 : 50 ). dcm ( 20 ml ) and water ( 10 ml ) were added to the mixture . the phases were separated and the organic layer was washed with water ( 10 ml ) and brine ( 10 ml ). the solvent was dried over mgso 4 and evaporated under reduced pressure affording a residue ( white oil ) which was purified by flash chromatography using hexane / etoac 70 : 30 → 40 : 60 as gradient which gave the title product as a colourless oil ( 563 mg , 81 %). polymer bound triphenylphosphine ( 0 . 75 g ; 2 . 25 mmol ) was shaken in thf ( 5 ml ) for 15 minutes , then 3 - benzoyluracil ( 290 mg , 1 . 35 mmol ) and tritylated alcohol ( 1 ) ( 300 mg ; 0 . 90 mmol ) were added to the suspension of the resin . a solution of diad ( 0 . 354 ml , 1 . 80 mmol ) in thf ( 2 ml ) was added to the mixture . the reaction was shaken 24 hours at room temperature and monitored by tlc ( hexane / etoac 50 : 50 ). the resin was filtered and washed twice with thf ( 5 ml ). the filtrate was concentrated under reduced pressure and taken in etoac ( 5 ml ), a white solid precipitated . the precipitate was filtered , the filtrate was concentrated again and purified by flash chromatography using hexane / etoac as eluent which gave the title compound as a colourless oil ( 136 mg , 29 %). a suspension of compound ( 2 ) ( 50 mg ; 0 . 095 mmol ) in meona / meoh 0 . 2 m ( 5 ml ) was stirred at room temperature for 24 hours . during such period of time the suspension became a colourless solution and the tlc ( dcm / meoh 90 : 10 ) showed the complete disappearance of the starting amide , and the presence of a new spot at lower r f . the solution was neutralised with dowex ion exchange resin . the resin was filtered off and washed twice with meoh ( 5 ml ). the filtrate was concentrated under reduced pressure and purified by flash chromatography using meoh / dcm 10 : 90 as eluent which gave the title compound as a white solid ( 38 mg , 90 %). r f : 0 . 66 in dcm / meoh 90 : 10 . 1 h - nmr ( 300 mhz , cdcl 3 ): δ 8 . 21 ( bs ; 1h ; nh ); 7 . 52 - 7 . 49 ( m ; 6h ; h - meta ); 7 . 41 - 7 . 29 ( m ; 9h ; h - orto + h - para ); 7 . 16 ( d ; j = 7 . 95 hz ; 1h ; h - 6 ); 6 . 09 - 6 . 01 ( m ; 1h ; h - 8 ); 5 . 69 - 5 . 98 ( m ; 2h ; h - 5 + h - 9 ); 4 . 28 ( d ; j = 7 . 40 hz ; 2h ; h - 10 ); 3 . 79 ( d ; j = 6 . 20 hz ; 2h ; h - 7 ). 13 c - nmr ( 75 mhz , cdcl 3 ): δ 164 . 0 ( c - 4 ); 1512 ( c - 2 ); 144 . 2 ( c - 6 ); 144 . 1 ( c - 12 ); 132 . 5 ( c - 8 ); 129 . 0 ( c - 13 ); 128 . 4 ( c - 14 ); 127 . 7 ( c - 15 ); 126 . 1 ( c - 9 ); 102 . 1 ( c - 5 ); 87 . 8 ( c - 11 ); 59 . 9 ( c - 10 ); 44 . 9 ( c - 7 ). a mixture of 3 - bromo - 1 - o - trityl propanol ( 400 mg , 1 . 05 mmol ), cesium carbonate ( 385 mg , 1 . 05 mmol ) and uracil ( 129 mg , 1 . 15 mmol ) in dmf ( 10 ml ) was warmed to 40 ° c . under atmosphere of nitrogen . after 4 hours the tlc showed the disappearance of the starting material , then water ( 10 ml ) was added into the suspension , and extracted with etoac ( 3 × 15 ml ). the organic layer was washed with brine , dried and the solvent was removed under reduced pressure to give a crude residue purified by flash chromatography to afford the desired compound as a white solid ( 134 mg , 31 %). 1 h - nmr ( 300 mhz ; cdcl 3 ) δ 2 . 08 ( 2h , m , 2 ′- h ), 3 . 22 ( 2h , t , j = 5 . 67 hz , 1 ′- h ), 4 . 02 ( 2h , t , j = 6 . 58 hz , 3 ′- h ), 5 . 47 ( 1h , dd , j = 2 . 37 , 7 . 87 hz , 5 - h ), 6 . 95 ( 1h , d , j = 7 . 87 hz , 6 - h ), 7 . 22 - 7 . 50 ( 15h , m , ph - h ), 8 . 10 ( 1h , bs , 3 - nh ). a solution of uracil ( 0 . 066 g , 0 . 59 mmol ) and caesium carbonate ( 0 . 135 g , 0 . 41 mmol ) in dry dmf ( 4 ml ) was stirred at room temperature under nitrogen for 10 min . 6 - bromo - 1 - o - tritylhexanol ( 0 . 170 g , 0 . 40 mmol ) in dry dmf ( 1 ml ) was added drop - wise via a syringe . the reaction mixture was stirred at 50 ° c . for 24 h and then left to cool down . water ( 10 ml ) was added and the solution was extracted with etoac ( 3 × 10 ml ). the organic extracts were pooled , washed with brine ( 10 ml ), dried over mgso 4 and concentrated in vacuo , yielding a transparent liquid . this crude material was chromatographed on a silica gel column ( isolute si column ) using a gradient elution of 0 → 2 % ch 3 oh in chcl 3 . the title compound was obtained as a white solid ( 115 mg , 63 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ1 . 28 - 1 . 52 ( 4h , m , 3 ′- h and 4 ′- h ), 1 . 69 ( 4h , m , 2 ′- h and 5 ′- h ), 3 . 11 ( 2h , t , j = 6 . 4 hz , 6 ′- h ), 3 . 72 ( 2h , t , j = 7 . 3 hz , 1 ′- h ), 5 . 73 ( 1h , d , j = 7 . 8 hz , 5 - h ), 7 . 12 ( 1h , d , j = 7 . 7 hz , 6 - h ), 7 . 23 - 7 . 40 ( 9h , m , ph - h ), 7 . 50 ( 6h , m , ph - h ), 9 . 98 ( 1h , bs , 3 - nh ). 13 c nmr ( 75 mhz , cdcl 3 ) δ 26 . 3 ( 3 ′- ch 2 or 4 ′- ch 2 ), 26 . 7 ( 3 ′- ch 2 or 4 ′- ch 2 ), 29 . 4 ( 2 ′- ch 2 or 5 ′- ch 2 ), 30 . 3 ( 2 ′- ch 2 or 5 ′- ch 2 ), 49 . 3 ( 1 ′- ch 2 or 6 ′- ch 2 ), 63 . 7 ( 1 ′- ch 2 or 6 ′- ch 2 ), 86 . 8 ( 1 ″- c ), 102 . 5 ( 5 - ch ), 127 . 3 ( ph - ch ), 128 . 2 ( ph - ch ), 129 . 1 ( ph - ch ), 144 . 8 ( ph - c ), 144 . 9 ( 6 - ch ), 151 . 5 ( 2 - c ), 164 . 7 ( 4 - c ). es + m / z (%) 477 ([ m + na ] + , 100 ), 243 ( ph 3 c + , 58 ). hrms ( es + ) found [ m + nh 4 ] + 472 . 2592 ; c 29 h 34 n 3 o 3 requires 472 . 2595 . ir ( kbr ) 3052 , 2940 , 1712 ( weak ), 198 , 1666 , 1468 , 1426 , 1359 , 758 , 704 cm − 1 . uracil ( 0 . 091 g , 0 . 78 mmol ) and caesium carbonate ( 0 . 169 g , 0 . 52 mmol ) were stirred in dry dmf ( 40 ml ) at room temperature under nitrogen for 30 min . a mixture of 4 - bromo - and 4 - chloro - 1 - o - tert - butyldiphenylsilyl - hexanol ( 0 . 218 g , ca 0 . 56 mmol ) in dry dmf ( 2 ml ) was added drop - wise . the reaction mixture was heated at 50 ° c . for 48 h . the crude solution was partitioned between water ( 10 ml ) and etoac ( 10 ml ). the organic layer was further washed with brine ( 2 × 5 ml ), then dried over mgso 4 and concentrated in vacuo to give a transparent oil . this product was further purified by silica gel column chromatography ( isolute si column ) using a gradient elution of 0 → 5 % ch 3 oh in chcl 3 . the fractions with r f = 0 . 03 ( 30 % etoac / hexane ) afforded the title compound as a transparent oil ( 0 . 103 g , ca 41 %). a small amount of dialkylated product was isolated as a transparent film ( 15 mg , ca 3 %) from the fractions with r f = 0 . 28 ( 30 % etoac / hexane ). 1 h nmr ( 300 mhz , cdcl 3 ) δ 1 . 11 ( 9h , s , tbu - ch 3 ), 1 . 41 ( 4h , m , 3 ′- h and 4 ′- h ), 1 . 67 ( 4h , m , 2 ′- h and 5 ′- h ), 3 . 73 ( 4h , m , 1 ′- h and 6 ′- h ), 5 . 76 ( 1h , dd , j = 2 . 0 , 7 . 9 hz , 5 - h ), 7 . 17 ( 1h , d , j = 7 . 9 hz , 6 - h ), 7 . 46 ( 6h , m , ph - ch ), 7 . 73 ( 4h , m , ph - ch ), 9 . 80 - 9 . 92 ( 1h , bm , 3 - nh ). 13 c nmr ( 75 mhz , cdcl 3 ) δ 19 . 7 ( tbu - c ), 25 . 9 ( 3 ′- ch 2 or 4 ′- ch 2 ), 26 . 6 ( 3 ′- ch 2 or 4 ′- ch 2 ), 27 . 3 ( tbu - ch 3 ), 29 . 5 ( 2 ′- ch 2 or 5 ′- ch 2 ), 32 . 8 ( 2 ′- ch 2 or 5 ′- ch 2 ), 49 . 3 ( 1 ′- ch 2 ), 64 . 1 ( 6 ′- ch 2 ), 102 . 5 ( 5 - ch ), 128 . 1 ( ph - ch ), 130 . 0 ( ph - ch ), 134 . 4 ( ph - c ), 136 . 0 ( ph - ch ), 144 . 9 ( 6 - ch ), 151 . 5 ( 2 - c ), 164 . 6 ( 4 - c ). hrms ( es + ) found [ m + h ] + 451 . 2409 ; c 26 h 35 n 2 o 3 si requires 451 . 2411 . 1 -( 4 ′- hydroxybutyl ) uracil ( 0 . 083 g , 0 . 45 mmol ), trityl chloride ( 0 . 140 g , 0 . 50 mmol ) and dmap ( 5 mg , 0 . 05 mmol ) were stirred in dry pyridine ( 6 ml ) at 50 ° c . under nitrogen for 64 h . the reaction mixture was left to cool to room temperature and then partitioned between cold water ( 20 ml ) and dcm ( 15 ml , 2 × 10 ml ). the organic extracts were combined , washed with brine ( 20 ml ), dried over mgso 4 and concentrated in vacuo . further purification by silica gel column chromatography ( isolute si column ) using a gradient elution of 0 → 3 % ch 3 oh in chcl 3 . the fractions with r f = 0 . 58 ( 10 % ch 3 oh / chcl 3 ) yielded the title compound as a white solid ( 0 . 165 g , 86 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 1 . 27 ( 2h , m , 3 ′- h ), 1 . 38 ( 2h , m , 2 ′- h ), 3 . 23 ( 2h , t , j = 6 . 1 hz , 4 ′- h ), 3 . 81 ( 2h , t , j = 7 . 1 hz , 1 ′- h ), 5 . 78 ( 1h , dd , j = 2 . 2 , 7 . 9 hz , 5 - h ), 7 . 18 ( 1h , d , j = 7 . 9 hz , 6 - h ), 7 . 17 - 7 . 56 ( 15 , m , ph - h ), 9 . 25 ( 1h , bs , 3 - nh ). 13 c nmr ( 75 mhz , cdcl 3 ) δ 26 . 5 ( 2 ′- ch 2 ), 29 . 2 ( 3 ′- ch 2 ), 49 . 2 ( 1 ′- ch 2 ), 63 . 0 ( 4 ′- ch 2 ), 87 . 0 ( ph 3 c ), 102 . 5 ( c - 5 ), 127 . 4 ( ph - ch ), 128 . 3 ( ph - ch ), 129 . 0 ( ph - ch ), 144 . 5 ( ph - c ), 144 . 9 ( 6 - c ), 151 . 2 ( 2 - c ), 164 . 1 ( 4 - c ). es + m / z (%) 449 ([ m + na ] + , 40 ), 55 ( 100 ). hrms ( es + ) found [ m + na ] + 449 . 1838 . c 20 h 14 n 2 nao 3 requires 449 . 1836 . ir ( kbr ) 3045 , 1681 ( c ═ o ), 1666 ( c ═ o ), 1448 , 1074 , 760 , 706 cm − 1 . 1 -( 4 ′- hydroxybutyl ) uracil ( 0 . 048 g , 0 . 26 mmol ) was dissolved in dry pyridine ( 1 . 5 ml ) and cooled in an ice - salt bath . a solution of triphenylsilyl chloride ( 0 . 099 g , 0 . 34 mmol ) in dry pyridine ( 1 . 5 ml ) was added drop - wise . the reaction mixture was kept at 0 ° c . under nitrogen for 2 h30 . ch 3 oh ( 15 μl ) was added and after 10 min the solution was concentrated on the rotary evaporator . the resultant crude transparent oil was purified by silica gel chromatography using a gradient elution of 0 → 3 % ch 3 oh in chcl 3 . the title compound was obtained as a white solid ( 0 . 085 g , 74 %) from the fractions with r f = 0 . 50 ( 10 % ch 3 oh / chcl 3 ). 1 h nmr ( 300 mhz , cdcl 3 ) δ 1 . 65 ( 2h , m , 3 ′- h ), 1 . 80 ( 2h , m , 2 ′- h ), 3 . 73 ( 2h , t , j = 7 . 2 hz , 1 ′- h ), 3 . 89 ( 2h , t , j = 5 . 9 hz , 4 ′- h ), 5 . 66 ( 1h , dd , j = 1 . 9 , 7 . 8 hz , 5 - h ), 7 . 02 ( 1h , d , j = 7 . 8 hz , 6 - h ), 7 . 44 ( 9h , m , ph - h ), 7 . 65 ( 6h , m , ph - h ), 9 . 59 ( 1h , bs , 3 - nh ). 13 c nmr ( 75 mhz , cdcl 3 ) δ 26 . 1 ( 2 ′- ch 2 ), 29 . 4 ( 3 ′- ch 2 ), 49 . 0 ( 1 ′- ch 2 ), 63 . 6 ( 4 ′- ch 2 ), 102 . 5 ( 5 - c ), 128 . 4 ( ph - ch ), 130 . 6 ( ph - ch ), 134 . 4 ( ph - c ), 135 . 8 ( ph - ch ), 144 . 9 ( 6 - c ), 151 . 4 ( 2 - c ), 164 . 4 ( 4 - c ). es + m / z (%) 465 ([ m + na ] + , 40 ), 55 ( 100 ). hrms ( es + ) found [ m + h ] + 443 . 1787 ; c 26 h 26 n 2 o 3 si requires 443 . 1785 . ir ( kbr ) 3053 , 1714 ( c ═ o ), 1682 ( c ═ o ), 1427 , 1117 , 703 cm − 1 . 1 -( 2 - hydroxy - ethoxymethyl ) uracil ( 0 . 50 g , 2 . 69 mmol ) and triphenylmethyl chloride ( 0 . 82 g , 2 . 96 mmol ) were stirred in dry pyridine ( 20 ml ) overnight at 50 ° c . under an atmosphere of nitrogen . h 2 o ( 10 ml ) was added and the mixture was extracted with chcl 3 ( 2 × 50 ml ), dried ( na 2 so 4 ) and reduced in vacuo to obtain a crude product , which was purified by column chromatography eluting with 0 → 3 % meoh / chcl 3 to obtain the title compound as a white solid ( 0 . 23 g , 20 %). 1 h nmr ( 300 mhz ; cdcl 3 ): δ 3 . 32 ( 2h , 4 ′- h ), 3 . 78 ( 2h , m , 5 ′- h ), 5 . 29 ( 2h , s , 1 ′- h ), 5 . 82 ( 1h , d , j = 7 . 9 hz , 5 - h ), 7 . 29 - 7 . 51 ( 16h , m , ph - h and 6 - h ); 13 c nmr ( 75 mhz ; cdcl 3 ): δ 63 . 32 ( 5 ′- ch 2 ), 69 . 70 ( 4 ′- ch 2 ), 77 . 38 ( 1 ′- ch 2 ), 103 . 58 ( 5 - ch ), 87 . 19 ( ph 3 c , 127 . 55 ( ph - ch ), 128 . 31 ( ph - ch ), 129 . 08 ( ph - ch ), 143 . 25 ( ph - ch ), 143 . 52 ( 6 - ch ), 151 . 43 ( 2 - c ), 163 . 81 ( 4 - c ); hrms ( es + ve ., m + na + ): calculated for c 26 h 24 n 2 o 4 , requires 451 . 1634 , found 451 . 1626 . ir vmax / cm − 1 ( kbr ): 703 . 2 and 760 . 0 ( aromatic - monosubstituted ), 1673 . 4 ( c ═ o ), 1701 . 8 ( c ═ o ), 3021 . 1 ( aromatic , c — h stretching ). 2 - butyn - 1 , 4 - diol ( 19 ; 11 . 64 mmol ) was dissolved in dry thf ( 25 ml ) under atmosphere of nitrogen . the solution was cooled to − 78 ° c . with a dry - ice / acetone bath . a cold solution of lah in thf 1m ( 12 . 7 ml ; 12 . 7 mmol ) was added with a syringe . the reaction was left worm to room temperature in 4 hours . the disappearance of the starting alkyne was observed by tlc ( hexane / etoac 30 : 70 ); then the solution was cooled to 0 ° c . with an ice bath and the quenched with naoh 1m , until no gas was developed . the ph was adjusted to 8 with hcl 1m and then silica was added to the solution . the solvents were removed under reduced pressure and the residue was loaded into a chromatographic column and purified using hexane / etoac 30 : 70 as eluent which gave the title compound as a colourless oil ( 817 mg , 79 %). r f : 0 . 11 in hexane / etoac 30 : 70 ( pma ) 1 h - nmr ( 300 mhz , cd 3 od ): δ 5 . 83 ( bs ; 2h ; h - 2 + h - 3 ); 4 . 07 ( d ; j = 3 . 57 hz ; 4h ; h - 1 + h - 4 ) 13 c - nmr ( 75 mhz , cd 3 od ): δ131 . 7 ( c - 2 & amp ; c - 3 ); 63 . 4 ( c - 1 & amp ; c - 4 ) a solution of trityl chloride ( 500 mg ; 1 . 81 mmol ), tea ( 0 . 277 ml ; 1 . 99 mmol ) and dmap ( 8 . 8 mg ; 0 . 072 mmol ) in dry dcm ( 5 ml ) was added with a syringe to a solution of the diol ( 10 ) ( 800 mg ; 9 . 07 mmol ) in dcm ( 15 ml ). the mixture was stirred at room temperature for 1 hour and 30 minutes , then other trcl , tea and dmap ( half quantities than before ) were added . the reaction was stirred at the same temperature until tlc ( hexane / etoac 50 : 50 ) showed complete disappearance of trityl chloride . after 1 . 5 hours water ( 20 ml ) was added and the reaction was stirred for few minutes , then the phases were separated . the organic layer was washed with water ( 25 ml ) and brine ( 25 ml ). the solvent was dried over mgso 4 and evaporated to afford a crude oil which was purified by flash chromatography using hexane / etoac 50 : 50 as eluent which gave the title compound as a colourless oil , 637 mg , 71 %. r f : 0 . 72 in hexane / etoac 50 : 50 ( uv / pma ). 1 h - nmr ( 300 mhz , cdcl 3 ): δ 7 . 54 - 7 . 51 ( m ; 6h ; h - 7 ); 7 . 39 - 7 . 27 ( m ; 9h ; h - 8 + h - 9 ); 6 . 12 - 6 . 03 ( m ; 1h ; h - 3 ); 5 . 91 - 5 . 83 ( m ; 1h ; h - 2 ); 4 . 24 ( bs ; 2h ; h - 4 ); 3 . 71 - 3 . 71 ( m ; 2h ; h - 1 ). 13 c - nmr ( 75 mhz , cdcl 3 ): δ 144 . 6 ( c - 6 ); 130 . 5 ( c - 3 & amp ; c - 2 ); 129 . 0 ( c - 8 ); 128 . 7 ( c - 7 ); 127 . 4 ( c - 9 ); 87 . 3 ( c - 5 ); 64 . 5 ( c - 4 ); 63 . 8 ( c - 1 ). polymer bound triphenylphosphine ( 0 . 75 g , 2 . 25 mmol ) was shaken in thf ( 5 ml ) for 15 minutes , then 3 - benzoyluracil ( 290 mg , 1 . 35 mmol ), trityl alcohol ( 11 ) ( 300 mg , 0 . 90 mmol ) were added to the suspension of the resin . a solution of diad ( 0 . 354 ml , 1 . 80 mmol ) in thf ( 2 ml ) was added to the mixture . the reaction was shaken 24 hours at room temperature and monitored by tlc ( hexane / etoac 50 : 50 ). the resin was filtered and washed twice with thf ( 5 ml ). the filtrate was concentrated under reduced pressure and taken in etoac ( 5 ml ), a white solid precipitated . the precipitate was filtered ; the filtrate was concentrated again and purified by flash chromatography using hexane / etoac 40 : 60 → 60 : 40 as gradient which gave the title compound as a white foam ( 222 mg , 48 %). r f : 0 . 55 in hexane / etoac 50 : 50 ( uv / pma ). 1 h - nmr ( 300 mhz , cd 3 od ): δ 8 . 00 - 7 . 91 ( m ; 2h ; h - 18 ); 7 . 74 - 7 . 66 ( m ; 2h ; h - 6 + h - 20 ); 7 . 56 - 7 . 43 ( m ; 8h ; h - 13 + h - 19 ); 7 . 34 - 7 . 25 ( m ; 9h ; h - 14 + h - 15 ); 5 . 94 - 5 . 79 ( m ; 3h ; h - 5 + h - 8 + h - 9 ); 4 . 40 ( d ; j = 5 . 35 hz ; 2h ; h - 10 ); 3 . 71 ( bs ; 2h ; h - 7 ). 13 c - nmr ( 75 mhz , cd 3 od ): δ 174 . 5 ( c - 16 ); 165 . 1 ( c - 4 ); 151 . 8 ( c - 2 ); 147 . 5 ( c - 6 ); 145 . 9 ( c - 12 ); 136 . 7 ( c - 17 ); 134 . 0 ( c - 8 ); 131 . 8 ( c - 20 ); 130 . 8 ( c - 19 ); 130 . 1 ( c - 13 & amp ; c - 18 ); 129 . 2 ( c - 14 ); 128 . 6 ( c - 15 ); 125 . 6 ( c - 9 ), 102 . 8 ( c - 5 ); 89 . 2 ( c - 11 ); 65 . 3 ( c - 10 ); 51 . 1 ( c - 7 ). lrms ( cl +): m / z 546 . 3 [ m + nh 4 ] + 100 %; m / z 529 . 3 [ m + h ] + 45 %. compound ( 12 ) ( 50 mg , 0 . 09 mmol ) was dissolved and stirred at room temperature in a solution 0 . 2 m ( 5 ml ) of meona in meoh . the reaction was left at room temperature overnight , then the solution was neutralized with dowex h + ion exchange resin . the resin was filtered off and the filtrate was concentrated under reduced pressure to an oil which was purified by chromatography using chcl 3 → chcl 3 / meoh 95 : 5 as gradient which gave the title compound as a white solid ( 38 mg , 90 %). r f : 0 . 51 in chcl 3 / meoh 90 : 10 , m . p . 70 - 72 ° c . 1 h - nmr ( 300 mhz , cdcl 3 ): δ 9 . 04 ( bs ; 1h ; nh ); 7 . 49 ( d ; j = 7 . 81 hz ; 6h ; h - 13 ); 7 . 39 - 7 . 27 ( m ; 9h ; h - 14 + h - 15 ); 7 . 19 ( d ; j = 7 . 90 hz ; 1h ; h - 6 ); 5 . 98 - 5 . 83 ( m ; 2h ; h - 8 + h - 9 ); 5 . 77 ( d ; j = 7 . 90 hz ; 1h ; h - 5 ); 4 . 42 ( d ; j = 5 . 63 hz ; 2h ; h - 10 ); 3 . 74 ( d ; j = 3 . 92 hz ; 2h ; h - 7 ). 13 c - nmr ( 75 mhz , cdcl 3 ): δ 163 . 9 ( c - 4 ); 151 . 1 ( c - 2 ); 144 . 3 ( c - 12 ); 144 . 1 ( c - 6 ); 133 . 3 ( c - 8 ); 129 . 0 ( c - 13 ); 128 . 3 ( c - 14 ); 124 . 1 ( c - 15 ); 124 . 1 ( c - 9 ); 102 . 9 ( c - 5 ); 87 . 5 ( c - 11 ); 64 . 0 ( c - 10 ); 49 . 6 ( c - 7 ). microanalysis calculated for c 27 h 24 n 2 o 3 × 0 . 2h 2 o the procedure described in example 1 was followed but using 1 , 5 - pentandiol ( 376 mg , 3 . 6 mmol ) as alcohol instead of cis - 2 - buten - 1 , 4 - diol , which gave the title compound ( 300 mg , 24 %). polymer supported triphenyl phosphine ( 2 . 5 eq , 3 mmol / g loading ) was swelled in dry thf for 15 minutes then the alcohol 14 ( 1 eq , 300 mg ) and the n 3 - benzoyluracil ( 1 . 5 eq ) were added into the suspension , which was shaken at room temperature under atmosphere of nitrogen . a solution of diad ( 2 eq ) in thf was added slowly into the suspension . the reaction was shaken overnight until the disappearance of the alcohol was observed by tlc . the resin was then filtered off and washed with thf ( 5 ml ). the solvent was removed under reduced pressure to afford a residue which was taken in a mixture of hexane / etoac ( 50 : 50 ). the formed white precipitate was removed and the solution was concentrated to an orange oil and purified by flash chromatography using a mixture of hexane / etoac ( 40 : 60 ) as eluent which gave the title compound ( 250 mg , 53 %). compound ( 15 ) ( 231 mg ; 0 . 42 mmol ) was stirred for 48 hours at room temperature in a mixture of naoh 1m and dioxane 1 : 1 ( 8 ml ). after 48 hours , brine ( 8 ml ) was added to the solution , and then extracted with etoac ( 3 × 8 ml ). the organic phase was dried over mgso 4 ; the solvent was removed in vacuo and the crude residue was purified by flash chromatography using dcm / meoh 90 : 10 as eluent . the title compound was obtained as a colourless oil which precipitated after treatment with a mixture of water / etoh 1 : 1 which gave the title compound as a white solid ( 112 mg , 60 %). r f : 0 . 64 in dcm / meoh 90 : 10 . 1 h - nmr ( 300 mhz ; cdcl 3 ): δ 9 . 13 ( bs ; 1h ; nh ); 7 . 57 - 7 . 55 ( m ; 6h ; h - 14 ); 7 . 46 - 7 . 34 ( m ; 9h ; h - 15 + h - 16 ), 7 . 21 ( d ; j = 7 . 87 hz ; 1h ; h - 6 ); 5 . 80 ( d ; j = 7 . 87 hz ; 1h ; h - 5 ); 3 . 83 ( t ; j = 7 . 32 hz ; 2h ; h - 11 ); 3 . 22 ( t ; j = 6 . 22 hz ; 2h ; h - 7 ); 1 . 84 - 1 . 74 ( m ; 4h ; h - 10 + h - 8 ); 1 . 60 - 1 . 50 ( m ; 2h ; h - 9 ). 13 c - nmr ( 75 mhz cdcl 3 ): δ 164 . 6 ( c - 4 ); 151 . 4 ( c - 2 ); 144 . 9 ( c - 6 ); 144 . 8 ( c - 13 ); 129 . 1 ( c - 14 ); 128 . 4 ( c - 15 ); 127 . 4 ( c - 16 ); 102 . 5 ( c - 5 ); 86 . 9 ( c - 12 ); 63 . 5 ( c - 11 ); 49 . 2 ( c - 7 ); 29 . 9 ( c - 10 ); 29 . 2 ( c - 8 ); 23 . 6 ( c - 9 ). hrms ( es +): found 458 . 2439 ; required 458 . 2438 for c 28 h 32 n 3 o 3 + [ m + nh 4 ] + . the title compound ( g , 24 %) was prepared as described in example 1 but using 5 - aminopentanol instead of cis - 2 - buten - 1 , 4 - diol in the reaction with trityl chloride . the title compound ( 187 mg , 53 %) was prepared as described in example 15 but using alcohol 17 instead of 14 in the coupling reaction with n 3 - benzoyluracil . compound 18 ( 187 mg ; 0 . 35 mmol ) was dissolved and stirred in a solution of meona 0 . 2 m in meoh ( 17 ml ) at room temperature . after 24 hours the ph was adjusted to 7 with dowex 50wx 8 - 200 ion exchange resin . the resin was removed by filtration and washed with meoh . the solution was evaporated and the residue was purified by flash chromatography with dcm / meoh 90 : 10 as eluent which gave the title compound as a white foam ( 240 mg , 52 %). r f : 0 . 50 in dcm / meoh 90 : 10 . 1 h - nmr ( 300 mhz ; cdcl 3 ): δ 8 . 70 ( bs ; 1h ; n — h ); 7 . 52 ( d ; j = 9 . 88 hz ; 6h ; h - orto ); 7 . 36 - 7 . 22 ( m ; 9h ; h - meta + h - para ); 7 . 14 ( d ; j = 7 . 87 hz ; 1h ; h - 6 ); 5 . 73 ( d ; j = 7 . 87 hz ; 1h ; h - 5 ); 3 . 74 ( t ; j = 7 . 32 hz ; 2h ; h - 7 ); 2 . 18 ( t ; j = 7 . 19 hz ; 2h ; h - 11 ); 1 . 75 - 1 . 63 ( m ; 4h ; h - 8 + h - 10 ); 1 . 49 - 1 . 36 ( m ; 2h ; h - 9 ). 13 c - nmr ( 75 mhz cdcl 3 ): δ 163 . 8 ( c - 4 ); 151 . 0 ( c - 2 ); 146 . 6 ( c - 13 ); 144 . 8 ( c - 6 ); 129 . 0 ( c - 14 ); 128 . 2 ( c - 15 ); 126 . 7 ( c - 16 ); 102 . 5 ( c - 5 ); 71 . 3 ( c - 12 ); 49 . 2 ( c - 7 ); 43 . 7 ( c - 11 ); 30 . 8 ( c - 8 ); 29 . 5 ( c - 10 ); 24 . 6 ( c - 9 ). lrms ( es +): m / z = 262 . 0 [( m + na ) + ; 100 %]; m / z = 139 . 9 [( m ) + ; 50 ° h ]; m / z = 243 . 1 [( tr ) + ; 100 %]. hrms ( es +): found 440 . 2333 ; required 440 . 2341 for c 28 h 30 n 3 o 2 + ; [ m + h ] + . to a solution of pentanediol ( 1 mmol ) in thf ( 5 ml ) was added a catalytic amount of dimethyltin dichloride ( 0 . 01 mmol ), solid k 2 co 3 ( 2 . 0 mmol ) and benzoyl chloride ( 1 . 2 mmol ), at room temperature . after stirring the mixture at room temperature until the diol disappeared ( checked by tlc ), the mixture was poured onto water and the organic portion was extracted with dcm . after evaporation of the solvent , a residue was obtained and purified by flash chromatography using a mixture of dcm / meoh as eluent . trityl chloride ( 0 . 358 g , 1 . 28 mmol ) was added to a solution of 1 -( 4 ′- aminobutyl ) uracil ( contaminated by 11 % 1 , 3 - bis ( 4 ′- aminobutyl ) uracil ) ( 0 . 168 g ) in anhydrous pyridine ( 15 ml ). the reaction mixture was heated at 50 ° c . for 44 h , left to cool to room temperature , poured into cold water ( 50 ml ) and extracted with dcm ( 3 × 25 ml ). the organic extracts were washed with brine ( 40 ml ), dried over na 2 so 4 and concentrated in vacuo . further purification was carried out by silica gel column chromatography , using jones chromatography isolute si columns with a gradient elution of 0 → 5 % ch 3 oh in chcl 3 . the fractions with r f = 0 . 51 ( 10 % ch 3 oh / chcl 3 ) gave the title compound as a white crystalline solid ( 94 mg , ca 24 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 1 . 58 ( 3h , m , 3 ′, 5 ′- h ), 1 . 80 ( 2h , m , 2 ′- h ), 2 . 23 ( 2h , t , j = 6 . 7 hz 4 ′- h ), 3 . 75 ( 2h , t , j = 7 . 2 hz , 1 ′- h ), 5 . 73 ( 1h , d , j = 7 . 9 hz , 5 - h ), 7 . 13 ( 1h , d , j = 7 . 9 hz , 6 - h ), 7 . 19 - 7 . 40 ( 9h , m , ph - h ), 7 . 53 ( 6h , m , ph - h ), 8 . 53 ( 1h , bs , 3 - nh ). 13 c nmr ( 75 mhz , cdcl 3 ) δ 27 . 3 ( 2 ′- ch 2 ), 28 . 1 ( 3 ′- ch 2 ), 43 . 5 ( 4 ′- ch 2 ), 49 . 3 ( 1 ′- ch 2 ), 71 . 3 ( 6 ′- c ), 102 . 5 ( 5 - ch ), 126 . 7 ( ph - ch ), 128 . 3 ( ph - ch ), 129 . 0 ( ph - ch ), 144 . 8 ( 6 - ch ), 145 . 5 ( ph - c ), 151 . 0 ( 2 - c ), 163 . 7 ( 4 - c ). es + m / z (%) 426 ([ m + h ] + , 18 ), 243 ( phc + , 100 ). hrms ( es + ) found [ m + h ] + 426 . 2176 ; c 27 h 28 n 3 o 2 + requires 426 . 2176 . ir ( kbr ) 3054 , 1694 , 1672 , 1454 , 768 , 706 cm − 1 . anal (%) found c , 73 . 10 ; h , 6 . 12 ; n , 9 . 45 ; cl , 3 . 61 . calcd for c 27 h 27 n 3 o 2 , 0 . 48 hcl c , 73 . 20 ; h , 6 . 25 ; n , 9 . 48 ; cl , 3 . 84 . a solution of triphenylsilyl chloride ( 0 . 337 g , 1 . 14 mmol ) in dry pyridine ( 3 ml ) was added drop - wise to a solution of 1 -( 6 ′- hydroxyhexyl ) uracil ( 0 . 200 g , 0 . 94 mmol ) in dry pyridine ( 4 ml ) cooled in an ice - salt bath . the reaction mixture was kept at 0 ° c . under nitrogen for 3 h30 . as tlc monitoring evidenced the presence of unreacted starting material , triphenylsilyl chloride ( 0 . 325 g , 1 . 10 mmol ) in dry pyridine ( 1 ml ) was added . after a further 45 min at 0 ° c ., the reaction had reached completion and was quenched with ch 3 oh ( 0 . 1 ml ). removal of the solvent in vacuo afforded a crude yellow oil which was purified by silica gel chromatography using a jones chromatography isolute si column with a gradient elution of 0 → 5 % ch 3 oh in chcl 3 . the title compound was obtained as a white solid ( 0 . 140 g , 32 %) from the fractions with r f = 0 . 52 ( 10 % ch 3 oh / chcl 3 ). some starting material ( 0 . 130 g , 65 %) was also recovered , possibly resulting from hydrolysis during the work up . 1 h nmr ( 300 mhz , cdcl 3 ) δ 1 . 29 - 1 . 53 ( 4h , m , 3 ′, 4 ′- h ), 1 . 67 ( 4h , m , 2 ′, 5 ′- h ), 3 . 72 ( 2h , t , j = 7 . 3 hz , 1 ′- h ), 3 . 88 ( 2h , t , j = 6 . 3 hz , 6 ′- h ), 5 . 74 ( 1h , d , j = 7 . 8 hz , 5 - h ), 7 . 12 ( 1h , d , j = 7 . 8 hz , 6 - h ), 7 . 47 ( 9h , m , ph - h ), 7 . 70 ( 6h , m , ph - h ), 9 . 83 ( 1h , bs , 3 - nh ). 13 c nmr ( 75 mhz , cdcl 3 ) δ 25 . 8 ( 3 ′- ch 2 or 4 ′- ch 2 ), 26 . 5 ( 4 ′- ch 2 or 3 ′- ch 2 ), 29 . 4 ( 2 ′- ch 2 ), 32 . 7 ( 5 ′- ch 2 ), 49 . 2 ( 1 ′- ch 2 ), 64 . 1 ( 6 ′- ch 2 ), 102 . 5 ( 5 - ch ), 128 . 3 ( ph - ch ), 130 . 5 ( ph - ch ), 134 . 8 ( ph - c ), 135 . 8 ( ph - ch ), 144 . 9 ( 6 - ch ), 151 . 4 ( 2 - c ), 164 . 5 ( 4 - c ). hrms ( es + ) found [ m + h ] + 471 . 2100 ; c 28 h 31 n 2 o 3 si + requires 471 . 2098 . ir ( kbr ) 3050 , 2938 , 2870 , 1698 , 1666 , 1428 , 1117 , 700 , 503 cm − 1 . anal (%) found c , 70 . 48 ; h , 6 . 42 ; n , 5 . 88 ; cl , 1 . 26 . calcd for c 28 h 30 n 2 o 3 si , 0 . 18 hcl c , 70 . 47 ; h , 6 . 37 ; n , 5 . 87 ; cl , 1 . 34 . the title compound ( 50 %) was prepared as described in example 15 but using the alcohol 20 instead of 14 in the coupling reaction with n 3 - benzoyluracil . 1 -( 3 ′- hydroxypropyl ) uracil ( 0 . 193 g , 1 . 134 mmol ) was dissolved in dry pyridine ( 4 ml ) and cooled in an ice - salt bath . a solution of triphenylsilyl chloride ( 0 . 432 g , 1 . 46 mmol ) in dry pyridine ( 3 ml ) was added drop - wise . the reaction mixture was kept at 0 ° c . under nitrogen for 4 h30 . as tlc monitoring evidenced the presence of unreacted starting material , more triphenyl silyl chloride ( 0 . 204 g , 0 . 69 mmol ) in dry pyridine ( 1 ml ) was added . after a further 15 min at 0 ° c ., the reaction had reached completion and was quenched with ch 3 oh ( 50 μl ). removal of the solvent in vacuo afforded a crude yellow oil which was purified by silica gel chromatography , using a jones chromatography isolute si column eluted with a gradient of 0 → 5 % ch 3 oh in chcl 3 . the title compound was obtained as a white solid ( 0 . 392 g , 81 %) from the fractions with r f = 0 . 52 ( 10 % ch 3 oh / chcl 3 ). some compound starting material was also recovered ( 34 mg , 18 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 2 . 01 ( 2h , m , 2 ′- h ), 3 . 94 ( 4h , m , 1 ′, 3 ′- h ), 5 . 54 ( 1h , d , j = 7 . 9 hz , 5 - h ), 7 . 04 ( 1h , d , j = 7 . 9 hz , 6 - h ), 7 . 51 ( 9h , m , ph - h ), 7 . 68 ( 6h , m , ph - h ), 9 . 49 ( 1h , bs , 3 - nh ). 13 c nmr ( 75 mhz , cdcl 3 ) δ 31 . 5 ( 2 ′- ch 2 ), 32 . 7 ( 5 ′- ch 2 ), 46 . 4 ( 1 ′- ch 2 ), 60 . 3 ( 6 ′- ch 2 ), 102 . 1 ( 5 - ch ), 128 . 3 ( ph - ch ), 130 . 8 ( ph - ch ), 134 . 0 ( ph - c ), 135 . 8 ( ph - ch ), 145 . 6 ( 6 - ch ), 151 . 3 ( 2 - c ), 164 . 3 ( 4 - c ). es + m / z (%) 879 ([ 2m + na ] + , 8 ), 451 ([ m + na ] + , 38 ), 87 ( 100 ). hrms ( es + ) found [ m + nh 4 ] + 446 . 1844 ; c 27 h 28 n 3 o 4 si + requires 446 . 1844 . m . p . 150 - 151 ° c . the benzoyl groups of compound 23 were removed according to the procedure described in example 16 which gave the title compound ( 50 mg , 50 %). a solution of triphenylsilyl chloride ( 81 mg ; 0 . 27 mmol ) in pyridine ( 1 ml ) was added to a solution of alcohol ( 25 ) ( 50 mg ; 0 . 25 mmol ) in dry pyridine ( 1 ml ) under atmosphere of nitrogen , at room temperature . the reaction was left stirring at 25 ° c . 24 hours , and then the solvent was removed under reduced pressure . the residue a slightly yellow oil was purified by chromatography using dcm / meoh 99 : 1 as eluent . light orange syrup , 30 mg ; 26 %. rf : 0 . 69 in dcm / meoh 95 : 5 1 h - nmr ( 300 mhz ; cdcl 3 ): δ 9 . 26 ( s ; 1h ; nh ); 7 . 68 - 7 . 65 ( m ; 6h ; h - 13 ); 7 . 54 - 7 . 43 ( m ; 9h ; h - 14 + h - 15 ); 7 . 08 ( d ; j = 7 . 87 hz ; 1h ; h - 6 ); 5 . 69 ( d ; j = 7 . 87 hz ; 1h ; h - 5 ); 3 . 87 ( t ; j = 6 . 13 hz ; 2h ; h - 7 ); 3 . 72 ( t ; j = 7 . 30 hz ; 2h ; h - 11 ); 1 . 76 - 1 . 66 ( m ; 4h ; h - 10 + h - 8 ); 1 . 51 - 1 . 43 ( m ; 2h ; h - 9 ). 13 c - nmr ( 75 mhz ; cdcl 3 ): δ 164 . 2 ( c - 4 ); 151 . 2 ( c - 2 ); 144 . 9 ( c - 6 ); 136 . 4 ( c - 13 ); 134 . 4 ( c - 14 ); 130 . 5 ( c - 15 ); 128 . 7 ( c - 12 ); 102 . 4 ( c - 5 ); 63 . 8 ( c - 11 ); 49 . 2 ( c - 7 ); 32 . 2 ( c - 10 ); 29 . 0 ( c - 8 ); 23 . 2 ( c - 9 ). hrms ( es +): found 479 . 1780 ; required 479 . 1761 for ch 27 h 28 n 2 sio 3 + ; [ m + na ] + . microanalysis calculated for c 27 h 28 n 2 o + 0 . 6h 2 o : 3 - bromo - 1 - tetrabutyldimethylsilyl propanol ( 641 mg , 2 . 68 mmol ) was added into a solution of uracil ( 300 mg , 2 . 68 mmol ) and cesium carbonate cs 2 co 3 ( 872 mg , 2 . 68 mmol ) in dmf ( 10 ml ), under n 2 . the reaction was warmed to 60 ° c . for 4 hours , until the tlc ( etoac / hexane 3 : 1 ) showed the complete disappear of the starting material . water ( 10 ml ) was added , and the mixture was extracted with etoac ( 3 × 10 ml ), dried and evaporated the solvent under reduced pressure . the obtained residue ( a colourless oil ) was purified by flash chromatography using a mixture of etoac / hexane as eluent which gave the title compound ( 250 mg , 33 %). 1 h - nmr ( 300 mhz ; cdcl 3 ) δ : 9 . 15 ( bs ; 1h ; n — h ); 7 . 30 ( d ; j = 7 . 87 hz ; 1h ; h - 6 ); 5 . 72 ( d ; j = 7 . 87 hz ; 1h ; h - 5 ); 3 . 91 ( t ; j = 6 . 58 hz ; 2h ; h - 9 ); 3 . 70 ( t ; j = 6 . 58 hz ; 2h ; h - 7 ); 1 . 94 ( q ; j = 6 . 58 hz ; 2h ; h - 8 ); 0 . 95 ( s ; 9h ; h - 11 ); 0 . 00 ( s ; 6h ; h - 10 ). 13 c - nmr ( 75 mhz ; cdcl 3 ) δ : 164 . 3 ( c - 4 ); 151 . 2 ( c - 2 ); 102 . 0 ( c - 5 ); 59 . 4 ( c - 9 ); 46 . 6 ( c - 7 ); 31 . 6 ( c - 8 ); 26 . 3 ( c - 11 ); 18 . 6 ( c - 12 ); - 5 . 0 ( c - 10 ). uracil ( 0 . 230 g , 2 . 05 mmol ) was stirred with cs 2 co 3 ( 0 . 462 g , 1 . 42 mmol ) in dmf ( 8 ml ) at room temperature for 30 min . a solution of 3 - bromo - 1 - tritylpropylamine ( 0 . 507 g , 1 . 33 mmol ) in dmf ( 3 ml ) was then added dropwise . the reaction mixture was heated at 40 ° c . under nitrogen for 58 h , left to cool to room temperature , poured into cold water ( 20 ml ) and extracted with etoac ( 25 ml ). the organic extracts were washed with brine , dried over na 2 so 4 and concentrated in vacuo . further purification was carried out by flash column chromatography performed using a isolute si column eluted with 20 → 50 % etoac in hexane . the fractions with r f = 0 . 38 ( 20 % etoac / hexane ) gave the title compound slightly contaminated with dmf as a white solid ( 0 . 203 g , app . 37 %). to remove the remaining traces of dmf , the compound was chromatographed again , this time using a 0 - 10 % ch 3 oh in chcl 3 as eluent . the title compound was isolated ( 0 . 116 g , 21 %). 1 h nmr ( 300 mhz , cdcl 3 + cd 3 od ) δ 1 . 87 ( 2h , m , 2 ′- h ), 2 . 20 ( 2h , t , j = 6 . 5 hz , 3 ′- h ), 3 . 85 ( 2h , t , j = 7 . 2 hz , 1 ′- h ), 5 . 61 ( 1h , d , j = 7 . 9 hz , 5 - h ), 7 . 09 ( 1h , d , j = 7 . 9 hz , 6 - h ), 7 . 15 - 7 . 35 ( 9h , m , 5 ″, 6 ″- h ), 7 . 47 ( 6h , m , 4 ″- h ). 13 c nmr ( 75 mhz , cdcl 3 + cd 3 od ) δ 30 . 3 ( 2 ′- ch 2 ), 40 . 4 ( 3 ′- ch 2 ), 47 . 2 ( 1 ′- ch 2 ), 71 . 2 ( 2 ″- c ), 102 . 4 ( 5 - ch ), 126 . 8 ( 6 ″- ch ), 128 . 3 ( 5 ″- ch ), 129 . 0 ( 4 ″- ch ), 144 . 9 ( 6 - ch ), 146 . 1 ( 3 ″- c ), 151 . 4 ( 2 - c ), 164 . 8 ( 4 - c ). es + m / z (%) 845 ([ 2m + na ] + , 3 ), 434 ([ m + na ] + , 22 ), 412 ([ m + h ] + , 10 ), 243 ( phc + , 42 ). hrms ( es + ) found [ m + h ] + 412 . 2018 ; c 26 h 26 n 3 o 2 + requires 412 . 2020 . anal calcd for c 26 h 25 n 3 o 2 , 0 . 19 (%): hbr c , 73 . 16 ; h , 5 . 95 ; n , 9 . 84 ; br , 3 . 56 found : c , 73 . 17 , h , 6 . 11 , n , 9 . 78 ; br , 4 . 91 . uracil ( 0 . 087 g , 0 . 776 mmol ) was stirred with cs 2 co 3 ( 0 . 169 g , 0 . 519 mmol ) in dmf ( 4 ml ) at room temperature for 1 h . a solution of o - tosyl - 6 - tritylaminohexanol ( 0 . 250 g , 0 . 487 mmol ) in dmf ( 2 ml ) was then added dropwise . the reaction mixture was heated at 40 ° c . for 64 h , left to cool to room temperature , poured into cold water ( 15 ml ) and extracted with etoac ( 25 ml ). the organic extracts were washed with brine ( 10 ml ), dried over na 2 so 4 and concentrated in vacuo . further purification was carried out by flash column chromatography ( isolute si column ) using a gradient elution of 20 → 50 % etoac in hexane . the fractions with r f = 0 . 49 ( 10 % ch 3 oh / chcl 3 ) gave the title compound slightly contaminated with dmf as a white solid ( 0 . 111 g , ca 50 %). remaining traces of dmf could be removed by recrystallisation from ch 3 oh or alternatively by water wash with a purification yield of 70 - 80 %. 1 h nmr ( 300 mhz , cdcl 3 ) δ 1 . 25 - 1 . 85 ( 9h , m , 2 ′, 3 ′, 4 ′, 5 ′- h and 1 ″- nh ), 2 . 17 ( 2h , t , j = 6 . 8 hz , 6 ′- h ), 3 . 74 ( 2h , t , j = 7 . 4 hz , 1 ′- h ), 5 . 73 ( 1h , d , j = 7 . 9 hz , 5 - h ), 7 . 16 ( 1h , d , j = 7 . 9 hz , 6 - h ), 7 . 20 - 7 . 65 ( 9h , m , 5 ″, 6 ″- h ), 7 . 53 ( 6h , m , 4 ″- h ). 13 c nmr ( 75 mhz , cdcl 3 ) δ26 . 8 ( ch 2 ), 27 . 3 ( ch 2 ), 29 . 4 ( ch 2 ), 31 . 1 ( ch 2 ), 43 . 8 ( 6 ′- ch 2 ), 49 . 3 ( 1 ′- ch 2 ), 71 . 3 ( 2 ″- c ), 102 . 4 ( 5 - ch ), 126 . 6 ( 6 ″- ch ), 1282 ( 5 ″- ch ), 129 . 1 ( 4 ″- ch ), 144 . 8 ( 6 - ch ), 146 . 7 ( 3 ″- c ), 151 . 2 ( 2 - c ), 164 . 2 ( 4 - c ). es + m / z (%) 929 ([ 2m + na ] + , 7 ), 907 ([ 2m + h ] + , 8 ), 476 ([ m + na ] + , 30 ), 454 ([ m + h ] + , 46 ), 243 ( phc + , 100 ). hrms ( es + ) found [ m + h ] + 454 . 2490 ; c 29 h 32 n 3 o 2 + requires 454 . 2489 . anal calcd for (%): c 29 h 31 n 3 o 2 , c , 76 . 79 ; h , 6 . 89 ; n , 9 . 26 . found : c , 76 . 61 ; h , 6 . 89 ; n , 9 . 19 . a suspension of nah ( 60 %, 90 g , 3 . 75 mol ) in dry thf ( 7 . 5 l ) was cooled to 0 ° c . and to this was added a solution of diethylmalonate ( 500 g , 3 . 12 mol ) over a period of 1 h . the reaction mixture was slowly allowed to warm to rt and stirred for another 1 . 5 h at rt . the reaction mixture was then cooled to 0 ° c . and added a solution of ethylbromoacetate ( 307 ml , 2 . 79 mol ) slowly for 30 min and finally stirred at rt for 2 . 5 h . the reaction mixture is poured into a mixture of 1 . 5 n hcl ( 250 ml ) and ice ( 5 kg ), extracted with ch 2 cl 2 ( 4 × 5 l ), dried and concentrated under vacuum to give crude product . the crude was purified by column chromatography over silica gel ( 4 % ethyl acetate in pet . ether ) to give the title compound ( 496 g , 64 %). tlc : pet . ether / etoac , 4 : 1 , r f = 0 . 4 to a solution of compound 30 ( 495 g , 2 . 01 mol ) in tert - butanol ( 4 l ) was added nabh 4 ( 434 g , 12 . 04 mol ) with vigorous stirring at rt under n 2 atmosphere . to this stirred solution was added methanol ( 250 ml ) in three portions during 45 mins maintaining a gentle reflux . the reaction mixture was slowly warmed to 80 ° c . and allowed to reflux at the same temperature for over night . the reaction mixture was cooled , added 5m hydrochloric acid to get ph = 7 ( app ). the mixture was filtered , the residue washed with ethanol ( 2 × 500 ml ) and combined the organic layers . the solvent was removed under vacuum and the crude product was purified by column chromatography on silica gel ( 10 % methanol in chloroform ) to give the title compound ( 160 g , 66 %). tlc : chloroform / methanol , 4 : 1 , r f = 0 . 2 a solution of compound 31 ( 160 g , 1 . 30 mol ) and 2 , 2 ′- dimethoxypropane ( 207 g , 1 . 90 mol ) in dry acetone ( 800 ml ) was added p - tsoh ( 92 g , 0 . 053 mol ) under n 2 and stirred at rt for 12 h . to this was added triethylamine drop - wise to neutral ph and then concentrated under vacuum below 35 ° c . the crude residue was purified by column chromatography over neutral alumina ( 12 % ethyl acetate in pet ether ) to give the title compound ( 84 g , 39 %). tlc : pet ether / etoac , 1 : 1 , r f = 0 . 2 to a solution of compound 32 ( 84 g , 0 . 528 mol ) in dry dmf ( 500 ml ) was added triphenylphosphine ( 207 g , 0 . 79 mol ) with vigorous stirring until it becomes a clear solution . the mature was cooled to 0 ° c . and added cbr 4 ( 260 g , 0 . 79 mol ) portion wise over a period of 30 min and allowed to stir at rt for 5 h . the reaction mixture was cooled to 0 ° c ., added saturated nahco 3 solution ( 200 ml ) and extracted with hexane ( 4 × 200 ml ). the combined organic layer was dried , concentrated under vacuum and the crude title compound ( 117 g ) was used for next reaction without any purification . tlc : pet . ether / etoac , 7 : 3 , r f = 0 . 6 to a solution of uracil ( 88 . 5 g , 0 . 79 mol ) in dry dmf ( 250 ml ) was added cesium carbonate ( 171 g , 0 . 527 mol ) at rt and stirred at the same temperature for 30 min . to the above reaction mixture was added a solution of compound 33 ( 117 g , 0 . 527 mol ) in dry dmf ( 250 ml ) over a period of 30 min and heated at 50 ° c . for 24 h . the reaction mixture was filtered , filtrate concentrated under vacuum and crude purified by column chromatography over silica gel ( 3 % methanol in chloroform ) to give the title compound ( 60 g , 45 %). tlc : chloroform / methanol , 4 : 1 , r f = 0 . 3 a mixture of compound 34 ( 60 g , 0 . 239 mol ) in 1n hcl ( 450 ml ) was heated to 110 ° c . for 30 min . the reaction mixture was cooled , carefully neutralized with potassium carbonate to ph = 7 and concentrated under vacuum . the residue was passed through small column using 20 % methanol in chloroform to give the title compound ( 45 g , 88 %) as a thick liquid . tlc : chloroform / methanol , 6 : 4 , r f = 0 . 2 to a solution of compound 35 ( 45 g , 0 . 213 mol ) in dry dmf ( 225 ml ) was added triethylamine ( 60 ml , 0 . 425 mol ) and stirred at rt for 15 min . the above reaction mixture was cooled to 0 ° c ., added tritylchloride ( 59 g , 0 . 213 mol ) followed by addition of catalytic amount of 4 - dmap ( app . 20 mg ) and allowed to stir at rt for 24 h . the reaction was diluted with water ( 100 ml ), extracted with ethyl acetate ( 5 × 200 ml ), dried and concentrated under vacuum . the crude was purified by column chromatography over silica gel ( 6 % methanol in chloroform ) to give the title compound ( 33 g , 34 %). tlc : chloroform / methanol , 9 : 1 , r f = 0 . 5 to a solution of compound 36 ( 33 g , 0 . 073 mol ) in dry dmf ( 200 ml ) was added triphenylphosphine ( 29 g , 0 . 11 mol ) with vigorous stirring at rt . the reaction mixture was cooled to 0 ° c ., added cbr 4 ( 36 g , 0 . 11 mol ) portion wise over a period of 30 min and allowed to stir at rt for 24 h . the reaction mixture was cooled to 0 ° c ., added saturated nahco 3 solution ( 100 ml ) and extracted with ethyl acetate ( 4 × 150 ml ). the combined organic layer was dried , concentrated under vacuum and the crude product was purified by column chromatography on silica gel ( 50 % ethyl acetate in hexane ) to give the title compound ( 22 g , 57 %). tlc : 100 % etoac , r f = 0 . 7 a solution of compound 37 ( 22 g , 0 . 042 mol ) in methanol ( 100 ml ) was treated with ptsa . h 2 o ( 0 . 80 g , 0 . 0042 mol ) and stirred for 6 h at rt . the reaction mixture was concentrated under vacuum and the crude compound was used for next reaction ( 10 . 5 g , crude product ). tlc : chloroform / methanol , 1 : 1 , r f = 0 . 2 a solution of compound 38 ( 10 . 9 g , 0 . 042 mol ) in dry dmf ( 40 ml ) was treated with nan 3 ( 4 . 1 g , 0 . 062 mol ) and heated to 70 ° c . for 24 h . the reaction mixture was concentrated under vacuum and crude purified by column chromatography over silica gel ( 30 % methanol in chloroform ) to give the title compound ( 5 . 2 g , 47 %). tlc : chloroform / methanol , 1 : 1 , r f = 0 . 2 a mixture of compound j ( 5 . 2 g , 0 . 022 mol ) in dry methanol ( 50 ml ) was treated with triethylamine ( 15 ml , 0 . 108 mol ) and 1 , 3 - propanedithiol ( 3 . 5 ml , 0 . 032 mol ) at rt and allowed to stir for 24 h . the reaction mixture was followed by tlc and further added same amount of triethylamine and 1 , 3 - propanedithiol . the reaction was continued for another 24 h and filtered off the solid . the filtrate was concentrated under vacuum and the residue was treated with ethyl acetate . the solid was filtered off and dried and the crude title compound ( 4 g , 86 %) was used in the next step without any purification . tlc : chloroform / methanol , 1 : 4 , r f = 0 . 1 to a solution of compound 40 ( 4 g , 0 . 0187 mol ) in thf / water ( 30 ml , 1 : 1 ) was added nahco 3 ( 1 . 9 g , 0 . 0225 mol ) at 0 ° c ., followed by addition of boc 2 o ( 4 . 9 ml , 0 . 0225 mol ) and was stirred at rt for 12 h . the reaction mixture was concentrated under vacuum and the residue was extracted with ethyl acetate ( 3 × 25 ml ). the combined organic layers were washed with brine , dried , concentrated and the crude product was purified by column chromatography on silica gel ( 10 % methanol in chloroform ) to give the title compound ( 4 . 6 g , 78 %). tlc : chloroform / methanol , 4 : 1 , r f = 0 . 6 a glass tube for microwave was charged with compound 41 ( 50 mg ; 0 . 155 mmol ), trityl chloride ( 54 mg ; 0 . 19 mmol ) and dry pyridine ( 2 ml ). the tube was sealed with a septum cap . the vial was irradiated with mw to reach the temperature of 160 ° c . for 5 minutes . the irradiating cycle was repeated 3 times , and then the mixture was poured into a round bottom flask . the solvent was removed under reduced pressure and the crude was purified by chromatography using hexane / etoac 40 : 60 as eluent which gave the title product as a white foam ( 70 mg , 79 %). r f : 0 . 27 in hexane / etoac 40 : 60 , m . p : 86 - 88 ° c . 1 h - nmr ( 300 mhz , cdcl 3 ): δ 8 . 08 ( bs ; 1h ; nh ): 7 . 48 ( d ; j = 7 . 04 hz ; 6h ; h - 14 ); 7 . 40 - 7 . 27 ( m ; 10h ; h - 6 + h - 15 + h - 16 ); 5 . 67 ( dd ; j 1 = 7 . 90 hz ; j 2 = 2 . 35 hz ; 1h ; h - 5 ); 4 . 58 ( t ; j = 6 . 13 hz ; 1h ; nhboc ); 3 . 84 - 3 . 76 ( m ; 2h ; h - 10 ); 3 . 31 - 323 ( m ; 3h ; h - 7 + 1 of h - 11 ); 3 . 10 - 3 . 05 ( m ; 1h ; 1 of h - 11 ); 1 . 85 - 1 . 67 ( m ; 2h ; h - 8 ); 1 . 62 - 1 . 53 ( m ; 1h ; h - 9 ); 1 . 47 ( s ; 9h ; h - 19 ). microanalysis calculated for c 33 h 37 n 3 o 5 × 0 . 2h 2 o alcohol 41 ( 200 mg , 64 mmol ) was dissolved in a solution of acetic anhydride : pyridine 1 : 2 ( 15 ml ) and the solution was stirred at room temperature for 3 h . the solution was then evaporated in vacuo and the afforded residue was purified by column chromatography on silica gel which gave the title compound ( 205 mg , 90 %). tfa ( 2 ml ) was added to a solution of compound 43 ( 200 mg , 0 . 56 mmol ) in dichloromethane ( 4 ml ). the solution was stirred at room temperature for 30 min where after the solvents were evaporated in vacuo which gave the title compound as the tfa salt . trityl chloride ( 128 mg , 0 . 46 mmol ) was added to a solution of ( 44 ) ( 100 mg , 0 . 43 mmol ) in dry dcm ( 5 ml ) in presence of tea ( 0 . 64 ml , 0 . 46 mmol ). the reaction was stirred at room temperature . after six hours the tlc ( dcm / meoh 90 : 10 ) showed still presence of starting material , then some more trcl ( 0 . 5 eq .) and tea ( 0 . 5 eq .) were added . the reaction was left stirring overnight . water ( 5 ml ) was added and the mixture was stirred other 5 minutes . the phases were separated and the organic phase was washed with hcl 0 . 1 m ( 5 ml ). the organic layer was dried over mgso 4 , concentrated and purified by flash chromatography using dcm → dcm / meoh 95 : 5 as gradient which gave the title product as a white solid ( 150 mg , 70 %). r f : 0 . 60 in chcl 3 / meoh 90 : 10 1 h - nmr ( 300 mhz , cdcl 3 ): δ 9 . 07 ( bs ; 1h ; nh ); 7 . 46 ( d ; j = 7 . 34 hz ; 6h ; h - 16 ); 7 . 30 - 7 . 19 ( m ; 9h ; h - 17 + h - 18 ); 7 . 02 ( d ; j = 7 . 88 hz ; 1h ; h - 6 ); 5 . 66 ( d ; j = 7 . 88 hz ; 1h ; h - 5 ); 4 . 27 ( d ; j = 5 . 00 hz ; 2h ; h - 10 ); 3 . 68 ( m ; 2h ; h - 7 ); 2 . 17 ( d ; j = 6 . 02 ; 2h ; h - 11 ); 2 . 03 ( s ; 3h ; h - 12 ); 1 . 83 - 1 . 65 ( m ; 3h ; h - 9 + h - 8 ). 13 c - nmr ( 75 mhz , cdcl 3 ): δ 171 . 5 ( c - 12 ); 1640 ( c - 4 ); 151 . 1 ( c - 2 ); 146 . 2 ( c - 15 ); 144 . 7 ( c - 6 ); 129 . 0 ( c - 16 ); 128 . 3 ( c - 17 ); 126 . ( c - 18 ); 102 . 7 ( c - 5 ); 71 . 3 ( c - 14 ); 65 . 3 ( c - 10 ); 47 . 4 ( c - 7 ); 44 . 6 ( c - 11 ); 37 . 0 ( c - 9 ); 29 . 7 ( c - 8 ). microanalysis calculated for c 30 h 31 n 3 o 4 × 1 . 5h 2 o compound ( 45 ) ( 110 mg , 0 . 22 mmol ) was dissolved in 5 ml of a solution of meona in meoh 0 . 2 m . the reaction was stirred at room temperature until tlc ( dcm / meoh 90 : 10 ) showed complete disappearance of the starting material . then the solution was neutralized with dowex h + resin . the polymer was filtered off , and the filtrate was concentrated and purified by filtration over a silica pad which gave the title compound as a white solid ( 100 mg , 99 %). r : 0 . 66 in chcl 3 / meoh 90 : 10 1 h - nmr ( 300 mhz , cdcl 3 ): δ 8 . 16 ( bs ; 1h ; nh ): 7 . 48 - 7 . 41 ( m ; 6h ; h - 14 ); 7 . 35 - 7 . 23 ( m ; 9h ; h - 15 + h - 16 ); 7 . 03 ( d ; j = 7 . 91 hz ; 1h ; h - 6 ); 5 . 65 ( d ; j = 7 . 90 hz ; 1h ; h - 5 ); 5 . 26 ( bs ; 2h ; oh + nh ); 3 . 95 - 3 . 90 ( m ; 1h ; 1 of h - 10 ); 3 . 82 - 3 . 57 ( m ; 3h ; h - 7 + 1 of h - 10 ); 2 . 48 - 2 . 40 ( m ; 2h h - 11 ); 1 . 84 ( bs ; 1h ; h - 9 ); 1 . 68 - 1 . 47 ( m ; 2h ; h - 8 ). 13 c - nmr ( 75 mhz , cdcl 3 ): δ 163 . 7 ( c - 4 ); 150 . 9 ( c - 2 ); 145 . 1 ( c - 13 ); 144 . 7 ( c - 6 ); 128 . 9 ( c - 14 ); 128 . 5 ( c - 15 ); 127 . 2 ( c - 16 ); 102 . 7 ( c - s ); 97 . 8 ( c - 12 ); 67 . 0 ( c - 10 ); 48 . 1 ( c - 11 ); 47 . 5 ( c - 7 ); 38 . 3 ( c - 9 ); 29 . 4 ( c - 8 ). microanalysis calculated for c 28 h 29 n 3 o 3 × 1 . 0h 2 o × hcl tfa ( 2 ml ) was added to a solution of compound 42 ( 100 mg , 0 . 18 mmol ) in dichloromethane ( 4 ml ) and the solution was stirred at room temperature . after 30 min the solvents were evaporated in vacuo and the afforded residue was purified by column chromatography on silica gel which gave the title compound ( 52 mg , 65 %). a solution of 2 - bromopyridine ( 5 g , 0 . 032 mol ) in dry thf ( 150 ml ) was cooled to − 70 ° c . to this cooled solution was added n - buli ( 2 . 8 m , 12 . 4 ml , 0 . 034 mol ) over a period of 20 min and allowed to stir for 2 h under n 2 atmosphere . a solution of benzophenone ( 5 . 8 g , 0 . 032 mol ) in dry thf ( 50 ml ) was added to the solution at the same temperature over a period of 30 min . the reaction mixture was warmed slowly to rt and allowed to stir another 5 h at rt . the reaction mixture was concentrated under vacuum and the residue was washed with petrolieum ether . the organic layer was filtered and the filtrate was concentrated under vacuum to give the title compound ( 8 g , 95 %). to a mixture of diphenyl ( pyridin - 2 - yl ) methanol ( 4 g , 0 . 015 mol ) in thionylchloride ( 50 ml ) was added acetylchloride ( 15 ml , 0 . 195 mol ) at rt and heated to 50 ° c . for 48 h . the reaction mixture was concentrated under vacuum and the residue was azeotroped with dry benzene ( 100 ml × 2 ) to give the title compound as the hydrochloride salt ( 4 . 4 g , & gt ; 95 %). the procedure described in example 49 was followed but using 4 - bromobenzonitrile ( 5 g , 0 . 027 mol ) instead of 2 - bromopyridine which gave the title compound ( 7 . 5 g , 94 %). to a mixture of 4 -[ hydroxy ( diphenyl ) methyl ] in dry toluene ( 60 ml ) was added acetylchloride ( 3 ml ) at rt and heated to 50 ° c . for 12 h . the reaction mixture was concentrated under vacuum . the residue was recrystallized from pet ether to give the product ( 1 . 7 g , 40 %). a solution of 5 - bromopyrimidine ( 10 g , 0 . 063 mol ) in a mixture of dry thf ( 150 ml ) and hexane ( 50 ml ) was cooled to − 100 ° c . to this cooled solution was added n - buli ( 4 g , 21 ml , 0 . 062 mol ) over a period of 30 min and stirred for another 30 min . a solution of benzophenone ( 11 . 5 g , 0 . 063 mol ) in dry thf ( 50 ml ) was added to this at the same temperature over a period of 30 min . the reaction mixture was warmed slowly to rt and allowed to stir another 1 h at rt . the reaction was quenched with cold water ( 200 ml ), ethyl acetate was added and the organic layer was separated . the organic layer was dried , concentrated and the crude product was purified by column chromatography on silica gel ( up - to 25 % ethyl acetate in pet ether ) to give the product ( 8 g ). tlc : pet . ether / etoac , 1 : 1 , r f = 0 . 3 to a suspension of lah ( 3 . 9 g , 0 . 104 mol ) in dry thf ( 200 ml ) was stirred at 0 ° c . for 20 min . a solution of 2 , 2 , 2 - triphenylacetic acid ( 10 g , 0 . 034 mol ) in dry thf ( 50 ml ) was added in a drop - wise manner . the reaction mixture was stirred at rt overnight . excess lah was quenched with 1 . 5 n hcl and the reaction mixture was further stirred for 2 h at rt . the reaction mixture was filtered through celite , washed with ethyl acetate and the filtrate was concentrated under vacuum . the crude product was purified by column chromatography on silica gel ( 4 % ethyl acetate in pet . ether ) to give the title compound ( 4 . 6 g , 48 %). tlc : pet . ether / etoac , 7 : 3 , r f = 0 . 2 to a magnetically stirred suspension of lah ( 8 . 3 g , 0 . 219 mol ) in dry thf ( 50 ml ) was added a solution of 3 , 3 , 3 - triphenylpropionic acid ( 9 . 5 g , 0 . 0314 mol ) over a period of 30 min at 0 ° c . the reaction mixture was allowed to stir at rt for 14 h . the reaction mixture was cooled and excess lah was quenched with 20 % naoh solution ( 50 ml ). the reaction mixture was passed through celite , washed with thf and the filtrate was concentrated under vacuum . the residue was washed with pet ether and dried which gave the title compound ( 8 g , & gt ; 85 %). to a suspension of mg ( 1 . 7 g , 0 . 07 mol ) in dry ether ( 25 ml ) was added a solution of benzyl bromide ( 10 ml , 1 . 5 equ .) in dry ether ( 25 ml ) drop - wise and allowed to stir at rt for 1 h . by the time all magnesium was dissolved and the reaction mixture was cooled to 0 ° c . to this was added a solution of benzophenone ( 10 g , 0 . 05 mol ) in dry ether ( 25 ml ) and allowed to stir at rt for 5 h . the progress of the reaction was followed by tlc and when it was ready the reaction mixture was quenched with saturated nh 4 cl solution , extracted with ether ( 100 ml ), washed with brine , dried and concentrated under vacuum . the crude product was purified by column chromatography on silica gel ( 10 % ethyl acetate in pet . ether ) to give the title compound ( 9 . 6 g , 65 %) as a white solid . tlc : pet . ether / etoac , 9 : 1 , r f = 0 . 4 a solution of 3 - bromopyridine ( 10 g , 0 . 063 mol ) in dry thf ( 200 ml )/ hexane ( 50 ml ) was cooled to − 90 ° c . to this cooled solution was added n - buli ( 2 . 2 m , 32 ml , 0 . 063 mol ) slowly and allowed to stir for 30 min under n 2 atmosphere . a solution of benzophenone ( 11 . 5 g , 0 . 063 mol ) in dry thf ( 50 ml ) was added to this at the same temperature over a period of 30 min . the reaction mixture was warmed slowly to rt and allowed to stir another 3 h at rt . the reaction mixture was cooled , quenched with water ( 200 ml ) and extracted with ethyl acetate ( 2 × 100 ml ). the organic layer was dried , concentrated under vacuum and the crude product was purified by column chromatography on silica gel ( 30 % ethyl acetate in pet . ether ) which gave the title compound ( 3 . 3 g ). two strains of p . falciparum are used in this study : the drug sensitive nf54 ( an airport strain of unknown origin ) and k1 ( thailand , chloroquine and pyrimethamine resistant ). the strains are maintained in rpmi - 1640 medium with 0 . 36 mm hypoxanthine supplemented with 25 mm hepes , 25 mm nahco 3 , neomycin ( 100 u / ml ) and albumax ® ( lipid - rich bovine serum albumin ) ( gibco , grand island , n . y .) ( 5 g / l ), together with 5 % washed human a + erythrocytes . all cultures and assays are conducted at 37 ° c . under an atmosphere of 4 % c0 2 , 3 % 0 2 and 93 % n 2 . cultures are kept in incubation chambers filled with the gas mixture . subcultures are diluted to a parasitaemia of 0 . 1 - 0 . 5 % and the medium changed daily . antimalarial activity is assessed using an adaptation of the procedures described by desjardins et al . ( antimicrob . agents chemother . 16 ( 6 ): 710 - 8 , 1979 ), and matile and pink ( in : lefkovits , i . and pernis , b . ( eds .). immunological methods . academic press , san diego , pp . 221 - 234 , 1990 ). stock drug solutions are prepared in 100 % dmso ( dimethylsulfoxide ) at 10 mg / ml , unless otherwise suggested by the supplier , and heated or sonicated if necessary . after use the stocks are kept at − 20 ° c . the compound is further diluted to the appropriate concentration using complete medium without hypoxanthine . assays are performed in sterile 96 - well microtiter plates , each well containing 200 μl of parasite culture ( 0 . 15 % parasitemia , 2 . 5 % hematocrit ) with or without serial drug solutions . seven 2 - fold dilutions are used covering a range from 5 μg / ml to 0 . 078 μg / ml . for active compounds the highest concentration is lowered ( e . g . to 100 ng / ml ), for plant extracts the highest concentration is increased to 50 μg / ml . each drug is tested in duplicate and repeated once for active compounds showing an ic 50 below 0 . 5 μg / ml . after 48 hours of incubation at 37 ° c ., 0 . 5 μci 3 h - hypoxanthine is added to each well . cultures are incubated for a further 24 h before they are harvested onto glass - fiber filters and washed with distilled water . the radioactivity is counted using a betaplate ™ liquid scintillation counter ( wallac , zurich , switzerland ). the results are recorded as counts per minute ( cpm ) per well at each drug concentration and expressed as percentage of the untreated controls . from the sigmoidal inhibition curves ic 50 values are calculated . k1 strain is used . the compounds are tested at 7 concentrations ( 5000 to 78 ng / ml ). artemisinin and chloroquine are included as reference drugs . if the ic 50 is & gt ; 5 μg / ml , the compound is classified as inactive if the ic 50 is 0 . 5 - 5 μg / ml , the compound is classified as moderately active if the ic 50 is & lt ; 0 . 5 μg / ml , the compound is classified as active and is further evaluated using two strains , k1 and nf54 . a new range of concentrations is chosen depending on the ic 50 determined ( e . g . 100 to 1 . 56 ng / ml ) and the assay is carried out 2 × independently . the standard drugs are chloroquine and artemisinin which are run in the same assay . the ic 50 values for chloroquine are 2 . 9 ng / ml for nf54 and 48 ng / ml for k1 ; for artemisinin 1 . 9 ng / ml for nf54 and 0 . 8 ng / ml for k1 . test compounds are tested against a panel of say , 14 different of different origin and some show resistances to chloroquine and / or pyrimethamine . if the range of the ic 50 values for the 14 strains is within a factor 3 - 5 × then the tested compound is considered not to show cross resistance . 2 ′- dutp , was purchased from pharmacia . mgcl 2 , bsa , and the ph indicator cresol red were from sigma . the buffer n , n - bis ( 2 - hydroxyethyl ) glycine ( bicine ) was obtained from usb ( united states biochemical ), ohio . all the concentrations of nucleotides were calculated spectrophotometrically ( hp - 8453 , hewlett packard ) at 280 nm , using the extinction coefficient ( ε 280 nm = 1 . 75 ml mg − 1 cm − 1 ). other chemicals used in these experiments were of the highest quality available . conserved motifs of the human dutpase enzyme were used as query to identify the pfdut gene in the www . tigr . org database of the plasmodium falciparum 3d7 strain . the entire coding sequence was amplified by the pcr using as template cdna and as primers the oligonucleotides atg - pfdut ( catatgcatttaaaaattgtatgtctg ) and tga - pfdut ( ggatcctcaatatttattatcgatgtcgatc ) which were designed so that ndei and bamhi restriction sites were introduced at the 5 and 3 ′ ends for convenient cloning in the expression vector pet11 ( stratagene ). the amplified product was cloned into pgemt ( promega ) and propagated in e . coli xl1b cells . in order to confirm the correct sequence after amplification , sequencing was performed using an applied biosystems automated sequencer , at the analytical services of the instituto de parasitología y biomedicina “ lópez neyra ”. these services also supplied the oligonucleotides designed for the sequencing recombinant p . falciparum dutpase was purified from e . coli bl21 ( de3 ) cells transformed with pet - pfdut . pellets from a liter of culture were resuspended in a solution consisting of buffer a ( 20 mm mes ph 5 . 5 , 50 mm nacl , 1 mm dtt ) plus the protease inhibitors 1 mm pmsf , 20 μg / ml leupeptin and 1 mm benzamidine . purification was carried out in a cold room ( 4 ° c .). the soluble crude extract was obtained by sonication in a vibra - cell ( sonics and materials inc . danbury , conn ., usa ) and centrifugation at 14000 × g . the extract was loaded onto a phosphocellulose column ( whatman ) pre - equilibrated with buffer a at a flow rate of 1 mil / min . after washing the column with 100 ml of buffer a , elution was performed using a linear nacl gradient of 50 to 1000 mm . peak fractions with a low concentration of contaminating protein , as judged by 15 % sds - page gels , were pooled and then loaded and chromatographed on a superdex 200 column at a flow rate of 0 . 5 ml / min . the column was equilibrated with buffer b ( 50 mm bicine , 1 mm dtt , 10 mm mgcl 2 ). peak fractions were pooled and concentrated to about 5 mg / ml by ultrafiltration in a centripep tube ( amicon ) and stored at − 80 ° c . nucleotide hydrolysis was monitored by mixing enzyme and substrate with a rapid kinetic accessory ( hi - tech scientific ) attached to a spectrophotometer ( cary 50 ) and connected to a computer for data acquisition and storage . protons , released through the hydrolysis of nucleotides , were neutralised by a ph indicator in a weak buffered medium with similar pk a and monitored spectrophotometrically at the absorbance peak of the basic form of the indicator . absorbance changes were kept within 0 . 1 units . the indicator / buffer pair used was cresol red / bicine ( 2 mm / 50 μm , ph 8 , 573 nm ). the measurements were performed at 25 ° c ., and the solutions were previously degassed . assays contained 30 nm purified recombinant enzyme , 50 μm dutp , 5 mm mgcl 2 and 2 . 5 mm dtt , 1 . 25 mg / ml bsa and 100 mm kcl . indicator absorbance changes corresponding to complete hydrolysis of nucleotides were recorded in the computer , and the kinetic parameters v max and k mapp ( or slope ) were calculated by fitting the data to the integrated michaelis - menten equation ( segel , 1975 ). solutions of potential inhibitors were prepared at 10 mg / ml and tested routinely at concentrations of 2 , 10 , and 50 μg / μl . a wider range of concentrations was further tested when necessary for k i determination . the different apparent k m values attained were plotted against inhibitor concentration and k i values were obtained according to the following equation : human recombinant dutpase was purified from e . coli bl21 ( de3 ) cells transformed with pethudut ( dr . p . o . nyman , lund university ). purification was accomplished as described for the dutpase above except that the last step in superdex 200 was omitted . likewise , conditions for enzyme assays were the same as described above except that the enzyme concentration was 50 nm . three strains of t . brucei spp . are used in this study : ( a ) trypanosomal brucei rhodesiense stib 900 , a clone of a population isolated in 1982 from a patient in tanzania which is known to be susceptible to all currently used drugs ; ( b ) trypanosoma bruncei gambiense stib 930 , a derivative of strain th1 / 78e ( 031 ) isolated in 1978 from a patient in ivory coast which is known to be sensitive to all drugs used , and ( c ) trypanosoma brucei brucei stib 950 , a clone of a population isolated in 1985 from a bovine in somalia which shows drug resistance to diminazene , isometamidium and quinapyramine . the bloodstream form trypomastigotes of the strains a and c are maintained in mem medium with earle &# 39 ; s salts supplemented with 25 mm hepes , 1 g / l additional glucose , 1 % mem non - essential amino acids ( 100 ×), 0 . 2 mm 2 - mercaptoethanol , 2 mm na - pyruvate , 0 . 1 mm hypoxanthine and 15 % heat inactivated horse serum . the bloodstream form trypomastigotes of strain b are maintained in mem medium with earle &# 39 ; s salts supplemented with 25 mm hepes , 1 g / l additional glucose , 1 % mem non - essential aminoacids ( 100 ×), 0 . 2 mm 2 - mercaptoethanol , 2 mm na - pyruvate , 0 . 1 mm hypoxanthine , 0 . 05 mm bathocuproine disulphonic acid , 0 . 15 mm l - cysteine and 15 % heat inactivated pooled human serum . all cultures and assays are conducted at 37 ° c . under an atmosphere of 5 % c0 2 in air . stock drug solutions are prepared in 100 % dmso ( unless otherwise suggested by the supplier ) at 10 mg / ml , and heated or sonicated if necessary . after use the stocks are kept at − 20 ° c . for the assays , the compound is further diluted to the appropriate concentration using complete medium . assays are performed in 96 - well microtiter plates , each well containing 100 μl of culture medium with 8 × 10 3 bloodstream forms with or without a serial drug dilution . the highest concentration for the test compounds is 90 μg / ml . seven 3 - fold dilutions are used covering a range from 90 μg / ml to 0 . 123 μg / ml . each drug is tested in duplicate and each assay is repeated at least once . after 72 hrs of incubation the plates are inspected under an inverted microscope to assure growth of the controls and sterile conditions . 10 μl of alamar blue ( 12 . 5 mg resazurin dissolved in 100 ml distilled water ) are now added to each well and the plates incubated for another 2 hours . then the plates are read with a spectramax gemini xs microplate fluorometer ( molecular devices cooperation , sunnyvale , calif ., usa ) using an excitation wave length of 536 nm and an emission wave length of 588 nm . data are analysed using the microplate reader software softmax pro ( molecular devices cooperation , sunnyvale , calif ., usa ). the preliminary screen uses the trypanosoma b . rhodesiense strain . the compounds are tested at 7 concentrations ( drug concentrations ranging from 90 μg / ml to 0 . 123 μg / ml in 3 - fold dilutions ). if the ic 50 is & gt ; 3 μg / ml , the compound is classified as inactive if the ic 50 is 0 . 2 - 3 μg / ml , the compound is classified as moderately active if the ic 50 is & lt ; 0 . 2 μg / ml , the compound is classified as active the standard drug is melarsoprol which is run in the same assay ; the ic 50 for melarsoprol is 1 . 6 ng / ml . active compounds ( ic 50 & lt ; 0 . 2 μg / ml ) are tested against the trypanosoma brucei gambiense stib 930 and the drug resistant t . b . brucei stib 950 following the same protocol as described above . the standard drug is melarsoprol which is run in the same assay ; the ic 50 for melarsoprol is 4 . 2 ng / ml for stib 930 and 2 . 8 ng / ml for stib 950 the trypanosoma cruzi tulahuen c2c4 strain , containing the galactosidase ( lac z ) gene , is used . the plasmid construct by dr . s . reed was obtained from dr . f . buckner , seattle , as epimastigotes in lit medium . the infective amastigote and trypomastigote stages are cultivated in l - 6 cells ( rat skeletal myoblast cell line ) in rpmi 1640 supplemented with 2 mm l - glutamine and 10 % heat - inactivated foetal bovine serum in 12 . 5 cm 2 tissue culture flasks . amastigotes develop intracellularly , differentiate into trypomastigotes and leave the host cell . these trypomastigotes infect new l - 6 cells and are the stages used to initiate an infection in the assay . all cultures and assays are conducted at 37 ° c . under an atmosphere of 5 % c0 2 in air . stock drug solutions are prepared in 100 % dmso ( dimethylsulfoxide ) unless otherwise suggested by the supplier at 10 mg / ml , and heated or sonicated if necessary . the stocks are kept at − 20 ° c . for the assays , the compound is further diluted to the appropriate concentration using complete medium . assays are performed in sterile 96 - well microtiter plates , each well containing 100 μl medium with 2 × 10 3 l - 6 cells . after 24 hours 50 μl of a trypanosome suspension containing 5 × 10 3 trypomastigote bloodstream forms from culture are added to the wells . 48 hours later the medium is removed from the wells and replaced by 100 μl fresh medium with or without a serial drug dilution . at this point the l - 6 cells should be infected with amastigotes and no free trypomastigotes should be in the medium . seven 3 - fold dilutions are used covering a range from 90 μg / ml to 0 . 123 μg / ml . each drug is tested in duplicate . after 96 hours of incubation the plates are inspected under an inverted microscope to assure growth of the controls and sterility . then the substrate cprg / nonidet ( 50 l ) is added to all wells . a colour reaction will become visible within 2 - 6 hours and can be read photometrically at 540 nm . data are transferred into a graphic programme ( e . g . excel ), sigmoidal inhibition curves determined and ic 50 values calculated . benznidazole is used as the reference drug and shows an ic 50 value of 0 . 34 μg / ml . if the ic 50 is & gt ; 30 μg / ml , the compound is classified as inactive . if the ic 50 is between 2 and 30 μg / ml , the compound is classified as moderately active . if the ic 50 is & lt ; 2 μg / ml , the compound is classified as active . the leishmania . donovani strain mhom / et / 67 / l82 obtained from dr . s . croft , london ) is used . the strain is maintained in the syrian golden hamster . amastigotes are collected from the spleen of an infected hamster amastigotes are grown in axenic culture at 37 ° c . in sm medium ( cunningham i ., j . protozool . 24 , 325 - 329 , 1977 ) at ph 5 . 4 supplemented with 10 % heat - inactivated foetal bovine serum under an atmosphere of 5 % c0 2 in air . primary peritoneal macrophages from nmri mice are collected 1 day after a macrophage production stimulation with an i . p injection of 2 ml of a 2 % potato starch suspension ( fluka , switzerland ) all cultures and assays are done at 37 ° c . under an atmosphere of 5 % co 2 in air . stock drug solutions are prepared in 100 % dmso ( unless otherwise suggested by the supplier ) at 10 mg / ml , and heated or sonicated if necessary . after use the stocks are kept at − 20 ° c . for the assays , the compound is further diluted in serum - free culture medium and finally to the appropriate concentration in complete medium . assays are performed in sterile 16 - well chamber slides ( labtek , nalgene / nunc int .) to each well 100 μl of a murine macrophage suspension ( 4 × 10 5 / ml ) in rpmi 1640 ( containing bicarbonate and hepes ) supplemented with 10 % heat inactivated fetal bovine serum is added . after 24 hrs 100 μl of a suspension containing amastigotes ( 1 . 2 × 10 6 / ml ) is added resulting in a 3 : 1 ratio of amastigotes / macrophages . the amastigotes are harvested from an axenic amastigote culture and suspended in rpmi / fbs . 24 hrs later , the medium containing free amastigotes is removed , washed 1 × and replaced by fresh medium containing four 3 - fold drug dilutions . in this way 4 compounds can be tested on one 16 - well tissue culture slide . untreated wells serve as controls . parasite growth in the presence of the drug is compared to control wells . after 4 days of incubation the culture medium is removed and the slides fixed with methanol for 10 min followed by staining with a 10 % giemsa solution . infected and non - infected macrophages are counted for the control cultures and the ones exposed to the serial drug dilutions . the infection rates are determined . the results are expressed as % reduction in parasite burden compared to control wells , and the ic 50 calculated by linear regression analysis . the compounds are tested in duplicate at 4 concentrations ranging from 9 to 0 . 3 μg / m . if the ic 50 is below 0 . 3 μg / ml then the range is changed to 1 to 0 . 03 μg / ml . miltefosine is used as the reference drug and shows an ic 50 value of 0 . 325 μg / ml ( 0 . 22 - 0 . 42 μg / ml ; n = 4 ) if the ic 50 is higher than 10 μg / ml , the compound is classified as inactive . if the ic 50 is between 2 and 10 μg / ml , the compound is classified as moderately active . if the ic 50 is & lt ; 2 μg / ml , the compound is classified as active and is further evaluated in a secondary screening . stock drug solutions are prepared in 100 % dmso ( dimethylsulfoxide ) unless otherwise suggested by the supplier at 10 mg / ml , and heated or sonicated if necessary . the stocks are kept at − 20 ° c . for the assays , the compound is further diluted to the appropriate concentration using complete medium . assays are performed in sterile 96 - well microtiter plates , each well containing 100 μl medium with 2 × 10 3 l - 6 cells . after 24 hours 50 μl of a trypanosome suspension containing 5 × 10 3 trypomastigote bloodstream forms from culture are added to the wells . 48 hours later the medium is removed from the wells and replaced by 100 μl fresh medium with or without a serial drug dilution . at this point the l - 6 cells should be infected with amastigotes and no free trypomastigotes should be in the medium . seven 3 - fold dilutions are used covering a range from 90 μg / ml to 0 . 123 μg / ml . each drug is tested in duplicate . after 96 hours of incubation the plates are inspected under an inverted microscope to assure growth of the controls and sterility . then the substrate cprg / nonidet ( 50 μl ) is added to all wells . a colour reaction will become visible within 2 - 6 hours and can be read photometrically at 540 nm . data are transferred into a graphic programme ( e . g . excel ), sigmoidal inhibition curves determined and ic 50 values calculated . benznidazole is used as the reference drug and shows an ic 50 value of 0 . 34 μg / ml . if the ic 50 is & gt ; 30 μg / ml , the compound is classified as inactive . if the ic 50 is between 2 and 30 μg / ml , the compound is classified as moderately active . if the ic 50 is & lt ; 2 μg / ml , the compound is classified as active . the leishmania donovani strain mhom / et / 67 / l82 ) is used . the strain is maintained in the hamster . amastigotes are collected from the spleen of an infected hamster and adapted to axenic culture conditions at 37 ° c . the medium is a 1 : 1 mixture of sm medium ( cunningham i ., j . protozool . 24 , 325 - 329 , 1977 ) and sdm - 79 medium ( brun , r . & amp ; schönenberger , m ., acta trop . 36 , 289 - 292 , 1979 ) at ph 5 . 4 supplemented with 10 % heat - inactivated fbs under an atmosphere of 5 % co 2 in air . stock drug solutions are prepared in 100 % dmso ( unless otherwise suggested by the supplier ) at 10 mg / ml , and heated or sonicated if necessary . after use the stocks are kept at − 20 ° c . for the assays , the compound is further diluted to the appropriate concentration using complete medium . assays are performed in 96 - well microtiter plates , each well containing 100 pt of culture medium with 10 5 amastigotes from axecic culture with or without a serial drug dilution . the highest concentration for the test compounds is 90 μg / ml . seven 3 - fold dilutions are used covering a range from 30 μg / ml to 0 . 041 μg / ml . each drug is tested in duplicate and each assay is repeated at least once . after 72 hours of incubation the plates are inspected under an inverted microscope to assure growth of the controls and sterile conditions . 10 μl of alamar blue ( 12 . 5 mg resazurin dissolved in 1 l distilled water ) are now added to each well and the plates incubated for another 2 hours . then the plates are read with a spectramax gemini xs microplate fluorometer ( molecular devices cooperation , sunnyvale , calif ., usa ) using an excitation wave length of 536 nm and an emission wave length of 588 nm . data are analysed using the microplate reader software softmax pro ( molecular devices cooperation , sunnyvale , calif ., usa ). the compounds are tested in duplicate at 7 concentrations . miltefosine is used as the reference drug and shows an ic 50 value of 0 . 12 μg / ml . if the ic 50 is & gt ; 3 μg / ml , the compound is classified as inactive if the ic 50 is 0 . 1 - 3 μg / ml , the compound is classified as moderately active if the ic 50 is & lt ; 0 . 1 μg / ml , the compound is classified as active active and moderately active compounds are tested in the macrophage assay with intracellular amastigotes in their host cells , murine macrophages . compounds of the invention , such as those in the examples above , typically show activities in the low micromolar range for plasmodium falciparum enzyme ( k i ) and cell culture ( ed 50 ), with selectivity ( si ) over the human enzyme of at least 10 - fold . throughout the specification and the claims which follow , unless the context requires otherwise , the word ‘ comprise ’, and variations such as ‘ comprises ’ and ‘ comprising ’, will be understood to imply the inclusion of a stated integer , step , group of integers or group of steps but not to the exclusion of any other integer , step , group of integers or group of steps .

US-58528305-A

in one embodiment , a fishing line bobber includes a bobber body having a length and an exterior surface . the bobber body includes an aperture that extends through the length of the bobber body and a slot extending along the length of the bobber body and connected to the aperture through sidewalls that extend from the exterior surface of the bobber body inward to the aperture . the fishing line bobber includes a closing mechanism movable with respect to the bobber body between an open position that permits insertion of a fishing line into the aperture and a closed position that retains the fishing line within the aperture . the closing mechanism is configured to enable the fishing line bobber to function as an attachment bobber that maintains a fixed position on the fishing line and as a slip bobber that is moveable along the fishing line .

embodiments of the present disclosure include fishing bobbers . one particular example of a fishing bobber 100 is shown in fig1 - 6 . it should be noted however that embodiments of the present disclosure are not limited to the specific example shown in the figures . embodiments of the present disclosure illustratively include fishing bobbers having any one or more features or combination of features described in this specification and / or shown in the figures . fig1 is a perspective view of bobber 100 having a fishing line 190 running through the bobber . in an embodiment , bobber 100 includes a main body portion 102 , a first shaft portion 104 , and , a second shaft portion 106 . main body portion 102 includes a slot 108 that extends from an outer surface of the main body portion towards the center of the main body portion . first shaft portion 104 includes a slot 110 that extends from the outer surface of the first shaft portion towards the center of the first shaft portion , and second shaft portion 106 includes a slot 112 that extends from the outer surface of the second shaft portion towards the center of the second shaft portion . the main body slot 108 , the first shaft slot 110 , and the second shaft slot 112 are illustratively aligned such that they form a channel that runs along the entire length of bobber 100 . the width of the channel is greater than the width of fishing line 190 such that fishing line 190 is able to be fit within and run through bobber 100 . bobber 100 also illustratively includes one or more closing mechanisms for connecting bobber 100 to fishing line 190 . in the particular example shown in fig1 , bobber 100 includes a first closing mechanism 120 and a second closing mechanism 130 . embodiments are not however limited to any particular number of closing mechanisms and may include more or less than the illustrated two ( e . g . 0 , 1 , 3 , 4 , etc . closing mechanisms ). first closing mechanism 120 includes a slot 121 and a tab 122 . first closing mechanism 120 is able to rotate within first shaft portion 104 in the directions shown by arrow 123 . second closing mechanism 130 includes a slot 131 and a tab 132 . second closing mechanism 130 is able to rotate within second shaft portion 106 in the directions shown by arrow 133 . in one embodiment , a user rotates first closing mechanism 120 using tab 122 such that the slot 121 of the first closing mechanism is aligned with the slot 110 of the first shaft portion to form an opening . the user is then able to position fishing line 190 within slot 121 of the first closing mechanism 120 . the user similarly rotates second closing mechanism 130 using tab 132 such that the slot 131 is aligned with the slot 112 of the second shaft portion to form another opening . the user is then able to position fishing line 190 within slot 131 of the second closing mechanism 130 . after fishing line 190 is positioned within the slots of the closing mechanisms and within the main body slot 108 , the first closing mechanism 120 and the second closing mechanism 130 are rotated to a closed position to connect bobber 100 to fishing line 190 . fig2 shows a perspective view of fishing bobber 100 with closing mechanisms 120 and 130 rotated to their closed positions . in fig2 , both the first closing mechanism tab 122 and the second closing mechanism tab 132 have been rotated such that the slots of the closing mechanisms 121 and 131 ( shown in fig1 ) are no longer aligned with the shaft slots 110 and 112 to form openings . as can perhaps be best seen in the bottom right hand corner of fig2 , when closing mechanism 130 is rotated into the closed position , fishing line 190 is enclosed within an inner wall 107 of the second shaft portion 106 and the wall of the second closing mechanism slot 131 . when first closing mechanism 120 is rotated into the closed position , fishing line 190 is similarly enclosed with an inner wall of the first shaft portion 104 and the wall of the first closing mechanism slot 121 . accordingly , bobber 100 is able to be connected to and released from fishing line 190 by rotating first and second closing mechanisms 120 and 130 into their open and closed positions . as can be seen in fig2 , in one embodiment , fishing line 190 is positioned within the closing mechanisms 120 and 130 such that the fishing line 190 is able to move throughout the length of bobber 100 . the surfaces of bobber 100 that may come into contact with fishing line 190 are optionally smooth such that there is a minimal amount of friction between the line 190 and the bobber 100 . in such a case , bobber 100 illustratively can be used as a slip bobber . additionally , as is described in greater detail below , certain embodiments of bobber 100 may also include features that enable the bobber to be used as an attachment bobber as well as a slip bobber . fig3 a is a close - up view of one illustrative end of a bobber . in the example shown in the figure , closing mechanism 130 includes two different slots that run along the entire length of the closing mechanism . the first slot 131 has a first edge 134 , a second edge 135 , and a circular wall 136 . circular wall 136 has a diameter 137 . in an embodiment , diameter 137 is larger than a diameter of a fishing line to be used with the bobber . accordingly , when a fishing line is positioned within first slot 131 , the bobber is able to freely move along the length of the fishing line and function as a slip bobber . the fishing line is prevented from escaping first slot 131 by an inner wall 107 of the shaft portion fig3 a also shows that closing mechanism 130 has a second slot 301 . in one embodiment , slot 301 is formed as a shallow groove that runs along the length of the closing mechanism 130 . in the example shown in the figure , second slot 301 is formed as one continuous curved surface . embodiments of second slot 301 are not however limited to any particular configuration and may have a different shape or design . fig3 b and 3c show how a fishing line 190 may be connected to fishing bobber 100 utilizing second slot 301 . in fig3 b , the closing mechanism has been rotated using tab 132 such that the closing mechanism second slot 301 is aligned with the shaft slot 112 . this allows for fishing line 190 to be placed within slot 301 . in fig3 c , the closing mechanism has been rotated using tab 132 such that the closing mechanism second slot 301 is aligned with an inner wall 107 of the shaft portion and not aligned with shaft slot 112 . accordingly , the second slot 310 and the shaft inner wall 107 form an enclosed space that captures fishing line 190 . in an embodiment , second slot 301 has a depth such that the distance 302 between the second slot 301 and the shaft inner wall 107 is less than the diameter / width of fishing line 190 . in such an embodiment , fishing line 190 is prevented from moving along the length of second slot 301 . second slot 301 can therefore be used to maintain bobber 100 at a fixed position on fishing line 190 . in other words , second slot 301 enables bobber 100 to be used as an attachment bobber . as can be seen in fig3 a - 3c , a closing mechanism 130 may include both a slot 131 that enables a bobber to move along the length of a fishing line ( i . e . a “ slip slot ”), and a slot 301 that enables a bobber to be maintained at a fixed position along the length of a fishing line ( i . e . an “ attachment slot ”). accordingly , in at least certain embodiments of the present disclosure , one single bobber can function both as a slip bobber and as an attachment bobber depending upon the positioning of the fishing line within the bobber . additionally , it should be noted that although fig3 a - 3c only show one closing mechanism having two slots ( i . e . slots 131 and 301 ), it should be recognized that each closing mechanism within a bobber ( e . g . both closing mechanisms 120 and 130 in fig1 ) illustratively include two slots . in such an embodiment , a bobber can be used as a slip bobber by enclosing the fishing line within the “ slip slots ” of each of the closing mechanisms , or the bobber can be used as an attachment bobber by enclosing the fishing line within the “ attachment slots ” of each of the closing mechanisms . embodiments of bobbers of the present disclosure are not however limited to any particular design . for instance , bobbers may have only “ slip slots ,” only “ attachment slots ,” or any combination of both “ slip slots ” and “ attachment slots .” also for instance , embodiments of bobbers may have any number of closing mechanisms ( e . g . 1 , 2 , 3 , etc .) with any number of slots within each of the closing mechanisms ( e . g . 1 , 2 , 3 , etc .). fig4 shows an exploded view of bobber 100 with each of the parts of bobber 100 separated from each other . in the embodiment shown in the figure , bobber 100 is made using five pieces . each of the pieces is optionally made using the same material ( e . g . a plastic ). however , embodiments of the present disclosure are not limited to any particular construction and may be made using more or less than the illustrated five pieces , and may be made from any material or combination of materials . bobber 100 illustratively includes a first closing mechanism 120 , a first combined shaft / main body portion 140 , a center portion 150 , a second combined shaft / main body portion 160 , and a second closing mechanism 130 . in an embodiment , first and second closing mechanisms 120 and 130 are the same , and first and second combined shaft / main body portions 140 and 160 are the same . this may reduce manufacturing costs by reducing the number of different parts that need to be made . the parts do not however necessarily need to be made to be the same and may be different . first closing mechanism 120 illustratively includes a tab 122 , a generally cylindrical portion 124 , and a slot 121 . first combined shaft / main body portion 140 illustratively includes a first shaft portion 104 , a first main body portion 142 , and a central aperture 144 that runs throughout the length of the portion 140 . the outer diameter of the closing mechanism generally cylindrical portion 124 is smaller than the diameter of the central aperture 144 such that the first closing mechanism 120 is able to be positioned within the central aperture 144 . in particular , first closing mechanism 120 is positioned within shaft portion 104 . first combined shaft / main body portion 140 also illustratively includes a tab channel 146 that runs perpendicular to the slot 110 . tab channel 146 provides space on either side of slot 110 such that tab 122 can be rotated between the open and closed positions . side walls 143 and 145 run between the central aperture 144 and the outer perimeter of the bobber . side walls 143 and 145 are illustratively smooth and enable a fishing line to be positioned within and removed from the bobber . first combined shaft / main body portion 140 optionally includes a ridge 147 that is smaller than a ridge 152 of center portion 150 . first combined shaft / main body portion 140 may be connected to center portion 150 by fitting ridge 147 within ridge 152 . in an embodiment , first combined shaft / main body portion 140 is hollow such that it has an air space 148 . first shaft / main body portion 140 is illustratively connected to center portion 150 such that water cannot or has difficulty entering air space 148 . in such a case , air space 148 provides buoyancy to the bobber enabling the bobber to float . in one embodiment , first shaft / main body portion 140 and center portion 150 may be connected using a water resistant adhesive . however , first shaft / main body portion 140 and center portion 150 do not necessarily need to be connected using an adhesive and can be connected by other means ( e . g . thermally sealed together , mechanically snap - fit to each other , etc .). center portion 150 also illustratively includes a second ridge 154 , a cross - sectional member 156 , and an aperture 158 . in an embodiment , aperture 158 is formed such that it has portions corresponding to the central aperture 144 and sidewalls 143 , 145 of the first combined shaft / main body portion 140 . accordingly , aperture 158 allows a fishing line to be positioned within the bobber and optionally run through the bobber ( e . g . for the bobber to be used as a slip bobber ). cross - sectional member 156 in at least some embodiments provides mechanical support for the bobber . for example , cross - sectional member 156 may make a bobber more rigid and less compressible . second ridge 154 is illustratively used to connect second shaft / main body portion 160 to center portion 150 . for instance , second shaft / main body portion 160 optionally includes a ridge 167 that is smaller second ridge 154 . second shaft / main body portion 160 can then be connected to center portion 150 by fitting ridge 167 within ridge 154 . second shaft / main body portion 160 may be secured to center portion 150 in the same or similar manner as first shaft / main body portion 150 is secured to center portion 150 ( e . g . adhesive or snap - fit ). second shaft / main body portion 160 , as well as first shaft main / body portion 140 , are not however limited to any particular method of attachment to center portion 150 . in another embodiment , bobber 100 does not include a center portion 150 . instead , first shaft / main body portion 140 is directly connected to second shaft / main body portion 160 . additionally , in yet another embodiment , bobber 100 does not need to include two separate pieces for first shaft / main body portion 140 and second shaft / main body portion 160 . instead , the first shaft / main body portion 140 and second shaft / main body portion 160 are formed as one piece . for instance , a bobber 100 may be constructed from only three pieces such as from two closing mechanisms ( e . g . closing mechanisms 120 and 130 ) and one single combined shaft / main body portion . embodiments of the present disclosure are not however limited to any particular construction and may be constructed using any of the methods described above or any other methods . second shaft / main body portion 160 illustratively includes a second main body portion 162 and a second shaft portion 106 . in an embodiment , such as in the one shown in fig4 , second shaft / main body portion 160 includes the same or similar components as first shaft / main body portion 140 . for instance , fig4 shows that second shaft / main body portion 160 also includes a slot 112 , a tab channel 166 , and a central aperture 164 . second shaft / main body portion 160 also optionally includes the other parts of first shaft / main body portion 140 such as sidewalls running from the central aperture to the outer perimeter of the bobber and an air space for providing buoyancy . in one embodiment , second closing mechanism 130 is the same or similar to first closing mechanism 120 and illustratively fits within second shaft / main body portion 160 the same or similar to as how first closing mechanism 120 fits within first shaft / main body portion 140 . for instance , in an embodiment , a tab 132 of second closing mechanism 130 fits with a tab channel 166 of the second shaft / main body portion 160 , and is used to align a slot 131 of the second closing mechanism 130 with a slot 112 of the second shaft / main body portion 160 to move the second closing mechanism into an open position to receive a fishing line . fig5 shows a cross - sectional view of the bobber 100 . as can be seen in the figure , a slot 121 of first closing mechanism 120 , a central aperture 144 of first shaft / main body portion 140 , a central aperture 158 of center portion 150 , a central aperture 164 of second shaft / main body portion 160 , and a slot 131 of second closing mechanism 130 illustratively form one continuous open tubular space that enables a fishing line to be positioned within and run through bobber 100 . fig5 also shows how ridge 147 of first shaft / main body portion 140 fits within ridge 152 of center portion 150 to connect the two pieces together in a water resistant manner , and how ridge 167 of second shaft / main body portion 160 fits within ridge 154 of center portion 150 to connect the two pieces together in a water resistant manner . furthermore , fig5 shows that first shaft portion 104 and first main body portion 142 are formed together as one piece , and that second shaft portion 106 and second main body portion 162 are formed together as one piece . fig6 is a side view of bobber 100 . fig6 is useful in showing some of the dimensions of bobber 100 . bobber 100 includes an overall length 602 and a maximum width 652 . in an embodiment , overall length 602 is between two and five inches , and maximum width 652 is between half an inch and two inches . bobber 100 also includes a minimum width 654 , a first shaft portion 104 length 604 , a main body portion 102 length 606 , and a second shaft portion 106 length 608 . minimum width 654 is illustratively between five and thirty percent of the maximum overall width 652 . first and second shaft lengths 604 and 608 are each illustratively between five and forty percent of the overall length 602 , and the main body portion length 606 is illustratively between forty and ninety percent of the overall length 602 . embodiments of the present disclosure are not however limited to any particular dimensions or ratios , and may include dimensions and ratios outside of those mentioned above . as can be seen in fig6 and in the other figures , both first shaft portion 104 and second shaft portion 106 have a generally cylindrical shape . the widths 654 of the first and second shaft portions 104 , 106 are more or less approximately uniform throughout the lengths 604 , 608 of the shaft portions . additionally , the lengths 604 and 608 of the shaft portions 104 , 106 are optionally the same or approximately the same as each other . main body portion 102 illustratively has a football or oval like shape such that it has a minimal width 654 at its two outer ends and the width increases going towards the center of the main body until the width reaches a maximum width of 652 at the center . embodiments of the present disclosure are not however limited to any particular shapes or designs , and shapes and designs other than those shown in the figures may be included within embodiments . as has been described above , embodiments of the present disclosure include fishing bobbers . in some embodiments , fishing bobbers include closing mechanisms that enable the bobbers to easily be connected to or removed from a fishing line by rotating the closing mechanisms between open and closed positions . bobbers may also have “ attachment slots ” and / or “ slip slots ” that enable a bobber to be used as either a slip bobber or as an attachment bobber . additionally , certain embodiments may be less expensive to manufacture by only including a limited number of separate components . for instance , a shaft and a main body are illustratively combined into one component as opposed to using separate components for the shaft and the main body . embodiments of the present disclosure also include any other feature or combination of features described above or shown in the figures . finally , it is to be understood that even though numerous characteristics and advantages of various embodiments have been set forth in the foregoing description , together with details of the structure and function of various embodiments , this detailed description is illustrative only , and changes may be made in detail , especially in matters of structure and arrangements of parts within the principles of the present disclosure to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed .

US-201213686386-A

for measuring an oxidative stress component in a patient , an optical analyzer having a light source and a light detector is used for measuring an optical property of a medium and generating optical measurement data . a processor analyzes the optical measurement data and generates a value for one or more oxidative stress component in the form of a redox signature for the patient . probability data of the presence of an oxidative stress dependent disease can be calculated . by observing at least one additional clinical condition of the disease , a diagnosis using said at least one additional condition and said redox signature can be obtained .

measurement of os from short wavelength near infrared ( swnir ) spectroscopy of blood plasma according to prior anamesis and testing , patients were grouped into the following categories : normal elderly control ( nec ) mild cognitive impairment ( mci ) alzheimer &# 39 ; s disease ( ad ) vascular cognitive impairment ( vci ) parkinson &# 39 ; s disease ( pd ) the patient population varied in terms of gender , age , medication , nutrition , other diseases ( if any ), and familial predisposition . initial experiments had shown that the nature of the anticoagulant ( edta versus heparin ), variations in freezing and thawing cycles ( storage at − 80 ° c . versus + 4 ° c . ), centrifugation time ( 1 min versus 30 min ) and preconditioning of the sample cell all had significant impact on the spectral signature of the plasma sample . consequently , the ensuing sample preparation procedure was developed : blood samples were drawn from the patients and , upon centrifugation , the separated plasma immediately stored at − 80 ° c . using either edta or heparin as an anticoagulant . storage time varied from 1 to 400 days . only classes comprising the same anticoagulant were compared to one another . prior to analysis samples were thawed for one hour to reach room temperature and then centrifuged for 30 min . for cleaning and preconditioning , the sample cell was first rinsed with 200 μl of 0 . 1 m naoh followed by 3 × 200 μl millipore water . a swnir spectrum was recorded of the third water rinse serving as a control . thereupon , 75 μl of sample was injected into the sample cell and a sample spectrum recorded using the apparatus as shown in fig2 . short wavelength near infrared spectra were obtained from the prepared plasma samples using the following protocol . for the measurements , an american holographic near infrared spectrophotometer was used . the spectrophotometer is equipped with a two channel input port so that a reference could be obtained simultaneous with the measurement sample . spectra acquired covered the 580 to 1100 nm region . integration time of the detector was 100 milliseconds . all samples were measured 50 times and the results averaged to reduce spectral noise . samples were introduced into a sample cell with 10 mm internal pathlength using an eppendorff pipette . approximately 75 microliter sample was used . after spectral data were obtained , the sample cell was washed using 200 microliter - 0 . 1 m naoh followed by 3 volumes of 200 microliter millipore water . after each sample a separate reference spectrum was taken of the third water rinse solution . this allowed monitoring of contamination of the sample cell or changes in alignment of the optical system . each sample spectrum was referenced to the consecutive water sample for later processing . two different methods of spectral analysis were used to identify and categorize plasma samples into neurological classes . method one used pre - selection of wavelength regions associated with functional groups identifiable by nir spectroscopy . linear models of class were then determined using all possible combinations of the wavelength regions selected . in method two , the best combination of wavelength regions were automatically selected using a haar transform based technique of the acquired swnir spectra at 256 wavelengths spanning 600 - 1100 nm . classification of samples from swnir spectra consisted of determining the most parsimonious combination of variables in the wavelet domain using a genetic algorithm ( ga ). to obtain data in the wavelet domain “ son ” haar wavelets were used . a more detailed overview of the data processing steps is given in the following sections . the swnir spectra contains absorptions from a variety of molecular species . to select for major molecular species present in blood plasma , wavelength regions ( 15 nm width ) associated with heme ( 700 nm ), ch ( 830 nm ), roh ( 940 nm ), h 2 o ( 960 nm ), oh ( 980 nm ) and nh ( 1020 nm ) moieties were identified as shown in fig3 . the integrated absorptions from these six regions were then used in the regression model described below . the haar transform ( ht ) is the oldest and simplest wavelet transform . similarly to the fourier transform , it projects data — for example a nir spectrum — onto a given basis set . unlike the fourier transform , which uses sine and cosine functions as a basis set , the ht uses haar wavelets . in this study , a discrete wavelet transform ( dwt ) was chosen over a continuous wavelet transform or a wavelet packet transform to maximize the simplicity and speed of calculations . for data defined over the range 0 ≦ x ≦ 1 , the family of haar wavelets for a dwt is given by : ϕ ⁡ ( x ) = { 1 if ⁢ ⁢ 0 ≤ x & lt ; 1 0 otherwise ( 1 ) ø ⁡ ( x ) = { 1 if ⁢ ⁢ 0 ≤ x & lt ; 1 2 - 1 if ⁢ ⁢ 1 2 ≤ x & lt ; 1 0 otherwise ( 2 ) ψ n , k ( x )= ψ ( 2 n x − k ), 0 ≦ k ≦ 2 n − 1 ( 3 ) carrying out a ht consists of decomposing a spectrum into a weighted sum of f , y , and yn , k , where the weightings are known as “ wavelet coefficients ”. to obtain the coefficient of the father wavelet , f , the signal over the entire data window is integrated . the weighting of the mother wavelet , y , is obtained by integrating the first half of the data points , and subtracting the sum of the second half of the data . daughter wavelets are scaled down and translated versions of the mother wavelet . in the notation yn , k , n represents the scaling , and k indicates translation . thus , ever smaller regions in the data are summed to find the coefficients of the daughter wavelets , down to the minimum element size of the data . daughter wavelets therefore behave like high - pass filters , while the father wavelet functions as a low - pass filter . overall , the number of wavelet coefficients obtained is the same as the number of points in the original data set . from the above description , it becomes apparent that haar wavelets are simple structures , since they only have three distinct levels : + 1 , − 1 or 0 . it is however possible to simplify them even further by introducing scaled down and shifted versions of the father wavelet called scaling functions or “ son ” wavelets : φ n , k ( x )= φ ( 2 n x − k ), 0 ≦ k ≦ 2 n − 1 and 0 ≦ x ≦ 1 ( 4 ) a “ son ” ht can therefore be carried out on a spectrum with z points using 2z - 1 wavelets that are constructed only of ones and zeros . the basis set for this wavelet transform is not orthogonal , since higher generation son wavelets are subsets of lower generations . however , son wavelets have the advantage of being monodirectional , i . e ., they only go positive . thus , unlike daughter wavelets , son wavelets do not inherently carry out a first derivative in the data processing . in the context of spectral analysis , the ht is particularly well suited . wavelet coefficients obtained contain both frequency and wavelength information ( where “ frequency ” is not used in the usual sense , but refers to whether wavelets describe small - and large - scale features ). due to the retention of wavelength information , it is easier to understand the spectral meaning of ht results than ft results . furthermore , it becomes possible to not only investigate the importance of separate wavelengths , but also spectral features of different sizes one common application of this property is to smooth data by deleting high frequency wavelet coefficients . alternately , large trends in data sets such as sloping baselines can be corrected by removing low frequency wavelets . [ absi , e ., et al ., decrease of 1 - methyl - 1 , 2 , 3 , 4 - tetrahydroisoquinoline synthesizing enzyme activity in the brain areas of aged rat . brain res , 2002 . 955 ( 1 - 2 ): p . 161 - 3 ] another important trait of the ht is its ability to compress a large mount of information into a very small number of variables . daughter wavelets are efficient in data compression , and this property is exploited in the present study to find the most parsimonious model to estimate sample properties . in comparison , the son ht does not perform as well for data compression since it is partially redundant , but it allows complete decoupling of adjacent wavelengths . therefore this basis set should allow more freedom in feature selection . furthermore , models built with son wavelets are easier to interpret . since n , k have only two discrete levels , either a wavelength region is chosen or not chosen by the optimization algorithm . based on the selected son wavelets , it should be possible to build a simplified instrument that uses slits or filters for sample analysis . both the daughter and son ht were calculated using programs written in matlab ( the mathworks inc ., natick , mass .). for the daughter ht , a fast ht program based on mallat &# 39 ; s pyramid algorithm determined the wavelet coefficients by carrying out a series of recursive sums and differences [ c . e . w . gributs , d . h . burns , applied optics , 2003 , 42 / 16 , p . 2923 - 2930 ]. for the son ht , simple sums were used . since the algorithms required the length of input data to be a power of 2 , experimental spectra were padded with the last data value to reach the nearest 2n . wavelet coefficients were determined and ordered from wide to more compact wavelets ( f , y , y1 , 0 , . . . , yn , k or f , f1 , 0 , . . . , fn , k ). the most parsimonious subset of variables ( either wavelengths from method 1 or wavelets from method 2 ) to estimate a class of interest was determined by inverse least squares ( ils ) regression . when few wavelengths were involved , as in method 1 , all possible combinations were modeled . when many wavelets were included in the classification ( i . e . method 2 ), a genetic algorithm ( ga ) optimization to determine the best choice of wavelets was used . using principles such as mating , crossover and mutation , many models were evaluated . for each variable combination , sample class were estimated according to y = α 0 + α 1 x 1 + α 2 x 2 + . . . + aα n x n ( 6 ) where y is the dependent variable ( neurological class , i . e . 0 - normal , 1 - ad ), x 1 , x 2 , . . . , x n are independent variables ( i . e ., intensity of a given wavelength or wavelet coefficients ), and α 0 , α 1 , . . . , α n are the coefficients determined from a set of calibration x &# 39 ; s . complete descriptions of ga optimization have previously been given elsewhere [ m . j . mcshane , b . d . cameron , g . l . cote , c . h . spiegelman , applied spectroscopy 1999 , 53 , p . 1575 - 1581 ] therefore only an overview of the method will be given here . the best fit ( optimal ) models containing 1 to 15 variables were sought using the ga method . a population of individuals ( i . e ., models ) was created by encoding chosen variables in binary and lexicographically stacking them . for preprocessed spectra of 2n variables , the binary encoding used n bits . population size was set to 1000 . every individual was used with a calibration set to build a model according to equation 6 . computation of the corresponding standard error of calibration ( sec ) was based on a test set . the two fittest individuals were identified based on their sec , and kept for the next generation without mutation . the rest of the new population was filled by randomly mating individuals with a crossover probability of 1 and a mutation rate of 0 . 02 . after following the population through 2000 generations , the algorithm converged to a stable solution . the same search was carried out for models constructed with 1 to 15 variables , and their sec were used to obtain a prediction residual error sum of squares ( press ) plot . let h designate the number of wavelets in the model with the minimum press value . the most parsimonious model was the one with the fewest number of wavelets such that the press for that model was not significantly greater than press for the model with h wavelets ( f - test , 99 % confidence level ). class values estimated were either 0 or 1 . however , the regression above determined continuous real values . class separation was determined using values greater that 0 . 5 as being from class 1 and values less than 0 . 5 from class 0 . for each model , the sensitivity and specificity were determined and used as the criterion for model selection . it will be appreciated that the present invention can work well with wavelengths from optical spectra in a variety of ranges , such as the nir , swnir and thz ranges , as would be apparent to a person skilled in the art . in addition to absorption spectra , raman spectra as illustrated in fig7 may be used . fig7 shows the average differences between nec and pd . fluorescence spectra can also be similarly analyzed . in the case of nmr , the analysis technique would be modified , as would be apparent to a person skilled in the art , to identify the desired oxidative stress components and / or perform the correlation with the desired disease or condition . it will also be appreciated that the present invention can be used to correlate spectra to a disease or condition state , in addition to providing one or more values of oxidative stress . in the latter case , the present invention provides that a processor can generate a value representing a weighted average of a plurality of values for oxidative stress components , such that the weighted average provides a value indicative of a degree of oxidative stress of the patient . through spectroscopic analysis of blood plasma in the swnir region a system has been demonstrated permitting rapid diagnosis and distinction between the following disease categories : alzheimer &# 39 ; s disease type ( ad ), mild cognitive impairment ( mci ), vascular cognitive impairment ( vci ) and parkinson &# 39 ; s disease ( pd ). the system provides for sensitive , reliable , rapid and inexpensive diagnosis of alzheimer &# 39 ; s disease . based on a hypothesis driven approach , this assignment to ad , mci , vci , pd or a normal elderly control ( nec ) category was enabled by relating the absorbance at preselected os - related wavelengths in the swnir region to each category . these wavelengths reflect non - specific functional groups of a variety of biomolecules ( i . e . oxidative stress components ) that , with respect to each category , are believed to be in a different state of oxidation as a result of oxidative stress . when comparing nec to ad samples , a sensitivity of 94 % and a specificity of 64 % were accomplished . measuring mci versus ad , a sensitivity of 88 % and a specificity of 72 % were obtained . these examples are illustrated in fig4 a and 4 b . for nec versus mci , the results were 72 % and 57 %, respectively ( see fig5 a ) the numbers rival results published for biological markers in cerebrospinal fluid [ blennow , k ., csf biomarkers for mild cognitive impairment . j intern med , 2004 . 256 ( 3 ): p . 224 - 34 ; de leon , m . j ., et al ., mri and csf studies in the early diagnosis of alzheimer &# 39 ; s disease . j intern med , 2004 . 256 ( 3 ): p . 205 - 23 ]. importance of this methodology becomes even more evident when emphasizing the simplicity of plasma collection and its relative non - invasiveness as compared to the much more invasive procedure for obtaining and analyzing cerebrospinal fluid . comparison between any of these three ( ad , mci and nec ) groups and vci resulted in sensitivities and specificities of 100 % ( an example is shown in fig5 b ) thereby possibly extending the applicability of this methodology towards distinction of mci and ad from vascular dementia . with respect to parkinson &# 39 ; s disease , comparison between nec and pd yielded both a sensitivity and a specificity of 100 % ( fig6 a ). a comparison between ad and pd resulted in a sensitivity of 95 % and a specificity of 84 % ( fig6 b ). possible interference stemming from medication was evaluated for aricept ™, a drug of the acetylcholinesterase inhibitor type prescribed to some patients in the ad group to decelerate progression of alzheimer &# 39 ; s disease . no correlation could be measured between spectral response and presence of this drug implying a profound robustness of this methodology with respect to this drug ( on a side note , this also indicates the possibility of a rather limited effect of this medication with respect to oxidative stress levels ). the analytical procedure was validated with respect to sample cell conditioning and sample preparation . a rinsing procedure was developed to prevent possible adsorption of plasma components to the sample cell walls . freezing and thawing cycles as well as centrifugation times were standardized since variations of these parameters were found to greatly influence on the spectral response . no dependence of the spectral response on the total storage time at − 80 ° c . was detected . the nature of anticoagulant added to the sample ( edta versus heparin ) was found to influence the spectral response as well . therefore , only collectives prepared with the same anticoagulant were considered . it should also be mentioned that sample and reagent consumption are minimal . the small size of the instrument further permits easy portability . as described above , there is ample evidence of oxidative substrate modifications in neural and systemic ad tissues that can be exploited in the development of novel biological markers of this disease . in this specification , we provide evidence that swnir spectra rapidly and effectively distinguish between plasma samples derived from early ad , mci and normal elderly control ( nec ) patients based on the differential oxidation of circulating protein constituents in these conditions . we show that a redox signature satisfies many of the criteria for a useful biological marker in sporadic ad as defined in a consensus report sponsored by the ronald and nancy reagan research institute ( alzheimer &# 39 ; s association ) and national institute on aging ( neurobiology of aging 19 : 107 - 167 , 1998 ): 1 ) swnir spectroscopy exhibits high sensitivity and specificity in differentiating sporadic ad from cognitively - normal elderly controls , and mci subjects from both nec and early sporadic ad patients . the test is thus capable of detecting ad in the very earliest phases of the illness and in pre - symptomatic ( mci ) individuals . 2 ) a test based on swnir spectroscopy is relatively non - invasive and inexpensive , and could be readily available in many hospital laboratories . 3 ) as a biophysical indicator of blood protein oxidation , the swnir spectroscopy - derived redox signature reflects an intrinsic aspect of ad pathophysiology , viz . central and systemic oxidative stress . a typical patient with memory complaints presents to a family practitioner or is referred to a neurologist or geriatrician for evaluation of the etiology ( cause ) of the symptoms . the diagnostic evaluation generally consists of ( i ) a detailed medical , neurological , social and family history , ( ii ) a general and neurological examination , ( iii ) a panel of blood tests to exclude metabolic and potentially reversible causes of memory loss and dementia , ( iv ) referral to a clinical neuropsychologist for formal ( quantitative ) neuropsychological testing , and ( v ) referral for a neuroimaging procedure ( ct or mri of the head ; occasionally , pet or spect scanning ). csf examination is not routinely performed in canada and the us as part of the dementia evaluation unless highly specific etiologies ( e . g . neurosyphilis , hiv encephalitis ) are entertained . swnir spectroscopy for the diagnosis of ad can entail the following protocol : ( i ) in the family physician &# 39 ; s office or memory clinic , 10 cc venous blood is drawn in an edta - anticoagulated tube and sent on ice to the swnir spectroscopy laboratory ; ( ii ) the whole blood is layered over a ficoll density gradient and centrifuged at 1000 g for 20 minutes . the top plasma layer is collected , aliquoted and frozen at − 80 ° c . ; ( iii ) in preparation for swnir analysis , the sample is thawed , injected into the spectrometer and swnir spectra are taken as described above ; and ( iv ) the spectra are classified as “ normal ”, “ mci ”, “ ad ”, “ vci / vd ” based on the aforementioned algorithms and comparison with reference spectra obtained from well - ascertained patients from each of these diagnostic categories . spectra not conforming to any of these diagnostic categories would be classified as “ other ” or “ inconclusive ”. the laboratory director provides a copy of the patient &# 39 ; s spectrum and its interpretation to the referring physician . the latter integrates the swnir data with the clinical neuropsychological , biochemical and neuroimaging data to arrive at a likely diagnosis that s / he communicates to the patient and / or the referring physician . alternatively , instead of drawing blood , blood can be measured transcutaneously . in addition to providing an important neurodiagnostic for early ad , we show that swnir spectroscopy may be particularly useful as a novel prognosticator in subjects with mci by differentiating mci patients with abnormal blood nir spectra at high risk for development of ad from neuropsychologically - identical cases manifesting nir spectra in the normal range who remain at low risk for conversion to incipient ad . as such , nir analysis of mci patients would provide vital prognostic information that could facilitate patient and family counseling , the stratification of sub - groups in the design of clinical drug trials and the interpretation of treatment outcome measures . there are clinical situations where swnir spectroscopy , in combination with one or more additional diagnostic tests , may significantly enhance the accuracy of diagnosing ad over performance of swnir spectroscopy or the other diagnostic modality alone . two examples follow . ( i ) diagnosing ad in a patient with major depression : patients with depression often complain of memory loss and the latter may constitute an initial symptom that leads the patient to be referred to a neurologist or memory clinic for work - up of possible dementia . due to overlapping symptomatology involving memory function , in general , a new diagnosis of ad cannot be made with any degree of precision until the depressive symptoms have been treated by pharmacological or other means ( a process usually requiring a minimum of three weeks ). thereafter , the patient can be re - tested for memory loss and other cognitive dysfunction and a diagnosis of ad , other dementia or normal cognition may be rendered . the advent of a method based on swnir spectroscopy that distinguishes ad blood samples from those of non - ad samples , including patients with depression but no ad pathology , would permit immediate rendering of an ad diagnosis ( or not ) in patients with depression without the necessity of first treating the underlying affective disorder . similar benefits of swnir spectroscopy would accrue in the course of evaluating patients for possible ad with other concomitant conditions that may confound clinical and neuropsychological testing , such as toxic or metabolic encephalopathy ( delirium ), language disorder ( aphasia ) or suppressed level of consciousness ( stupor , coma ). ( ii ) diagnosing ad in patients with chronic inflammatory disorders : as described above , the swnir spectra of plasma that distinguish ad are thought to represent aberrant oxidation of specific plasma proteins in the circulation of ad patients . conceivably , potentially similar patterns of plasma protein oxidation may arise in patients with chronic inflammatory or metabolic disorders characterized by sustained systemic oxidative stress , such as rheumatoid arthritis . the presence of said disorder in a patient under investigation for memory loss may therefore confound the diagnosis of ad rendered solely on the basis of swnir spectroscopy . in the latter situation , a second diagnostic modality , such as formal neuropsychological testing , determination of csf — amyloid and tau concentrations or neuroimaging , would be required in addition to swnir spectroscopy to confirm or refute a diagnosis of ad . although cholinesterase inhibitors are routinely used in clinical practice to ameliorate the symptoms of ad , there is currently no approved medication that unequivocally attenuates neuronal degeneration and disease progression in these patients . on the basis of the data reviewed above , there is considerable interest in developing safe and effective antioxidants to retard or arrest os - related neuronal damage and attrition in ad . current monitoring of the efficacy of such interventions is not trivial and requires serial neuropsychological testing and neuroimaging that is labor - intensive , expensive , and often highly - dependent on the cooperation of the test subjects . as an indicator of potential therapeutic efficacy , swnir spectroscopy may be used to detect normalization ( or not ) of aberrant blood spectra in ad patients and in subjects with other os - related conditions following oral or parenteral administration of a test antioxidant compound . in such situations , we show that swnir spectroscopy would allow objective , non - invasive , rapid , repeated and reproducible monitoring of the drug &# 39 ; s antioxidant potential and pharmacokinetics irrespective of the patients &# 39 ; level of consciousness and degree of cognitive / behavioural impairment . data accruing from these swnir - based analyses could be used to rapidly and effectively screen candidate pharmaceuticals for inclusion in subsequent conventional clinical trials . oxidative stress ( free radical damage ) has been implicated in the pathogenesis of numerous neurological and medical disorders . as a result , efforts are currently underway to prevent , ameliorate , arrest or reverse some of these conditions by administration of antioxidants as pharmaceutical agents or dietary supplements . because monitoring of clinical outcomes of such treatments is generally labor - intensive , costly and subjective , there exists a great need to develop surrogate biological markers of effective therapeutic interventions . there currently exists the capacity to monitor , in quantitative fashion , levels of oxidized blood proteins , lipids and nucleic acids before , during and after antioxidant administration as surrogate markers of potentially effective interventions . however , these biochemical determinations tend to require sophisticated sample preparation and analyses that are expensive , time and labor - intensive , difficult to standardize and restricted to highly specialized laboratories . swnir spectroscopy for detection and measurement of plasma protein oxidation can greatly facilitate clinical and experimental monitoring of antioxidant interventions in said conditions ( including ad ) because ( i ) this method , based on swnir spectroscopy is a far more rapid methodology for detecting oxidation of plasma constituents than conventional ( elisa , hplc ) methods . refinement of the method to accommodate in vivo whole blood measurements ( akin to oximetry ) would permit repeated analyses of drug efficacy and / or a component of pharmacokinetics in real - time . in ad , for example , swnir spectroscopy could be performed on plasma samples or whole blood in vivo prior to , at regular intervals during , and following cessation of orally or intravenously administered antioxidant compounds . partial or complete normalization of ad - specific spectra resulting from the administration of a candidate antioxidant compound may provide essential data concerning the potency of the medication , the duration of its biochemical effect , and its appropriateness for large - scale , long - term testing as a potential anti - ad drug . ( ii ) swnir spectroscopy is more economical and versatile than existing techniques for monitoring plasma oxidative stress and can be made readily available in all hospitals and diagnostic facilities . in certain os - related conditions , like acute systemic bacterial sepsis ( albuszies , g . and u . b . bruckner , antioxidant therapy in sepsis . intensive care med , 2003 . 29 ( 10 ): p . 1632 - 6 ; abu - zidan , f . m ., l . d . plank , and j . a . windsor , proteolysis in severe sepsis is related to oxidation of plasma protein . eur j surg , 2002 . 168 ( 2 ): p . 119 - 23 ], we show that the pattern and extent of abnormalities in the swnir spectra can be correlated in real time with the immediate clinical status of the patient . care for such individuals in an icu setting can benefit from serial , non - invasive swnir spectroscopic measurements of oxidative stress components in blood as a marker of disease severity and efficacy of acute ( pharmacological and non - pharmacological ) medical interventions . novel implementation of swnir spectroscopy as a real - time ‘ redoximeter ’ in such patients would be akin to the common use of pulse oximetry to monitor hemoglobin saturation and oxygenation status of acutely - ill patients in an icu setting , as shown in fig8 . for example , a ‘ redoximeter ’ monitoring oxidative stress in icu patients in real - time can be set to trigger an alarm whenever swnir spectra corresponding to oxidation of plasma protein constituents shift more than 1 - 2 standard deviations ( to be determined empirically ) from normal control values . the swnir evidence of augmented oxidative stress may indicate exacerbation of an underlying medical condition ( e . g . worsening hyperglycemia in a diabetic ), the development of an intercurrent illness ( e . g . bacterial sepsis ) or an iatrogenic effect ( e . g . adverse reaction to medication ). the icu staff may respond to the redoximetry alarm by confirming disease exacerbation or development of concomitant conditions using conventional testing , reviewing ongoing therapeutic regiments , and possibly administration of antioxidant medications . partial or complete re - normalization of the swnir spectra would silence the alarm and provide evident of effective intervention , disease amelioration and stabilization of the patient . the embodiments of the invention described above are intended to be exemplary only . the scope of the invention is therefor intended to be limited solely by the scope of the appended claims .

US-35706006-A

a surgical tool may include a circular surgical stapler and an anvil initially disconnected and separate from the surgical stapler ; where at least one of the circular surgical stapler and the anvil is magnetic .

referring to fig2 , a circular stapler 20 may include a stapler 22 that is initially separate and disconnected from an anvil 24 . a first guidewire 26 or other control structure may extend from the stapler 22 , and a second guidewire 28 or other control structure may extend from the anvil 24 . one or both of the stapler 22 and anvil 24 may be magnetic . that is , one or both of the stapler 22 and anvil 24 may emit a magnetic field . the stapler 22 and / or anvil 24 may be passively magnetic or actively magnetic . “ passively magnetic ” means that the stapler 22 and / or anvil 24 is fabricated from a material that is magnetized , such that the stapler 22 and / or anvil 24 emits a magnetic field without the need for application of energy thereto . “ actively magnetic ” means that the stapler 22 or anvil 24 is fabricated from a material that is not magnetized , such that the stapler 22 and / or anvil 24 emits a magnetic field only upon the application of energy thereto . where the stapler 22 and / or anvil 24 is actively magnetic , the actively magnetic components may include an electromagnet , solenoid or other such mechanism that emits a magnetic field upon application of energy thereto . where only one of the stapler 22 and anvil 24 is magnetic , the other is made from a ferrous or other material that is susceptible to a magnetic field , such that moving the stapler 22 and anvil 24 into proximity causes the component that is magnetic to attract the other component to it . referring also to fig3 , the stapler 22 is inserted into a first segment 14 a of the intestine or other tissue . the anvil 24 is inserted into a second segment 14 b of the intestine or other tissue . the insertion of the stapler 22 and anvil 24 into tissue 14 is accomplished in a conventional manner known to those skilled in the art , or may be performed in any other suitable manner . the segments 14 a , 14 b may initially be spaced apart from another , and are brought into proximity to one another in a conventional manner or any other suitable manner . as seen in fig3 , the stapler 22 and anvil 24 are brought into proximity with one another . referring to fig4 , the stapler 22 and anvil 24 self - align with one another as they are brought into proximity . if the stapler 22 and / or anvil 24 are actively magnetic , then before or after they are brought into proximity with one another , energy is transmitted to the stapler 22 and / or anvil 24 to cause the stapler 22 and / or anvil 24 to emit a magnetic field . the stapler 22 and / or anvil 24 are magnetic , as set forth above , and if either component is not magnetic it is susceptible to magnetism . as a result , when the stapler 22 and anvil 24 are brought into proximity , the effect of the magnetic field emitted by one or both of the stapler 22 and anvil 24 pulls the stapler 22 and anvil 24 together and causes them to self - align with one another . intact tissue of the intestine 14 is then present between the stapler 22 and anvil 24 , such that the two segments 14 a , 14 b of the intestine are held together without a break or opening in the tissue of either segment 14 a , 14 b of the intestine . referring also to fig5 , a piercing fastener 30 may then be extended from the anvil 24 toward the stapler 22 . the fastener 30 may be sharp , threaded , or configured in any suitable manner . as one example , the fastener 30 may be a pointed and threaded screw . as another example , the piercing fastener 30 may be extended from the stapler 22 toward the anvil 24 . as another example , a piercing fastener 30 may be extended from each of the stapler 22 and the anvil 24 toward the other . as the piercing fastener 30 is extended , it penetrates each segment 14 a , 14 b of the intestine and is received in and held by the stapler 22 . referring also to fig6 , the piercing fastener 30 may be rotated or otherwise advanced to bring the stapler 22 and anvil 24 closer to one another and compress the tissue of the segments 14 a , 14 b of the intestine that is positioned and held between the stapler 22 and the anvil 24 . the stapler 22 is then actuated , such as by the guidewire 26 , to deploy one or more staples toward the anvil 24 through the tissue of the segments 14 a , 14 b of the intestine held between the stapler 22 and anvil 24 . the segments 14 a , 14 b are thereby connected together . a cutter may then be advanced from the stapler 22 toward the anvil 24 in order to cut an opening through the segments 14 a , 14 b of the intestine held between the stapler 22 and anvil 24 . alternately , the cutter may be advanced from the anvil 24 toward the stapler 22 . advantageously , the stapler 22 deploys a plurality of staples in a circular or other closed pattern , and the cutter cuts an opening through the stapled segments 14 a , 14 b of the intestine within the perimeter defined by the staples in tissue . the piercing fastener 30 is then disengaged from the stapler 22 and retracted toward the anvil 24 . if the stapler 22 and / or anvil 24 are actively magnetic , the application of energy to the stapler 22 and / or anvil 24 is ceased . the stapler 22 and anvil 24 are then moved away from one another , such as by applying force to the guidewire 26 attached to the stapler 22 and the guidewire 28 attached to the anvil 24 . the intestinal segments 14 a , 14 b are securely connected , and the procedure is complete . while the invention has been described in detail , it will be apparent to one skilled in the art that various changes and modifications can be made and equivalents employed , without departing from the present invention . it is to be understood that the invention is not limited to the details of construction , the arrangements of components , and / or the method set forth in the above description or illustrated in the drawings . statements in the abstract of this document , and any summary statements in this document , are merely exemplary ; they are not , and cannot be interpreted as , limiting the scope of the claims . further , the figures are merely exemplary and not limiting . topical headings and subheadings are for the convenience of the reader only . they should not and cannot be construed to have any substantive significance , meaning or interpretation , and should not and cannot be deemed to indicate that all of the information relating to any particular topic is to be found under or limited to any particular heading or subheading . therefore , the invention is not to be restricted or limited except in accordance with the following claims and their legal equivalents .

US-201113185679-A

a boot suitable for use in association with various sports related gliding devices having a stirrup embedded in the sole of the boot containing a pair of opposed arms for removably supporting a pin therebetween .

the object of the invention is to provide a design of that region of the boot that has the metal pin which allows easy moulding , avoiding the use of special tooling while at the same time retaining a high anchorage capability . thus , the boot in accordance with the invention is of the type comprising a sole the underside of which has a recess delimited by two more or less vertical walls pointing towards the bottom of the boot , the said recess having passing through it a pin which is intended to interact with means for attaching to the gliding member and comprising a rigid piece embedded in the sole and having two extensions extending into the said walls and intended to accommodate the said pin . this boot is characterized in that the extensions and the ends of the pin have means intended to make this pin removable . in other words , the metal pin is removable and is secured to the boot for example by being screwed to a piece embedded within the sole . this embedded piece constitutes the anchoring points for the pin . the invention therefore consists in using an anchoring piece and a pin which are separate , the anchoring piece being at least partially embedded during the moulding of the sole so that it does not form any undercut . in this way , the moulding tools are simple , and this in particular allows the sole to be moulded directly on the upper . in a first embodiment , the embedded rigid piece is a u - shaped stirrup piece , the opening of which points towards the metal pin and the legs of which form the extensions which are intended to accommodate the characteristic pin . in practice , the rear portion of the u - shaped stirrup piece is situated in a plane more or less parallel to the plane of the underside of the sole of the boot , the front ends of this stirrup piece being arranged in a plane which is also more or less parallel to the plane of the sole , but below the plane of the rear portion of the stirrup piece . advantageously , the legs of the said stirrup piece have a discontinuity , the end of each leg being offset downwards with respect to the plane of the stirrup piece . in this way , the ends of the stirrup piece which act as anchoring points for the pin are closer to the underside of the sole , while the anchoring part proper is situated right at the heart of the moulded portion of the front of the boot . in another embodiment , the embedded metal piece is a plate bent into three portions , namely a first , central , portion , more or less parallel to the sole of the boot , and two lateral portions extending into the side surfaces , these lateral portions being designed to accommodate the transverse pin . this design makes it possible to increase the area of contact between the anchoring piece and the moulded material , and this improves the resistance of the unit as a whole to pulling out . as regards the catching of the characteristic pin on the boot , a number of embodiments can be envisaged . thus , in a first alternative form , the end of the pin , which is for example metal , has a tapped hole into which the threaded shank of a bolt is screwed . in a second alternative form , the pin has at least one end which is telescopic and retractable , and the two ends of the pin can be housed in housings provided for this purpose in the extensions of the embedded metal piece . in a third alternative form , the pin may be integral with two hollow sleeves intended to be pushed over visible parts of the extensions of the embedded piece . quite obviously , a number of pin geometries and / or cross sections may prove advantageous for use in accordance with the invention . in particular , the pin may be cylindrical but also formed of a strip shaped to suit its purpose . the provisions in accordance with the invention prove particularly advantageous when manufacturing boots intended for cross - country skiing , and in which the recess is forward of the metatarsophalangeal joint , the extensions then pointing forwards . as a side issue , the invention makes it possible to solve the problem with wear on the front part of the boot , where repeated contact with the binding causes deformation and even sometimes breakages . for this , the front end of the sole which corresponds to the region of wear can be detached from the boot . it has housings that complement the lateral extensions of the metal piece to allow it to be pushed on , and perforations to allow the transverse pin to pass . in another embodiment , using the anchoring points formed by the extensions of the embedded piece , the boot has a wide longitudinal groove on the underside of the sole . in combination , the boot has a strip attached inside this wide groove , the lowermost face of this attached strip having a profile which complements the region of the ski and / or of the binding on which it rests . furthermore , the boot also towards the rear of said wide groove , has means of anchoring the rear of the said attached strip , the front part of the attached strip being anchored by the extensions of the embedded metal piece in combination with the transverse pin . with this arrangement it is therefore easy , starting from a common boot , to make various versions intended to be adapted to suit various shapes of binding . this design proves particularly advantageous as regards the various types of groove and rib that there are on the underside of the soles of cross - country ski boots . the arrangements in accordance with the invention may also prove advantageous when producing boots intended for snowboarding , where the recess is then at the instep and the extensions of the embedded piece point downwards , the pin being along the longitudinal plane of the boot . these arrangements may also advantageously apply when producing boots intended for ice - or roller - skating , where the sole has arrangements liable to allow the blade or roller support plate to be secured by means of the metal pin and the extensions of the embedded piece . the way in which the invention can be produced , and the advantages that stem therefrom , will emerge clearly from the description of the embodiment which follows , supported by the appended figures . fig1 is an outline perspective view of a stirrup piece in accordance with the invention , showed viewed from above in fig2 and viewed from the side in fig3 . fig4 and 5 are front views of the front recess in the sole , showing the pin when it is dismantled from , and respectively mounted in , the stirrup piece . fig6 is a longitudinal section through the sole equipped with the device in accordance with the invention . fig7 is a view of the same sole , from below . fig8 is an outline perspective view of an alternative form of the piece embedded in the front of the sole . fig9 is an exploded outline perspective view of one embodiment of the invention , with removable wearing pieces . fig1 is an outline perspective view of the underside of a sole which has a wide groove capable of accommodating the profiled strips shown in fig1 and 12 . fig1 and 14 are cross sections showing the integration of the strips of fig1 and 12 into the sole . fig1 and 16 are outline perspective views illustrating two alternative forms of the attachment of the pin to the moulded piece . fig1 is an outline perspective view of the sole of a snowboarding boot in accordance with the invention . fig1 is a detail view of an embedded piece in accordance with the invention , in the case of a snowboarding boot . fig1 is a side view of an in - line roller skate in accordance with the invention . in the remainder of the description , it will be assumed that the boots described are lying flat , which means that the underside of the sole is horizontal . as already stated , the invention relates to boots for gliding sports , especially cross - country skiing . as is known , a cross - country ski boot is composed mainly of an upper and of a sole ( 1 ) in which the arrangements inherent to the invention are more particularly located . as is known , cross - country ski boots have a recess ( 2 ) in the front part of the sole , around the mid plane and which has an opening towards the front and towards the underside of the sole . the lateral walls ( 3 , 4 ) of this recess ( 2 ) consist of two more or less vertical portions forming the bearing surfaces for a transverse pin ( 5 ). the novel feature of the invention lies in the way in which the pin is attached to the sole ( 1 ). in contrast to all existing boots , the boot in accordance with the invention has a pin which is secured to the sole after the sole has been moulded . for this , in its front part , the sole has an embedded piece ( 6 ) which constitutes the anchoring points for the pin ( 5 ). in the embodiment illustrated in fig1 to 6 , the embedded piece ( 6 ) is in the form of a u - shaped stirrup piece . the base ( 7 ) of this stirrup piece ( 6 ) constitutes a transverse bar which is embedded within the sole , at the first toe phalanx . the length of this bar ( 7 ) slightly exceeds the width of the recess ( 2 ). the legs ( 8 , 9 ) of the stirrup piece ( 6 ) point forwards , and are directed slightly downwards to prevent the leg ( 7 ) of the stirrup piece ( 6 ) from passing through the central groove in the sole . the ends ( 11 , 12 ) of the legs ( 8 , 9 ) are intended to accommodate the transverse pin ( 5 ). for this , these ends have holes ( 13 , 14 ) pierced transversely and opposite one another . in the alternative form illustrated in fig4 the end of the pin has a tapped hole ( 16 ) into which the threaded shank ( 19 ) of the bolt ( 18 ) is screwed . of course , it would not be departing from the scope of the invention if any method that allowed effective attachment were used to attach the pin ( 5 ), i . e . for example , a tapping in one of the holes ( 13 , 14 ) into which the threaded end of the pin ( 5 ) could be screwed . in the alternative form illustrated in fig1 , the pin ( 60 ) consists of a hollow body ( 61 ) inside which two coaxial pegs ( 62 , 63 ) can slide . a return member ( not depicted ) of the coil spring type keeps these pegs ( 62 , 63 ) in the deployed position , and opposes their retraction into the body ( 61 ). the pin ( 60 ) is fitted between the extensions ( 22 , 23 ) of the embedded piece ( 20 ) by pushing the pegs ( 62 , 63 ) into the body ( 61 ) stressing the return member ( not depicted ). then , once this pin ( 60 ) is precisely positioned between the holes ( 13 , 14 ) in the piece ( 20 ), the pegs ( 62 , 63 ) are released and become housed in the holes ( 13 , 14 ). in another embodiment illustrated in fig1 , the pin ( 5 ) is secured to hollow tubes ( 65 , 66 ) so that it forms a stirrup piece ( 64 ). this stirrup piece ( 64 ) can be pushed onto the extensions ( 11 , 12 ) of the embedded metal piece . this stirrup piece ( 64 ) is secured by means of pins ( 67 ) inserted into the holes ( 68 and 69 ) in the tube ( 66 ) and in the extension ( 12 ) of the piece embedded within the sole , respectively . to optimize the anchorage of this stirrup piece , the legs ( 8 , 9 ) have a discontinuity which means that their ends ( 11 , 12 ) are offset slightly downwards so that the bar ( 7 ) is embedded as deeply as possible within the sole , to avoid it from passing through the central rib . furthermore , these ends ( 11 , 12 ) are not as thick as the central bar ( 7 ) because they are machined to have flat surfaces , particularly to allow them to be positioned in the mould . during the moulding of the sole ( 1 ), the stirrup piece ( 6 ) is positioned in such a way that the bearing surfaces ( 3 , 4 ) are moulded around the ends ( 11 , 12 ) of the stirrup piece . it is held within the sole during moulding by any means known in the field of moulding , such as centring stakes for example . after moulding , all that is required is for the walls ( 3 , 4 ) to be pierced at the holes ( 13 , 14 ) in order to obtain the passage for the pin ( 5 ). the stirrup piece could also be moulded by fitting the said holes ( 13 , 14 ) with removable pieces to avoid subsequent piercing . in an alternative form , the opposing internal faces of the legs ( 11 , 12 ) may be tangential to the mould insert which then acts as a centring device . as can be seen , the sole of a boot in accordance with the invention can be distinguished fundamentally from all existing boots by the fact that the sole is moulded without any metal pieces forming a bridge , which makes this moulding operation far easier by dispensing with undercuts . in an embodiment shown in fig8 the embedded piece ( 20 ) comes from bending a metal sheet into three portions ( 21 , 22 , 23 ). the central portion ( 21 ) is intended to be embedded in the material of the front of the sole . it has holes ( 25 ) allowing the plastic to spread out during moulding . the large area of a portion ( 21 ) of this kind allows effective anchorage . this portion ( 21 ) has bent lateral extensions ( 22 ) and ( 23 ), the front ends ( 26 ) and ( 27 ) of which are offset slightly downwards and have holes ( 13 ) and ( 14 ) for attaching the pin ( 5 ). as can be seen in fig9 the portions ( 30 , 31 ) of the walls ( 3 , 4 ) are advantageously mounted extractably on the ends ( 11 , 12 ) of the stirrup piece ( 6 ). this region of the boot is the part where the most wear takes place because it is at the lower front edge of the sole . it therefore rubs directly on the binding and forms one of the regions which is most exposed when walking . these extractable portions ( 30 , 31 ) have longitudinal drillings ( 33 , 34 ) allowing them to be pushed onto the ends ( 11 , 12 ) of the stirrup piece ( 6 ). these portions ( 30 , 31 ) also have a transverse drilling ( 32 ) allowing the passage of the pin ( 5 ) which will catch on the ends ( 11 , 12 ) of the stirrup piece and thus attach the wearing pieces ( 30 , 31 ). of course it would not be departing from the scope of the invention if these wearing pieces were given any advantageous shape that could be secured to the visible portions of the stirrup piece ( 6 ). in particular , these wearing pieces could form one single portion . of course , the anchoring points mentioned hereinabove can also be used for attaching some other piece to the sole ( 1 ). as is known , in the field of cross - country skiing , there are two major standards that define the structure and design of the underside of the sole . in a first standard , generally denoted “ nnn ”, the sole ( 1 ) has two longitudinal parallel grooves placed symmetrically about the mid - plane of the boot . in another standard , denoted “ sns ”, the sole has a single , wider , groove arranged along the longitudinal axis . this or these groove ( s ) are intended to interact with corresponding rails situated on the ski or on the bindings . by adding a small - sized piece , a common boot can be adapted to suit one of these two standards . as shown in fig1 , 11 , 12 , this common boot has a wide groove ( 40 ) situated along the longitudinal axis of the sole ( 1 ). the dimensions of this wide groove ( 40 ) are sufficient to accommodate a strip ( 41 ) which has two thinner parts ( 43 ) and a central rib ( 42 ). when this strip ( 41 ) is inserted inside the wide groove ( 40 ), the lateral slopes of this groove define , with the flat portions ( 43 ) and the rib ( 42 ), two grooves ( 47 ) which are placed symmetrically with respect to the longitudinal axis of the boot . thanks to wings ( 48 ) with holes ( 49 ) in , this strip ( 41 ) can be slipped at the front into the ends ( 11 , 12 ) of the stirrup piece ( 6 ) for attaching the pin ( 5 ). the strip has means ( not depicted ) allowing it to be attached to the rear end of the sole . the profile thus obtained corresponds to the one described earlier for the “ nnn ” standard ( see fig1 ). the profile depicted in fig1 has a strip ( 50 ) which along its longitudinal axis has a central groove ( 52 ) to the dimensions laid down in the “ sns ” standard . as before , inserting this strip makes it possible to form on the underside of the sole a groove which has the dimensions laid down in said standard ( see fig1 ). the operation of mounting an additional rib as described hereinabove can easily be substituted , in a way which is obvious to a person skilled in the art , by the attachment on the underside of the sole of a plate which , on its underside , has an ice - skating blade or a line of rollers . as already stated , the arrangements in accordance with the invention may prove advantageous when producing soles for snowboarding shoes in which , as illustrated in fig1 , there is a recess ( 70 ) at the instep between the heel region ( 71 ) and the front part ( 72 ) of the sole . thus , in this housing ( 70 ) more or less at the middle , there are two bearing surfaces ( 73 , 74 ) between which the pin ( 75 ) for interacting with the binding ( not depicted ) is located . in accordance with the invention , the sole accommodates an embedded piece ( 76 ) drawn in dotted line . this piece ( 76 ), illustrated in fig1 , consists of a bent plate , of which the central part ( 79 ), which is advantageously perforated , is parallel to the horizontal plane of the sole and of which the end parts ( 77 , 78 ) form the extensions extending into the bearing surfaces ( 73 , 74 ). these extensions ( 77 , 78 ) have pierced holes ( 80 , 81 ) intended to accommodate , removably , and according to the various alternative attachment forms described hereinabove , the pin ( 75 ) that interacts with the binding . in this instance , for fitting the pin in the recess , it may prove advantageous to use a pin with retractable ends , like the one illustrated in fig1 . as already stated , the invention can also be used for manufacturing boots intended for skating . thus , as illustrated in fig1 , the boot ( 90 ) at the front has an embedded piece ( not depicted ) intended to accommodate the transverse pin . ( 95 ). this pin ( 95 ) allows the plate ( 92 ) supporting the rollers to be attached temporarily . it emerges from the foregoing that cross - country ski boots , skating boots or snowboarding boots in accordance with the invention have a main advantage which lies in the fact that the boot can be moulded without a visible pin , and this considerably simplifies the moulding equipment , avoiding devices with slides , and that advantageously allows the sole to be produced directly on the upper . the characteristic use of this embedded piece creates robust anchoring points , and this allows special adaptor pieces or wearing pieces to be pushed on .

US-53220000-A

a clamping device , preferably for use on a retractor support , has an upper clamp and a lower clamp . the clamps include a movable jaw and a fixed jaw pivotal between a locked configuration and an unlocked configuration which both locks the clamps in a shut configuration and fixes the angular position of the clamps relative to one another . a drawbar and cam act together to compress the upper and lower clamps into a clamping or locking position .

the retractor clamp 10 of fig1 - 4 may be utilized as a replacement for or instead of the clamp illustrated in fig1 of u . s . pat . no . 5 , 020 , 195 . however , the clamp 10 of the present preferred embodiment is believed to improve on the basic design of that prior art retractor clamp and others . the clamp 10 of fig1 is comprised of two clamping members 45 , 90 with each having at least one moveable jaw member 55 , 100 , respectively . the moveable jaw members 55 , 100 preferably rotate about respective pivots 56 , 101 when forces are exerted on lever arms 57 , 102 which are located opposite the pivot points 56 , 101 at moveable jaws 55 , 100 . the moveable jaw members 55 , 110 are pivotably connected to the clamping members 45 , 90 by upper clamp dowel 50 and lower clamp dowel 95 , respectively . in the preferred embodiment , each of the moveable jaws 55 , 100 cooperates with a second jaw member 60 , 105 , which is preferably a fixed , or non - moving jaw member . in a more preferred embodiment , the fixed jaw members 60 , 105 are of unitary construction with a significant portion of the upper and lower clamps 45 , 90 respectively . the fixed jaw members 60 , 105 have a gripping surface 61 ( obscured from view on jaw member 60 ) and 106 which cooperate with gripping surfaces 58 and ( obscured from view on jaw 100 ) of the moveable jaw members 55 , 100 to hold rod sections such as a shaft of a retractor and a rod section of a retractor support . the jaw faces such as gripping surfaces 106 , 58 are preferably curved to aid in holding the rod sections once they are in place . the clamping members 45 , 90 are separated by a bushing such as lock bushing 64 . the lock bushing 64 consists of top lock 65 and lower lock 70 . the locks 65 , 70 illustrated as disks are preferably constructed with serrated interfaces 71 , as best seen in fig5 which cooperate with one another to maintain the upper clamp 45 in a fixed radial position relative to the lower clamp 90 when the clamping members 45 , 90 are locked , at least angularly , relative to one another . the serrated interfaces 66 , 71 in the preferred embodiment resemble a starburst type shape characterized by radially extending ridges . the upper and lower discs 65 , 70 are separated by pre - load spring 75 . the pre - load swing 75 keeps the serrated interfaces 71 from contact when the clamping members 45 , 90 are in an unlocked or release position . the spring 75 therefore assists in the free rotation of the clamping members 45 , 90 . in the preferred embodiment , a drawbar 20 is utilized to operate the moveable jaws 55 , 100 and to lock the upper and lower clamping members 45 , 90 in a fixed angular relationship relative to one another . the drawbar 20 extends through bores 46 , 91 in the clamping members 45 , 90 . the drawbar 20 also extends through channels 59 , 104 in lever arms 57 , 102 . the drawbar 20 may be rotated within clamping members 45 , 90 by handle 15 . the handle 15 or gripping surface is positioned to receive handle ball 25 as shown in fig2 . handle spring 30 biases the handle ball into the handle 15 . when handle 15 is raised it pivots around handle dowel 35 while maintaining contact with ball 25 . the handle ball 25 is preferably received within a recess ( obscured from view ) in base 16 of handle 15 when the handle 15 is pivoted to be substantially perpendicular to the drawbar 20 . when the handle 15 is released the handle spring 30 may assist to bias the handle to a closed position as shown in fig2 . the drawbar 20 has drawbar head 21 with lip 22 , which rests on washer 23 , such as a friction washer . the drawbar head 21 when turned rotates on the washer 23 , which abuts lever arm 57 . the turning of the drawbar drives the drawbar head 21 downward applying sufficient downward forces on the lever arm 57 with the lip 22 to actuate a closed or clamping position as will be explained in further detail below . the drawbar 20 is secured within the clamping members 45 , 90 by a cam illustrated as a cam nut 85 , best seen in fig3 a . cam nut 85 is engineered to receive cam nut dowel 86 , which extends from the hole 23 in the distal end 24 of the drawbar shaft 19 . the cam nut dowel 86 is positioned to fit within the cam nut 85 such that when the drawbar 20 is turned the nut dowel 86 moves relative to the cam nut 85 . the shape of the cam nut 85 may be any shape that allows it to be housed within the lower clamp 90 so that the cam nut 85 preferably will not rotate when the drawbar 20 is rotated . referring to fig3 a , the cam nut 85 is illustrated upside down in a preferred embodiment showing three sides of a hexagonal nut base 87 with each side having a turret 84 . fig3 a further illustrates the cam portions 81 , 82 . fig3 b shows the cam nut 85 as it is placed in the retractor clamp 10 . dowel channel 89 holds the cam nut dowel 86 and separates a first cam ramp 81 and a second cam ramp 82 . when the drawbar 20 is turned the cam nut dowel 86 preferably rotates up both cam ramps 81 , 82 . as shown in fig3 b the cam dowel 86 can only turn in one direction , in this case clockwise , however the cam nut 85 can be constructed to turn in the opposite direction with equal effect . if the article to be gripped by the clamping members has a diameter too small to be gripped by the retractor clamp 10 the cam nut dowel 86 may ride over the cam ramps 81 , 82 and fall back into the dowel channel 89 . referring back to fig1 the cam nut 85 is supported from below by cam nut dowel 86 and is prevented from upward vertical movement by the compression spring 80 , which presses against the cam nut 85 and the lever arm 102 . the cam nut 85 is prevented from rotating or lateral movement by cam nut housing 83 located in the interior of lower clamp 90 as shown in fig4 a . the hexagonal shape of the cam nut housing 83 of the lower clamp 91 is shown in this figure . the shape of the cam nut housing 83 has been designed to accept the cam nut turrets 84 of the cam nut 85 thereby preventing the cam nut 85 from rotating in the lower clamp bore 91 . the compression spring 80 positioned between the cam nut 85 and lower clamp moving jaw 100 preferably performs the dual function of biasing the lever arm 102 to a static clamping position thereby placing the clamp 90 in a shut configuration , but not a locked configuration , i . e ., when in an unlocked configuration , and biasing the cam nut 85 to the cam dowel 86 such that when the cam dowel 86 is turned a predetermined amount , the spring 80 is compressed further tightening the upper and lower clamps 45 , 90 into a locked configuration . accordingly , when inserting a rod to be fixed by the lower clamp 90 , the rod may be pushed into the clamping member 90 so that it “ snaps ” into position even while the retractor clamp 10 is in an unlocked configuration loading surfaces 120 , 122 on jaws 55 , 105 may also be present on jaws 60 , 100 to assist in spreading the jaws 55 , 60 and 100 , 105 upon insertion of a rod ( i . e ., the curved surface of the rod would spread the jaws apart until the diameter was reached , and the jaws would come back together about the rod .) the lower clamp moving jaw 100 is biased downward by the spring 80 since the spring 80 pushes upward on the lever arm 102 forcing moving jaw 100 downward toward the fixed jaw 105 . the force exerted by the compression spring 80 is preferably sufficient to secure the retractor clamp 10 to a rod . after the lower clamp 90 has been placed into position the drawbar 19 can be turned which turns the cam dowel 86 . this movement causes the dowel 86 to ride up the cam ramps 81 , 82 compressing spring 80 and moving or exerting upward force on the lever arm 102 and places the clamp 90 in a locked configuration . the upward force on lever arm 102 provides additional grip to further secure a rod section . in order to lock the upper clamp 45 about a rod section the drawbar 20 may be rotated , such as by handle 15 by the same rotation that locks clamp 90 . in the preferred embodiment , less than 270 degrees , and less than 180 degrees of rotation have each been found satisfactory to lock the clamping members 45 , 90 about a rod section . once again the rotating action of the handle 15 causes the cam nut dowel 86 to turn and ride up the cam ramps 81 , 82 . this motion pulls the draw bar head 21 down and forces the lip 22 to place pressure on the friction washer 40 , which in turn pushes down on lever arm 57 into a locked configuration . lever arm 57 pushes moving jaw 55 upward and toward the fixed jaw 60 until the upper clamp 45 has secured the inserted rod section . another effect associated with the downward force applied by the drawbar head 21 and / or action of the drawbar 20 with the cam nut 85 is the compression of the pre - load spring 75 in lock bushing 64 . this forces the serrated disc faces 71 , 66 to contact one another and cooperate with one another to maintain the upper clamp 45 in a fixed radial position relative to the lower clamp 90 in a locked configuration . rotation can be reestablished by turning the drawbar 19 in the opposite direction riding the cam dowel 86 back down the cam ramps 88 . while a single drawbar 20 and cam nut 85 are utilized to lock and unlock the clamps 45 , 90 and the bushing 64 , a plurality of similar or dissimilar mechanisms could be utilized in other embodiments . numerous alterations of the structure herein disclosed will suggest themselves to those skilled in the art . however , it is to be understood that the present disclosure relates to the preferred embodiment of the invention , which is for purposes of illustration only and not to be construed as a limitation of the invention . all such modifications , which do not depart from the spirit of the invention , are intended to be included within the scope of the appended claims .

US-15466902-A

the invention relates to head or neck supports which support the head or neck in a tilted back position and comprises or includes : a ) a harness locatable to the upper body portions of a person , b ) a rigid member extending from a region of said harness stabilised in respect of and by the use of the harness relative to the body , wherein , when in use , said harness is attached to the body of a person , said rigid member extending therefrom to provide a support region thereof which when said person is in a substantially upright position , and the head is tilted backwards to allow viewing of an object above the horizontal , said support region comes in contact with at least part of the back of the head and provides at least vertical support to the head .

one preferred form of the present invention will now be described with reference to the accompanying drawings in which : [ 0038 ] fig1 is a perspective view of the back of a user of the present invention illustrating the head support located with the user in the preferred condition , [ 0039 ] fig2 is a front view in direction aa of fig3 of the head support of the present invention , [ 0040 ] fig3 is a perspective view of the head support as shown in fig2 [ 0041 ] fig4 is a view from the back of an alternative and preferred form of the head support of the present invention [ 0042 ] fig5 illustrates the rigid member of the head support in association with a lateral stabilising means with which the straps of the harness can locate . [ 0043 ] fig6 illustrates a side perspective view of a preferred form of the rigid member of the head support . [ 0044 ] fig7 illustrates a front view in the direction aa of fig3 of the preferred form of fig6 . [ 0045 ] fig8 illustrates a front view in the direction aa of fig3 of an alternative form of the invention , being a back pack . [ 0046 ] fig9 illustrates the invention in use by , for example , a belayer fig1 illustrates the invention in use by , for example , a climber . [ 0047 ] fig1 illustrates the invention in use by , for example , a decorator or painter . [ 0048 ] fig1 illustrates the invention according to a further preferred form . with reference to fig1 there is shown a head support 1 which consists of a rigid member 2 and a harness 3 located or secured with said rigid member . the rigid member and harness are adapted to be located to the user of the head support of the present invention such that when the user is standing upright and tilts his / her head backwards , there is a region of said rigid member 2 with which the tilted back head can contact and be provided with a vertical support thereby . it is to be noted that the support of the present invention may simply provide neck support for viewing above the horizontal rather than head support , without departing from the scope of the present invention . with reference to fig2 , 10 and 11 there is shown a user of the head support with his head tilted backwards and a part of the head locating against a portion of the rigid member to provide the user with a comfortable and vertical support for the head or neck . in reference to fig2 and 3 in the preferred form of the present invention the head support consists of harness which is locatable about the upper body regions of a user of the present invention . the harness is of a configuration which can provide at least vertical stability to the rigid member . it is to be noted that the “ harness ” can also include a backpack without departing from the scope of the invention . in fig2 in the preferred form there is shown a harness which consists of two shoulder straps 4 which are locatable over the shoulder and underneath the armpits to return back to a region of attachment 5 between the rigid member 6 and the harness 3 . in the preferred form the region of attachment is at or towards a lower distal end of the rigid member 6 of the present invention however it is envisaged by the inventor that such location points can vary . with reference to fig1 there is illustrated the shoulder straps 4 running from the region of attachment to the rigid member , over the shoulders under the arms and back towards the region of securement . it will be appreciated by a person skilled in the art that such shoulder straps may be provided with buckles and / or adjustment means to allow for the head support of the present invention to be reconfigured to allow users of different body shapes and sizes to use the particular head support . furthermore , as discussed the shoulder straps may be those of a backpack configuration . as indicated in fig2 , 6 and 7 in the preferred form the rigid member 6 is preferably made up from a sheet material such as a moulded plastic , composite or metallic or non - metallic material . the rigid member 6 preferably consists of a vertically extending region 7 and an outwardly extending region 8 . the vertically extending region 7 is provided and adapted in association with the harness to lie parallel to and in engagement with the back of a user of the head support of the present invention . preferably said vertically extending region 7 is of sufficient length to be pressed when said harness is engaged to the user , against the back of the user to provide some stable support in respect of the user of the present invention . the outwardly extending portion 8 of the rigid member has a head contacting region 9 with which , when said head support is in use , the tilted back head of a user can comfortably located . as indicated in fig6 and 7 , the outwardly extending portion may be concave to allow engagement of the head as shown in fig3 and 4 , for comfort in the wearing of the head support of the present invention there is preferably provided a padded surface 10 on that side of the rigid member which is to be in contact with the body of the user . [ 0054 ] fig4 shows and alternative configuration or an additional configuration to the harness of the head support of the present invention . to encourage the rigid means to remain in stable and close contact with the back of a user a further portion of the harness is provided to encompass the chest or waist of the user of the device . this portion 11 may be attached to the shoulder straps 4 and / or be attached to the rigid member of the present invention . again a person skilled in the art will appreciate that this strap 11 may be provided with a buckle and / or strap length adjusting means to allow a particular head support of the present invention to be adapted for use by different sized and shaped people . for further support to the rigid means of the present invention a lateral stabiliser may be rigidly attached or form part of the rigid member 6 . with reference to fig5 such a lateral stabiliser may for example be arms 20 which extend outwardly ( and preferably upwardly ) from a region of the rigid member 6 . preferably the region from which the lateral stabilisers extend is a lower or lower most region of the rigid member . the lateral stabilisers are preferably made of a material similar to that of the rigid member or may alternatively be made from any other material and which although preferably deformable , does have its own inherent rigidity . in the preferred form the lateral stabilisers locate at the distal ends with the shoulder straps 4 . the shoulder straps will tend to draw the lateral stabiliser to conform with the upper back and shoulder shape of the user of the present invention and hence in the preferred form such lateral stabilisers are of a sheet material or strip wherein the plane of the sheet or strip is in a general parallel direction with the back of the user . such an orientation of the plane of the lateral stabilisers will allow for it to be conformed or at least in part contoured with the back of the user . preferably at the distal ends of the lateral stabiliser there is the provision of the slot through which the shoulder straps 4 can extend while still allowing the distal ends of the lateral stabilisers to have some association with said shoulder straps . [ 0057 ] fig1 illustrates an embodiment of a further preferred form of the invention . this figure includes shows the head support 1 including the rigid member 2 , and the shoulder straps 4 of the harness . in this embodiment the head supporting region 40 of the head support 1 is of a substantially arcuate form , providing further support towards the sides of the head of the user . it also includes a padded surface 41 for comfort . [ 0058 ] fig1 further illustrates the use of a support or strut 42 which holds and retains the rigid member 2 at a distance from the back of the user . in some situtations ( such as on medical or particularly orthopaedic advice ) it may be preferable for the rigid member 2 to have no contact with the user &# 39 ; s back . this embodiment is appropriate for such situations . [ 0059 ] fig1 also illustrates additional adjustment means 43 which may be employed to raise and lower the rigid member and ( in this particular embodiment ) the head supporting region 40 with respect to the head of the user . it is envisaged than a number of adjustment means may be employed individually or in combination in an embodiment according to the invention , without departing from the scope of the invention . such adjustment means may be used to raise and and lower the rigid member together with , or separately from the head supporting region ; to alter the position of the head supporting region with respect to the rigid member and / or head of the user ( in respect of height , and tilt for example ) and additionally to alter the distance between the rigid member and / or head supporting region and the back of the head , for example .

US-21716402-A

a walker is provided with a non - rotatable glide assembly that easily slides over the ground surface when a walker is lifted and advanced forwardly . as soon as a predetermined downward force is exerted on the walker legs , the glides retract and non - slip crutch tips engage the ground surface . moreover , an individual glide may be easily removed and substituted by a wheel that provides rolling contact with the ground surface . the remainder of the mounting structure is used so that the walker may be easily converted from a glide to wheeled arrangement .

referring now to the drawings wherein the showings are for purposes of illustrating the preferred embodiment of the invention only and not for purposes of limiting same , the figures show a walker a constructed in accordance with the teachings of the subject invention . more specifically , the walker includes a frame 10 that is comprised of a pair of mirror image side frames 12 , 14 . hand grip regions 16a , 16b are provided at upper support regions 18a , 18b of each side frame . spaced from the hand grips are side braces 20a , 20b which extend transversely between a pair of downwardly extending legs , more specifically , first and second or front legs 22a , 22b , and third and fourth or rear legs 24a , 24b . each side frame is of substantially identical construction , and to facilitate identification , like elements are referred to by like numerals with an a or b suffix , while new elements are identified by new numerals . a cross brace 30 interconnects the front legs 22a , 22b together . although shown in a deployed or in use position , a pair of handle releases 32a , 32b are received on each front leg so that when handle 34a , 34b is actuated , the side frames 12 , 14 can be rotated inwardly toward one another into a collapsed position ( not shown ) against the cross brace 30 for storage purposes . each of the handles 32a , 32b is secured to the side frames by suitable fastening means , such as pop rivets 36 . more particular details of the collapsible structure and its operation are not provided since they are well known in the art and form no part of the subject invention . to provide for height adjustment , each of the legs includes a telescoping assembly along its lower portion . more specifically , adjustable leg portions 42a , 42b ( front ) and 44a , 44b ( rear ) are provided , one leg portion for each leg . in the preferred arrangement , the adjustable legs are tubular constructions of slightly greater diameter than the remainder of the legs . in this manner , the adjustable leg portions are slidably received over the lower ends of the respective legs . to selectively lock the adjustable leg portions in place , i . e ., at a desired height , an opening 46 is provided adjacent the lower end of each of the legs 22 , 24 , disposed within the hollow tubular leg is a snap button assembly , which according to the preferred arrangement is comprised of a wire spring 48 and a snap button 50 . the bent configuration of the wire spring secures the assembly in place within the hollow tubular leg and biases the snap button s0 outwardly through the respective opening 46 . as shown , each leg includes its own snap button assembly so that the lengths of all legs may be adjusted to alter the height of the walker . as perhaps best illustrated with reference to fig4 a series of axially spaced openings 52a - f are provided in each adjustable leg portion . these openings are dimensioned to receive the snap button therethrough when the desired opening is aligned over the snap button extending through opening 46 of a respective leg . by selectively depressing the snap button , the adjustable leg portions are then slid upwardly or downwardly on the lower ends of the legs to adjust the height . the biasing action provided by the wire spring urges the snap button 50 outwardly through aligned openings 46 , 52 to secure the adjustable leg at the desired height . turning again to fig1 it is important to provide relative sliding movement between the adjustable leg portions and the remainder of the legs . however , too loose a fit provides an undesirable rattle between the telescoping components . accordingly , an anti - rattle plug 54 is inserted into and closes off the lower ends of the hollow tubular legs . additionally , an anti - rattle collar 56 is received over an upper end of each of the adjustable leg portions 42 , 44 . preferably , the anti - rattle components 54 , 56 are formed from plastic or similar material that exerts a close - forming fit on the components , allowing sliding movement without an attendant rattle . as shown in the preferred embodiment of fig1 each of the front leg portions 42 receives a caster wheel 62 . each caster wheel is secured to a lower end of the adjustable leg portion by means of an adaptor bushing 64 . as is well known in the art , the caster wheel assembly provides for free rotational movement through 360 ° about a vertical axis . thus , the patient can easily steer the walker and the casters will rotate in the desired direction in response to the applied forces . of course , it will be recognized that fixed wheels , i . e ., unable to rotate about a vertical axis , are sometimes used in place of the caster wheels . with continued reference to fig1 and additional reference to fig2 - 5 , there is shown a glide assembly 70 disposed on each rear leg , particularly on the adjustable leg portions 44 thereof . thus , although only one adjustable leg portion of a rear leg is illustrated in fig2 - 5 , the other rear leg accommodates a glide assembly also and the description of one is equally applicable to the other . each glide assembly includes a spring housing 72 having a circumferentially continuous cylinder or collar 74 ( fig5 ) which is secured to the adjustable leg portion by a fastener , such as pop rivet 76 . a recess or cavity 78 is adapted to receive a spring , such as coil spring 80 , therein . the cavity is dimensioned to receive one end of the coil spring , while another end of the coil spring extends outwardly , preferably downwardly from the spring housing . also formed in the spring housing 72 are a pair of generally key - shaped openings or recesses 82 that are located on diametrically opposite portions of the spring housing . these openings face generally downward and receive rounded or bulbous ends 84 of a pair of arms 86 of fork assembly 88 . also provided on the fork assembly 88 are a second pair of arms or forks 94 . each fork arm 94 has an opening 96 at an outer end that defines a pivot axis for limited pivotal movement of glide member 100 . a pin member 102 is received along the axis to secure the glide member to the fork assembly . a protrusion or raised dimple 104 is also defined on the fork assembly 88 . the protrusion receives the other end of the coil spring 80 so that the glide member 100 is normally biased downward , exerting the spring biasing force against the fork assembly . thus , the fork assembly is urged to pivot about the rounded end 84 in a generally clockwise direction as viewed in fig2 and 3 by the coil spring . in this manner , a smooth curvilinear base surface 106 of the glide member is urged into sliding contact with the ground surface . this contoured surface facilitates sliding movement of the entire walker over the ground surface , particularly where a patient would otherwise have a tendency to drag the legs along the ground surface , as opposed to a lifting action for each forward advancement of the walker . also provided on the lower end of the adjustable leg portions 44 is a crutch tip or other anti - slip surface 110 . as described above , use of a non - slip tip on the base of a leg is a well known and commonly used feature . in the preferred arrangement , it is defined by a one - piece rubber structure that is tightly received over the end of the tubular leg and has a serrated lower surface that frictionally engages the ground surface . since the structure and operation of these tips is well known in the art , further discussion is deemed unnecessary to a full and complete understanding of the invention . the main pivoting action of the glide 100 is about the rounded end 84 of the fork assembly . since the curvilinear surface 106 extends over a major portion of the glide member , only a small surface area of the glide contacts the ground surface at one time . additionally , a pair of stops 12o , 122 are integrally molded with and extend outwardly from an upper surface of the glide 100 . the stops 120 , 122 cooperate with the top side and underside , respectively , of the pair of fork arms 94 . the stops allow only a limited degree of pivotal movement of the glide about the pin member 1o2 and primarily function to maintain the proper orientation of the curvilinear surface 106 toward the ground surface . of course , alternative arrangements may be used without departing from the scope and intent of the subject invention . as additionally shown in fig6 and 7 , the glide member 100 may be easily removed and substituted with a wheel 130 . removal of pin member 102 from the openings in the ends of the fork arms 94 allows the glide member 100 to be slid outwardly from receipt between the arms in the fork assembly . thereafter , a wheel 130 is positioned between the fork arms . a journal 132 and a removable fastener , such as a nut and threaded bolt assembly 134 , that is received through the journal , cooperate to hold the wheel in place . as will be apparent , the remainder of the glide assembly structure is retained on the lower portion of the adjustable leg . that is , the spring housing , fork assembly , spring , and crutch tip all operate in substantially the same way . the wheel 130 , however , is adapted for rotation about a horizontal axis defined by the fastener whereas the glide member did not rotate . thus , the wheel 130 is normally biased by the spring into rolling contact with the ground surface until a predetermined force is exerted on the walker leg . this force overcomes the outward bias of the spring 80 and the wheel pivots upwardly about the rounded end 84 of the fork assembly so that the crutch tip 11o engages the ground surface . as soon as the downward force is removed , the spring 80 returns the wheel into contact with the ground surface and the crutch tip is lifted upwardly . a tab 140 extends outwardly from the spring housing and is disposed outwardly of the spring 80 in a location overlying the wheel . the tab acts as a secondary support for the assembly to prevent the fork arms from being overstressed . that is , the arms 86 engage the spring housing as the assembly pivots about end 84 relative to the spring housing . if the tip could proceed further downwardly than the wheel , for example if the wheel is supported by a curb or step and the tip is located over the edge of the curb , additional stresses could be imposed on arms 94 of the assembly . the tab 140 , however , will engage the wheel and prevent further upward deflection of the fork assembly relative to the spring housing . the invention has been described with reference to the preferred embodiment . obviously , modifications and alterations will occur to others upon a reading and understanding of this specification . it is intended to include all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof .

US-49437595-A

a machine for making one or more cigarette rods or analogous smokers &# 39 ; products is provided with a cooling apparatus for one or more cooling elements , one for each rod . each such element has a finger which frictionally contacts and is thus heated by the respective advancing rod preferably immediately downstream of a station where one or more tobacco streams is or are converted into one or more rod - like fillers , and a guide wall which carries the finger and frictionally contacts and is thus heated by the advancing filler at a wrapping station for the rod . the cooling apparatus has at least one part which is cooled by a circulating fluid coolant and is movable into and from surface - to - surface contact with the finger and the guide wall .

fig1 shows a cigarette making machine 50 which is designed to produce a single continuous cigarette rod 28 . this machine comprises a distributor including a gate 1 which is arranged to supply ( when necessary ) batches of shredded tobacco leaf laminae or other suitable smokable material ( such as substitute or reconstituted tobacco ). it will be appreciated that the machine 50 of fig1 constitutes but one of numerous machines which can be equipped with the cooling apparatus of the present invention . thus , fig2 to 4 illustrate a cooling apparatus 60 capable of being assembled with or incorporated in a machine which is designed to simultaneously turn out two cigarette rods . such machines are disclosed , for example , in commonly owned u . s . pat . no . 4 , 893 , 640 granted jan . 16 , 1990 to heitmann et al . for “ multiple - rod cigarette making machine ” as well as in numerous other us patents of the assignee of the present application . it is also possible to embody the improved cooling apparatus in cigarette making or analogous machines which are designed to simultaneously turn out three or more continuous cigarette rods . the gate 1 of the distributor in the machine 50 is arranged to supply batches of comminuted smokable material ( hereinafter called tobacco shreds for short ) to a preliminary distributor 2 . the latter includes a rotary drum - shaped withdrawing member 3 which supplies shredded tobacco to a storage facility 4 , e . g ., a magazine which is arranged to maintain an at least substantially constant supply of tobacco shreds adjacent the ascending reach or stretch of an endless elevator conveyor 5 serving to deliver controlled quantities of tobacco shreds to a tobacco gathering duct 6 . a rotary carded drum 7 is arranged to withdraw a uniform layer of tobacco particles from the bottom portion of the duct 6 and cooperates with a rotary picker roller 8 having radially outwardly extending needles which propel tobacco particles from the carding of the drum 7 onto the upper reach of a driven constant - speed wide endless band 9 serving to gather and advance a layer of tobacco . the leader of such layer is propelled against an air curtain which is generated and maintained by a classifying device 11 . the less acceptable heavier particles of the layer on the endless band 9 penetrate through the air curtain of the device 11 but the latter intercepts the more satisfactory lighter particles and causes them to descend into a funnel 14 having a stationary wall 13 and a carded roller 12 . the latter propels the satisfactory tobacco particles from the funnel 14 into a guide channel 16 which gathers a stream of particles for transfer to the underside of the elongated lower reach of an endless foraminous belt conveyor 17 . the lower reach of the conveyor 17 is disposed at the underside of a suction chamber 18 which attracts the tobacco stream to the underside of the belt conveyor 17 . this conveyor advances the stream lengthwise . the manner in which the foraminous belt conveyor 17 gathers and advances ( lengthwise ) a continuous stream of comminuted smokable material is fully disclosed , for example , in commonly owned german patents nos . 4215059 and 19733443 a1 . successive increments of the tobacco stream which is advanced by the underside of the lower reach of the belt conveyor 17 are equalized by a trimming device 19 which removes the surplus so that the stream is converted into a continuous rod - like tobacco filler ready to be draped into a continuous web 21 of cigarette paper supplied by an expiring bobbin or reel 22 in a wrapping mechanism 26 . successive increments of the web 21 advance through a printing mechanism 23 which applies thereto information ( such as the name and / or the trademark of the manufacturer ) before such increments advance to the upper reach of an endless belt conveyor 24 ( known as garniture ) which converts the web into a tubular envelope surrounding the rod - like tobacco filler coming from the foraminous belt conveyor 17 . the lower reach of the conveyor 17 is deflected upwardly and away from the trimmed tobacco stream ( filler ) by a pulley 17 a . the draping of the cigarette paper web 21 around the rod - like tobacco filler is carried out in such a way that one longitudinal marginal portion of the web is provided with a coat of a suitable adhesive and is thereupon folded over the other longitudinal marginal portion to form therewith a seam extending lengthwise of the thus obtained tubular envelope of the finished cigarette rod 28 . the reference character 27 denotes a customary tandem sealer which heats and thus strengthens the aforementioned seam before the cigarette rod 28 advances through a standard density measuring device 29 and thereupon into a severing device or cutoff 31 serving to subdivide the rod 28 into a continuous series of discrete plain cigarettes 32 of twice unit length . a cooling apparatus for certain parts of the cigarette making machine 50 is located at and can form part of the wrapping mechanism 26 . a modification of such cooling apparatus , namely a cooling apparatus 60 adapted for use in a cigarette making machine which is designed to simultaneously produce two continuous cigarette rods , will be described with reference to fig2 to 4 . the density measuring device 29 controls the operation of the trimming device 19 so that the latter converts the tobacco stream into a rod - like filler having an optimum density . the cigarettes 32 of double unit length issuing from the cutoff 31 are taken over by the controlled arms 33 of a transfer device 34 which delivers such cigarettes to a drum - shaped conveyor 36 for introduction into a filter cigarette making machine 37 , e . g ., a machine of the type disclosed in commonly owned u . s . pat . no . 5 , 135 , 008 granted aug . 4 , 1992 to oesterling et al . for “ method of and apparatus for making filter cigarettes ”. the machine 37 comprises a rotary drum - shaped conveyor 38 cooperating with a driven circular knife serving to divide each cigarette 32 into a pair of plain cigarettes of unit length . the machine 50 of fig1 further comprises two endless belt conveyors 39 , 41 which serve to transport trimmed - off surplus tobacco from the equalizing device 19 to a receptacle 42 which is installed in the distributor beneath the magazine 4 adjacent the upwardly advancing ( ascending ) stretch or reach of the elevator conveyor 5 , i . e ., the trimmed - off surplus tobacco is delivered to the duct 6 for readmission into the tobacco stream at the underside of the lower reach of the foraminous conveyor 17 . fig2 is a side elevational view of the aforementioned cooling apparatus 60 which embodies one form of the present invention , which is designed for use in conjunction with a machine for simultaneously producing plural continuous cigarette rods 28 , and which can be readily modified for use in the cigarette making machine 50 of fig1 . as concerns the utilization of guide walls in the region of the cooling apparatus 60 and the installation of such guide walls in a cigarette making machine , reference may be had again to the aforementioned japanese patents nos . 2997246 b1 and 2000253864 . the section 17 b of an endless foraminous belt or band conveyor 17 of fig1 is trained over the pulley 17 a which is adjacent a transfer zone 62 immediately upstream of one wrapping mechanism 26 ( it will be appreciated that the cigarette making machine which embodies or cooperates with the cooling apparatus 60 of fig2 to 4 comprises two foraminous conveyor belts 17 having sections 17 b , and that such machine employs two wrapping mechanisms 26 ). in the transfer zone 62 , one of the two continuous rod - like tobacco fillers ( not shown in fig2 to 4 ) is guided first by the tip ( free end portion ) 64 of a so - called finger 66 on a guide element or wall 68 , thereupon by the major portion of the finger 66 and further by a strip - shaped cover 70 of the guide wall 68 . the finger 66 and the cover 70 effect a narrowing or reduction of the cross - sectional area of the rod - like filler which entails a compression of the filler to a cross - sectional area which is desirable or necessary for the draping of the filler into the cigarette paper web 21 , i . e ., for the making of a continuous cigarette rod 28 having a desired diameter and cross - sectional area . the guide wall 68 is heated as a result of frictional engagement with the rapidly advancing rod - like filler , and the purpose of the cooling apparatus 60 is to maintain the temperature of this wall within a desired ( acceptable ) range ( e . g ., between room temperature and about 100 ° c .) or at an optimum value . this apparatus comprises conduits or pipes 72 or like conveying means which serve to convey a suitable fresh flowable coolant ( e . g ., water ) to and to convey the spent ( heated ) coolant from the cooling station ( s ) in or at the wrapping mechanism ( s ) 26 . the reference character 71 ( see fig3 and 4 ) denotes a connector for the conduits 72 which attaches the conduits to a source ( not shown ) of flowable coolant and to an arrangement ( not shown ) which receives spent coolant . the apparatus 60 further comprises one or more additional conduits ( not shown in fig2 to 4 ) serving to convey the coolant from the coolant supplying conduit ( s ) 72 to first contact surfaces 74 for the cover 70 and to second contact surfaces 76 ( see fig3 ) for the fingers 66 . the first contact surfaces 74 are provided on plates 73 and the second contact surfaces 76 are provided on rods or bars 78 a , 78 b , 78 c and 78 d having free end portions 80 . the plates 73 and the rods 78 a to 78 d together constitute a composite cooling element of the apparatus 60 . fig3 is a perspective view of the cooling apparatus 60 . the purpose of the rods 78 a to 78 d is to establish large - area contact between the second contact surfaces 76 on these rods and the adjacent sides of the two fingers 66 ( not shown in fig3 ). to this end , the rods 78 a to 78 d are substantially parallel to each other . in the embodiment of fig2 to 4 , the contact surfaces 76 diverge slightly from each other , as seen in directions toward the free ends 80 of such rods ; this ensures or makes it possible to pivot the rods 78 a to 78 d over the fingers 66 and to thus ensure that progressive pivoting entails the establishment of increasing pressure between the fingers and the rods . such progressive increase of pressure is attributable to the rather slight conicity of the rods . the cooling apparatus 60 preferably further comprises means ( not specifically shown ) for biasing the first and second contact surfaces 74 and 76 to thus further enhance the exchange of heat between the contact surfaces and the surfaces of adjacent parts in the operative positions of mobile parts of the apparatus ; such operative positions are shown in fig3 in which the contact surfaces 74 are in abutment with the cover 70 and the contact surfaces 76 abut the fingers 66 . the biasing means can comprise one or more coil springs and / or any other suitable resilient elements . the cooling action ( output ) of the cooling element including the parts 73 and 78 a to 78 d of the apparatus 60 is selected in such a way that the temperature of the guide wall 68 ( which includes the fingers 66 and the strip - shaped cover 70 ) is maintained at an optimum value or , at the very least , within an acceptable range . as already mentioned hereinbefore , a presently acceptable range in a high - speed cigarette making machine is between the room temperature and about 100 ° c . the character 82 denotes in fig3 and 4 the pintle ( pivot pin ) of a hinge or an analogous device which pivotably connects the cooling apparatus 60 to the housing or body of the cigarette making machine . the pivot axis of the pintle 82 is preferably at least substantially parallel to the axes of the rod - like fillers which are produced by the cigarette making machine . fig3 shows the cooling apparatus 60 in its operative ( lowered ) position . in fig4 , the apparatus 60 is lifted ( to this end , it comprises a handle or the like ) so that its parts and the neighboring parts of the cigarette making machine are more readily accessible ( e . g ., for inspection and / or cleaning ). an advantage of the improved machine ( such as the machine 50 of fig1 ) and cooling apparatus ( such as the apparatus 60 of fig2 to 4 ) is that the guide wall 68 and the fingers 66 need not be pivoted or otherwise moved away from their operative positions . in presently known cooling apparatus , the fingers are pivotable with the conveyor including the endless band 17 . fig3 and 4 further show that the position of the conduit 72 need not be changed when the cooling apparatus 60 is pivoted ( at 82 ) to or from its operative position . another important advantage of the improved cooling apparatus 60 and of the rod making machine ( such as 50 ) embodying or cooperating with such apparatus is that the guide wall 66 , and hence the finger or fingers 66 and the cover 70 , are readily accessible because such component parts are not integral parts of the improved cooling apparatus . this is of particular advantage in cigarette rod making or analogous machines for making rod - shaped smokers &# 39 ; products which are designed to simultaneously turn out two or more rod - shaped fillers and cigarette rods 28 because access to such fillers or rods is not blocked by the coolant supplying conduits , pipes or channels which , in conventional cooling apparatus ( such as those disclosed in the aforementioned japanese patents ), are necessarily integral with the guide wall or guide walls of the rod making machine . thus , the improved cooling apparatus 60 can afford access to all of the rod - like fillers which are about to be draped into cigarette paper or other suitable wrapping material . all that is necessary is to pivot the improved cooling apparatus 60 from the position which is shown in fig3 to that which is depicted in fig4 . it is also within the purview of the present invention to assemble the cooling apparatus 60 of several components , e . g ., a first component which is pivotable or otherwise movable to and from a heat - exchanging ( operative ) position with the plate or plates 73 , and a second component which is pivotable or otherwise movable into and from heat - exchanging position with the finger or fingers 66 . without further analysis , the foregoing will so fully reveal the gist of the present invention that others can , by applying current knowledge , readily adapt it for various applications without omitting features that , from the standpoint of pror art , fairly constitute essential characteristics of the generic and specific aspects of the above outlined contribution to the art of apparatus for cooling cigarette rod making machines or the like and , therefore , such adaptations should and are intended to be comprehended within the meaning and range of equivalence of the appended claims .

US-99252504-A

a non - invasive cardiac monitoring device for calculating the cardiac performance parameters of heartbeat , stroke volume , and cardiac output for an individual . the device receives a plurality of electrocardiogram waveform signals from the individual and selects the r - wave component having the maximum value of the electrocardiogram waveform signals and the t - wave component having the maximum value of the electrocardiogram waveforms . from these values , the stroke volume of the individual and the cardiac output of the individual may be calculated according to the equation : stroke volume = 6 × r / t + 26 . 0 . the periodicity of subsequent electrocardiogram waveforms are utilized to calculate the cardiac performance of the individual .

referring first to fig2 a , there is illustrated a typical electrocardiographic waveform 10 which is a graphical representation of depolarization and repolarization of cardiac tissue during normal cardiac functioning . the waveform is a graphically representation of the current changes between two electrode sensors over a time period . this waveform is representative of one heartbeat and is repeated during each heartbeat . the waveform 10 is comprised of a number of component portions , namely a p - wave component 12 , qrs - complex wave component 13 , r - wave component 14 , and t - wave component 15 . the p - wave component is actually the graphical representation of depolarization of the atrium , the qrs - complex wave component is the graphical representation of depolarization of the ventricles , and the t - wave component is the graphical representation of repolarization of the cardiac tissue . the waveform illustrates the electrocardiographic waveform of a healthy individual . cardiac abnormalities are detected by analysis of the electrocardiographic waveforms taken of an individual and discerning the deviations of the waveform from the waveform of a healthy individual . in fig1 b the waveforms appearing in a horizontal row commencing with waveform 10 is illustrative , as labeled normal , a normal waveform of a heartbeat derived using a lead identified by reference numeral 1 . a series of waveforms following the waveform labeled normal are illustrative of abnormal conditions which are also labeled above each waveform . similarly , beneath the first row of waveforms there is a second row of waveforms derived from a lead identified by reference numeral ii in which the first waveform is indicative of normal and the series of waveforms in the remaining part of the row are indicative of and which are identified as in the waveforms obtained from reference lead 1 . lastly , a lead identified by reference numeral iii illustrates a third series of waveforms beginning with , as labeled , a normal waveform in column number 1 and proceeding with the abnormal waveforms within the series . the abnormalities are identified by legends above each column of waveforms . these waveforms in fig1 b are illustrative of the general form , the electrocardiogram waveforms take using leads positioned at different parts of the body and the widely varying characteristics indicative of abnormalities in relation to a normal waveform . the present invention utilizes information derived from the electrocardiogram waveforms for measuring the stroke volume based on a ratio of an r - wave amplitude which is maximum to the t - wave amplitude which is also maximum . the r - wave amplitude is determined by an r - wave vector and similarly the t - wave amplitude is determined from a t - wave vector . these vectors are only in exceptional cases parallel to each other in most individuals , however , in all cases either of right heart or left heart axis deviation both vectors are also sufficiently misaligned . because of this misalignment two separate sensors must be employed to create one signal with the largest r - wave amplitude and another signal with the largest t - wave amplitude for forming the ratio of r / t and to derive the stroke volume . the electrocardiographic vectors are defined conventionally in a coordinate system . in fig2 there is shown the axis system frequently utilized in order to describe current vectors formed during cardiac functioning . currents through cardiac tissue are formed during depolarization and repolarization of the cardiac tissue , a current vector is formed which , by definition , is described by both a magnitude and a direction . the axis system of fig2 is utilized to describe these cardiac current vectors . the origin of the axis system is usually considered to be located at the center of the heart of an individual . a line extending through the origin towards the left arm of the individual is defined to be zero degrees . positive angles are defined in the clockwise direction relative to the zero degree line , and negative angles are defined by counterclockwise rotation relative to the zero degree line . a vertical line extending upwardly from the origin towards the head of an individual extends at an angle of minus ninety degrees . normally , a cardiac current vector has a direction of between minus thirty degrees and positive one hundred five degrees . in fig2 the axis corresponding to line i -- i is the horizontal axis , the axis corresponding to line ii -- ii passes through sixty and two hundred forty degrees , and the axis corresponding to line iii -- iii passes through minus sixty and plus one hundred twenty degrees . turning now to fig3 there is illustrated the standard geometry of positioning a conventional , multi - sensor electrocardiogram sensor set positioned upon an individual 18 wherein a plurality of electrocardiographic electrode sensors 20 have been positioned in a conventional geometry . pairs of sensors 20 form leads to allow measurement of currents in cardiac tissue and to detect waveforms such as the waveforms of fig1 a and 1b . each of the electrode sensor pairs forming leads detect cardiac current vectors formed during cardiac functioning . since the individual sensors of an electrocardiographic sensor set are positioned at different body surface locations of the individual , waveforms having different magnitudes are detected by the leads formed by different pairs of sensors . this can be clearly seen by comparing the waveform derived from leads i , ii , and iii in fig1 b . in particular , the magnitudes of the detected current vectors which form the waveforms are dependent upon the positioning of the electrode sensors . electrode sensors placed parallel to the r - vector detect the largest voltage . when electrodes are not placed parallel to the r - vector substantially less voltages are measured . additionally , measurement of the electrocardiographic waveforms from certain electrocardiographic leads may fail to detect deviations from normal waveforms . this can result in a diagnosis of an individual &# 39 ; s cardiac performance to be dependent upon which electrocardiographic leads are selected for analysis . the present invention is based on the relationship between the amplitude of the r - wave component and t - wave component of the electrocardiogram . specifically , however , a series such as the usual 12 waveforms are analyzed for selecting the r - wave component having a maximum value , and the t - wave component having a maximum value . upon evaluation of experimental data , it has been shown that there is a linear relationship between the ratio of the maximum r - wave amplitude to the maximum t - wave amplitude and the stroke volume of the individual 18 . this relationship between the ratio of r / t and stroke volume was experimentally derived and is defined by the equation : wherein sv is the stroke volume of the individual , and r / t is the ratio of the r - wave component with a maximum amplitude to the t - wave component with a maximum amplitude . the invention employs two electrode pairs with one pair creating the wave form having the largest r - wave component and the other pair creating the wave form having the largest t - wave component . only when the r - wave vector is parallel to the t - wave vector which is seldom the case are the maximum wave form components for both r - wave and t - wave obtained by only one electrode pair . the teachings of this invention become readily apparent when viewing the case of left ventricular hypertrophy of fig1 a . one electrode sensor pair identified as lead i must be employed to obtain the largest r - wave component and another electrode pair identified as lead iii must be used to determine the largest t - wave amplitude . the stroke volume sv is then derived from the ratio of maximum r - wave component over maximum r - wave component . thus it can be seen , if only one electrode pair such as lead i is employed a negative stroke volume would result because of the negative t - wave amplitude . alternatively , if only one electrode pair such as lead iii ( left ventricular hypertrophy ) would be employed the stroke volume would be zero as because of the absence of the r - wave component in this lead . as previously mentioned , the stroke volume of an individual is the amount of blood pumped by the individual &# 39 ; s heart in one heartbeat . this relationship may also be shown by utilizing data measured during practice of the previously mentioned thermodilution and dye method . referring now to fig4 there is illustrated a plot of typical temperature change of an individual &# 39 ; s heart subsequent to the injection of a cold fluid into the bloodstream . by measuring the time t required for the temperature of the heart to recover , the cardiac output for this period of time may be accurately calculated . by dividing this value by the number of heartbeats ( as measured by an electrocardiogram ), the stroke volume of the individual &# 39 ; s heart may be calculated . the stroke volume calculated in this manner similarly correlates with the r / t wave ratio using the maximum component wave forms . illustrated in the embodiment of fig5 is a block diagram of the cardiac performance monitoring apparatus of the present invention . monitoring apparatus functions to calculate the stroke volume of the heart of an individual when supplied with data concerning the plurality of electrocardiographic waveforms of the individual at least two waveforms produced simultaneously must be analyzed although a more accurate determination of stroke volume will be obtained in using multi - leads preferably all twelve of the standard electrocardiographic waveforms . electrocardiogram leads 20 are electrically connected to detector 32 . detector 32 functions to measure the amplitudes of the r - wave and the t - wave components of each waveform measured by each of the leads 20 all measured amplitudes of the r and t - wave forms are passed to a selector circuit 34 where the waveform having a t - wave with the greatest amplitude and the r - wave with the greatest amplitudes are selected and signals are generated on lines 35 and 36 indicative of the magnitude of waveform 10 which is greatest of all the 14 and t - wave amplitudes 15 respectively . lines 35 and 36 coupled to stroke volume calculator 38 wherein the ratio of the selected maximum amplitude of the r - wave to the selected maximum amplitude of the t - wave is calculated for use in arriving at a stroke volume signal according to the equation : r / t is the ratio of maximum valves of r and t components of electrocardiographic waveforms . the stroke value signal is applied by line 40 to an output device 42 and to a memory device 44 . output device 42 may be comprised of an alphanumeric display of light emitting diodes , a line printer , or any other conventional interface apparatus . the stroke volume calculator calculates the stroke volume of the individual according to the previously - mentioned equation which is a regression equation . memory device 44 allows long - term storage of each of the stroke volume values , and allows later display of these values on output device 42 by connection of memory device through line 41 . memory 44 is used to store stroke volume signals determined at multiple intensity of time . the plurality of stroke volume signals are outputs from memory 44 by lines 45 , 46 , and 47 to ratio calculator 48 , time average calculating 49 and sliding average calculator 50 , respectively . in the preferred embodiment , the device includes alarm means 51 in order to generate an alarm in the event that any of the values of the calculated stroke volume differs from desired values . the ratio calculator 48 utilizes stroke volume values derived from memory 44 for calculating the ratio of a stroke volume value taken during exercise when compared to a stroke volume taken at rest . the ratio is output from the ratio calculator by line 52 as an input to the output device 42 and by a branch line 53 which will be utilizes for other purposes , preferably according to the present invention , during oxygen inhalation and cardiovascular rehabilitation . such a utilization of the stroke volume ratio will be described in greater detail hereinafter . time average calculator 49 utilizes stroke volume calculations derived from memory 44 to provide an average stroke volume signal formed by the addition of a number of stroke volume values and the sum thereof divided by the number of stroke volume values which occur in a predetermined time interval . the average stroke signal derived from the time average calculator is delivered by line 54 to output device 42 for display or utilization as discussed above . lastly , stroke volume signals derived from memory 44 are utilized in the sliding average calculator 50 by averaging stroke volume values taken over a predetermined number of heart beats and updating the average stroke volume values through deleting the earliest occurring stroke volume value and adding a newest occurring stroke volume value to the average calculation . in this way , updated stroke volume average values are produced which are delivered by line 55 to output device 42 for display and other utilization purposes . referring now to the schematic illustration of fig6 there is illustrated a further embodiment of the instant invention . in this embodiment , the signals needed by the cardiac performance monitoring device 30 to function are supplied by transmitter means 52 to receiver means 53 . receiver 53 is connected to the cardiac monitoring device 30 to supply electrocardiographic signals to the detector device 32 of the apparatus 30 to allow remote monitoring of the cardiac functions of an individual . the monitoring system for this purpose may be positioned at the patient &# 39 ; s bedside or at a remote location , for example , a central nurse &# 39 ; s station . the cardiac monitoring system contains an alarm 51 to be activated in the event that the stroke volume differs from desired preset values . in the embodiment of fig6 the apparatus 30 may , for example , be utilized to monitor an individual during postoperative care , and during therapeutic management . in similar manner , monitoring may be adapted to function as an alarm device to generate alarms during sleep irregularities , such as sleep apnea . the stroke volume data serves particularly well in cardiac performance monitoring to provide a quantitative evaluation of the cardiac pumping performance of an individual . this quantitative information concerning the individual is virtually instantaneously , and importantly continuously , all of which is of particular utility because the monitoring device allows calculation of the stroke volume of an individual during the performance of medical procedures , such as open heart surgery , and other times at which prior art devices were incapable of functioning . the apparatus of the present invention further allows the effects of various procedures , such as induction of anesthesia , sternotomy , dissection , going - on bypass , and returning from bypass to be quantitatively measured and analyzed . still further , stroke volume monitoring may be utilized to monitor the individual during oxygen inhalation and cardiovascular rehabilitation programs , such as an oxykinetic exercise program . referring to the schematic illustration of fig7 the cardiac performance monitoring apparatus 30 shown in fig5 is useful together with transmitter 52 in order to monitor the individual during such exercise . the individual is supplied an oxygen - air mixture from tank 70 through mask 72 . the supply of oxygen from tank 70 is regulated by operation of value 71 . such operation can be manually operated by , but preferably by a controller 71a , which is responsive to the stroke volume signal in line 53 . the individual then engages in intermittent periods of exercise , the intensity and duration of such exercise being controlled by the magnitude of the individual &# 39 ; s stroke volume calculated by the apparatus 30 illustrated in fig5 . oxykinetic programs such as this aid in the improvement in cardiopulmonary performance to progressively elevate the maximum oxygen consumption of the individual 18 , in some instances by as much as ten percent . used in this manner , stroke volume data is also utilized as a safety device to prevent overexertion of the individual during performance of cardiopulmonary rehabilitation programs . in fig8 a and 8b the graph lines thereof demonstrate typically changes to cardiac pumping as measured by stroke volume of an individual under different circumstances . in both figures the abscissa is time and the ordinate axis 55a is stroke volume . in fig8 a graph line segment 100 depicts a stroke volume of an individual at rest whereupon , beginning at a point in time identified by reference numeral 101 , the individual undergoes exercise . during the exercise period it can be seen that the stroke volume increases to a maximum value and remains constant for a period of time until exercise terminates as indicated at a point of time identified by reference numeral 103 . after termination of exercise , the stroke volume reduces in value as indicated by graph line segment 105 . by way of contrast , in fig8 b where medication , namely , oxygen enriched air is administered to the individual , the stroke volume is initially determined at a value indicated by graph line segment 106 during which period oxygen enriched air would also be supplied to the individual . commencement of exercise at point of time identified by reference numeral 107 brings about a increase to the stroke volume to a point in time where the stroke volume reaches a maximum value and thereafter actually reduces to a significantly lower value throughout the period of exercise . termination of exercise occurs at a point in time identified by reference numeral 109 . thereafter the stroke volume reduces as indicated by graph line segment 110 . by comparing these two graph lines it can be seen that the administering of the oxygen enriched air serves to reduce the demand for cardiac performance during exercise . the present invention is also particularly useful in such a program which may consists of repetitive exercise bouts during oxygen inhalation . the information provided by the stroke volume data is especially useful for controlling the duration of intensity of exercise by the individual because of the ability to continuously and almost instantaneously monitor the cardiac stroke volume performance by the individual . while the present invention has been described in connection with the preferred embodiments of the various figures , it is to be understood that other similar embodiments may be used or modifications and additions may be made to the described embodiment for performing the same function of the present invention without deviating therefrom . therefore , the present invention should not be limited to any single embodiment , but rather construed in breadth and scope in accordance with the recitation of the appended claims .

US-37322989-A

a deboning apparatus of the type for effecting a separation of boney material from the meat portion of fish , fowl , or other animals , and includes an auger means that is arranged through an adjoining pressure housing and perforated housing , with the auger means being coupled to for direct drive by a motor , for effecting its rotation within the said housing to achieve this meat - bone separation ; the auger means includes a motor coupling section that connects directly to the motor , and which section incorporates a thrust bearing for absorbing axial thrust generated during functioning of the apparatus , a pressure auger section that is disposed within the pressure housing , and which includes an infeed section for deposition of the bone laden material therein , and wherein significant pressure is developed upon said boney material prior to its being conducted to a conveying auger section located within the perforated housing of the apparatus , and wherein the bone and meat material are substantially separated , with said auger further including a valved section that cooperates with a valved sleeve for maintaining back pressure for sustaining some of the pressure housing forces generated upon the bone laden material as it is being conveyed along the auger , with all segments of the auger , and the various pressure and perforated housings being supported by a base member that bearing mounts the two approximate ends of the auger for providing total and firm stability for the apparatus throughout its extent .

in referring to the drawings , and particularly fig1 the deboning apparatus d of this invention is disclosed as comprising a base member 1 that is essentially shown as extending almost the full length of the apparatus , and in this embodiment , is formed as a solid cast aluminum base that provides a rigid support for the operating instrumentalities of the apparatus located thereabove . but , extending downwardly from the base member 1 are a series of reinforced legs 2 being substantially braced laterally , transversely as at 3 , and longitudinally as at 4 , so as to provide very stable support for the apparatus when both in transit , but particularly , when in use . to facilitate the former , provided downwardly from each leg 2 of the apparatus is a caster 5 , with each caster being provided with an adjustable type of locking mechanism 6 so as to allow for the apparatus to be fixed in position as during usage , thereby preventing its shifting as might be caused under circumstances generated by the inherent torque created during operation of this high speed deboning apparatus . as also shown in fig1 provided upon the one end of the base member 1 is an electrical motor 7 which contains the usual electronic component motor control box 8 that furnishes particular control to the electrical energy supplied to the motor 7 . for example , rectifiers or other components may be contained in the housing 8 , such as for creating a rectification of the usual alternating current in the event that the motor 7 comprises a direct current motor . in any event , in the preferred embodiment , the motor 7 comprises a 50 horsepower motor that is capable of operating at speeds of 1160 rpm , and can be energized as either a 220 or 440 d . c . voltage . as previously described in the summary of this invention , other motor speeds may be used in conjunction with the operation of this deboning apparatus , and speeds as low as 500 rpm , as generated from a motor of smaller size , or speeds as even as high as 1800 rpm , as from a larger capacity motor , could work in conjunction with the deboning mechanisms as wil be hereinafter described in this apparatus . extending forwardly from the motor 7 internally along the remaining length of the apparatus and terminating at an auger shaft extension 9 is the auger means 10 of this apparatus . this auger means , as will be later more fully described , is primarily disposed within various components that complement the operation of this apparatus , but essentially , one end of the auger means is connected by means of a flexible coupling 11 to the shaft of the rotor of the motor , and this particular coupling is of the type that provides for a direct connection and direct drive of the auger means by the motor 7 . obviously , many other forms of couplings may be made between the auger means and the motor , but the particular coupling utilized in this embodiment may be of the type acquired from dodge corporation , of mishawaki , indiana , under model no . px - 120 . extending upwardly approximately at the midpoint of the base member 1 are a pair of pillow blocks 12 and 13 , which pillow blocks are disclosed as being integrally formed extending from said base . each said pillow block , as will be hereinafter described , mounts a bearing that provides for the very near frictionless rotation of the auger means 10 therethrough . but , in order to cushion and absorb any longitudinal thrust that may be generated through the cooperative operation between the auger means 10 and the various associated mechanisms of this deboning apparatus , intermediate the two pillow blocks 12 and 13 there is provided a thrust bearing 14 designed to provide for this dampening of any axial thrust generated during functioning of the deboning apparatus . such a bearing may be acquired from torrington company , of south bend , ind ., under model no . 30tp106 . further forwardly of the apparatus and provided integrally extending upwardly from the base member 1 are a pair of supports 15 and 16 which are designed for providing the means for mounting of the pressure housing 17 within the deboning apparatus , in addition to the pivotal mounted infeed sleeve 18 of the apparatus , and through which the ground bone laden material yet to be deboned enters into the influence of the auger means of this invention . provided further forwarded of the base member 1 of this invention is another support member 19 , which support member may be slidably mounted upon the base member 1 for purposes that will be subsequently described . in any event , secured intermediate the support 16 , and the support 19 , is a perforated housing 20 , which housing is held in place between these two supports 16 and 19 by means of a pair of fastening rods , one as shown at 21 , that span the distance between the two said supports , with the outer end of the rod 21 having a threaded fastener , such as a wing nut connection for snug retention on the perforated housing therebetween . as can be seen in fig4 this slidable support member 19 includes a pair of integral guides 22 that are arranged for slidably mounting within the slideways 23 provided in this segment of the base member 1 . a series of plates 24 , 25 and 26 are fastened by means of bolts 27 to the base member 1 , to provide the means for retention of the guides 22 within the said waves 23 . hence , once the support member 19 is slid into the position shown in fig4 and the wing nuts 27a tightened to the rod 21 , this particular support , in conjunction with the previously described support 16 , firmly hold the perforated housing 20 in place . extending out of the support member 19 , and concentrically surrounding the extension shaft 9 is the valve sleeve 28 that cooperates with the valved section of the auger means as will be subsequently described . it is to be noted that the base member 1 below the vicinity of the location of the perforated housing 20 provides a substantial opening , as at 29 , the base member actually being flared as at 30 , on both sides , to provide substantial spacing for provision of this opening 29 , and it is through this opening that the meat material separated from the boning components as it expresses from the perforated housing 20 may fall downwardly therethrough for collection within a bin or basket ( not shown ). the base member 1 , further proximate this end , is cast having an upwardly and inwardly disposed integral portion 31 , that is further provided having an aperture 32 arranged therein and in which a bearing 33 is disposed for providing a near frictionless rotation of the auger means 10 , or more particularly its shaft portion 9 thereat . the bearing 33 at this location may be any type of journal bearing for providing full support but as near frictionless rotation as possible for the auger means . such a bearing may be acquired from dodge corporation , of mishawaki , ind ., under model no . 060252 . hence , full bearing support is provided at both ends of the auger means 10 by means of the bearinged pillow blocks 12 and 13 , and the bearing 33 . a more detailed analysis of the operating components of the deboning apparatus d of this invention can be made up reviewing fig2 and 3 . as can be seen , the base member 1 includes the motor 7 thereon , with the shaft 34 from the motor being connected by the coupling 11 to the motor coupling section 35 of the auger means 10 . this motor coupling section 35 is supported by the two pillow blocks 12 and 13 , as previously described , and each of these pillow blocks contain a bearing means 36 and 37 that provides for unemcumbered rotation of the section 35 therethrough . these bearings may be of the general radial type and may be acquired from rexnord corporation , of downers grove , illinois , and having model no . zmc9 - 2215 . the upper half of the blocks 12 and 13 might be separable , and removed , so as to provide a means for insertion or replacing of the section 35 , or the bearings 36 and 37 . the threaded apertures 38 may accommodate fasteners for holding the upper halves of these pillow blocks in place . also disclosed between these blocks 12 and 13 , and as previously briefly analyzed , is the thrust bearing 14 . this bearing 14 may seat within a counterbore , as at 39 , provided within one face of the pillow block 12 , so as to provide for its proper centering and fixation with respect to the block , and the motor coupling section 35 that rotates there within , and this bearing is of the type having the usual radial bearing face plates , as at 40 , with a series of bearings intermediate thereof . just adjacent to the thrust bearing 14 are a pair of thrust collars , as at 41 and 42 , and each of these collars are provided with a set screw therein for rigidly securing the said collars to the auger section 35 , and to achieve their revolving therewith . hence , the collar 41 is biased tightly against the thrust bearing 14 , with the collar 42 being also fixed in place upon the section 35 and tightly against its adjacent collar 41 . preferably these collars will be preloaded in their relationship with respect to the thrust bearing 14 so as to insure a fixed longitudinal positioning of the auger means 10 within the apparatus . counterbored into the opposite end of the motor coupling section 35 of the auger means 10 is a bore hole 43 , which may have internal threads provided therein , and threadedly engaged therein is the pressure auger section 44 of the auger means 10 . this proximate end of the auger section 44 is likewise threaded , as at 45 , and is provided with a shoulder 46 for biasing tightly against the approximate end of the section 35 to insure a rigid fastening of these two auger sections together . this pressure auger section 44 extends further into the pressure housing 17 of the apparatus , which housing , as previously defined , is rigidly held in place by means of the supports 15 and 16 . the auger section 44 , arranged with the pressure housing 17 , disposes a series of helical vanes that are integrally formed having a significantly increasing diametrical dimension , along the length of this auger section , as at the base of each vane , so as to provide a means for building up excessive pressure upon the bone laden material as it enters into the pressure housing through the infeed sleeve 18 . the continuous vane is shown at 47 , and is continuous in its deposition around the auger but has the decreasing depth the further it is disposed within the pressure housing of this apparatus . as previously briefly explained , the pressure housing 17 contains a slot , as at 48 , generally around its upper half circumference , and through this slot is disposed the infeed sleeve 18 of the intake region of the apparatus . this slot 48 is arranged around the upper circumference of the pressure housing 17 so that the infeed sleeve 18 , and its connecting integral sleeve 49 , may be pivotally revolved to various angular locations radially around the upper portion of this housing 17 , so as to dispose the infeed sleeve 18 at that location found to be most convenient for facilitating the intake of the bone laden material into the apparatus . obviously , any such adjustment will be made while the apparatus is in idle , since to attempt any such adjustment during operation of the apparatus will only encounter the enormous compressive pressures built up upon the bone laden material between the auger 44 and the interior of the sleeve 49 , and which would prevent any such pivotal movement to the sleeve 18 . it should also be noted that the infeed sleeve 18 may additionally have connected thereto a grinder 50 , of the conventional type , and which may grind the carcass of either poultry , fish , or the red meat animal down to that size particle that may be fed under the pressure of the grinder through the infeed sleeve 18 and into the auger section of the pressure housing 17 . such a grinder as may be acquired from the weiler grinder co ., of whitewater , wisconsin , has been found satisfactory for this purpose , and capable of reducing the bone particle size and the residue meat down to the vicinity of one - thirtysecond to one - half inch components that can be easily accommodated by the pressure auger section of this deboning apparatus . once the grinder 50 pressure feeds the reduced particle bone laden material into the pressure housing 17 , such material will be further pressurized within this housing to the high pressures as previously explained as it rises along the five degree inclining pitch of the pressure auger section 44 through the urging movement of the helical vane 47 . obviously , othe degrees of pitch to this section of the auger can be used . the opposite end of the pressure auger section 44 is also counterbored , as at 51 , with said counterbore being threaded to provide for a mating engagement with the threads provided at this end 52 of the auger means shaft extension 9 . coupled with the pressure auger section 44 at this location is the conveying auger section 53 of the auger means 10 . this section of the auger means is in the form of a shaft 54 that is axially aligned with the other sections of the auger means 10 , so as to enter into uniform rotation therewith , and includes a contiguous helical rib 55 secured to its surface to thereby provide a means for conveying the bone laden material , as compressed within the pressure housing 17 , along the interior of the perforated housing 20 . the shaft 54 may be of either uniform diameter from one end to the other end , or it may have a slight rise at a fraction of a degree along its length so as to maintain some of the pressure developed by the pressure auger section 44 as the bone laden material is conveyed along the interior of the housing 20 , thereby forcing the meat material through the perforations or apertures provided through the housing 20 while continuing to agitate and convey the boney components therealong by operation of the helically arranged rib 55 . as previously analyzed , the brunt of the pressure upon the bone laden material is developed within the pressure housing 17 , whereas the conveyor auger section 53 of the apparatus is designed to provide conveyance of this prepressurized material along the interior of the perforated housing 20 so as to attain the bone separation from this material . as further previously analyzed , the meat material being expressed from the perforated housing 20 will fall through the opening 29 provided at the flared portion 30 of the base member 1 . where the shaft 54 has a slightly increasing diameter , an increase in diameter of one - eighth inch from the intake end of the perforated housing 20 to the outlet end has been found satisfactory for maintaining some of the pressure developed within the pressure housing 17 . hence , it is not desired to continuously and forcefully press the bone laden material passing through the perforated housing 20 , but rather , it is desired to have some release of pressure by means of the passage of the meat material through the perforated housing , and while this pressure release is occurring its boney components may be agitated or ground together so as to effect a further release of residue meat from the same for its eventual passage through the perforations of the housing 20 . the perforated housing 20 , itself , contains a series of predrilled apertures therethrough , and these apertures will vary in size depending upon the type and consistency of the meat product being separated . generally a hardened stainless steel cylinder having conically drilled holes has been found satisfactory for this purpose . for example , in the poultry field , the apertures may be anywhere in the vicinity of 0 . 8 millimeters , with an overall range of 0 . 3 to 2 . 5 millimeters being found operative , with the commulative aperture area comprising 20 to 50 percent of the surface area of the housing . as a point of illustration , where the calcium content of ground meat can be of a higher percentage , as in europe , then aperture sizes at the upper end of the range can be accommodated . also , the aperture size will depend upon whether the meat will be cooled , or in the raw state . in the rod meat field ,, these apertures may be in the range of 0 . 2 to 2 . 5 millimeters in diameter , and comprise a similar type percentage of the perforated housing surface area . in the fish field , the size of perforations may be more dictated by the bone size , with fine bone fish meat having aperture sizes ranging from 0 . 3 to 1 . 5 millimeters , and course bone meat having apertures ranging from 0 . 3 to 3 . 0 millimeters . in any event , the main object of this invention is to provide sufficient surface area along the perforated housing 20 , and with the properly designed and sized apertures disposed therethrough , so that as the prepressurized boney material is being conveyed at high speeds through the perforated housing , it is forced out of the said housing while the boney content is precluded from doing such , and is agitated and promptly conveyed into its valved discharged end . in addition , it has been found useful not to place the conveying auger too contiguous the interior of the perforated housing , and a five to fifteen thousandths clearance allows for sufficient agitation of the bones to achieve the desired results of this invention . it should also be noted that where the contiguous ends of the pressure auger section 44 and the conveying auger section 53 connect , each is provided with one or more holes therein , as at 56 and 57 , and into which a pin 58 is disposed for holding these two sections together for achieving their simultaneous rotation during functioning of this apparatus . the downstream end of the conveying auger section 53 has integrally formed a valved section 59 , which comprises a decreasing pitch tapered annulus that cooperates with a similar type surface , as at 60 , formed upon the interior 61 of the valve sleeve 28 . these cooperating surfaces of the valved section 59 , and the sleeve 28 , are designed to furnish some amount of back pressure upon the boney material being conveyed thereto by means of the conveying auger section 53 , in a manner that is generally known in the prior art . in any event , the valve sleeve 28 is threadedly engaged within another sleeve 62 that is secured within the slidable support 19 , and through a turning of the sleeve 28 , the gap between these tapered surfaces of the cooperating valved members may be adjusted so as to provide the proper amount of clearance for passage of the now substantially ground boney material therethrough to achieve its discharge from the apparatus . further provided integrally beyond the location of the cooperating tapered surfaces 59 and 60 are integrally formed discharge blades 63 that are designed having the proper slant so as to furnish an immediate disposal and discharge of the boney material exiting from this valve gap so as to totally eliminate any clogging at this location . since the valve sleeve 28 is hollow through its interior , as can be seen , the boney material just falls from its end and downwardly into any conveniently arranged hopper provided at this location . as can also be seen cooperating with this end of the auger means 10 , the shaft extension 9 has a shoulder 64 that is arranged for abutting against the end of the discharge blades 63 , so as to provide a means for tightly securing the pressure auger section 44 and the conveying auger section 53 together , as they are threadedly engaged as at 52 . the other proximate end of the shaft extension 9 is bearing mounted within the upwardly inturned end 31 of the base member 1 , and , as previously described , the bearing 33 is arranged within the formed aperture 32 to provide the means for providing full bearing support at this end of the auger means of the apparatus . the bearing provided thereat may be any form of shaft bearing as available in the art , but preferably is of the type previously identified . another unique feature of this invention is its complemental assembly and securing of its various components together , which allows for both their ease of installing into an operative apparatus , and likewise , for quick disassembly , as when it is desired to cleanse the same . for example , it can be seen that the shaft extension 9 , as previously explained , is threadedly engaged at 52 with the pressure auger section 44 . when this threaded engagement is removed , as by the turning of a wrench upon the hexagonal end 65 , it may be withdrawn from its positioning through the center of the conveying auger section 53 , and further removed from its bearing mount 33 . then , the valved sleeve 61 may be turned for its withdrawal from its threaded connection with the sleeve 62 . to facilitate the turning of this member 61 , it can be seen , from fig 3 , that its exposed end 66 is knurled so as to facilitate its grasping at this location . when this sleeve 61 is removed , the conveying auger section 53 can be slid longitudinally forwardly of the machine to also achieve its removal . this is attained by a simple withdrawal of the section 53 from its pinned connection to the pressure auger section 44 . at the same time , the wing nuts 27a may be withdrawn from their mounting upon the rods 21 , and once removed , the slide mounted support 19 can be withdrawn from the ways 23 of the base member 1 thereby withdrawing with it the threaded sleeve 62 . it can be seen that this threaded sleeve 62 has a shoulder 67 that seats the proximate end of the perforated housing 20 , and when this sleeve is removed , this also allows for a withdrawal of the perforated housing 20 from the apparatus . the opposite end of the perforated housing 20 is embraced by the proximate shoulder 68 of the pressure housing 17 . thus , when the perforated housing 20 is removed , the pressure housing 17 may then likewise be slid axially of the apparatus to acquire its removal . furthermore , by inserting a wrench upon the hexagonal surface 69 of the pressure auger section 44 , its threaded engagement by means of the threads 45 within the bored end 43 of the motor coupling section 35 may also be disengaged , allowing this pressure auger section 44 to also be withdrawn from the apparatus . hence , all of the elements and components of this invention that are exposed to the bone laden material during functioning of the deboning apparatus can be quickly removed through disassembly , thereby facilitating their cleaning , as usually required daily , by various government regulations . as easy as the machine has been disassembled , it may be facily reassembled for immediate functioning of the deboning apparatus as required . various modifications to the various structured components of this deboning apparatus may occur to those skilled in the art upon reviewing this detailed disclosure . the preferred embodiment is set forth for illustrative purposes only , and any variations or modifications to the invention , but yet within the scope of the appended claims , are intended to be fully protected by any patent issuing hereon .

US-6556779-A

a live bacteria product including dormant viable bacteria suspended in a liquid carrier . the carrier contains mineral oil and polymers and may also include an adsorbent . the product is stored and shipped in a plastic bag and is sprayed onto its target host or the like . the moisture and ph of the target host then activates the bacteria .

in this invention , conventional live viable harmless bacteria is mixed with a substantially moisture - free liquid carrier or medium . in general , the live bacteria used in the product of this invention will be any lactic acid producing bacteria that is permissible for use in animal related products . the united states food and drug administration ( fda ) and the american association of feed control officials ( aafco ) have published a list of the microorganism species which are “ generally recognized as safe ” ( gras ) for use in direct - fed microbial products . table i hereinbelow lists presently approved bacteria for use with animal related products . table i 36 . 14 -- dfm microorganisms under the “ grass ’ status aspergillus niger aspergillus oryzae bacillus coagulans bacillus lentus bacillus licheniformis bacillus pumilus bacillus subtilis bacteroides amylophilus bacteroides capillosus bacteroides ruminocola bacteroides suis bifidobacterium adolescentis bifidobacterium animalis bifidobacterium bifidum bifidobacterium infantis bifidobacterium longum bifidobacterium thermophilum lactobacillus acidolphilus lactobacillus brevis lactobacillus buchneri lactobacillus bulgaricus lactobacillus casei lactobacillus cellobiosus lactobacillus curvatus lactobacillus delbruekii lactobacillus fermentum lactobacillus helveticus lactobacillus lactis lactobacillus plantarum lactobacillus euterii leuconostoc mesenteroides pediococcus acidilacticii pediococcus cervisiae pediococcus pentosaceus propionibacterium freudenreichii propionibacterium shermanii saccharomyces cerevisiae entercococcus cremoris entercococcus diacetylactis entercococcus faecium entercococcus intermedius entercococcus lactis entercococcus thermophilius yeast ( as defined elsewhere ) preferably , the moisture - free liquid carrier is comprised of a product marketed under the trademark “ synergel ®” manufactured by penreco of 138 petrolia street , karns city , pa . 16041 - 9799 . the product is generally referred to as a gelled mineral oil , reference number 1004 - 100 , having a brookfield viscosity of 1242 cps . the carrier product is clear , odorless and is insoluble in water . the carrier also includes polymers . other suspension agents such as cobisal ™ ( polymer fiber ) may also be used from time to time to aid or reduce the possibility of the settling of the bacteria therein . the product of this invention is designed to only activate the bacteria at the physical point of contact with the target host . upon contact , the target host ambient moisture content will activate ( i . e ., initiate the life cycle thereof ) the dormant bacteria found within the liquid microbial medium or carrier . the liquid microbial medium or carrier of this invention has undergone a special production process developed by penreco . the process consists of first passing the mineral oil through an advanced filtration system which specifically targets and absorbs any ambient moisture . secondly , the mineral oil is heated and polymers are added to increase the oil viscosity and suspension qualities . thirdly , the oil is packaged into controlled shipping vessels that reduce the risk of moisture contamination of any kind . upon receipt of the packaged carrier , applicant then preferably adds a moisture scavenger product such as a hydrophilic molecular sieve adsorbent as an insurance program . the adsorbent may comprise a natural or synthetic zeolite consisting of crystalline metal aluminosilicate , alkali metal aluminosilicate or sodium aluminosilicate . finally , whatever bacteria are needed for a particular purpose will then be added . the final blend is then packaged in moisture and ultraviolet retardant containers such as collapsible polyurethane bags , very similar to i . v . bags . the product is then sold and shipped directly to the retailer and / or end user . the end user will then take the collapsible bag of liquid microbial blend and hook it directly to an applicator so that extremely small droplets are created which are sprayed upon the target host the invention described herein provides the ability to inoculate other products with dormant live bacteria , by means of a light spraying application . whereas the bacteria is protected with the oil / polymer blend allowing the host bacteria to survive longer in a non - favorable environment , the coating of the bacteria cell walls with the oil / polymer covering provides a physical chemical moisture barrier . the above provides the ability to permit the live bacteria to be introduced onto a pelleted feed without immediately inadvertently activating the oil / polymer / host bacteria through ambient moisture contamination from the feed itself . the product of this invention permits it to be applied to its target host at a preferred micro - treatment rate of 2 to 28 grams per one ton ( 2 , 000 pounds ) of forage or the material treated ( with no additional water or carriers needed ). in some cases , higher or lower ratios may be employed . such micro - treatment is substantially less than prior art products that have treatment rates that range from 37 . 88 grams to 8 . 3453 pounds per one ton of forage treated . the product of this invention and its packaging limits its exposure to possible contamination from outside sources , such as moisture - laden air or fluid water of any kind . the product of this invention is designed to only activate at the physical point of contact with the target host . upon contact with the target host , the change in ph and moisture activates the dormant bacteria . thus it can be seen that the invention accomplishes at least all of its stated objectives .

US-70046407-A

an apparatus for supporting a work object having a pair of deformable elongated members , a mount adapted to support the deformable elongated members in substantially side - by - side relation , and a securing member mounted on the deformable elongated members in spaced relation to the mount and movable therealong so as releasably to capture a work object between the deformable elongated members , the mount and the securing member .

referring more particularly to the drawings , the support apparatus of the present invention is generally indicated by the numeral 10 in fig1 . the support apparatus can be employed in a wide variety of operative embodiments and , similarly , possesses a virtually unlimited number of environments within which it can be used . in the illustrative operative environment , shown in the drawings and described herein , two of the support apparatuses 10 are mounted in depending relation on an upright structure , or wall , 20 having a vertical surface 21 . for purposes of visualizing the specific environment of use , the wall 20 can be visualized as being the wall of a room , such as within a house , dormitory , apartment or the like . as shown in fig1 and as hereinafter described in greater detail , the two support apparatuses 10 are supporting and storing a first work object , or long board , 30 , having opposite end portions 31 and bounded by a peripheral edge 32 . the long board , thus , has opposite sides , or faces , 33 and is of a substantially flat configuration characteristic of surf boards . a second work object , or surf board , is generally indicated by the numeral 34 in fig1 . the surf board 34 has opposite end portions 35 and is bounded by a peripheral edge 36 . the surf board 34 has opposite sides , or faces , 37 and is similarly of a substantially flat configuration . a third work object , or surf board , is generally indicated by the numeral 38 in fig1 . the surf board 38 has opposite end portions 39 and is bounded by a peripheral edge 40 . the surf board is , again , of a substantially flat configuration and has opposite sides , or faces , 41 . the support apparatus 10 has a mounting assembly generally indicated by the numeral 50 and shown best in fig3 . the mounting assembly has a support member 51 of metal construction and has an annular portion 52 defining a hole 53 . a screw assembly 54 is employed to mount the support member 51 on the wall 20 in facing engagement with the surface 21 thereof in the desired position , as will hereinafter be described in greater detail . the support member 51 has a pin or shaft portion 55 extending outwardly from the surface 21 of the wall 20 in substantially right angular relation thereto and extends to a distal end portion 56 . the support apparatus 10 further includes a resilient support assembly generally indicated by the numeral 60 and , perhaps , best shown in fig2 . as previously discussed , the support apparatus of the present invention can be constructed in a wide variety of specific operative embodiments . the embodiment shown and described herein is merely one such embodiment , but possesses a number of operative advantages , as will hereinafter become more clearly apparent . in the preferred embodiment , the resilient support assembly is constructed from an elastic cord 61 . while a variety of types of elastic cords can be employed for this purpose , in the preferred embodiment , the elastic cord is , more specifically , a bungee cord consisting of a multiplicity of individual elastic strands running longitudinally thereof and captured , or housed , in a woven synthetic outer jacket or wall . thus , the elastic cord 61 has a woven outer surface 62 of a substantially cylindrical configuration . the elastic cord has opposite end portions 63 and an intermediate portion 64 . the resilient support assembly 60 further includes a mounting ring 70 , preferably , although not necessarily , constructed of metal . the mounting ring has opposite front and rear side surfaces 71 and a concave peripheral surface 72 forming an annulus about the mounting ring . the mounting ring has an interior cylindrical surface 63 defining a hole 74 dimensioned slidably to be received on the shaft portion 55 of the support member 51 . as shown in fig2 and 3 , the intermediate portion 64 of the elastic cord 61 is extended about the mounting ring 70 and fitted within the concave peripheral surface 72 thereof . a metal band 75 is affixed about the elastic cord , as shown in fig3 to mount the mounting ring within the intermediate portion of the elastic cord , as shown in fig3 . the mounting ring is , thus , securely mounted in position and forms a unitary entity with the elastic cord 61 . a pair of deformable , or elastic , linear members 80 is thereby formed from the elastic cord 61 . the elastic linear members have upper end portions 81 , central portions 82 and lower end portions 83 . the lower end portions 83 extend to distal end portions 84 . the distal end portions 84 of the elastic linear members are bound together by a metal band 85 . thus , the elastic linear members are securely fastened to each other at the opposite ends of the resilient support assembly 60 , as best shown in fig2 . a plurality of securing members are received about and thereby mounted on the pair of elastic linear members 80 , as shown in fig1 and 2 . each of the securing members has an interior metal sleeve 96 having an outer cylindrical surface 97 and an interior cylindrical surface 98 . the interior cylindrical surface bounds an interior passage 99 of predetermined diameter . the interior passage extends through the opposite ends of the metal sleeve through a beveled upper annulus 100 and an opposite beveled lower annulus 101 . the metal sleeve is preferably encapsulated in an outer clear vinyl tube 102 . as shown in fig2 the resilient support assembly 60 can be visualized as having an upper storage area 110 bounded by the metal band 75 , the pair of elastic linear members 80 immediately therebeneath and the securing member 95 nearest the metal band 75 . similarly , the support assembly 60 can be visualized as having a central storage area 111 bounded by the securing members 95 at opposite ends thereof and the pair of elastic linear members 80 . the support assembly 60 can be visualized as having a lower storage area 112 bounded by the lowermost securing member 95 , the metal band 85 and the pair of elastic linear members 80 . as will hereinafter be described in greater detail , the operation of the support apparatus 10 is depicted , in part , in fig4 and 5 and , for this purpose , a pair of human hands are indicated by the numeral 120 . the operation of the described embodiment of the subject invention is believed to be clearly apparent and is briefly summarized at this point . as previously noted , the support apparatus 10 can be employed in a wide variety of embodiments and environments of use . in the illustrative environment depicted in fig1 a pair of the support apparatuses 10 are mounted in laterally spaced relation to each other on their respective mounting assemblies 50 in supported relation on the vertical surface 21 of wall 20 . each of the resilient support assemblies 60 is slidably received , through the medium of its respective mounting ring 70 , about the shaft portion 55 of the support member 51 . each resilient support assembly 60 is , thus , gravitationally suspended from its respective support member 51 in juxtaposition to the vertical surface 21 of the wall 20 . the length of each resilient support assembly 60 can be of any suitable measurement and is controlled , in part , by the number and size of the work objects to be supported and stored thereon . for illustrative convenience , the support apparatus 10 depicted in the drawings hereof , is of the length sufficient to support the long board 30 , surf board 34 and surf board 38 . the particular height on the wall 20 at which the support apparatuses are mounted is purely dependent upon the preferences of the user . thus , the support apparatuses can be positioned in side - by - side relation so that the distal end portions 84 thereof are immediately above the floor surface , not shown , in the room in which they are employed . alternatively , the support apparatuses can be mounted in a much more elevated position so that the distal end portions 84 are well above the floor surface . for example , they can be mounted at an elevation such that the work objects borne thereby are , for example , visible , but not accessible without the use of a ladder or other means of support . thus , for example , the support apparatuses can be employed for display purposes as , for example , in a store to display the work objects supported thereby for sale . however , in the illustrative environment , it will be understood that the specific environment of use is the wall of a room , such as a bedroom , and wherein the work objects borne thereby are stored for frequent use and are conveniently accessible . in the described environment of use , each of the support apparatuses can be adjusted to receive the particular work objects to be borne thereby . such adjustment is achieved , as may best be visualized upon reference to fig4 and 5 . the securing member 95 is shown in fig4 in a secured , immovable and at rest position relative to the support assembly 60 on which it is mounted . this is because the support assembly is not tensioned longitudinally thereof and , therefore , the securing member constrictively engages the elastic linear members 80 . this causes the securing member firmly to be retained in position , resisting displacement along the elastic linear members . as may be visualized upon reference to fig5 repositioning of a securing member 95 along the elastic linear members 80 is achieved by tensioning the elastic linear members at the position of the securing member which is desired to be adjusted . this can be achieved by any desired means including in the manner depicted in fig5 by pulling the elastic linear members , on opposite sides of the securing member desired to be adjusted , from each other . this causes the portion of the elastic linear members 80 within the securing member 95 to constrict transversely as they lengthen longitudinally which frees the securing member for slidable movement along the elastic linear members . alternatively , adjustment of the position of a given securing member 95 can be achieved simply by grasping the elastic linear members 80 , on the opposite side of the securing member relative to the direction in which it is desired to move the securing member , and pulling the securing member in the desired direction away from the position of such grasping . since the securing member constrictively engages the elastic linear members in its at rest position , movement of the securing member away from the stationary grasping position similarly causes the elastic linear members to constrict sufficiently to permit the securing member to be moved along the elastic linear members from the position of such grasping . using any of these methods for adjustment of the relative positions thereof , the securing members 95 are positioned so as to define an upper storage area 110 , a central storage area 111 and a lower storage area 112 of the desired dimensions . the desired dimensions are determined by the sizes of the respective work objects to be received therein . the work objects are then simply individually inserted through the corresponding storage areas of the two support assemblies 60 so as to position them in the relative positions shown in fig1 . each work object gravitationally assumes a position within its respective storage area resting against the securing members 95 of the support apparatuses 10 immediately therebeneath . the resistance of the securing members 95 on their respective elastic linear members 80 is sufficient to support the weight of each work object within its respective storage areas . the elastic linear members bounding each storage area retain the work object therewithin resiliently in the attitude in which it has been positioned within the storage areas . the weight of the work objects is supported by the mounting assemblies 50 on the wall 20 . when it is desired to use any of the work objects , the work object is simply grasped and slidably removed from its respective storage areas of the support apparatuses . the other work objects continue to be retained in their respective storage areas freely available for use as desired while being retained in their respective supported positions and in clear view . the work objects are thereafter simply removed from , and returned to , their respective storage areas , as desired . since the storage areas of the support apparatuses 10 are fully repositionable , the work objects stored therein can be changed from time to time as desired and can be of varying type . for example , a surf board could be stored with snow skis and poles and a baseball bat , golf equipment and the like . preferably , although not necessarily , each such work object is positioned in its own storage areas of the support apparatuses . depending upon the preferences of the user , the support apparatuses 10 can be supported in such a position on a wall as to be fully visible all of the time . alternatively , since the support apparatuses bearing the work objects thereof are disposed in juxtaposition to the surface 21 of the wall 20 , the support apparatuses and their respective work objects can be fully concealed , if desired , such as behind a piece of furniture , such as a dresser or other form of cabinetry , of sufficient size . therefore , the support apparatus of the present invention is capable of storing a diverse variety of work objects , such as personal possessions ; is capable of adjusting to the particular work objects to be supported and stored ; supports such work objects in a manner which makes them readily accessible for use while protecting them in a manner most conducive to ensuring long operational lives ; permits such work objects to be stored in proximity to areas for use while being fully concealed and protected when desired ; facilitates the ease by which the work objects can be inventoried ; is of inexpensive construction permitting usage by virtually anyone desiring such a capability ; and is otherwise fully effective in achieving its operational objectives . although the invention has been herein shown and described in what is conceived to be the most practical and preferred embodiment , it is recognized that departures may be made therefrom within the scope of the invention which is not to be limited to the illustrative details disclosed .

US-99901697-A

an intraurethral , foley - type catheter shaft contains a microwave antenna capable of generating a cylindrically symmetrical thermal pattern , within which temperatures are capable of exceeding 45 ° c . the antenna , which is positioned within the shaft , is surrounded by means within the shaft for absorbing thermal energy conducted by the tissue and asymmetrically absorbing electromagnetic energy emitted by the antenna -- a greater amount of electromagnetic energy being absorbed on one side of the shaft . this asymmetrical absorption alters the thermal pattern generated by the microwave antenna , making it cylindrically asymmetrical , which effectively focuses microwave thermal therapy toward undesirous benign tumorous tissue growth of a prostate anterior and lateral to the urethra , and away from healthy tissue posterior to the urethra .

fig1 is a vertical sectional view of a male pelvic region showing the effect benign prostatic hyperplasia ( bph ) has on the urinary organs . urethra 10 is a duct leading from bladder 12 , through prostate 14 and out orifice 16 of penis end 18 . benign tumorous tissue growth within prostate 14 around urethra 10 causes constriction 20 of urethra 10 , which interrupts the flow of urine from bladder 12 to orifice 16 . the tumorous tissue of prostate 14 which encroaches urethra 10 and causes constriction 20 can be effectively removed by heating and necrosing the encroaching tumorous tissue . ideally , with the present invention , only periurethral tumorous tissue of prostate 14 anterior and lateral to urethra 10 is heated and necrosed to avoid unnecessary and undesirous damage to urethra 10 and to adjacent healthy tissues , such as ejaculatory duct 24 and rectum 26 . a selective heating of benign tumorous tissue of prostate 14 ( transurethral thermal therapy ) is made possible by microwave antenna - containing catheter 28 of the present invention , which is shown in fig2 a and 2b . fig2 a shows a side view of a distal end of catheter 28 . fig2 b shows an enlarged sectional view of a proximal end of catheter 28 . as shown in fig2 a and 2b , catheter 28 generally includes multi - port manifold 30 , multi - lumen shaft 32 , shaft position retention balloon 34 , connection manifold 35 , cooling system 36 and microwave generating source 38 . manifold 30 includes inflation port 40 , urine drainage port 42 , microwave antenna port 44 , cooling fluid in port 46 and cooling fluid out port 48 . ports 40 - 48 communicate with corresponding lumen within shaft 32 . manifold 30 is preferably made of medical - grade silicone sold by dow corning under the trademark silastic q - 7 - 4850 . shaft 32 is connected to manifold 30 at shaft distal end 50 . shaft 32 is a multi - lumen , foley - type urethral catheter shaft which is extruded from a flexible , medical - grade silicone sold by dow corning under the trademark silastic q - 7 - 4850 . shaft 32 , which has an outer diameter of about 16 french , includes outer surface 52 , which is generally elliptical in cross - section as shown in fig3 . shaft 32 is long enough to permit insertion of proximal shaft end 54 through urethra 10 and into bladder 12 . in one preferred embodiment , shaft 32 , is coated with a hydrophilic solution sold by hydromer , inc . under the mark hydromer , which lubricates outer surface 52 of shaft 32 and facilitates its advancement within urethra 10 . as shown in fig2 b - 4 , shaft 32 includes temperature sensing lumen 56 , microwave antenna lumen 58 , urine drainage lumen 60 , balloon inflation lumen 62 , cooling fluid intake lumens 64a and 648 , and cooling fluid exhaust lumens 66a and 66b . lumens 56 - 66b generally extend from distal shaft and 50 to proximal shaft end 54 . temperature sensing lumen 56 is positioned near first side 68 of shaft 32 . temperature sensing lumen 56 communicates with microwave antenna port 44 and permits insertion of thermometry sensor 69 within shaft 32 to monitor the temperature of surrounding tissue when shaft 32 is inserted within urethra 10 . sensor 69 exits through port 44 and is connected through connection manifold 33 to urethral thermometry unit 178b ( shown in fig9 ). in a preferred embodiment , thermometry sensor 69 is a fiber optic luminescence type temperature sensor sold by luxtron corporation . temperature sensing lumen 56 is sealed at proximal end 54 by silicone plug 70 . microwave antenna lumen 58 is eccentric to the longitudinal axis of shaft 32 , antenna lumen 58 being positioned nearer first side 68 of shaft 32 than second side 72 of shaft 32 . antenna lumen 58 is sealed at proximal end 54 by silicone plug 70a . at its distal end , antenna lumen 58 communicates with microwave antenna port 44 . microwave antenna 74 is permanently positioned within antenna lumen 58 near balloon 34 . antenna 74 is positioned within antenna lumen 58 so as to be generally situated adjacent the benign tumorous tissue of prostate 14 when shaft 32 is properly positioned within urethra 10 . as shown in fig2 a - 2b , antenna 74 is bonded within antenna lumen 58 by adhesive bond 75 . antenna 74 is carried at the proximal - most end of coaxial cable 76 . the distal - most end of coaxial cable 76 is connected to connection manifold 35 by a conventional quick - coupling fitting 73 . coaxial cable 76 communicates with microwave generating source 38 by connection cable 76a , which is connected between microwave generating source 38 and connection manifold 35 . in one embodiment , connection cable 76a is a standard rg 400 coaxial cable . microwave generating source 38 produces a maximum of 100 watts of electrical power at about 915 mhz frequency , +/- 13 mhz , which is within the fcc - ism standards . when antenna 74 is energized by microwave generating source 38 , antenna 74 exits electromagnetic energy which causes heating of tissue within prostate 14 . urine drainage lumen 60 is positioned adjacent antenna lumen 58 , between antenna lumen 58 and second side 72 . urine drainage lumen 60 communicates with urine drainage port 42 and defines a drainage path for urine when proximal end 54 of shaft 32 is inserted within bladder 12 . urine drainage lumen 60 is connected to urine drainage lumen extension 78 at proximal and 54 . urine drainage lumen extension 78 is bonded within proximal end cap 80 . end cap 80 is further bonded over outer surface 52 of shaft 32 at proximal shaft end 54 , with cavity 82 surrounding lumen extension 78 . with end cap 80 and urine drainage lumen extension 78 in place , opening 84 to lumen extension 78 permits urine to drain from bladder 12 through urine drainage lumen 60 and out urine drainage port 42 when proximal shaft end 54 is inserted within bladder 12 . drainage of urine from bladder 12 is necessary due to frequent bladder spasms which occur during transurethral thermal therapy . balloon inflation lumen 62 is positioned near second side 72 , generally between urine drainage lumen 60 and second side 72 . balloon inflation lumen 62 communicates with inflation port 40 and is sealed at proximal end 54 by silicone plug 70b . balloon inflation lumen 62 communicates with interior 86 of balloon 34 by opening 88 . balloon 34 , which is formed from a tubular section of a flexible , medical - grade silicone sold by dow corning under the trademark silastic q - 7 - 4720 , is secured over shaft 32 by bonding balloon waists 90 and 92 over exterior surface 52 of shaft 32 near proximal shaft end 54 . balloon 34 is inflated by an inflation device 188 ( shown in fig9 ), which is connected to inflation port 40 and which supplies positive fluid pressure to interior 86 of balloon 34 . balloon 34 is deflated when inflation device 188 supplies a negative fluid pressure ( i . e ., a vacuum ) to interior 86 of balloon 34 . balloon 34 serves to retain shaft 32 in a fixed position within urethra 10 when balloon 34 is inflated within bladder 12 near bladder neck 22 , as shown in fig5 . as shown in fig2 b - 4 , cooling fluid intake lumens 64a , 64b are positioned circumjacent first side 68 , between first side 68 and antenna lumen 58 . cooling fluid intake lumens 64a , 64b extend from distal shaft end 50 to proximal shaft end 54 where lumens 64a , 64b are exposed to cavity 82 of end cap 80 . intake lumens 64a , 64b are relatively narrow in cross - section and have a relatively small cross - sectional surface area . water contained within intake lumens 64a , 64b performs two essential functions . first , water contained within lumens 64a , 64b absorbs some of the microwave energy emitted by antenna 74 . this assists , in part , in controlling the volume of tissue adjacent first side 68 of shaft 32 that is heated above about 45 ° c . second , the water within lumens 64a , 643 absorbs heat energy generated by the microwave energy from adjacent tissues ( i . e ., urethra 10 ) via thermal conduction . this prevents the portion of urethra 10 adjacent first side 68 from being overheated and damaged when antenna 74 is energized . cooling fluid exhaust lumens 66a , 66b are circumjacent second side 72 with lumens 66a , 66b generally positioned between second side 72 and antenna lumen 58 . like intake lumens 64a , 64b , exhaust lumens 66a , 66b extend from shaft distal end 50 to shaft proximal end 54 where exhaust lumens 66a , 66b are exposed to cavity 82 of end cap 80 . exhaust lumens 66a , 66b are wider in cross - section than intake lumens 64a , 64b , and have a cross - sectional area greater than the cross - sectional area of intake lumens 64a , 64b . water within exhaust lumens 66a , 66b is therefore capable of absorbing a greater amount of microwave energy when antenna 74 is energized . as a result , for a given power output from microwave generating source 38 , the temperature of tissue adjacent second side 72 will remain below about 45 ° c . water within exhaust lumens 66a , 66b also absorbs heat energy from adjacent tissue ( i . e ., urethra 10 ) when antenna 74 is energized , which prevents the portion of urethra 10 adjacent second side 72 from being overheated and damaged when antenna 74 is energized . intake lumens 64a , 64b and exhaust lumens 66a , 66b are supplied with deionized water from cooling system 36 . water from cooling system 36 is chilled to between about 12 - 15 ° c . and pumped at a rate of between about 100 - 150 milliliters per minute via water feed line 94a to connection manifold 35 . the water flows through connection manifold 35 to water feed line 94b and to water intake port 46 , which communicates with water intake lumens 64a , 64b . under fluid pressure , the water circulates through intake lumens 64a , 64b to cavity 82 of end cap 80 . the water returns to cooling system 36 through exhaust lumens 66a , 66b to fluid exhaust port 48 . the water is carried from water exhaust port 48 via water return line 96b to connection manifold 35 , and from connection manifold 35 to cooling system 36 via water return line 96a . the water is then re - chilled and re - circulated . water feed line 94b and water return line 963 are each provided with a conventional quick - coupling fitting 65a and 65b , respectively , which permits catheter 28 to be easily disconnected from cooling system 36 . fig5 shows an enlarged view of the male pelvic region of fig1 with catheter 28 properly positioned within urethra 10 . orientation strips 98 along exterior surface 52 on first side 68 , as shown in fig4 ensures the proper orientation of shaft 32 within urethra 10 . as shown in fig5 shaft 32 is positioned within urethra 10 with second side 72 of shaft 32 oriented toward rectum 26 . water exhaust lumens 66a , 66b are oriented posteriorly , toward rectum 26 and water intake lumens 64a , 64b are oriented anteriorly toward fibromuscular tissue 100 of prostate 14 . the portion of transition zone 101 anterior and lateral to urethra 10 is the most frequent location of the tumorous tissue growth which causes bph . since water exhaust lumens 66a , 66b are capable of absorbing more microwave energy than water intake lumens 64a , 64b , the radiation patterns created by microwave energy emitted from antenna 74 are asymmetrical . thus , a relatively large volume of tissue enveloping the anterior portion of transition zone 101 , adjacent first side 68 , is heated to a temperature above about 45 ° c ., which effectively necroses the tumorous tissue of prostate 14 which encroaches upon urethra 10 . in comparison , the temperature of tissue adjacent second side 72 remains below about 45 ° c ., thereby eliminating the harmful effects of the microwave energy to ejaculatory duct 24 and rectum 26 . fig6 is a graph which generally demonstrates a microwave thermal therapy procedure and a temperature distribution which was generated by catheter 28 of the present invention , with shaft 32 inserted into a polyacrylamide gel formulation which simulates biological tissue . the formulation and preparation procedures for the polyacrylamide gel are discussed in detail in d . andreuccetti , m . bini , a . ignesti , r . olmi , n . rubino , and r . vanni , use of polyacrylamide as a tissue - equivalent material in the microwave range , 35 ieee transactions on biomedical engineering 275 ( no . 4 , april 1988 ). fig6 shows temperature measurements taken from eight temperature sensors . four sensors were aligned at fixed distances adjacent first side 68 . sensor 1a was positioned immediately adjacent shaft 32 ; sensor 1b was positioned about 0 . 66 cm from shaft 32 ; sensor 1c was positioned about 1 . 33 cm from shaft 32 ; and sensor 1d was positioned about 2 . 0 cm from shaft 32 . four sensors were also aligned at fixed distances adjacent second side 72 . sensor 2a was positioned immediately adjacent shaft 32 ; sensor 2b was positioned about 0 . 66 cm from shaft 32 ; sensor 2c was positioned about 1 . 33 cm from shaft 32 ; and sensor 2d was positioned about 2 . 0 cm from shaft 32 . the x - axis represents a relative period of time over which the microwave thermal therapy procedure was performed . the y - axis represents temperature in degrees celsius , with horizontal line x representing 45 ° c . ( the temperature at or above which cells are necrosed ). as generally shown in fig6 the microwave thermal therapy procedure of the present invention includes five operating phases , p1 - p5 . lines 1a - 1d and 2a - 2d correspond with sensors 1a - 1d and 2a - 2d , respectfully . during first phase p1 , cooling system 36 is turned on and chilled water is pumped through cooling lumens 64a , 64b and 66a , 66b . a drop in temperature immediately adjacent shaft 32 is represented by lines 1a , 2a . at the end of first phase p1 , cooling system 36 is turned off . at the beginning of second phase p2 , a relatively small amount of power ( about 5 watts ) is applied to microwave antenna 74 . the temperature immediately adjacent shaft 32 rises asymmetrically due to the greater absorptivity of water in the larger exhaust lumens 66a , 66b on second side 72 , as shown by lines 1a , 2a . the power is applied long enough to merely warm adjacent tissue to about 40 ° c . by the end of second phase p2 , temperatures generally return to base line temperature . in a preferred embodiment of the present invention , the tissue responses to the chilling during p1 and the heating during p2 aid in determining the vascularity of the tissue to be treated . this information aids in determining the amount of power necessary to treat tumorous tissue of prostate 14 . at the beginning of third phase p3 , cooling system 36 is again turned on thereby pumping chilled water through cooling lumens 64a - 66b . the temperature immediately adjacent shaft 32 correspondingly drops as indicated by lines 1a , 2a . prechilling of the tissue immediately adjacent shaft 32 aids in protecting the tissues immediately adjacent shaft 32 ( i . e ., urethra 10 ) from overheating due to a relatively rapid application of power from antenna 74 . microwave generating source 38 is again turned on at the beginning of fourth phase p4 at a sustained power output of about 20 watts . as shown in fig6 due to the absorptivity differential between water in the narrower intake lumens 64a , 64b and water in the wider exhaust lumens 66a , 66b , temperatures adjacent second side 72 , represented by lines 2a - 2d , are cooler than temperatures adjacent first side 68 , represented by lines 1a - 1d . the temperature differentials are most profound within a target volume of tissue 0 . 66 cm from shaft 32 , within this target volume , as shown by lines 1a , 2a and 1b , 2b , the difference in temperature from first side 68 and second side 72 is on the order of about 10 ° c . thus , by adjusting cooling system parameters or power output from microwave generating source 38 , tissue within 0 . 66 cm of first side 68 can be heated to temperatures at or above about 45 ° c ., while tissue within 0 . 66 cm of second side 72 can remain at temperatures substantially below 45 ° c . in this manner , tissue - necrosing temperatures within the target volume are essentially restricted only to tissue near first side 68 , which is the most frequent location of periurethral tumorous prostatic tissue . alternatively , by adjusting the power output or cooling system parameters , a relatively small volume of tissue adjacent second side 72 can be heated above about 45 ° c . to necrose some of the tumorous prostatic tissue which is posterior and lateral to the urethra . in the preferred embodiment , during fourth phase p4 , microwave generating source 38 is operated for at least about 45 minutes . as shown by lines 1a , 2a , during p4 , the temperature of tissue immediately adjacent shaft 32 ( which is representative of temperatures of urethra 10 ), as well as temperatures of tissue beyond 0 . 66 cm from shaft 32 , as shown by lines 1c , 2c and 1d , 2d , are maintainable well below 45 ° c . this is accomplished by adjusting cooling system parameters and , if necessary , power output from microwave generating source 38 . at the end of fourth phase p4 power is turned off . at the beginning of fifth phase p5 , cooling system 36 continues to operate , circulating water through cooling lumens 64a - 66b . a temperature drop immediately adjacent shaft 32 is relatively rapid as shown by lines 1a , 2a within p5 . in a preferred embodiment of the present invention , cooling system 36 continues to operate for a period of time ( on the order of 10 to 120 minutes ) after the procedure to cool urethra 10 and reduce edema resulting from the application of heat to the periurethral tissues of prostate 14 . in an alternative embodiment , water feed line 94b , water return line 96b and thermometry sensor 69 ( as shown in fig2 a ) are disconnected from connection manifold 35 . water feed line 948 and water return line 96b of catheter 28 are then connected to another cooling system similar to cooling system 36 and water is then circulated through cooling lumens 64a - 66b in a manner similar to that previously described . in this fashion , recovery from the previously described procedure can be accomplished away from the treatment area thereby enabling microwave generating source 38 and cooling system 36 to be readily available for treatment of another patient . fig7 shows a partial sectional view of microwave antenna 74 of the present invention . antenna 74 is positioned at a proximal - most and of shielded coaxial cable 76 . cable 76 is a standard rg 178u coaxial cable and includes inner conductor 120 , inner insulator 122 , outer conductor 124 , and outer insulator 126 . outer insulator 126 , outer conductor 124 and inner insulator 122 are stripped away to expose about 3 millimeters of outer conductor 124 , about 1 millimeter of inner insulator 126 and about 1 millimeter of inner conductor 120 . capacitor 128 includes first end 130 , which is connected to inner conductor 120 by soldering , and second end 132 , which connects to antenna 74 . capacitor 128 serves to counteract a reactive component of antenna 74 , thereby providing a 50 ohm match between coaxial cable 76 and microwave generating source 38 , and antenna 74 . tubular extension 134 , which is a hollow section of outer insulator 126 of coaxial cable 76 , is positioned over capacitor 128 and the exposed length of inner insulator 122 and secured by bond 136 . tubular extension 134 includes hole 138 , which provides an exit for second end 132 of capacitor 128 . wound about outer insulator 126 and tubular extension 134 is flat wire 140 . flat wire 140 is a single piece of flat copper wire with dimensions of about 0 . 009 inch by about 0 . 032 inch in cross - section , which provides a relatively large surface area for maximum current flow while minimizing the cross - sectional size of antenna 74 . fig8 is an exploded view of a portion of antenna 74 which shows its helical dipole construction . generally , the efficiency of any dipole antenna is greatest when the effective electrical length of the antenna is generally one half the wavelength of the radiation emitted in the surrounding medium . accordingly , a relatively efficient simple dipole antenna , operating at about 915 mhz , would require a physical length of about 8 centimeters which , according to the present invention , would needlessly irradiate and damage healthy tissue . furthermore , the physical length of a relatively efficient simple dipole antenna operating at about 915 mhz cannot be varied . as shown in fig8 flat wire 140 is soldered to outer conductor 124 at solder point 146 . flat wire 140 is then wound in a distal direction about outer insulator 126 and in a proximal direction about tubular extension 134 , thereby forming first wire section 142 and second wire section 144 , both of which are of equal length . in one embodiment , first and second wire sections 142 and 144 are each comprised of eight , equally - spaced windings of flat wire 140 . the combined length of first and second wire sections 142 and 144 , and hence the overall length of antenna 74 , ranges from about 1 . 5 centimeters to about 4 . 0 centimeters , and varies according to the length of the area of prostate 14 which requires treatment . a standard medical - grade silicone tube ( not shown ), which has been allowed to soak in a solvent , such as freon , is positioned over first and second wire sections 142 and 144 . as the solvent evaporates , the silicone tube shrinks , thereby securing flat wire 140 to outer insulator 126 and tubular extension 134 . the helical dipole construction of the present invention , allows antenna 74 to range in physical length from about 1 . 5 to 4 centimeters , while electrically behaving like an eight centimeter - long simple dipole antenna . in other words , antenna 74 has an effective electrical length generally equal to one half of the wavelength of the radiation emitted in the surrounding medium , independent of its physical length . for purposes of definition , the surrounding medium includes the catheter shaft and the surrounding tissue . this is accomplished by varying the number and pitch of the windings of first and second wire sections 142 and 144 . a family of catheters , which contain relatively efficient helical dipole antennas of different physical lengths , permits selection of the antenna best suited for the particular treatment area . in addition , antenna 74 of the present invention is capable of producing a constant heating pattern in tissue , concentrated about antenna 74 , independent of the depth of insertion into the tissue . second end 132 of capacitor 128 , which exits hole 138 , is soldered to second wire section 144 at tap point 148 , as shown in fig7 . tap point 148 is a point at which the resistive component of the combined impedance of first wire section 142 and second wire section 144 matches the characteristic impedance of coaxial cable 76 . the impedance of either first wire section 142 or second wire section 144 is expressed as z , where z = r + jx . the impedance z varies from a low value at solder point 146 to a high value at a point farthest from solder point 146 . there exists a tap position where r is equal to 50 ohms , but an imaginary component , x , is inductive . this inductive component can be canceled by inserting a series capacitance , such as capacitor 128 , which has a value of - jx ohms . this results in an impedance match of 50 ohms real . the resulting method of feeding antenna 74 is commonly called gamma matching . in one embodiment of the present invention , where the physical length of flat wire 140 is about 2 . 8 cm , tap point 148 is about 3 . 5 turns from solder point 146 on second wire section 144 . in the preferred embodiment , the value of capacitor 128 is about 2 . 7pf . the helical dipole construction of antenna 74 achieves a relatively small size , which permits intraurethral application . the helical dipole construction is also responsible for three features which enable antenna 74 to achieve greater efficiency than prior known interstitial microwave antennas good impedance matching , good current carrying capability and an effective electrical length which is generally one half of the wavelength of the radiation emitted in the surrounding medium , independent of the physical length of antenna 74 . first , the good impedance match between antenna 74 and inner conductor 120 minimizes reflective losses of antenna 74 , with measured reflective losses of less than 1 % in a preferred embodiment . second , the use of flat ribbon wire 140 for first wire section 142 and second wire section 144 minimizes resistive losses of antenna 74 by providing a greater surface area upon which rf current can be carried . finally , the helical dipole design of antenna 74 has an effective electrical length which is generally one half of the wavelength of the radiation emitted in the surrounding medium , independent of the physical length of antenna 74 . this permits the physical length of antenna 74 to be varied to accommodate varying sizes of individual prostates while maintaining the same efficient , effective electrical length of antenna 74 . the use of an efficient microwave antenna is critical to the ability to focus thermal energy a distance from the antenna within a target volume . an inefficient antenna produces a lesser intensity of microwave radiation within the target volume than desired . it also produces undesired heat close to the urethra , which will damage the urethra if not carried away by an increased coolant flow . this added burden on the cooling system reduces its capacity to protect the urethra , thereby limiting the microwave power that can be radiated without elevating urethra temperatures above safety limits . with microwave power limited by cooling system capacity , the heat delivered to the desired target area of the prostate will not be sufficient for effective therapy . the efficient helical dipole design of antenna 74 of the present invention , however , ensures that almost all heat delivered during the treatment is delivered in the form of microwave energy , rather than conductive heat energy . fig9 is a block diagram of transurethral microwave thermal therapy system 170 , with which urethral catheter 28 is used . system 170 includes cooling system 36 microwave generating source 38 , user interface 172 , real , time controller ( rtc ) 174 , directional coupler 176 , thermometry sensors 182 and 184 , coolant pressure sensor 186 , balloon inflation device 188 , and urine collection container 190 . as shown in fig9 control of microwave generating source 38 and cooling system 36 is effected by real time controller 174 , which is in turn controlled by user interface 172 . user interface 172 is an ibm compatible machine containing two hard drives for data storage : one for backup , and one for normal operation of system 170 . user interface 172 communicates with rtc 174 , which is responsible for all closed loop feedback to run system 170 . rtc 174 has direct closed loop control of microwave power from microwave generating source 38 , and coolant flow and coolant temperature of cooling system 36 . closed loop feedback tracks out variations in gain , drift and cable losses inherent in microwave generating source 38 , and variability in pump output and refrigeration system efficiency of cooling system 36 . in addition to monitoring microwave generating source 38 and cooling system 36 , rtc 174 also monitors and controls several channels of thermometry via inputs from thermometry unit 178 . cooling system thermometry 178a measures the coolant and chiller temperatures based upon signals from coolant temperature sensors 182 and 184 and a chiller temperature sensor ( not shown ) of cooling system 36 . urethral thermometry 178b measures urethral temperature based upon signals from temperature sensor 69 within catheter 28 . rectal thermometry 178c measures rectal temperature based upon signals received from a sensor ( not shown ) within rectal probe 180 . rtc 174 transmits all closed - loop feedback to user interface 172 , which processes the input and transmits corrections and instructions back to rtc 174 . rtc 174 interprets the instructions given to it by process control language received from user interface 172 and executes the instructions in real time . all corrections from user interface 172 are made to maintain a given thermal profile throughout the transurethral thermal therapy . in addition , system 170 includes a hardware fail - safe circuit which shuts down system 170 should any parameter fall outside a given range of values . while the beneficial uses of the microwave antenna - containing catheter of the present invention have been described with respect to the urethra , other intracavitary applications are implied . although the present invention has been describe with reference to preferred embodiments , workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention .

US-89275897-A

a bifurcated balloon for in vivo use , comprises : a proximal hollow tubular element , two bifurcating hollow tubular elements extending distally from a distal end of the proximal hollow tubular element , each of the two elements comprising : a first distal tubular element guidable into a first branch of a vessel bifurcation , and a second distal tubular element guidable into a second branch of the vessel bifurcation . the bifurcated balloon further comprises a longitudinal chamber extending from a distal end of the first distal tubular element , and a first substantially longitudinal guidewire channel passing through the longitudinal chamber , the first guidewire channel having two ends of which a first end passes through a proximal portion of the longitudinal chamber .

the present embodiments concern a bifurcated balloon having , at any given cross section throughout the length of the bifurcated balloon , a maximum of one guidewire lumen , thereby accruing a bifurcated balloon having a low bulk that is easily maneuvered through the vasculature . the principles and operation according to the present invention may be better understood with reference to the drawings and accompanying descriptions . before explaining at least one embodiment of the invention in detail , it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings . the invention is capable of other embodiments or of being practiced or carried out in various ways . also , it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting . generally , the nomenclature used herein and the laboratory procedures utilized in the present invention include techniques from the fields of medicine , biology , chemistry , material sciences and engineering . such techniques are thoroughly explained in the literature . unless otherwise defined , all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs . in addition , the descriptions , materials , methods , and examples are illustrative only and not intended to be limiting . methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention . fig1 b shows an embodiment of a bifurcated balloon 100 in an expanded form having a trunk , herein proximal main branch ( mb ) balloon portion 130 and two distal balloon portions extending distally therefrom : distal mb balloon portion 132 and side branch ( sb ) balloon portion 134 . as used herein with respect to balloon 100 , the term “ proximal ” refers to a portion of balloon 100 that is nearer to the operator ; the term “ distal ” refers to a portion of balloon 100 that is farther away from the operator . longitudinal mb guidewire lumen 136 extends from a proximal opening 108 catheter through proximal end of mb portion 130 and through a distal opening 135 through distal end of mb portion 132 . a guide wire 156 has been fed through guidewire lumen 136 into a catheter 111 . in embodiments , guidewire 156 exits a proximal end opening 117 , a configuration referred to as an “ over the wire ” system . in other embodiments , guide wire 156 exits out of a catheter side hole 113 proximal to bifurcated balloon 100 , a configuration referred to as a “ rapid exchange ” system . the proximal opening can be an end - opening ( 117 ) or a side opening ( 113 ) or may open at any segment of the balloon catheter shaft proximal to the balloon itself . typically , catheter 111 connects to bifurcating balloon 100 with a halo tube ( not shown ) through which contrast material is introduced during inflation and withdrawn during deflation of bifurcated balloon 100 . in embodiments , an sb extension tube 112 extends distally from a distal end of sb balloon portion 134 and typically has a smaller diameter than sb balloon portion 134 . sb extension tube 112 includes an sb guidewire lumen 116 having a proximal side opening 118 passing through sidewall of sb extension tube 112 and a distal end opening 115 through the distal end of sb extension tube 112 . sb guidewire lumen 116 comprises a rapid exchange configuration that is significantly more distal and not traversing via the lumen of bifurcated balloon 100 as opposed to the case of lumen 107 of bifurcated balloon 180 ( fig1 a ); and allows rapid loading of balloon 100 , via sb guidewire lumen 116 onto a guidewire 146 ( fig1 b ). while opening 118 is shown approximately at about 1 . 5 centimeters distal to the distal end of sb balloon portion 134 , opening 118 could be located further proximally , closer to the distal end of sb balloon portion 134 or further distally , closer to distal end opening 115 . alternatively , distal end opening 115 could be positioned proximally on the side of sb extension tube 112 , nearer to the distal end of sb balloon portion 134 . the many options for configuring openings 115 and 118 , providing easy mounting of sb guidewire housing on guidewire 146 , are well known to those familiar with the art . sb guidewire 146 passes externally to mb balloon portion 130 and sb balloon portion 134 so that only mb guidewire lumen 136 passes through bifurcated balloon 100 ; a configuration that greatly reduces the bulk of bifurcated balloon 100 both in the predeployed and expanded configurations as compared to bifurcated balloon 180 ( fig1 a ). additionally , the inclusion of one guidewire channel 136 through bifurcated balloon 100 ( fig1 b ) reduces the complexity of bifurcated balloon 100 , and related manufacturing costs . furthermore , as sb guidewire 146 passes externally to mb balloon portion 130 , distance 109 ( fig1 b ) between guidewires 156 and 146 is considerably greater than distance 109 ( fig1 a ) associated with bifurcated stent 180 ; a distance that aids in preventing entanglement of guidewires 146 and 156 while maneuvering bifurcated balloon 100 through the vasculature in a predeployed state . fig2 shows a constricted , herein stenotic , vessel 152 with stenotic plaques 126 located along mb proximal vessel segment 120 , mb distal vessel segment 122 and sb vessel segment 124 . as used herein , the term “ distal ” refers to a downstream position in vessel 152 , while the term “ distally ” refers to downstream movement in a distal direction 140 . additionally , as used herein , the term proximal refers to an upstream position in vessel 152 , while the term proximally refers to an upstream movement in a proximal direction 142 . mb guidewire 156 has been fed distally in direction 140 to pass through mb proximal vessel segment 120 and an mb distal vessel segment 122 . sb guidewire 146 has been fed distally in direction 140 to pass through mb distal vessel segment 120 and sb vessel segment 124 . with mb guidewire 156 and sb guidewire 146 in place , as seen in fig3 , bifurcated balloon 100 is loaded on mb guidewire 156 and sb guidewire 146 so that sb guidewire 146 passes through sb guidewire lumen 116 and mb guidewire 156 passes through mb guidewire lumen 136 . bifurcated balloon 100 is then advanced in distal direction 140 through mb vessel proximal segment 120 toward mb distal vessel segment 122 and sb vessel segment 124 , herein a targeted bifurcation 138 . longitudinal sb extension tube 112 has a smaller cross - sectional area than sb proximal balloon portion 134 , aiding in ease of advancement , and positioning sb proximal balloon portion 134 in spite of narrowing that may be present in mb proximal vessel branch 120 prior to reaching targeted bifurcation 138 . fig4 shows bifurcated balloon 100 in an unexpanded configuration , within targeted bifurcation 138 . fig5 shows preparation of bifurcated balloon 100 for inflation . in deployment of bifurcated balloon , there are two options , either of which may be used by the operator . the most common scenario as seen in some embodiments , sb guidewire 146 is left in place until bifurcated balloon 100 has been inflated and deflated . then the bifurcating balloon is withdrawn over wires both wire 146 and wire 156 which are maintained in segments 124 and 122 respectively . alternatively , wire 146 is removed at any stage prior to withdrawing balloon 100 and balloon 100 is withdrawn over wire 156 . fig6 shows stenotic tissue 126 being displaced outwardly in response to the inflation of bifurcated balloon 100 . bifurcated balloon 100 can be inflated and deflated several times to ensure that stenotic tissue 126 assumes a substantially fixed radial outward position with respect to bifurcated vessel 152 . at the conclusion of the intervention , bifurcated balloon 100 is withdrawn proximally , in direction 142 , over guidewire 146 and guidewire 156 ; or ( as noted above ) over guidewire 156 alone . after vessel imaging demonstrates satisfactory results guidewire 146 and / or 156 are withdrawn proximally in direction 142 . fig7 shows bifurcated stent balloon 190 adapted for transporting a stent 150 to targeted bifurcation 138 . bifurcated stent 150 includes a proximal mb stent portion 160 aligned with proximal mb balloon portion 130 , a distal mb stent 162 aligned with distal mb balloon portion 132 and an sb stent 164 aligned with side branch ( sb ) balloon portion 134 . bifurcated stent balloon 190 and stent 150 are introduced through mb proximal vessel segment 120 in the unexpanded configuration , similar to that shown in fig3 through 5 . prior to inflation of bifurcated balloon 190 , sb guidewire 146 is removed in proximal direction 142 and bifurcated balloon 190 has been inflated , thereby expanding stent 150 radially outward to compress and to clear vessel 152 of stenotic tissue 126 . bifurcated stent balloon 190 typically minimally protrudes ( overhangs ) beyond the edges of stent 150 . fig8 shows stent 150 in an expanded configuration at targeted bifurcation 138 while bifurcated stent balloon 190 and mb guidewire 156 are withdrawn in proximal direction 142 out of mb vessel 120 at the end of the procedure . fig9 shows a bifurcating balloon 190 configured with a distal mb extension tube 182 having a guidewire lumen 186 that includes a proximal opening 181 and a distal opening 185 through which guidewire 156 is fed prior to deployment of stent 150 . similar to sb extension tube 112 noted above , distal mb extension tube 182 has a smaller cross - sectional area than mb distal balloon portion 132 to aid in placement of stent 150 . distal mb extension tube 182 in addition to sb extension tube 112 has potentially simplifies manufacture and design of bifurcating balloon 190 . additionally , distal mb extension tube 182 reduces the profile of bifurcating balloon 190 , rendering this application desirable where proximal segment 120 and / or distal mb vessel branch segment 122 are significantly constricted . there is further provided a method of providing a bifurcated self - expanding stent and advancing and positioning the bifurcated self - expandable stent using either one or two longitudinal tubular extension tubes which may be positioned distal to the stent and which accommodate the guide wire on which the self expandable stent is advanced . the materials and dimensions that follow reference both fig1 and 7 : in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 have a minimal inflation diameter of at least about 2 . 0 millimeter . in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 have a maximum inflation diameter of no more than about 40 millimeters applicable to all coronary and peripheral interventions at any vascular location . in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 have a wall thickness of at least about 0 . 01 millimeters . in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 have a wall thickness of no more than about 0 . 5 millimeters . however , thickness of material will depend on technology and minimal traits and characteristics as require by current industry standards for a given targeted bifurcation 138 . in embodiments of the present invention , distal mb balloon portion 132 and sb balloon portion 134 are optionally of substantially different dimensions , including length , expanded diameter , and / or unexpanded diameter . in other embodiments of the present invention distal mb balloon portion 132 and proximal mb balloon portion 130 are optionally substantially of different dimensions , including length , expanded diameter and / or unexpanded diameter . in further embodiments of the present invention distal sb balloon portion 134 and proximal mb balloon portion 130 are optionally substantially of different dimensions , including length , expanded diameter and / or unexpanded diameter . in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 have an unexpanded and expanded length between 12 - 150 mm , depending on the dimensions of targeted bifurcation 138 . in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 have an expanded diameter of 2 - 50 mm depending on the dimensions of targeted bifurcation 138 . in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 have a pre - deployed diameter of 0 . 2 - 8 mm , depending on the dimensions of targeted bifurcation 138 . in embodiments inflated and deployed bifurcated balloon 100 , bifurcated stent balloon 190 and stent 150 have an angle between their bifurcated portions ranging from 0 - 180 degrees depending on the angulation of targeted bifurcation 138 . in embodiments , bifurcated balloon 100 , bifurcated stent balloon 190 and stent 150 have an angle between their bifurcated portions of an angle of less than about 30 °, in their pre - inflated and pre - deployed configuration . in embodiments , bifurcated balloon 100 and bifurcated stent balloon 190 comprise a material selected from the group consisting of : synthetic biostable polymer , a natural polymer , and an inorganic material . in embodiments , the biostable polymer comprises a material from the group consisting of : a polyethylene , a polyolefin , a polyurethane , a fluorinated polyolefin , a chlorinated polyolefin , a polyamide , an acrylate polymer , an acrylamide polymer , a vinyl polymer , a polyacetal , a polycarbonate , a polyether , an aromatic polyester , a polyether ( ether keto ), a polysulfone , a silicone rubber , a thermoset , and a polyester ( ester imide ). in embodiments , the natural polymer comprises a material from the group consisting of a polyolefin , a polyurethane , a mylar , a silicone , a polyester and a fluorinated polyolefin . although described with respect to treating bifurcated vessels of the cardiovascular system , and especially bifurcated arteries , the teachings of the present invention are generally applicable to many different cardiovascular and non - cardiovascular applications . specific cardiovascular applications include , but not limited to , the deployment of bifurcated balloon 100 , bifurcated stent balloon 190 , bifurcated self expandable stent and bifurcated stent 150 in atherosclerotic , or other occlusive arterial and / or venous vascular disease , ectatic arteries and ectatic arteries containing an obstructive lesion , aneurismatic arteries , saphenous vein grafts and native arteries , coronary or any arterial perforation , coronary arterial fistula , aortic abdominal aneurysm and other aneurismatic peripheral arteries , transjugular intrahepatic portal shunt , percutaneous transluminal angioplasty , fistula closing and neuro interventions ( such as aneurysms and arterial - venous malformations ), small vessel intraluminal grafting , and ostial renal artery lesions . with respect to the teachings of the present inventions , cardiovascular vessels include , inter alia , coronary arteries , carotid arteries , renal arteries , iliofemoral popliteal and infra - popliteal arteries , aorta and aortic arch arteries , and mesenteric arteries . additional non - cardiovascular applications include , intra alia , urological , gastroenterological , respiratory , venous and neurological applications . it is expected that during the life of this patent many relevant bifurcated balloon designs and materials will be developed and the scope of the term bifurcated balloon is intended to include all such new technologies a priori . additional objects , advantages , and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples , which are not intended to be limiting . additionally , each of the various embodiments and aspects of the present invention as delineated herein above and as claimed in the claims section below finds experimental support in the following examples . it is appreciated that certain features of the invention , which are , for clarity , described in the context of separate embodiments , may also be provided in combination in a single embodiment . conversely , various features of the invention , which are , for brevity , described in the context of a single embodiment , may also be provided separately or in any suitable subcombination . although the invention has been described in conjunction with specific embodiments thereof , it is evident that many alternatives , modifications , and variations will be apparent to those skilled in the art . accordingly , it is intended to embrace all such alternatives , modifications , and variations that fall within the spirit and broad scope of the appended claims . all publications , patents , and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification , to the same extent as if each individual publication , patent or patent application was specifically and individually indicated to be incorporated herein by reference . in addition , citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention .

US-51574108-A

a self - levelling lift system is provided , to transport payloads in dynamic settings . the lift comprises a superstructure , first and second support members , a carriage and a drive . the superstructure has rails along which the carriage moves . the support members allow for the superstructure to change angle in response to a changing relationship between a first surface and a second surface , such as the shore and a boat . also provided is a use of the system for concurrently transporting a payload and allowing for pedestrian traffic .

an overhead self - levelling lift system , generally referred to as 10 is shown in fig1 . the lift system 10 has a superstructure , generally referred to as 12 , as shown in fig2 . the superstructure 12 has two girders 14 extending along the length of the superstructure and trusses 16 therebetween to form an a - frame - type structure . in one embodiment , the girders 14 functional so as rails 18 . alternatively , the superstructure supports two rails 18 that are affixed to the girders 14 and extend the length of the superstructure 12 . the rails 18 function as mounts . the superstructure is pivotally mounted proximate to a first end 20 and a second end 22 to a first and second supporting frame work 24 , 26 , each of which has two support members 28 , 30 , respectively and a header 32 . each support member 28 of the first supporting framework 24 is terminated with a roller 34 at a distal end 36 relative to the header 32 . each support member 30 of the second supporting framework 26 is terminated with a pivot mount 38 at or near a proximal end 40 relative to the header 32 , for pivotal engagement with the girders 14 . the distal end 42 of each support member 30 is affixed to an anchor block 44 by a bottom flange plate 46 . the anchor block 44 is suitably affixed to the shore and is also the attachment point for a gangway 48 . the gangway can be any design of gangway , as the overhead self - levelling lift system 10 can be manufactured to the appropriate dimensions . a carriage , generally referred to as 50 is rollably suspended from the rails 18 as shown in fig3 . the carriage 50 , as shown in fig4 has car 52 and a framework 54 that connects the car 52 to a transporter 56 , which is located above the car 52 . the car 52 has a platform 58 , a proximate side 60 , an opposing side 62 , a back door 64 and a front door 66 . the proximate side 60 assists in supporting the remainder of the car 52 and is telescopically attached to the framework 54 by a telescoping arm 68 , which forms part of the framework 54 . the telescoping arm 68 allows the car 52 to be raised and lowered . the opposing side 62 consists of two safety rails that are pivotally mounted on the proximate side 60 . the doors 64 , 66 are pivotally mounted on the platform 58 by hinges 63 . the doors 64 , 66 function as a ramp when in the open position . two door hydraulic rams 70 are located between the platform 58 and the back and front doors 64 , 66 , respectively , to assist in opening and closing the doors 64 , 66 . two retractor hydraulic rams 72 are located between the platform 58 and the framework 54 to assist in folding the car 52 by raising the platform 58 into a vertical position . a fifth hydraulic ram 74 is located between the framework 54 and the transporter 56 , and aids in maintaining the platform 54 level . the transporter 56 has trucks 76 mounted on the undersides 78 of the transporter 56 such that the wheels 8 o of the trucks 76 rollably suspend the carriage 50 from the rails 18 . the transporter 56 additionally has teflon sides 57 . a cable drive , generally referred to 82 , as shown in fig5 is connected to the carriage 50 . the cable drive 82 has a cable 84 , a winch 86 , a motor 88 and a worm drive go . additionally , a brake 92 is integrated into the cable drive 82 . controls 94 are in electronic communication with the brake 92 and the cable drive 82 and are housed within the carriage 50 , more specifically in the transporter 56 , as shown in fig4 . a pan 59 covers the cable drive 82 . the worm drive go transfers power from the motor 88 to the winch 86 and the winch 86 advances the cable 84 to move the carriage 50 along the rails 18 . the direction that the cable 8 o moves determines the direction that the carriage 50 moves . in use , the overhead self - levelling lift system 10 can transport cargo , people in wheelchairs , powerchairs and scooters , able - bodied people and essentially any payload that weighs less than about 3000 pounds , in dynamic settings , such between a static surface , for example a runway , or the shore and a non - static surface for example a plane deck , a float deck or a ship . at the first end 20 the appropriate door 64 or 66 is opened , and the payload is loaded . as mentioned above , the door 64 or 66 becomes a ramp in the open position , to allow wheelchairs for example , to roll onto the platform 58 . the door 64 or 66 is closed , the brake 92 is released and the cable drive 82 is actuated to move the carriage 50 along the rails 18 . once the carriage 50 reaches the second end 22 , the brake 92 is engaged , the appropriate door 64 or 66 is opened , again becoming a ramp , and the payload is unloaded . when used in conjunction with a gangway 48 , as shown in fig6 , the overhead self - levelling lift system 10 can concurrently move pedestrian traffic along the gangway 48 and a payload in the car 52 . the car 52 can be folded away when not in use . as shown in fig7 , the opposing side 62 is pivoted upward , the front and back doors 64 , 66 are opened , the platform 58 and the front and back doors 64 , 66 are raised into the vertical position with the assistance of the retractor hydraulic rams 72 and the car 52 is raised by retracting the telescoping arm 68 . the foregoing is a description of an embodiment of the invention . as would be known to one skilled in the art , variations in the design that do not alter the scope of the invention are contemplated . for example , one rail could be used rather than two , and a cable system that is suspended by pulleys could replace the rail system . the girders and trusses could be replaced by any supporting superstructure , including joists and rafters , for example . the rollers terminating the columns of the first supporting framework could be replaced with a single roller or with any means to permit horizontal movement between the column and the float , for example , but not limited to , a slide mechanism . similarly , the columns can be affixed to an existing gangway and utilize the system that allows the gangway to move across the float . the anchor block could be , for example , but not limited to a steel framework , or a concrete block . the cable drive can be replaced with any drive as would be known to one skilled in the art , including for example , but not limited to a chain drive or a belt drive . similarly the wheels of the trucks can replaced with belts that move along cogs . the controls can be located on the gangway as an alternative to having them in the carriage , or can be both in the carriage and at each end of the gangway , for example . this would permit remote operation of the system by an operator . the car can be , for example , but not limited to , a platform , a box , or a specialized structure for carrying cargo .

US-77969807-A

the present application describes a an image - guided , vacuum assisted , percutaneous , coring , breast biopsy instrument which may be conveniently mounted to an x - ray machine , and incorporate into it a firing fork that is easy to remove and includes a means of maintaining the firing fork perpendicular to the base when the biopsy probe is fired into the patient . it would further be advantageous to design an image - guided , vacuum assisted , percutaneous , coring , breast biopsy instrument which may be conveniently mounted to an x - ray machine which would incorporate a firing fork with a means to maintain the firing fork perpendicular to the base when the biopsy probe is fired into the patient that is easy to remove without the use of special tools .

[ 0038 ] fig1 is an isometric view showing a surgical biopsy system 10 comprising biopsy device 40 , a control unit 100 , and remote 20 . biopsy device 40 comprises probe assembly 42 operatively and removably attached to base 44 . base 44 is removably attached to a moveable table 12 such as a stereotactic guidance system as may be found on mammographic x - ray machines , an example of which is model mammotest plus / s available from fischer imaging , inc ., denver , colo . probe assembly 42 includes an elongated piercer 70 having a piercer tip 72 for penetrating soft tissue of a surgical patent . piercer 70 comprises a piercer tube 74 and vacuum chamber tube 76 . vacuum chamber tube 76 of piercer 70 may be fluidly connected to control unit 100 . similarly , axial vacuum to probe assembly 42 may be obtained by fluid connection to control unit 100 . mammotome ™ system tubing set model no . mvac1 available from ethicon endo - surgery inc ., cincinnati , ohio is suitable for use to permit detachable fluid connection of lateral vacuum line 32 and axial vacuum line 34 to control unit 100 . lateral vacuum line 32 and axial vacuum line 34 are made from a flexible , transparent or translucent material , such as silicone tubing , allowing for visualization of the material flowing through them . lateral connector 33 and axial connector 35 are female and male luer connectors , respectively , commonly known and used in the medical industry . base 44 is operatively connected to control unit 100 by control cord 26 , translation shaft 22 , and rotation shaft 24 . translation shaft 22 and rotation shaft 24 are preferably flexible so as to permit for ease of mounting of biopsy device 40 to moveable table 12 . control unit 100 is used to control the sequence of actions performed by biopsy device 40 in order to obtain a biopsy sample from a surgical patient . control unit 100 includes motors and a vacuum pump , and controls the activation of vacuum to probe assembly 42 and the translation and rotation of the cutter ( not visible ) in probe assembly 42 . a suitable control unit 100 is a mammotome ™ system control module model no . scm12 with software model no . scms1 available from ethicon endo - surgery inc ., cincinnati , ohio . remote 20 is operatively and removably connected to control unit 100 . remote 20 may be used by the surgical biopsy system operator to control the sequence of actions performed by biopsy device 40 . remote 20 may be a hand operated or foot operated device . a suitable remote 20 is mammotome ™ remote key - pad model no . mkey1 available from ethicon endo - surgery inc ., cincinnati , ohio . [ 0042 ] fig2 is an isometric view showing probe assembly 42 and base 44 separated . upper base housing 50 is normally fixedly attached to base 44 , but has been shown removed from base 44 to provide a view of transmission 301 . top shell tab 46 is located on the distal end of cantilever beam 41 and projects above the top surface of gear shell 18 . top shell tab 46 inserts into tab window 48 in upper base housing 50 upon assembly of probe assembly 42 to base 44 . once probe assembly 42 and base 44 are properly assembled , top shell tab 46 must be pushed down through tab window 48 by the user before probe assembly 42 and base 44 can be separated . a plurality of raised ribs 58 is provided on gear shell 18 to improve the user &# 39 ; s grip on the instrument . post 14 extends above the top surface of base shell 38 and inserts into keyhole 16 ( not visible ) located on the underside of gear shell 18 . tube slot 68 in upper base housing 50 provides clearance for axial vacuum line 34 . first tang 54 and second tang 56 protrude from opposite sides of probe housing 52 and insert into first recess 64 and second recess 66 , respectively , in firing fork 62 . the proximal end of probe housing 52 fits slidably within gear shell 18 and firing fork 62 fits slidably within base shell 38 . thus , once probe assembly 42 and base 44 are operatively assembled , probe housing 52 and firing fork 62 are able to move a fixed linear distance in a distal and proximal direction in front of gear shell 18 and base shell 38 . fig1 and 2 show probe housing 52 and firing fork 62 in their most distal position . [ 0043 ] fig3 and 4 are views of probe assembly 42 . fig3 is an isometric view of probe assembly 42 with the top shell 17 and bottom shell 19 shown separated , the top shell 17 rotated ninety degrees , to expose internal components . fig4 is an exploded isometric view of the same probe assembly 42 without top shell 17 or bottom shell 19 . gear shell 18 is formed from top shell 17 and bottom shell 19 , each injection molded from a rigid , biocompatible thermoplastic material such as polycarbonate . upon final assembly of probe assembly 42 , top shell 17 and bottom shell 19 are joined together by ultrasonic welding along joining edge 15 , or joined by other methods well known in the art . probe assembly 42 comprises piercer 70 having an elongated , metallic piercer tube 74 and a piercer lumen 80 ( see fig4 and 5 ). on the side of the distal end of piercer tube 74 is port 78 for receiving tissue to be extracted from the surgical patient . joined along side piercer tube 74 is an elongated , tubular , metallic vacuum chamber tube 76 having a vacuum lumen 82 ( see fig4 and 5 ). piercer lumen 80 is in fluid connection with vacuum lumen 82 via a plurality of vacuum holes 77 ( see fig5 ) located in the bottom of the “ bowl ” defmed by port 78 . vacuum holes 77 are small enough to remove the fluids but not large enough to allow excised tissue portions to be removed through lateral vacuum line 32 , which is fluidly connected to vacuum lumen 82 . a metallic , sharpened piercer tip 72 is fixedly attached to the distal end of piercer 70 . it is designed to penetrate soft tissue , such as the breast tissue of a female surgical patient . in the present embodiment piercer tip 72 is a three sided , pyramidal shaped point , although the tip configuration may also have other shapes . refer now , momentarily , to fig5 . fig5 is a section view of the distal end of probe assembly 42 , illustrating primarily probe housing 52 , piercer 70 , and union sleeve 90 . the proximal end of piercer 70 is fixedly attached to union sleeve 90 having a longitudinal bore 84 through it . union sleeve 90 contains a first o - ring groove 27 and second o - ring groove 28 , spaced apart so as to allow for a traverse opening 37 between them in fluid communication with longitudinal bore 84 . first o - ring 29 and second o - ring 30 mount in first o - ring groove 27 and second o - ring groove 28 , respectively . sleeve gear 36 is integral to union sleeve 90 and is located at its most proximal end . lead - in cone 25 is a conical shaped metallic structure that attaches to the proximal end of union sleeve 90 . union sleeve 90 is inserted into housing bore 57 located in the distal end of probe housing 52 , and rotatably supports the proximal end of piercer 70 . positioning wheel 31 slides over piercer 70 and the distal end of union sleeve 90 and rotatably attaches to probe housing 52 , hence trapping lead - in cone 25 and union sleeve 90 within housing bore 57 in the distal end of probe housing 52 . locating projection 11 on the distal end of union sleeve 90 functionally engages alignment notch 13 in positioning wheel 31 . thus , rotating positioning wheel 31 likewise causes the rotation of piercer 70 . this allows port 78 to be readily positioned anywhere within the 360 ° axis of rotation of piercer 70 . referring again to fig3 and 4 , housing extension 47 is located at the proximal end of probe housing 52 . housing flange 53 is located at the most proximal end of housing extension 47 on probe housing 52 and is assembled just inside of top shell front slot 55 in top shell 17 . shell insert 39 is assembled into top shell front slot 55 . first insert tab 59 and second insert tab 60 , both located on shell insert 39 , engage first shell recess 61 and second shell recess 63 , located within top shell front slot 55 , respectively . thus , upon complete assembly of probe assembly 42 , the most proximal end of probe housing 52 containing housing flange 53 is trapped within gear shell 18 , yet slideable along housing extension 47 distal and proximal within top shell front slot 55 . tissue sampling surface 65 is a recessed surface within probe housing 52 which provides a surface where each tissue sample will be deposited during the operation of the present invention , prior to retrieval by the clinician . an elongated , metallic , tubular cutter 96 ( see fig5 ) is axially aligned within cutter bore 51 of probe housing 52 , longitudinal bore 84 of union sleeve 90 , and piercer lumen 80 of piercer 70 so that cutter 96 may slide easily in both the distal and proximal directions . cutter 96 has a cutter lumen 95 through the entire length of cutter 96 . the distal end of cutter 96 is sharpened to form a cutter blade 97 for cutting tissue held against cutter blade 97 as cutter 96 is rotated . the proximal end of cutter 96 is fixedly attached to the inside of cutter gear bore 102 of cutter gear 98 . cutter gear 98 may be metal or thermoplastic , and has a plurality of cutter gear teeth 99 , each tooth having a typical spur gear tooth configuration as is well known in the art . cutter seal 79 is a lip type seal and is fixedly attached to the proximal end of cutter gear 98 , and is made of a flexible material such as silicone . tissue remover 132 fits rotatably and slidably through cutter seal 79 . probe seal 81 is also a lip type seal made of a flexible material such as silicone rubber and is fixedly inserted into the proximal end of cutter bore 51 at the proximal end of probe housing 52 . cutter 96 fits rotatably and slidably through cutter seal 79 . cutter seal 79 and probe seal 81 operate to prevent fluids from entering the space within gear shell 18 during a surgical biopsy procedure . still in fig3 and 4 , cutter gear 98 is driven by elongated drive gear 104 having a plurality of drive gear teeth 106 designed to mesh with cutter gear teeth 99 . the function of elongated drive gear 104 is to rotate cutter gear 98 and cutter 96 as they translate in both longitudinal directions . elongated drive gear 104 is preferably made of a thermoplastic material , such as liquid crystal polymer . distal drive axle 108 projects from the distal end of elongated drive gear 104 and mounts rotatably into an axle support rib ( not visible ) molded on the inside of top shell 17 and held in place by first gear support rib located on bottom shell 19 . gear shaft 110 projects from the proximal end of drive gear 104 and is rotatably supported by a gear shaft slot 69 located in the proximal end of top shell 17 and by second gear support rib 137 located on bottom shell 19 . drive gear slot 101 is located on the most proximal end of gear shaft 110 as a means for rotationally engaging drive gear 104 . still referring to fig3 and 4 , cutter carriage 124 is provided to hold cutter gear 98 and to carry cutter gear 98 as it is rotated and translated in the distal and proximal directions . cutter carriage 124 is preferably molded from a thermoplastic material and is generally cylindrically shaped with a threaded bore 126 through it and with carriage foot 130 extending from its side . carriage foot 130 has a foot recess 128 formed into it and foot slot 127 for rotatably holding cutter gear 98 in the proper orientation for cutter gear teeth 99 to mesh properly with drive gear teeth 106 . lower carriage guide 103 projects down from cutter carriage 124 and slidably engages lower guide slot 107 molded on the inside surface of bottom shell 19 . upper carriage guide 105 projects up from carriage foot 130 and slidably engages a upper guide slot 109 molded on the inside of top shell 17 . cutter carriage 124 is attached via threaded bore 126 to elongated screw 114 , which is parallel to drive gear 104 . screw 114 has a plurality of conventional lead screw threads 116 and is preferably made of a thermoplastic material . the rotation of elongated screw 114 in one direction causes cutter carriage 124 to move distally , while the reverse rotation of elongated screw 114 causes cutter carriage 124 to move proximally . as a result , cutter gear 98 moves distally and proximally according to the direction of the screw rotation , which in turn advances cutter 96 distally or retracts it proximally . in the present embodiment , elongated screw 114 is shown with a right hand thread so that clockwise rotation ( looking from the proximal to distal direction ) causes cutter carriage 124 to translate in the proximal direction . distal screw axle 118 projects from the distal end of elongated screw 114 and mounts rotatably into an axle support rib ( not visible ) molded on the inside of top shell 17 and held in place by first screw support rib 111 located on bottom shell 19 . screw shaft 120 projects from the proximal end of elongated screw 114 and is rotatably supported by a screw shaft slot 71 located in the proximal end of top shell 17 and by second screw support rib 112 located on bottom shell 19 . lead screw slot 122 is located on the most proximal end of screw shaft 120 as a means for rotationally engaging elongated screw 114 . at this point in the detailed description it should be pointed out that during the operation of the biopsy instrument cutter 96 translates in either direction between a fully retracted position , just proximal to tissue sampling surface 65 as referenced by cutter blade 97 , and a fully deployed position wherein cutter blade 97 is located just distal to port 78 . as cutter 96 translates between these end points there are a number of intermediate positions wherein adjustments may be made to the cutter rotational and translational speed as commanded by control unit 100 . these intermediate positions and the adjustments made to the cutter depend on the programming of control unit 100 . referring now to fig5 the distal end of lateral vacuum line 32 is attached to lateral fitting 92 located on the distal end of probe housing 52 . lateral fitting 92 has lateral hole 117 through it along its axis in fluid communication with housing bore 57 . lateral hole 117 in lateral fitting 92 is positioned within housing bore 57 such that when union sleeve 90 is inserted into housing bore 57 lateral hole 117 is located in the space created between first and second o - rings , 29 and 30 respectively . locating lateral hole 117 in the space between first and second o - rings 29 and 30 , respectively , allows for the communication of fluids between vacuum lumen 82 and control unit 100 . referring again to fig3 and 4 , axial vacuum line 34 is fluidly attached to tissue remover support 129 which is in turn fluidly attached to the proximal end of an elongated , metallic , tubular tissue remover 132 . axial vacuum line 34 allows for the communication of fluids between piercer lumen 80 , cutter lumen 95 , and control unit 100 . tissue remover support 129 fits into axial support slot 73 located in the proximal end of top shell 17 . strainer 134 is located on the distal end of tissue remover 132 and functions to prevent passage of fragmented tissue portions through it and into control unit 100 . tissue remover 132 inserts slidably into cutter lumen 95 of cutter 96 . during the operation of the biopsy instrument , tissue remover 132 is always stationary , being fixedly attached at its proximal end to tissue remover support 129 which is fixed within axial support slot 73 located in the proximal end of top shell 17 . when cutter 96 is fully retracted to its most proximal position , the distal end of tissue remover 132 is approximately even with the distal end of cutter 96 ( see fig5 ). the distal end of cutter 96 , when at its most proximal position , and probe housing 52 at its most distal position , is slightly distal to housing wall 67 which is proximal and perpendicular to tissue sampling surface 65 . probe rotation rod 85 is an elongated , solid metal rod . rotation rod gear 86 is a spur gear fixedly attached to the distal end of probe rotation rod 85 . rotation rod flat 87 is located at the proximal end of probe rotation rod 85 . rotation rod flat 87 is approximately one - third to one - half the rod diameter in depth and extending from its proximal end approximately one inch in length . rotation rod flat 87 thus creates a “ d ” shaped geometry at the proximal end of probe rotation rod 85 . rod bushing 88 is made of molded thermoplastic and is cylindrical in shape . at its distal end is bushing bore 89 which is a “ d ” shaped hole approximately one inch in depth , designed to slidably receive the proximal end of probe rotation rod 85 . rod bushing 88 fits rotatably into axial support slot 73 below tissue remover support 129 at the proximal end of top shell 17 . the longitudinal position of rod bushing 88 is fixed by the raised sections on both sides of bushing groove 93 , upon assembly into the proximal end of top shell 17 . rod bushing drive slot 91 is located on the most proximal end of rod bushing 88 as a means for rotationally engaging rod bushing 88 . rotation gear 86 is rotatably fixed into gear cavity 115 on the underside of probe housing 52 , the opening being in communication with housing bore 57 ( see fig5 ). rotation rod gear 86 operably engages sleeve gear 36 located at the proximal end of union sleeve 90 . the distal end of probe rotation rod 85 with rotation rod gear 86 attached is rotatably fixed to the underside of probe housing 52 by rotation gear cover 94 . rotation gear cover 94 is molded from a thermoplastic material and is fixedly attached to probe housing 52 by four raised cylindrical pins which press fit into four holes ( not visible ) in probe housing 52 . probe rotation rod 85 inserts rotatably and slidably through rod hole 43 in shell insert 39 . the proximal end of probe rotation rod 85 slidably engages bushing bore 89 in rod bushing 88 . thus , rotation of rod bushing 88 causes rotation of probe rotation rod 85 which is fixedly attached to rotation rod gear 86 causing rotation of union sleeve 90 which is fixedly attached to piercer 70 , which contains port 78 . it is important for the user of the surgical biopsy system of the present invention to be able to “ fire ” the piercer 70 into the tissue of a surgical patient . it is also important that the user be able to rotate piercer 70 about its axis so as to properly position port 78 , regardless of linear position of piercer 70 pre - fired vs . post - fired ( positions discussed later ). the slidable interface between probe rotation rod 85 and rod bushing 88 plays an important role in providing this capability . probe rotation rod 85 follows the linear movement of piercer 70 , while the linear movement of rod bushing 88 is restricted by the fact that it is rotatably attached to top shell 17 . thus the “ d ” shaped geometry on the proximal end of rotation rod 85 and the “ d ” shaped hole in the distal end of rod bushing 88 , designed to slidably receive the proximal end of rotation rod 85 , permit the user to turn port rotation knob 45 , which is operably connected to rod bushing 88 through a chain of elements described later , and effect the rotation of piercer 70 , irrelevant of the linear position of piercer 70 . bottom shell 19 fixedly attaches to top shell 17 as described earlier . its function is to hold in place and contain the elements previously described , which have been assembled into top shell 17 . keyhole 16 is centered at the distal end of bottom shell 19 . it slidably and removably engages post 14 ( see fig2 ), permitting probe assembly 42 to be operatively and removably connected to base 44 . first screw support rib 111 and second screw support rib 112 are each integrally molded to bottom shell 19 and support the distal and proximal ends , respectively , of elongated screw 114 . first gear support rib 136 and second gear support rib 137 likewise are each integrally molded to bottom shell 19 and support the distal and proximal ends , respectively , of elongated drive gear 104 . rod bushing support rib 139 integrally molded to bottom shell 19 supports the distal end of rod bushing 88 . [ 0055 ] fig6 is an exploded isometric view of lower transmission assembly 302 . translation shaft 22 and rotation shaft 24 is each a flexible coaxial cable comprising a flexible rotatable center core surrounded by a flexible tubular casing , as is well known in the art . at their most proximal ends is provided a coupling means for removably and operatively connecting translation shaft 22 and rotation shaft 24 to control unit 100 . the distal ends of translation shaft 22 and rotation shaft 24 each insert through first boot bore 309 and second boot bore 311 , respectively . flex boot 303 is molded from a thermoplastic elastomer such as , for example , polyurethane , and functions as a “ flex relief ” for translation shaft 22 , rotation shaft 24 , and control cord 26 . rotation shaft ferrule 305 is a metallic tubular structure comprising a through bore with a counter bore at its proximal end for fixedly attaching , via crimping or swaging as is well known in the art , to the outer tubular casing of rotation shaft 24 . at the distal end of rotation shaft ferrule 305 is a flared , counter bored section for receiving first bearing assembly 315 . a suitable example of first bearing assembly 315 is model no . s9912y - e1531pso , available from stock drive products , new hyde park , n . y . rotation shaft adapter 319 is made of stainless steel and has a proximal end with a counter bore . its proximal end inserts through the bore of first bearing assembly 315 and the counter bore slips over the distal end of the rotatable center core of rotation shaft 24 and is fixedly attached by crimping or swaging . the distal end of rotation shaft adapter 319 is inserted through the bore in first bevel gear 321 and is fixedly attached by a slotted spring pin . similarly , translation shaft ferrule 307 is a metallic tubular structure comprising a through bore with a counter bore at its proximal end for fixedly attaching , via crimping or swaging , to the outer tubular casing of translation shaft 22 . at the distal end of translation shaft ferrule 307 is a flared , counter bored section for receiving thrust washer 317 . translation shaft adapter 323 is made of stainless steel and has a proximal end with a counter bore . its proximal end inserts through the bore of thrust washer 317 and the counter bore slips over the distal end of the rotatable center core of translation shaft 22 and is fixedly attached by crimping or swaging . the distal end of translation shaft adapter 323 is slotted as a means to engage the proximal end of encoder shaft 312 , which extends through encoder 310 . encoder 310 communicates information to control unit 100 about the translation position and translation speed of cutter 96 . encoder 310 includes an electrical cord containing a plurality of electrical conductors , which has an electrical connector affixed at its most distal end for removable electrical connection to printed circuit board 262 ( see fig9 ). a suitable miniature encoder 310 is commercially available as model sed10 - 300 - eth2 from cui stack , inc . encoder shaft 312 has two opposing flats on its proximal end , which engage translation shaft adapter 323 , and a cylindrical distal end which is inserted into a counter bore in the proximal end of gear adapter 316 and is fixedly attached by a slotted spring pin . the distal end of gear adapter 316 is inserted through the bore of second bearing assembly 318 , through the bore of shaft spacer 322 , and finally through the bore in second bevel gear 325 which is fixedly attached to gear adapter 316 by a slotted spring pin . encoder housing assembly 329 comprises left encoder housing half 326 and right encoder housing half 328 , which are molded thermoplastic shells . when assembled , left encoder housing half 326 and right encoder housing half 328 encase encoder 310 and capture the distal end of translation shaft 22 and rotation shaft 24 . left encoder housing half is attached to transmission plate 330 ( see fig7 ) using a cap screw . encoder 310 is placed in first shell cavity 332 , preventing rotational or lateral movement of the outer housing of encoder 310 . the distal end of rotation shaft ferrule 305 rests in second shell cavity 334 , which prevents lateral movement of rotation shaft 24 . the distal end of translation shaft ferrule 307 rests in third shell cavity 336 , which again prevents lateral movement of translation shaft 22 . second bearing assembly 318 rests in fourth shell cavity 338 . right encoder housing half 328 , containing essentially a mirror image of the cavities found inside left encoder housing half 326 , assembles to left encoder housing half 326 and transmission plate 330 via two cap screws . still referring to fig6 control cord 26 is flexible and contains a plurality of electrical conductors for communication information between biopsy device 40 and control unit 100 ( see fig1 ). at the proximal end of control cord 26 is provided a means of removable electrical connection to control unit 100 . the distal end of control cord 26 inserts through third boot bore 313 located in flex boot 303 . control cord strain relief 369 is a flexible thermoplastic material and is over molded to the distal end of control cord 26 and is fixedly attached to transmission plate 330 in a recessed area at strain relief bore 371 ( see fig7 ), to restrict linear and rotational movement of the distal end of the cord . the most distal end of control cord 26 contains a connector for removably and electrically affixing control cord 26 to printed circuit board 262 ( see fig9 ). [ 0058 ] fig7 is an isometric view of transmission 301 . upper transmission assembly 304 is shown exploded . translation coupling assembly 337 consists of translation drive coupling 340 , third bearing assembly 344 , first coupling spacer 348 , and third bevel gear 350 . third bearing assembly 344 is press fit into first counter bore 345 in transmission plate 330 . translation drive coupling 340 has a flat bladed distal end which will operatively couple with lead screw slot 122 ( see fig8 ) located at the proximal end of elongated screw 114 . the cylindrical proximal end of translation drive coupling 340 inserts through first counter bore 345 , through the bore of third bearing assembly 344 , through the bore of first coupling spacer 348 , and finally through the bore in third bevel gear 350 which is fixedly attached to translation drive coupling 340 by a slotted spring pin . the gear teeth of third bevel gear 350 mesh with the gear teeth of second bevel gear 325 . thus , rotation of the center core of translation shaft 22 results in the rotation of translation drive coupling 340 . when translation drive coupling 340 is operatively coupled to elongated screw 114 via lead screw slot 122 , rotation of translation shaft 22 causes rotation of elongated screw 114 which results , as discussed earlier , in the distal or proximal translation of cutter 96 , depending on the direction of translation shaft 22 rotation . in a similar manner , rotation coupling assembly 339 consists of rotation drive coupling 342 , fourth bearing assembly 346 , second coupling spacer 349 , and fourth bevel gear 351 . fourth bearing assembly 346 is press fit into second counter bore 347 in transmission plate 330 . a suitable example of fourth bearing assembly 346 , as well as second and third bearing assemblies 318 and 344 , respectively , is available as model no . s9912y - e1837pso , available from stock drive products , new hyde park , n . y . rotation drive coupling 342 has a flat bladed distal end which will operatively couple with drive gear slot 101 ( see fig8 ) located at the proximal end of elongated drive gear 104 . the cylindrical proximal end of rotation drive coupling 342 inserts through second counter bore 347 , through the bore of fourth bearing assembly 346 , through the bore of second coupling spacer 349 , and finally through the bore in fourth bevel gear 351 , which is fixedly attached to rotation drive coupling 342 by a slotted spring pin . the gear teeth of fourth bevel gear 351 mesh with the gear teeth of first bevel gear 321 . thus , rotation of the center core of rotation shaft 24 results in the rotation of rotation drive coupling 342 . when rotation drive coupling 342 is operatively coupled to elongated drive gear 104 via drive gear slot 101 , rotation of rotation shaft 24 causes rotation of elongated drive gear 104 , which results in the rotation of cutter 96 . a suitable example of first , second , third , and fourth bevel gears 321 , 325 , 350 , and 351 , respectively , is model no . a1m - 4 - y32016 - m available from stock drive products , new hyde park , n . y . continuing in fig7 port drive coupling 353 has a flat bladed distal end which will operatively couple with rod bushing drive slot 91 ( see fig8 ) located at the proximal end of rod bushing 88 . the cylindrical proximal end of port drive coupling 353 inserts through the bore in first port gear 355 , which is fixedly attached by a slotted spring pin , then inserted through first port coupling bore 359 . first coupling washer 362 slips over the proximal end of drive port coupling 353 and first coupling e - ring 364 snaps into a groove at the most proximal end of drive port coupling 353 , which now rotatably secures the assembly to transmission plate 330 . knob post 367 is made of stainless steel , is generally cylindrical , and has a flange on its most distal end and a flat approximately one - third to one - half its diameter in depth and extending from its proximal end one half inch in length . knob post 367 inserts through the bore of second port gear 357 , which is fixedly attached by a slotted spring pin to the distal end of knob post 367 . suitable examples of first and second port gears 355 and 357 , respectively , are available as model no . a1n1 - n32012 , available from stock drive products , new hyde park , n . y . the proximal end of knob post 367 is inserted through second port coupling bore 360 until second port gear 357 aligns and meshes with first port gear 355 . second coupling washer 363 slips over the proximal end of knob post 367 and second coupling e - ring 365 snaps into a groove located adjacent to the distal end of knob post 367 , thus rotatably securing the assembly to transmission plate 330 . port rotation knob 45 fixedly attaches to the proximal end of knob post 367 . a suitable port rotation knob 45 is model no . pt - 3 - p - s available from rogan corp ., northbrook , ill . thus , when port drive coupling 353 is operatively coupled to rod bushing 88 via rod bushing drive slot 91 , user rotation of port rotation knob 45 causes rotation of rod bushing 88 which results in the rotation of piercer 70 . this allows port 78 to be readily positioned anywhere within the 360 ° axis of rotation of piercer 70 . transmission plate 330 attaches to the proximal end of upper base shell 161 via two screws . there is an important benefit derived from the design of transmission 301 just described . the fact that the translation shaft 22 , rotation shaft 24 , and control cord 26 enter the biopsy device 40 at a right angle to the device &# 39 ; s center axis permits for a short overall length for the biopsy device . this allows the device to fit into a smaller area than would accommodate a device with the shafts protruding directly out the back ( proximal end ) parallel to the center axis . [ 0063 ] fig8 is an isometric view of probe assembly 42 and base 44 , as viewed from their proximal ends . upper base housing 50 is not shown so as to permit a clear view of transmission 301 fully assembled . also clearly visible are lead screw slot 122 , drive gear slot 101 , and rod bushing drive slot 91 , which operably connect to transmission 301 as previously described . [ 0064 ] fig9 is an exploded isometric view of firing mechanism 160 . upper base shell 161 is shown exploded and lower base shell 204 is shown exploded and rotated 90 degrees clockwise . also exploded and rotated 90 degrees clockwise for clarity is printed circuit board 262 and frame screw 163 . firing mechanism 160 , shown in fig9 operates to fire the distal end of probe assembly 42 into tissue . base shell 38 ( see fig2 ) supports and houses firing mechanism 160 , and is assembled from upper base shell 161 and lower base shell 204 . base hooks 165 on lower base shell 204 insert into base slots 162 in upper base shell 161 to enable assembly of the components to create base shell 38 . frame screw 163 inserts through a clearance hole in frame bottom 204 and fastens into firing latch block 242 to tie upper base shell 161 and lower base shell 204 together . firing fork 62 extends from firing mechanism 160 through to the exterior of base shell 38 to accept probe housing 52 of probe assembly 42 ( see fig2 ). fig9 shows firing fork 62 in its most distal allowable position and shows other components of firing mechanism 160 in appropriate positions for firing fork 62 to be at its most distal allowable position . upon mating of the probe assembly 42 with the base 44 , first tang 54 and second tang 56 insert into first recess 64 and second recess 66 , respectively , in firing fork 62 at the distal end of firing fork assembly 164 . features on firing fork 62 also include probe slot 167 , which is approximately “ u ” shaped to accept probe assembly 42 , and clearance slot 169 , allowing clearance for probe rotation rod 85 . firing fork assembly 164 , shown exploded in fig1 , is a unique assembly which is particularly adapted to maintain the firing fork 62 perpendicular to the biopsy probe when the biopsy probe is fired into tissue and is detachable from the rest of firing mechanism 160 without the use of tools . firing fork 62 slides over the outer diameter of firing spade 178 while firing fork keys 181 insert into firing spade slots 180 . firing spade slots 180 prevent rotation of firing fork 62 relative to firing spade 178 . firing spade 178 possesses a threaded internal diameter at its distal end and a proximal spade end 196 at its proximal end . proximal spade end 196 can comprise a flattened section , resembling , for example , the working end of a flathead screwdriver . the threaded diameter at the distal end of firing spade 178 receives screw 182 to hold firing fork 62 to firing spade 178 . the head 184 of screw 182 abuts the distal end of firing spade 178 upon tightening . abutting the head 184 of screw 182 against the distal end of firing spade 178 prevents tightening of the screw against the firing fork 62 . the head 184 of screw 182 and the proximal end 186 of firing spade slot 180 provide proximal and distal stops for firing fork 62 while allowing slight axial play . firing spacer 188 attaches at the proximal end of firing spade 178 with the aid of dowel pins 190 . firing spacer 188 slips onto and is rotatable relative to firing spade 178 . it should be noted that minimizing the clearance between the inside diameter of firing spacer 188 and the outside diameter of firing spade 178 improves the stability of firing fork assembly 164 , an important attribute . in one embodiment of the present invention , the clearance between the inner diameter of firing spacer 188 and the outer diameter of firing spade 178 would be approximately 0 . 002 inches all the way around . near the proximal end of firing spacer 188 , easily visible depth marker line 189 is inscribed . dowel pins 190 press into receiving holes 192 on firing spacer 188 and ride within firing spade groove 194 to allow rotation of firing spacer 188 relative to firing spade 178 while preventing axial movement of firing spacer 188 relative to firing spade 178 . a threaded internal diameter at the proximal end of firing spacer 188 facilitates assembly and removal of the firing fork assembly 164 for cleaning . [ 0071 ] fig9 shows that firing fork assembly 164 threads onto end fitting 166 , pinned at the distal end of firing fork shaft 168 . end fitting 166 can be made of a soft stainless steel for easy machining of slot and threads while firing fork shaft 168 can be made of a hardenable stainless to accommodate induced stress . proximal spade end 196 fits into spade slot 198 of end fitting 166 to prevent rotation of firing fork assembly 164 relative to firing fork shaft 168 . the threaded internal diameter of the proximal end of firing spacer 188 screws onto the threaded outer diameter of end fitting 166 to removably attach firing fork assembly 164 . small firing bushings 170 , fashioned from a plastic such as acetal , support firing fork shaft 168 and allow it to move proximally and distally . proximal saddle support 172 and distal saddle support 173 , machined into upper base shell 161 , support small firing bushings 170 while long clamp plate 174 and short clamp plate 175 capture and retain small firing bushings 170 into proximal and distal saddle supports 172 and 173 , respectively . long clamp plate 174 and short clamp plate 175 can attach to proximal saddle support 172 and distal saddle support 173 using fasteners , such as , for example , clamp plate mounting screws 176 . flanges at each end of the small firing bushings 170 bear against the proximal and distal sides of saddle supports 172 and clamp plates 174 to restrain small firing bushings 170 from moving proximally and distally with the movement of firing fork shaft 168 . additional support is gained by the large firing bushing 200 surrounding firing spacer 188 . large firing bushing 200 , split for easy assembly , resides in firing bushing housing 202 machined into upper base shell 161 and lower base shell 204 . firing fork shaft 168 carries other parts that facilitate the operation of firing mechanism 160 . spring collar roll pin 212 fixedly attaches spring collar 214 to firing fork shaft 168 . shock pad 216 adheres to the distal side of spring collar 214 and contacts distal interior wall 218 of base shell 38 when firing fork shaft 168 is in its distal position . shock pad 216 can be made from many shock - absorbing materials , such as , for example , rubber . main spring 217 surrounds firing fork shaft 168 and bears against the distal side of distal saddle support 173 and the proximal side of spring collar 214 to force firing fork shaft 168 distally . magnet holder roll pin 208 fixedly attaches magnet holder 206 to firing fork shaft 168 . magnet 210 is crimped into magnet holder 206 . nearer the proximal end of firing fork shaft 168 , firing main link pin 224 passes through firing fork shaft slot 225 to hold firing fork shaft 168 to carriage 220 . firing main link pin 224 also captures curved firing levers 222 retaining them to the carriage 220 . firing main link pin 224 is flanged on one end . the other end of firing main link pin 224 extends through carriage 220 to retain carriage 220 , firing fork shaft 168 , and curved firing levers 222 , where it is retained by welding to the lower curved firing lever . curved firing levers 222 and firing linkages 226 drive the arming of firing mechanism 160 . curved firing levers 222 pin to firing linkages 226 using firing link pins 228 which are welded to firing levers 222 . firing linkages 226 in turn pin to upper base shell 161 using frame link dowel pins 230 pressed into upper base shell 161 . long clamp plate 174 retains firing linkages 226 using clamp plate mounting screws 176 . each pinned joint of curved firing levers 222 , firing linkages 226 , and carriage 220 is rotatably movable about the axis of the pin . each curved firing lever 222 has a portion that extends laterally outwards through a slot located on either side of base shell 38 ( see fig2 ). a curved firing lever end 232 is attached to each curved firing lever 222 on the extension of curved firing lever 222 external to base shell 38 . curved firing lever end 232 provides a convenient user interface for arming the firing mechanism . arming the mechanism will be described later . the coil of torsion spring 234 surrounds each pinned joint of curved firing levers 222 and firing linkages 226 . the legs of link torsion springs 234 extend outwardly to hook into curved firing levers 222 and firing linkages 226 , applying a torque rotating them relative to each other . locating firing linkages 226 and curved firing levers 222 at different distances from upper base shell 161 allows them clearance to pass by each other upon operation . curved firing levers 222 have bends to offset them in a direction perpendicular to upper base shell 161 . the offset bends let them move within planes at different distances from upper base shell 161 while having the curved firing lever ends emerge from the slot created for that purpose in upper base shell 161 . spacer 223 separates the links on the pin 230 . having a curved firing lever 222 and firing linkage 226 on each side of the longitudinal centerline allows access by the user to operate firing mechanism 160 from either side of base shell 38 . fasteners secure a printed circuit board 262 to lower base shell 204 and latch block 242 . printed circuit board 262 contains hall - effect switch 264 for sensing the proximity of magnet 210 . a suitable hall - effect switch 264 is model no . a3142elt available from allegro microsystems , inc ., worcester , mass .. when firing fork 168 and associated magnet 210 are in the most proximal position ( pre - fired position , as described later ), magnet 210 is held in a position near hall - effect switch 264 . [ 0077 ] fig1 is an exploded isometric view of triggering mechanism 235 , seen in fig9 . triggering mechanism 235 safely latches and fires firing fork shaft 168 . triggering mechanism 235 comprises firing latch 236 , firing latch block 242 , firing button shaft 244 and roller 241 , firing latch spring 246 , firing button shaft spring 247 , safety block 248 , safety latch 250 , safety latch torsion spring 251 , safety latch cover 252 , and firing button 254 . firing latch block 242 encloses the proximal portion of firing latch 236 and serves as a mounting platform for components of triggering mechanism 235 . firing latch pin 237 and firing block pin 239 rigidly retain firing latch block 242 to upper base shell 161 . firing latch pin 237 rotatably pins firing latch 236 to upper base shell 161 while passing through firing latch block 242 . firing latch 236 pivots within a slot in upper base shell 161 . firing latch spring 246 is compressed between firing latch block 242 and firing latch 236 , thereby forcing the distal end of firing latch 236 towards firing fork shaft 168 . firing latch 236 possesses a firing latch hook 238 at its distal end , which removably latches into a firing fork shaft retainer 240 located at the proximal end of firing fork shaft 168 . firing button shaft 244 slidably moves proximally and distally within a bore in firing latch block 242 and has roller 241 rotatably pinned to its distal portion to engage firing latch 236 to cause rotation of firing latch 236 . firing button shaft spring 247 forces firing button shaft 244 proximally . firing button shaft 244 is retained by safety block 248 , which is mounted to the proximal side of firing latch block 242 . safety latch 250 resides within a counter bore on the proximal side of safety block 248 and is retained by safety latch cover 252 . fasteners such as screws hold safety latch cover 252 in place . safety latch 250 is designed to facilitate locking and unlocking of the firing mechanism . safety latch 250 can be rotated within the counter bore on safety block 248 through a rotation angle , while safety latch torsion spring 251 has extending legs hooked into safety block 248 and safety latch 250 to apply torque to safety latch 250 . safety block 248 defines a locked position safety latch stop 245 and an unlocked position safety latch stop 243 separated by the rotation angle . safety latch handle 249 extends radially from safety latch 250 to facilitate grasping and rotating of safety latch 250 by the user . safety latch handle 249 also forms surfaces to abut safety latch stops 245 and 243 to limit the rotation angle . in the locked position , safety latch torsion spring 251 forces safety latch handle 249 against the locked position safety latch stop 245 , while in the unlocked position , the user forces safety latch handle 249 against unlocked position safety latch stop 243 . in the illustrated embodiment of the invention , the rotation angle through which safety latch 250 can be rotated is about thirty - five degrees . fig1 shows that safety latch 250 contains two firing button stops 256 with one firing button stop 256 on each side of the longitudinal axis of firing button 254 at assembly . the firing button stops 256 interact with firing button 254 to effect locking ( preventing lateral movement ) and unlocking ( allowing lateral movement ) of firing button 254 . [ 0080 ] fig1 shows an isometric view of firing button 254 . firing button 254 fixedly attaches to firing button shaft 244 ( see fig1 ), extends proximally through the center of safety latch 250 ( see fig1 ), and presents a proximal , flattened , cylindrical thumb pad 257 located at its most proximal end to the user . firing button 254 comprises a smaller firing button outer diameter 258 having narrow flats 259 and wide flats 261 angularly offset from each other by the rotation angle traveled by safety latch 250 . larger firing button outer diameter 260 is free of flats . a distal contact surface 255 exists proximally of narrow flats 259 and is substantially perpendicular to the longitudinal axis of firing button 254 . firing button stops 256 , located on safety latch 250 , are separated by a distance slightly larger than the distance between wide flats 261 and less than the smaller firing button outer diameter 258 . firing button stops 256 can flex in the radial direction , but resist flexing in the axial direction . the difference in stiffness in different directions can be accomplished by , for example , different thicknesses of the firing button stops 256 in the axial direction and in the radial direction . when safety latch 250 is in the locked position , pushing firing button 254 will force distal contact surface 255 against firing button stops 256 . firing button stops 256 prevent further proximal axial movement of firing button 254 because of rigidity in the axial direction . following is a functional description of the operation of the firing mechanism of the present invention : a user arms and fires the firing mechanism during use of the probe assembly 42 in a surgical procedure . the user begins in the fired position depicted in fig1 and 15 , grasps one of the curved firing lever ends 232 , and moves outboard end of curved firing lever 222 proximally . this begins action wherein each grasped curved firing lever 222 , each firing linkage 226 , carriage 220 , and upper base shell 161 act as four - bar linkage systems with upper base shell 161 being the stationary link and carriage 220 being a translational link . motion can be described of all three movable links relative to the upper base shell 161 . either curved firing lever end 232 can be moved by the user . duplicity exists in the illustrated embodiment of the invention to facilitate user access from either side of base 44 . rotating either curved firing lever 222 in a direction that moves the curved firing lever end 232 proximally effects motion of the two members pinned to curved firing member 222 . curved firing member 222 transfers motion through one pinned joint to carriage 220 to move it proximally along firing fork shaft 168 . curved firing member 222 also transfers motion through a second pinned joint to firing linkage 226 , rotating the pinned joint towards firing fork shaft 168 . firing linkage 226 is pinned to stationary upper base shell 161 and rotates about the pinned joint located on upper base shell 161 . carriage 220 , driven by curved firing member 222 , translates proximally along firing fork shaft 168 carrying main link pin 224 within firing fork shaft slot 225 until firing main link pin 224 reaches the proximal end of firing fork shaft slot 225 . further proximal motion of carriage 220 and firing main link pin 224 begins to drive proximal motion of firing fork shaft 168 . firing fork shaft 168 translates proximally through small firing bushings 170 . as firing fork shaft 168 translates proximally , it carries with it attached firing fork assembly 164 . firing fork shaft 168 also carries proximally attached spring collar 214 , decreasing the distance between spring collar 214 and distal saddle support 173 . main spring 217 , located between spring collar 214 and distal saddle support 173 , becomes more compressed exerting more force against spring collar 214 . firing fork shaft 168 continues to move proximally and continues to compress main spring 217 until the proximal end of firing fork shaft 168 reaches firing latch 236 ( see fig1 ). the proximal end of firing fork shaft 168 contacts firing latch 236 and exerts a force rotating it out of the path of proximally advancing firing fork shaft 168 . the proximal end of firing fork shaft 168 and the distal end of firing latch 236 have contoured surfaces to act as cams to assist in lifting firing latch 236 . rotating firing latch 236 compresses firing latch spring 246 , exerting a force to hold firing latch 236 onto the proximal end of firing fork shaft 168 . once the firing fork shaft retainer 240 has proceeded proximally to a position under firing latch hook 238 , firing latch spring 246 urges firing latch hook 238 into firing fork shaft retainer 240 by rotating firing latch 236 towards firing fork 168 . firing assembly 160 is now in the pre - fire position shown in fig1 and 17 . the user can now release curved firing lever end 232 . once the user releases curved firing lever end 232 , main spring 217 applies force urging firing fork 168 distally along its axis . the distal force moves firing fork shaft retainer 240 towards firing latch hook 238 extending down into firing fork shaft retainer 240 ( see fig1 ). the proximal wall of firing fork shaft retainer 240 is angled so that the reactive force of the proximal wall of firing fork shaft retainer 240 against firing latch hook 238 rotates firing latch hook 238 further into the firing fork shaft retainer 240 , preventing inadvertent release . the proximal wall of firing latch hook 238 is angled to mate with the angle of the proximal wall of firing fork shaft retainer 240 . after the user has released curved firing lever end 232 , link torsion springs 234 apply torque to curved firing levers 222 and firing linkages 226 rotating them towards each other . rotating curved firing levers 222 and firing linkages 226 towards each other initiates motion that returns carriage 220 to its distal position . with firing fork 168 held by firing latch 236 while firing levers 222 and firing linkages 226 are in the most distal position , firing mechanism 160 is in the relaxed position shown in fig1 and 19 . when carriage 220 returns to its distal position , curved firing levers 222 contact stops on the sides of raised bosses on upper base shell 161 . firing fork shaft 168 has now carried magnet 210 ( see fig9 ) which is located within magnet holder 206 proximally into a position near hall - effect switch 264 on printed circuit board 262 . hall - effect switch 264 senses the presence of magnet 210 and communicates with control unit 100 that firing fork 168 is in a proximal position and ready to fire . safety latch 250 “ guards ” firing button 254 . in the locked position shown in fig2 , firing button stops 256 on the safety latch 250 are located distally of distal contact surface 255 on firing button 254 . firing button stops 256 on safety latch 250 are also located on either side of narrow flats 259 ( see fig1 ). smaller firing button outer diameter 258 is larger than the distance between firing button stops 256 . attempting to push firing button 254 distally will cause distal contact surface 255 to contact firing button stops 256 . the rigidity of the firing button stops 256 in the axial direction prevents further distal movement of the firing button and prevents inadvertent firing of the mechanism . after the user has determined the proper location in which to insert the piercer 70 of biopsy device 40 into a surgical patient , the user can now unlock and fire firing mechanism 160 . unlocking and firing the mechanism requires two separate actions , rotating the safety latch 250 and pressing the firing button 254 . the operator first grasps safety latch handle 249 to rotate safety latch 250 against the torque applied to it by safety latch torsion spring 251 ( not visible ). fig2 shows rotating safety latch 250 so that safety latch handle 249 travels from locked position safety latch stop 245 to unlocked position safety latch stop 243 which aligns firing button stops 256 with wide flats 261 on smaller firing button outer diameter 258 . since the distance between firing button stops 256 is larger than the distance between wide flats 261 , clearance now exists for wide flats 261 to pass between firing button stops 256 . safety latch 250 is now in the “ firing ” position . in the next step , the operator presses firing button 254 by placing force on cylindrical thumb pad 257 to urge firing button 254 distally . when firing button 254 is pressed , wide flats 261 move between firing button stops 256 allowing firing button 254 to proceed distally . firing button 254 , attached to firing button shaft 244 , pushes firing button shaft 244 distally . the roller 241 on firing button shaft 244 contacts the cam surface on firing latch 236 to rotate firing latch 236 so that firing latch hook 238 lifts out of firing fork shaft retainer 240 ( see fig1 ). once firing latch hook 238 is clear of firing fork shaft retainer 240 , main spring 217 drives firing fork shaft 168 distally carrying firing fork assembly 164 and piercer 70 of probe assembly 42 towards the target . distal motion of firing fork shaft 168 continues until shock pad 216 contacts distal interior wall 218 of base shell 38 ( see fig1 ). hall - effect switch 264 senses the departure of magnet 210 distally and communicates the departure to control unit 100 . after firing the firing mechanism 160 the user releases firing button 254 , then releases safety latch handle 249 . when the user releases firing button 254 , firing button shaft spring 247 forces firing button shaft 244 proximally . firing button 254 moves proximally as well , returning distal contact surface 255 and firing button smaller diameter 258 proximal of firing button stops 256 . the proximal movement of firing button 254 also places narrow flats 259 between firing button stops 256 . releasing safety latch handle 249 allows safety latch torsion spring 251 to rotate safety latch 250 back towards the locked position with safety latch handle 249 forced against locked position safety latch stop 245 . with only narrow flats 259 and wide flats 261 between firing button stops 256 , safety latch 250 can freely rotate without interference from firing button stops 256 . when firing button shaft 244 travels proximally , the roller 241 of firing button shaft 244 and cammed surface of firing latch 236 separate ( see fig1 ). firing latch spring 246 then rotates firing latch 236 into a position where firing latch hook 238 is moved towards firing fork shaft 168 . an arming and firing cycle is now complete . firing assembly 160 has returned to the post - fired position depicted in fig1 and 15 . it should be noted that if , after firing , the user of the firing mechanism 160 does not release firing button 254 before releasing safety latch handle 249 , the mechanism still operates properly because of incorporated unique design features . when firing button 254 is in the distal , pressed position , smaller firing button outer diameter 258 is between firing button stops 256 . clearance for firing button stops 256 is made by alignment of firing button stops 256 with wide flats 261 . releasing safety latch handle 249 before releasing firing button 254 causes safety latch torsion spring 251 to rotate safety latch 250 back towards the locked position and causes firing button stops 256 to rotate out of alignment with wide flats 261 . when the firing button stops 256 rotate out of alignment with wide flats 261 smaller firing button outer diameter 258 comes between firing button stops 256 . smaller firing button outer diameter 258 is larger than the distance between firing button stops 256 . however , firing button stops 256 , designed to flex in the radial direction , separate by bending away from each other in the center when forced apart by smaller firing button outer diameter 258 . because of the radial flexibility of firing stops 256 , firing button stops 256 apply little force to smaller firing button outer diameter 258 . with little force applied , firing button 254 slides easily through firing button stops 256 while returning to the proximal position . firing button 254 returning to its proximal position brings smaller firing button outer diameter 258 between firing button stops 256 to allow safety latch 250 to continue to rotate back to the locked position . the difference in flexibility of the firing button stops radially and axially allows latching and release of triggering mechanism 235 regardless of order of operation of the components . rigidity in the axial direction stops inadvertent operation of firing button 254 and flexibility in the radial direction allows interference with smaller firing button outer diameter 258 while still maintaining smooth release operation . if desired , firing fork assembly 164 can be disassembled without tools from the rest of firing mechanism 160 and cleaned . before a subsequent firing , an operator can attach a clean firing fork assembly 164 by mating proximal spade end 196 with spade slot 198 and threading firing spacer 188 onto end fitting 166 . when assembling firing fork assembly 164 with the firing mechanism in the post - fired position , an assembler can use depth marker line 189 to ensure proper assembly . the assembler can check alignment of depth marker line 189 with the outside surface of base shell 38 . a depth marker line 189 aligned with base shell 38 denotes a proper assembly . a depth marker line 189 that is misaligned with base shell 38 could indicate an improper assembly such as cross threading of firing spacer 188 or incomplete tightening of firing spacer 188 . [ 0096 ] fig2 shows an alternate embodiment of firing fork assembly 164 . thumbscrew 191 threads into a threaded hole 187 on firing fork 62 . threaded hole 187 on firing fork 62 passes through to a larger counter bore hole with flats on either side , commonly called a double - d hole 213 . firing fork assembly 164 comprises thumbscrew 191 threaded onto firing fork 62 . undercut 195 has an outer diameter less than the minor diameter of threaded hole 187 on firing fork 62 and thus maintains clearance between threaded hole 187 and undercut 195 . thumbscrew 191 , after assembly to firing fork 62 , can thus turn freely on firing fork 62 utilizing the clearance between threaded hole 187 and undercut 195 . an alternate embodiment of firing fork shaft end fitting 166 , shown in fig2 , has end fitting flats 211 machined on either side of the second embodiment of end fitting 166 . end fitting 166 is welded to the distal end of firing fork shaft 168 . the configuration of end fitting 166 with end fitting flats 211 will accept double - d hole 213 of the alternate embodiment of firing fork 62 . use of end fitting flats 211 with double - d hole 213 prevents rotation of firing fork 62 relative to end fitting 166 and firing fork shaft 168 . the alternate embodiment of firing fork assembly 164 threads into alternate embodiment of end fitting 166 which is welded onto firing fork shaft 168 . the alternate embodiment end fitting 166 has a threaded internal diameter 193 to accept the threaded proximal end of thumbscrew 191 . thumbscrew 191 has a knurled , easily grasped surface so that the alternate embodiment of firing fork assembly 164 can be assembled and disassembled without the use of tools . dual four - bar mechanisms have been utilized in the present embodiment of the invention to facilitate ease of use by providing access by the user from either side of base 44 . a variation that would become evident to one skilled in the art after reading the description would be a single four - bar mechanism to create the firing mechanism . while preferred embodiments of the present invention have been shown and described herein , it will be obvious to those skilled in the art that such embodiments are provided by way of example only . numerous variations , changes , and substitutions will now occur to those skilled in the art without departing from the invention . accordingly , it is intended that the invention be limited only by the spirit and scope of the appended claims .

US-96724601-A

speckle contrast optical tomography system provided with at least one point source and multiple detectors , means for providing different source positions , the point source having a coherence length of at least the source position - detector distance and means for arranging the source position - detector pairs over a sample to be inspected , the system being further provided with means for measuring the speckle contrast ; the speckle contrast system of the invention thus capable of obtaining 3d images .

for the method of the invention , measurements at multiple detectors from more than one source position are needed . this can be done in following ways : if x source positions are needed , the source has to be scanned through the sample in x different locations . this can be made by different approaches : ( a ) arrange x separate laser sources in such a way to illuminate on the x different scanning locations we need to have . now switch on each of the x lasers one at a time and record the corresponding measurements . ( b ) use only one laser source but couple this laser light into x different optical fibres and arrange each of the optical fibres in x different scanning locations on the sample . the laser light must come out from one fibre at a time ; for this an optical switch can be used . by controlling the optical switch the laser source can be coupled to each fibre one at a time . ( c ) use only one laser source , employing a galvo mirror arrangement controlled by a computer to achieve x different locations . the preferred embodiment is the method c . a coherent light source , a focusing lens to make a point source , a detection unit , for example , a ccd , cmos or spad array with objective lens , data acquisition and processing unit for acquiring raw intensity images and processing speckle contrast data . the block diagram in fig1 depicts the scot system . the method developed for the reconstruction of flow to be used in conjunction with the optical instrumentation for scot is explained in fig2 . multiple sources and detectors are arranged so as to sample the tissue surface over the tissue volume of interest . the light source is a point source , for example a focused or fiber guided laser that can be modeled as a point source at the surface of the sample according to the photon diffusion model . that is , the source can be considered as a point source after traveling a distance of l * inside the turbid media , where l * is the mean scattering length . for our purpose , the diameter of the source should be much smaller than the source - detector distance , rd , typically less than 100 microns . the source is a continuous wave meaning that it should be continuous during a time approximately equal to or longer than the exposure time of the detection system . the coherence length should be larger than all the photon path - lengths in the turbid media . the minimum coherence length should be equal to rd , but typically is around 10 m . the multiple source positions can be achieved by scanning one point source , e . g . using galvanometric mirrors or by using multiple point sources switching on one at a time . the different source positions do not need to be coherent with each other since the interference patterns are measured separately for each source illumination position . to detect the transmitted or reflected light the invention comprises at least one aperture and a detector array . the aperture can be an adjustable magnification objective . examples of suitable detectors are ccd cameras , scmos cameras , arrays of photon counting detectors or spads . the distance from the point source to the detectors , rd , should be larger than 3 l *. detectors should also allow the control and / or the variation of the exposure time in the data acquisition in a range where the lower limit is defined by signal to noise ratio ( snr ) greater than 1 and the upper limit is determined when the calculated speckle contrast is smaller than the shot noise of the pixel measurements . the sc data may be corrected for intensity gradients and for shot noise errors that would otherwise corrupt the pattern of sc and corrupt the imaging . specifically , the data can be corrected for shot noise using a mathematical model based on poisson statistics . specifically , a corrected speckle contrast measure can be created that is equal to the square root of the square of the raw speckle contrast minus the square of the shot noise ( computed using the poisson statistics model ) before proceeding to tomography . further , for intensity gradient correction with in the region of interest ( roi ), a theoretical model for intensity based on diffusion equation is computed and then divide the raw intensity at each pixel by the theoretical / fitted intensity . this removes the variance in the speckle values due to the intensity gradient . a block diagram showing the correction procedure for intensity gradients is shown in fig3 . a sc forward model ( as shown in the block diagram in fig4 ) for the imaging array and the tissue volume is constructed for sc contrasts that predicts sc measurements for hypothetical flow images . the sc data is inverted , using the sc forward model , to generate images of flow . 1 . measurements of speckle contrast are made between a plurality of source and detector pairs that transverse a tissue volume . the detectors each consists of a region of multiple pixel samplings of speckles . in one embodiment , a lens relays the speckle pattern from a tissue surface to a ccd camera . the field of view of the camera ( e . g . 512 × 512 pixels ) is decimated into a grid of 7 × 7 pixel regions . each 7 × 7 is a sc detector , where the speckle contrast ( k ) is calculated as the standard deviation of the full 49 pixels — divided by — the mean value of the full 49 pixels as , the light detection is integrated over a defined exposure time . in the simplest version the exposure time is the same for all detectors and sources . in another embodiment , exposure time scenarios , including multiple exposure times can be used to optimize the signal to noise ratio of each measurement . 2 . the arrangement of the sources and detectors samples the tissue surface over the tissue volume of interest , with multiple source - detector pair distances and overlapping measurement volumes ( see fig5 ). two possible geometries include reflectance and transmission . in reflectance ( see fig6 a ) the sources and detectors are on the same side of the sample . in the transmission geometry ( see fig6 b ), the sources are on one side of the sample , and the detectors are on the other side . in each case a simple sampling pattern is a rectangular evenly spaced grid . for instance if the sample is 1 cm thick , and the volume interest is 3 . 2 cm × 3 . 2 cm by 1 cm , then a 32 × 32 array of source positions would illuminate one side of the sample . a similar 32 × 32 array of detectors would be constructed from a ccd image of the opposite side of the sample . each source would be paired with each detector to construct a full measurement list of each source detector grid . for each source - detector measurement , the speckle contrast is computed for each assigned exposure time . more complex source - detector geometries can be constructed in which a flexible mesh of sources is interpolated within a flexible mesh of detectors to cover and arbitrary tissue volume ( for example see arrangement for a human head in fig7 ). 3 . the data is corrected for homogeneous gradients and shot - noise ( explained in the following ). a forward model relating speckle contrast to medium flow profile based on field autocorrelation function is given as where g 1 ( r , τ ) is the field autocorrelation function , τ is the correlation time , t is the exposure time of the detector array , and β is 0 . 5 unlike the case of laser speckle contrast imaging with uniform source illumination where the field autocorrelation depends only on correlation time , τ , g 1 , in the case of scot , it depends also on the spatial co - ordinate r as given by the correlation diffusion equation ( cde ): −∇. d ∇ g ( r , t )+( μ a + ⅓ ( μ s · k 0 ) 2 & lt ; δr 2 ( r , τ )& gt ;) g ( r , t )= q 0 ( r ) equation 3 where g ( r , τ ) is the un - normalized field autocorrelation which is related to g 1 as here d , μ a , μ s ′, and k 0 are diffusion coefficient , absorption coefficient , reduced scattering coefficient and magnitude of wave vector respectively . the laser point source is represented by q 0 ( r ) where r is the spatial co - ordinates . the term & lt ; δr 2 ( r , t )& gt ; is called the mean square displacement which models the brownian motion as well as the random flow given by 6d b τ and v 2 τ 2 respectively . here d b is called particle diffusion coefficient ( in cm 2 / sec ) and v is the random flow with unit of velocity . the relation connecting source - detector ( representing the flow ) to field autocorrelation as given in equation 3 along with the expression for speckle contrast k in terms of g 1 , as given in equation 2 , constitutes the forward model for scot . note that the diffusion equation used for correcting intensity gradient is different from the cde in equation 3 . cde can be reduced to diffusion equation for intensity by substituting msd = 0 which gives l ( r )= g ( r , 0 ). 4 . the forward model is used to compute sc for each source - detector pair . the data corrected for the natural gradient in light intensity by normalizing the data within the speckle region of interest . the measured speckle contrast is corrected for shot noise ( k c ) using the equation : k c =√{ square root over ( k 2 − k s 2 )} equation 4 here k is the sc measured from raw intensity images and k s is the speckle contrast due to shot noise given by 5 . a sc forward model ( equations 2 and 3 ) for the imaging array and the tissue volume is constructed for sc contrasts . to reconstruct the three dimensional distribution of flow , δv a differential forward model that predicts differential sc contrasts for arbitrary hypothetical flow contrasts is derived based on first born approximation : where k co is the baseline sc corresponding to case from which the flow contrast is to be measured . the baseline is defined as the sc measurement made on a tissue at resting or reference state or on a tissue simulating phantom . the change in sc from k co to k c can be due to flow contrast induced by an externally applied stimulus . the stimulus [ 6 , 7 ] can be neural ( eg :. stimulating the forepaw ), pharmacological ( eg : drug - induced stimulus ) and physiological ( eg : tilting the head etc .). the contrast in sc can also be due to the flow contrast in some part of the tissue compared to the rest due to a physiological change induced by diseases like cancer etc . here g 1 0 and g 1 0 corresponds to rest / reference state of the tissue and c v = ⅓ ( μ s · k 0 ) 2 . the spatial co - ordinates of the sources and detectors are denoted by r s and r d respectively . the differential forward model is derived from the forward model ( comprising equations 2 and 3 ) by expanding the sc in taylor &# 39 ; s series as a function of flow and then truncating the second and higher order differentials , which is precisely the first born approximation . 6 . the source - detector measurement data is reconstructed into an image of flow . the inverse problem ( based on equation 5 ) is solved to estimate the flow contrasts , δv , from the measured source - detector pair sc contrast ( left hand side of equation 5 ). equation 5 is discretized in the source - detector geometry shown in fig5 a to get a linear system of equations , y = ax , where y = k c 2 − k co 2 , a is called the jacobian matrix evaluated using the integral in right hand side of equation 5 and x = δv is the flow contrast to be determined . the solution of this linear system of equations gives the flow contrast δv . here we adopt the standard regularization procedures reported in the context of optical tomography to solve the the speckle contrast forward model in step 3 comprises the calculation of the speckle contrast with spatial or temporal statistics . unlike traditional sc , the method of the invention uses a model for the propagation of speckle contrast through tissue . as photons propagate through the tissue , they are multiply scattered and absorbed and this is , generally , described by the photon diffusion model . if the scatterers , namely red blood cells , are in motion then the diffused light and the resultant speckles fluctuate . the statistics of these fluctuations can be described by a photon diffusion model for temporal autocorrelation functions , which is the correlation diffusion equation ( cde ) given in equation 3 . sc is the integral of this function as shown in equation 2 . the forward model takes the dynamics of the red blood cells (“ blood flow ” which is modeled as mean square displacement ), the absorption and scattering properties , their heterogeneities and the boundaries around the tissues to predict the measured sc . then , the forward model is inverted . the data can be inverted using techniques developed for diffuse optical tomography , optimized against the noise present in sc data sets . there are two basic approaches : either iterative inversion or direct inversion . with iterative inversion each source - detector pair or group of data are projected through the use of the forward model onto an estimated image , step by step , iterating across different measurements . with a direct inversion approach , the forward model matrix is directly inverted numerically , and the image reconstruction is accomplished in a single matrix multiplication of the inverted sensitivity matrix times the sc data . the sensitivity matrix can be computed using the differential forward model given in equation 5 . a specific example according to the above preferred embodiment of the present invention , can be effectively employed to recover the three dimensional flow distribution embedded inside a tissue phantom . the scot experimental apparatus is depicted in fig8 where a liquid phantom having same optical and dynamical properties as that of the biological tissue as the sample is used . specifically , a transparent plastic container of size 3 . 8 cm × 1 . 5 cm × 5 cm is filled with 1 % lipofundin ® mct / lct solution in water resulting in a phantom with μ a = 0 . 026 cm − 1 , μ s ′ = 10 cm − 1 and a temperature controlled continuous laser diode ( thorlabs l785p090 , 785 nm , 90 mw ) is focused down to a beam of 1 mm diameter to probe the sample . the transmission geometry as shown in fig6 ( b ) is used , where the light source is focused on the bottom of the sample and the produced speckle patterns were imaged from the top with a camera ( scmos ; orca ash4 . 0 , hamamatsu ). a f - number of 16 is set in the objective lens of the camera to match the speckle size to pixel size . the exposure time , t , of the camera was set to 1 ms . a tube of 0 . 4 cm diameter is introduced inside the rectangular container through which the same liquid phantom is pumped using a peristaltic pump with the following velocities : using the galvo - mirror unit the source is scanned in three rows each having 25 source positions . the laser is set in every position during 0 . 5 seconds to acquire 35 intensity images per source , with a 1 ms exposure time and for each velocities , the transmitted intensity images are recorded . for each source in the image , 300 detectors are defined , located at xz plane for y = 1 . 5 cm ( 25 detectors in each of the 12 lines ) thus comprising a total of 22500 source - detector pairs which serves as the scot data . for each detector position , a 5 × 5 pixel window is considered for which the intensity gradient corrections are applied and subsequently the mean and the standard deviation of intensities in those 25 pixels are calculated . these values are averaged over time ( frames ) for all the images corresponding to each source and using equation 1 the speckle contrast for each detector is computed . finally using the equation 4 , the sc is corrected for shot noise ( k c ). fig9 shows speckle contrast as a function of source detector separation where k c is the baseline sc with shot noise correction computed using equation 4 and k is sc without shot noise correction . the baseline sc is computed from raw speckle intensity images acquired using the above mentioned experiment on lipofundin ® phantoms . we would like to briefly explain the need of baseline sc measurement in the medium . the method of tomographic reconstruction has two parts 1 ) to measure a baseline data and 2 ) based on above measured baseline data , reconstruct the quantity of interest . aim of scot is to reconstruct the flow contrast from the baseline scenario . so first acquire the baseline measurement . then introduce the stimulus which will alter the flow in one or more spatial locations in the medium and acquire another set of speckle contrast measurement . then use the above two sets of data to reconstruct the flow distribution . for this particular experiment to demonstrate one of the several applications of the present invention , we chose the baseline to be the sc measurement in the absence of flow . the stimulus in this case is the peristaltic pump which will introduce the flow to the system . in fig9 we have shown sc for baseline measurement only in order to show the effect of shot noise and the correction procedure . in order to apply differential model in equation 5 to reconstruct the flow from k c , the background sc in the absence of flow ( k co ) has to be determined . the experimentally determined k c , is fitted against the k obtained using the forward model ( equations 2 and 3 ) for different d b values using nonlinear least square fitting algorithm . the experimentally measured values of optical absorption ( μ a = 0 . 026 cm − 1 ) and the scattering coefficient ( μ s ′= 10 cm − 1 ) were used for the fitting algorithm which gives d b = 1 . 86 × 10 − 8 cm 2 / sec whereas the experimentally determined ( using diffuse correlation spectroscopy , dcs ) d b has a value of 0 . 92 × 10 − 8 cm 2 / sec . from this fitted d b , k co is determined using the forward model . equation 5 is discretized in the rectangular grid geometry shown in fig5 ( a ) to get a matrix equation which is solved for flow velocity v . the distribution of reconstructed and original v in the xy plane is shown in fig1 ( a ) and 10 ( b ) respectively . the original velocity distribution in xy plane as shown in fig1 ( b ) shows the presence of a flow represented by the brighter region of the plot whereas the darker region indicates the absence of the flow . the reconstructed velocity distribution using the sc obtained from a sample , containing the original velocity distribution as shown in fig1 ( b ), is shown in fig1 ( a ). the reconstructed plot in fig1 ( a ) contains grey levels in between the brighter ( high velocity flow ) and darker regions ( absence of flow ) which shows that the reconstructed velocity is not exact but a distributed representation of the original velocity which is quite common in these type of nonlinear inverse problems . the maximum value of the reconstructed velocity is approximately one seventh of the maximum value of the original velocity . similar plots for xz and yz planes are shown in fig1 and 12 respectively . the reconstructed normalized flow is plotted against the normalized original flow as shown in fig1 . these reconstructed flow values are obtained by averaging the reconstructed flow velocity in predetermined area ( matching the original position of the tube ) defined on the yz planes . the standard deviation of the reconstructed flow in this region is also shown in the same figure . the normalization is done by dividing the original and reconstructed flow corresponding to the flow value of 1 . 0616 cm / sec . a linear fit of the reconstructed flow gives a slope of 0 . 6 showing that the born approximation under estimate the original flow value by approximately 40 %. the invention has clear utility in preclinical studies of rodents . it may also have application in humans , either intra - operatively or possibly non - invasively . in this text , the term “ comprises ” and its derivations ( such as “ comprising ”, etc .) should not be understood in an excluding sense , that is , these terms should not be interpreted as excluding the possibility that what is described and defined may include further elements , steps , etc . on the other hand , the invention is not limited to the specific embodiment ( s ) described herein , but also encompasses any variations that may be considered by any person skilled in the art ( for example , as regards the choice of materials , dimensions , components , configuration , etc . ), within the general scope of the invention as defined in the claims .

US-201314141227-A

a balloon dilatation catheter for use in percutaneous transluminal coronary angioplasty has a balloon having proximal and distal segments in which the proximal segment of the balloon is smaller in diameter than the distal segment . the catheter is adapted for use in the &# 34 ; kissing balloon &# 34 ; technique . the smaller diameter proximal sections reduce the distension of the common artery and bifurcation where the kissing balloon technique is utilized .

fig1 illustrates the catheter which has a proximal end ( at the left in the drawing ) and a distal end ( at the right in the drawing ). the catheter has a relatively long proximal segment 10 which may be formed from narrow , solid wall tubing , such as hypodermic tubing . in the illustrative embodiment , the proximal segment 10 may be of the order of 150 cm long . in the illustrative embodiment , the proximal segment 10 may be rigid torsionally so that it can transmit rotation from its proximal to its distal end . the distal end preferably can be bent to a curve so that the device may be steered and directed as it is advanced through the patient &# 39 ; s vasculature . the proximal segment 10 also is flexible and can bend longitudinally to follow the curvature of the patient &# 39 ; s arterial system . preferably , the proximal segment 10 of the catheter is sufficiently flexible so that it can bend to follow the curve of a patient &# 39 ; s aortic arch which has a radius of the order of between 2 . 5 and 3 . 5 inches in an adult . as shown more clearly in enlarged fig4 in the preferred embodiment of the invention the hollow tubular proximal segment 10 may have an outer diameter of 0 . 018 &# 34 ;, a wall thickness of about 0 . 002 &# 34 ; and an internal diameter passage 14 of 0 . 014 &# 34 ;. a conventional fitting 16 is attached to the proximal end of segment 10 to facilitate connection with an inflation / deflation device , such as a syringe ( not shown ). the catheter includes a distal segment 12 which extends from the distal end of the proximal segment 10 to the distal end of the catheter . the distal segment 12 includes a narrow diameter elongate support wire 18 which is connected to and extends distally of the tubular proximal segment 10 . the support wire 18 is connected to the proximal tubing 10 by a short transition tube 20 . the transition tube 20 is about 3 &# 34 ; long and also is formed from a slender , flexible hypodermic tubing with a smaller diameter than the proximal tube 10 . in the illustrative embodiment , the transition tube 20 is formed from hypodermic tubing having an outer diameter of 0 . 014 &# 34 ;, a wall thickness of 0 . 003 &# 34 ; and an inner diameter of 0 . 008 &# 34 ;. the proximal end of the tubing 20 is received within the distal end of the internal passage 14 of the proximal segment 10 and is secured thereto as by soldering or brazing . the solid support wire 18 is attached to the distal end of the transition tube 20 . the wire 18 , which in the illustrative embodiment is very slender , preferably 0 . 008 &# 34 ; diameter , is received in the distal end of the passage 22 of the tubing 20 and is secured by soldering or brazing . the support wire 18 plugs the distal end of the tubing 20 . the transition tube 20 is provided with apertures 24 on opposite sides of the tubed wall to provide communication with internal passages 22 , 14 so as to provide communication with a balloon 26 mounted on the distal region of the catheter . the apertures 24 may be defined by forming a pair of longitudinal slots in the wall of the tubing 20 . the support wire 18 provides support for the balloon 26 and also extends distally beyond the balloon 26 , to form the core of a leader segment 28 . the leader segment includes a helically wound radiopaque coil spring 30 which is attached to the distal end of the core wire 18 as described below . the balloon 26 is formed by molding a high strength polymeric material in a manner which provides a thin balloon wall , not greater than about 0 . 001 &# 34 ; thickness and preferably having a thickness of the order of 0 . 0005 &# 34 ;. the balloon may be manufactured as described in u . s . pat . no . 4 , 490 , 421 issued dec . 25 , 1984 and reference is made thereto for further details concerning the manufacture of the balloon . as shown in enlarged detail in fig6 the balloon 26 is of a stepped configuration having a proximal section 32 that is of smaller diameter than a distal section 34 . both sections 32 , 34 are cylindrical and are joined by a proximally tapering generally conical portion 36 . by way of illustrative example , the balloon may have an overall length of about 25 mm , with the proximal segment being approximately 12 to 13 mm in length and about 2 . 0 mm in diameter and the distal segment being approximately 12 to 13 mm in length and 2 . 5 mm in diameter . the balloon is formed from a high strength material which will not tend to stretch when inflated . for example , polyethylene terepthalate is a desirable material for the balloon . the balloon is formed to include tapering portions 38 , 40 at the proximal and distal ends respectively . the distal tapering portion 40 merges into a narrowed neck 42 which fits snugly about and against the proximal end of the coil spring 30 . the distal neck 42 of the balloon 26 is adhesively attached to the coil spring 30 . the proximal end of the coil spring 30 is soldered securely to the core wire 18 at the region where the distal neck 42 is joined . the proximal tapering portion 38 merges into a narrowed proximal neck 44 . in order to communicate the interior of the balloon 26 with the inflation / deflation passages 14 , 22 of the tubing , an extension sleeve 46 is adhesively attached to the proximal neck 44 . the extension sleeve 46 extends proximally over one support wire 18 . the proximal end of the extension sleeve 46 preferably is formed from the same material as the balloon 26 and is securely and adhesively attached to the outer surface of the transition tube 20 , where it joins the main tube 10 . the extension sleeve 46 defines an annular passage 48 about the support wire 18 . the annular passage 48 provides communication between the apertures 24 and the interior of the balloon 26 for inflation and deflation of the balloon . as shown in fig6 the leader segment 28 which extends distally of the balloon 26 is of increasing flexibility in a distal direction to provide a relatively soft flexible leading tip which reduces the chance of trauma or injury to the blood vessel . in the illustrative embodiment , the leader segment may be about 3 cm long . the coil spring 30 is soldered at its proximal end , to the support wire 18 as indicated at 50 . the distal end of the support wire 18 also is soldered to the coil spring 30 as indicated at 52 . soldered joint 52 and the distal tip 54 of the support wire 18 terminate short of the distal tip 56 of the coil spring 30 . the distal segment 58 of the coil spring 30 may extend about 5 mm beyond the soldered joint 52 and defines a highly flexible bumper tip . a rounded weld bead 56 forms and defines the distal tip of the spring 30 . the leader segment 28 is of increasing flexibility in a distal direction . the support wire 18 is taper ground and , for example , may be ground smoothly to a 0 . 002 &# 34 ; diameter at its distal tip 54 . the distal segment 58 of the coil spring 30 includes a flexible and bendable stainless steel shaping ribbon 60 which is secured to the distal tip 54 of the support wire at one end and to the distal weld bead 56 at its other end . the shaping ribbon is of slender , rectangular cross - section , of the order of 0 . 001 &# 34 ; by 0 . 002 &# 34 ;. the shaping ribbon is adapted to be bent to a desired curve and to retain that curve when relaxed . the preset curve enables the catheter to be steered by rotation of the catheter from its proximal end to direct the bent distal tip in selective directions as desired within the patient &# 39 ; s blood vessels . the catheter also may be provided with a radiopaque marker band 62 which preferably is formed from platinum . the marker band 62 is located proximally of the main portion of the balloon 26 . in the illustrative embodiment , it is securely attached to the support wire 18 . the marker band 62 provides a means by which the physician can verify , fluoroscopically , the position of the catheter . fig2 illustrates the kissing balloon technique using conventional balloon catheters . fig3 illustrates the manner in which the balloon dilatation catheter of the present invention is used in the kissing balloon technique . as shown diagrammatically in each of fig2 and 3 , a bifurcated blood vessel has a trunk portion 64 and a pair of bifurcated blood vessels 66 , 68 in communication with the trunk 64 . the blood vessel 68 has a stenosis 70 adjacent the junction of the blood vessels . as is common , the stenosis may extend partially around the bifurcation and into the other blood vessel . in the kissing balloon technique illustrated in fig2 a pier of balloon dilatation catheters are inserted through the trunk vessel 64 with one of the balloons being disposed in each of the vessels 66 , 68 . the proximal ends of the balloons typically remain in the trunk vessel 64 and contact or &# 34 ; kiss &# 34 ; each other . as illustrated in fig2 when the balloons are inflated , that may tend to risk injury to the trunk vessel 64 from over inflation . as illustrated in fig3 with the present invention , the proximal smaller diameter portions of the balloon are disposed in the trunk and will not over distend the trunk vessel 64 . it should be understood that although the invention has been illustrated in fig3 utilizing two catheters of the present invention , the invention also may be practiced using a conventional balloon dilatation catheter together with one catheter having a balloon with a reduced proximal diameter in accordance with the invention , depending on the coronary anatomy of the particular patient . thus , the invention provides a dilatation catheter configuration adapted specifically for reduced risk in the practice of the kissing balloon technique . it should be understood that the foregoing description of the invention is intended to be illustrative thereof and that other embodiments and modifications may be apparent to those skilled in the art .

US-18367388-A

a high quality soy protein isolate with significantly reduced aluminum content and substantially free of phytic acid and phytate complexes is prepared by aqueous extraction of defatted particulated soybeans at ph 8 to 10 , and at a temperature above 65 ° c ., separating the extract and then precipitating the protein out of solution , at a ph slightly higher than its isoelectric point , i . e ., ph 5 . 3 .

in a typical commercial process , the soy proteins are extracted at slightly alkaline ph from soy flake or soy flour . the major protein fraction is then precipitated from the clarified extract by adjusting the ph to the isoelectric point of the proteins ( ph 4 . 5 ). since the proteins are insoluble at this ph , the protein can be separated from soluble sugars , salts , etc ., by centrifugation . to complete the purification , the protein curd is washed with water at least once at this isoelectric ph , then the protein spray - dried either as is or after resolubilization at neutral ph . under such conditions , a major portion of the phytate present in the soy flake will complex with the protein and will be present in the soy isolate . typically , commercial soy isolates have a phytate content of 2 . 0 - 2 . 5 % and in some instances as much as 3 % by weight . the treatment of soy proteins at high alkalinity ( ph 11 . 6 ) may adversely affect the nutritive value or safety of such proteins . during many of the commercially available processes for preparing soy protein isolates , the proteins are precipitated at about ph 4 . 5 . however , at this ph , a strong phytate - protein interaction takes place and most of the phytate will precipitate with the protein , resulting in a soy protein isolate having more than 2 % phytate . the present invention provides further improvements to the prior commercial process by eliminating the exposure to extreme alkalinity and most important provides for the first time an economic process for the production of soy isolates in good yield and having phytate concentrations of 0 . 3 % by weight or below . the soy protein raw material for the process is particulate defatted soybean , preferably defatted soy flour or defatted soy flakes . the process involves forming an aqueous solution of soy protein at an alkaline ph from the soy protein containing raw material . it is not intended to limit the invention to any type of raw material , nor is it intended to limit the invention to any specified manner of preparing this initial soy extract since many modifications may be made depending upon the various objectives of the process . the initial extraction slurry is formed by adding with agitation , one part by weight of soy protein containing raw material to 10 to 20 parts by weight of aqueous slurry media at a ph of 8 to 10 and a temperature above 65 ° c . although higher ph &# 39 ; s may be employed , it has been found that at such higher ph &# 39 ; s , there is a tendency to increase the undesirable formation of lysinoalanine . preferably , the ph is maintained at 8 . 5 to 9 . 5 at a temperature of 70 ° c . to 85 ° c . and most preferably 75 ° c . to 80 ° c . although temperatures higher than 85 ° c . may be satisfactorily employed during extraction , it has been found that at such higher temperatures there is a tendency to increase the undesirable formation of lysinoalanine . the slurry is maintained at the desired ph and temperature for about 1 to 15 , and preferably 2 to 5 minutes . thereafter , the temperature is reduced rapidly to 25 ° c . to 65 ° c ., preferably 50 ° c . to 60 ° c ., and most preferably to 55 ° c . to 60 ° c . and the slurry maintained at such temperature for an additional 10 to 60 minutes , and preferably 10 to 30 minutes , to continue extraction of the soy protein from the raw material . the insoluble fraction containing a substantial portion of the phytates and carbohydrates is separated from the solubilized protein fraction by conventional solid separation unit processes such as filtration or centrifugation . the foregoing temperature ranges are the optimum values for dissociation of the soluble soy protein from the phytic acid complex and for maintaining the phytates and phytic acid derivatives substantially insoluble . under some manufacturing conditions , however , other temperature ranges may prove to be more suitable since the temperature at which the phytate solubility is formed has an effect on the physical nature thereof which affects its filtration and centrifugation characteristics . empirical selection of the optimum phytate solubilization temperature for any given manufacturing arrangement is , of course , desirable . the ph of the solubilized protein fraction is adjusted to ph 5 . 0 to 5 . 5 and preferably ph 5 . 2 to 5 . 4 and most preferably 5 . 3 with a non - toxic water soluble acid such as hydrochloric acid to precipitate the solubilized soy protein . although ph &# 39 ; s higher than 5 . 5 may be employed , such ph &# 39 ; s tend to decrease the yield of soy protein . the protein is precipitated out of the solubilized protein fraction at a temperature of 25 ° c . to 65 ° c ., preferably 50 ° c . to 60 ° c . the precipitated protein is separated from sugars , soluble phytate , etc ., by centrifugation or other conventional means . the ph selected will precipitate the heat sensitized proteins , but will allow the soluble phytate to be washed out in the whey . protein - phytate complex will not form , since at this ph both proteins and phytates are negatively charged . such a complex would form at or below ph 4 . 5 . the precipitated and separated protein may be washed with water , then it may be resuspended in water , the suspension wet milled , and then spray dried or lyophilized . alternatively , protein curd may be redissolved in dilute aqueous solution at a ph in excess of the isoelectric range and the resulting solution spray dried as is known in the art for the production of so - called soy proteinates . finally , rather than spray drying , the precipitated and separated protein may be redissolved at a ph in excess of the isoelectric range , and the resulting soy proteinate solution may then be formulated without drying into dietary products by combination with the desired carbohydrate and fat ingredients and , if desired , vitamins , minerals , flavors , etc . this is not only a convenient mode of operation from the standpoint of combining the various ingredients , but also it affords a liquid dietary product having improved functional characteristics such as solubility , suspendability , viscosity , mouth feel and emulsion stability . in carrying out the process of the present invention , it has been found that temperature of extraction , ph of extraction , ph of precipitation , temperature of precipitation and the amount of washing are important in obtaining the desired results . the yield is also affected by the length of extraction , and the number of times the soy flour is re - extracted . one kilogram of defatted soy flour is slurried with 16 kilograms of hot water at ph 9 and maintained at 75 ° c . for 2 minutes . the slurry is then cooled rapidly to 50 °- 60 ° c . and extracted for 10 - 30 minutes longer . the insoluble portion is separated by centrifugation . the ph of the supernatant is adjusted to ph 5 . 3 with hydrochloric acid , and the insolubilized protein curd which precipitates out is separated by centrifugation . the curd then may be washed once by resuspending it in 10 - 16 kilograms of water at ph 5 . 3 - 5 . 4 and at a temperature of 50 °- 60 ° c . and then recentrifuged . the washed curd is collected and may be spray dried as is , or neutralized first with an appropriate alkali and the spray dried . the process of example 1 was repeated six times with the following results : ______________________________________percent phytate and yield of soy isolatesprepared according to the process of the invention % phytate . sup . a % yield ( g soy isolate / 100 g soy flour ) ______________________________________0 . 02 31 . 30 . 03 28 . 90 . 05 30 . 50 . 05 30 . 90 . 11 29 . 90 . 07 30 . 4______________________________________ . sup . a commercial soy isolates have a phytate content of 2 - 2 . 5 % and these values illustrate that the soy isolate of the instant invention has only about 1 - 5 % of the phytate content found in commercial soy isolates . ______________________________________comparison of aluminum content of soy isolatesprepared according to the process of theinvention and commercial soy isolate ( edipro a ) sample 1 sample 2 edipro a______________________________________aluminum 7 . 5 6 . 2 24 - 40 ( mcg / g ) phytate % 0 . 11 0 . 13 & gt ; 2______________________________________ the above data clearly demonstrates the ability of the instant process to produce soy isolate having substantially no phytates at relatively good yields with significant reduction in aluminum content . soy isolate samples were prepared according to the procedures of example 1 with variation in extraction temperature and ph , and precipitation ph , as shown in the following table . the % phytate in finished soy isolate and yield is also included . ______________________________________sample extraction precipitation % no . temp in ° c . ph ph phytate % yield______________________________________1 75 9 . 0 5 . 3 0 . 02 31 . 32 65 9 . 0 5 . 3 0 . 46 32 . 73 88 9 . 0 5 . 3 0 . 04 29 . 94 75 8 . 0 5 . 3 0 . 20 28 . 65 75 10 . 0 5 . 3 0 . 08 32 . 56 75 9 . 0 5 . 2 0 . 06 31 . 47 75 9 . 0 5 . 5 0 . 02 29 . 48 40 8 . 0 5 . 3 0 . 41 28 . 09 75 9 . 0 4 . 5 0 . 54 31 . 310 40 8 . 0 4 . 5 1 . 96 32 . 9______________________________________ as shown above , very low phytate content can be achieved when the soy isolate is prepared under the experimental conditions described in this patent application . medium range phytate content can be achieved if some of the teachings of this application are employed , such as when commercial extraction conditions are combined with the acid precipitation conditions of instant application ( sample 8 ), or when the protein extract conditions of instant application is combined with the typical ph of precipitation ( sample 9 ). sample 10 shows typical conditions for preparation of commercial soy isolate with its high phytate content .

US-77348185-A

systems , methods and computer program products used creating online or web or app based fantasy games and integrated betting systems .

in the following description , for purposes of explanation , specific details are set forth in order to provide a thorough understanding of different aspects of the present invention . it will be evident , however , to one skilled in the art that the present invention as defined by the claims may include some or all of the features or embodiments herein described and may further include obvious modifications and equivalents of the features and concepts described herein . “ sports lines ”: the numbers assigned by the linesmakers which can handicap one team or player and favors another or otherwise makes predictions relating to sporting events or predicts player performance during future sporting events . “ linesmaker ”— act as a market maker for sports wagers , most of which have a binary outcome : a team either wins or loses . “ sporting event ”— includes professional , college , national , olympics and other events including competitive sports . “ fantasy game period ”— daily , weekly , monthly , and seasonally depending on the sport . “ fantasy line ”— a projected total for a single player that incorporates the opinions of a various fantasy experts . “ house user ” or “ the house ”: a facility or system which houses , accommodates , implements , or manages gambling activities or fantasy games . for example , a casino or online game website . the invention relates to systems or computer - based or application or website based methods for performing or conducting a fantasy game . according to one aspect of the invention , users would compete against each other (“ open competition ”). the underlying goal of the game or competition is for the users to have a higher difference margin versus the “ sports - lines ” in the user &# 39 ; s fantasy team lineup based on the real - word sporting event ( s ). that is , the users focus on building a fantasy team with individually selected team members who the user believes will beat the team member &# 39 ; s expected playing metrics ( e . g ., the sports - lines ). for example , if the professional football player drew brees is projected to have 25 fantasy points , but later in the real - world game achieves 33 points , the player selecting brees would have a scoring margin of + 8 . thus , according to this preferring embodiment , the game is about picking players who the users feel will have better games than the sports lines suggest . for example , in future weeks , it may make more sense to start the buffalo bills middling qb ryan fitzpatrick than the pro bowl qb peyton manning if the user believes fitzpatrick will outperform relative to manning in the specific game dates involved . the open competition methods of the invention comprise varying preferred embodiments . according to one embodiment , users would compete against each other in a league . instead of a winner being determined by a house model or linesmaker , the user with the highest cumulative difference among the playing users would win that week . also , this model eschews the utopian score by relying on you to select players that you believe will outperform their projections . as such , looking at quarterbacks , peyton manning is projected to score 25 points and tom brady is projected to score 15 . however , you believe brady &# 39 ; s cumulative difference will be higher than manning &# 39 ; s , and thereby you insert brady into your starting lineup . players are selected either via a draft or a salary cap . there are a number of nuances we can employ for the procurement of players . for instance , perhaps you draft a new team each week and the league essentially resets after monday night football . or , like most standard leagues , the team you draft pre - season is your permanent team less trades , add / drops , etc . for example , in the 2013 nfl season , user a and user b are in a league amongst our college fraternity brothers . user b plays user a in week 1 and user b &# 39 ; s cumulative difference is + 3 whereas user a &# 39 ; s is + 2 . 5 . user b would win that week and being 1 - 0 going into week 2 . according to another embodiment , the set - up is rotisserie - style . for example , looking back to the prior example of user a and user b being in the same league , we no longer use a binary system of wins and losses . in essence , after week 1 , user a &# 39 ; s record isn &# 39 ; t 0 - 1 but rather + 2 . 5 . in week 2 , if user a &# 39 ; s cumulative difference is + 3 , his aggregate score going into week 3 is + 5 . 5 . with a score of + 5 . 5 , user a is in 3rd place in his league because his cumulative difference score ranks third amongst his league competitors . another embodiment relates to a computer - based method for conducting a fantasy game comprising : receiving assignments of a plurality of players from a first user forming a first user fantasy team , each player having one or more predicted playing metrics ; receiving , by way of a computer , real - world playing metrics from one or more real - world competitive events including one or more real - world playing metrics from said plurality of players of said first user fantasy team ; calculating award points for said first user based on the cumulative differences between said one or more real - world playing metrics and said one or more predicted playing metrics ; and awarding said first player based said calculated award points . preferably , the first user competes against one or more other users and wherein the user with the highest calculated award points wins the fantasy game . preferably , the first user competes against a specified number of other users and wherein the user with the highest calculated award points wins the fantasy game . according to preferred embodiments , awarding according to the fantasy game is performed after a predetermined timed interval . preferably , the awarding is performed after a predetermined number of real - world events . preferably , the fantasy game lasts one day , one week , one month , one season or one year . according to one version of open competition according to the invention (“ version 1 ”), one user would play against one user each “ league week .” league week is generally seven days . nfl teams play once a week whereas the mlb , nba , and nhl have multiple games during each league week . at the end of the league week , the user with the higher cumulative difference would be deemed the winner and awarded one “ win .” the last two or three weeks of the respective season would be devoted to the fantasy playoffs where the top four to eight teams ( based on team &# 39 ; s winning percentage ) in each league will compete and one will be eventually anointed as the “ league winner .” according to a second version (“ version 2 ”), one user would compete against all other users each league week . at the end of each league week , the said users cumulative difference will be added to their previous week &# 39 ; s cumulative difference thus comprising one total “ aggregate difference .” the standings hierarchy is derivative of the teams with the highest aggregate cumulative difference . in this model , there will be no playoff system and the team with the highest aggregate difference at the end of the league year will be deemed the league winner . according to a third version (“ version 3 ”), users will utilize version 1 as their regular - season scoring model and version 2 as their playoff scoring model . according to a fourth version (“ version 4 ”), users will utilize version 2 as their regular - season scoring model and version 1 as their playoff scoring model . preferably , the players are assigned salary information and a first user is allocated fantasy money for forming said first user fantasy team within specified salary caps . according to preferred embodiments , the players are professional sports players , college players or olympic players . preferably , professional players selected from football , baseball , basketball , hockey , soccer , cricket , cycling , racing , tennis , or rugby . preferably , the players are professional players selected from nfl , mlb , nhl , nba , pga , or mls . according to preferred embodiments , the players are baseball players and the one or more playing metrics including one or more metrics selected from the group consisting of : hits , hr , rbi , sb , ba , avg , slg %, ops , ob %, w , whip , k / 9 , tb and ibb . according to preferred embodiments , the players are football players and the one or more playing metrics including one or more metrics selected from the group consisting of those listed in table a below . another embodiment of the invention relates to a method of conducting a fantasy sports competition adapted to be played by a plurality of participants , comprising awarding a winner for said fantasy sports completion based on highest cumulative differences between one or more real - world playing metrics and one or more predicted playing metrics . another embodiment of the invention relates to methods of or systems for conducting a fantasy sports competition adapted to be played by a plurality of participants , each having a fantasy team , the method comprising awarding a winner for said fantasy sports competition based on highest cumulative differences between one or more real - world playing metrics of individual players on each fantasy team and one or more predicted playing metrics of said individual players on each fantasy team . yet another embodiment of the invention relates to methods of or systems for conducting a fantasy competition defined by a sequence of actual events comprising : ( b ) creating fantasy teams for enrolled users in said fantasy competition by enabling users to select team players to create fantasy teams for said fantasy competition , said selected team players being assigned predicted performance values ; and ( c ) determining points utilized for awards based on actual performance values of said selected team players in said corresponding actual events , wherein point values are assigned based on the cumulative differences between the actual performance values of said selected team players and said predicted performance values of said selected team players . another embodiment of the invention relates to a system for conducting a fantasy competition comprising : a computer system to conduct a fantasy competition defined by a sequence of actual events , said computer system including : a join module to enroll users within said fantasy competition ; a draft module to create fantasy teams for enrolled users in said fantasy competition by enabling enrolled users to select team players to create fantasy teams for said fantasy competition , said selected team players being assigned predicted performance values ; and a points module to determine points utilized for awards based on corresponding actual events and actual performance values of said selected team players in those corresponding actual events , wherein said point are assigned based on the cumulative differences between the actual performance values and assigned performance values . preferably , the fantasy games according to the invention include a number of variables that pre - existing fantasy games do not account for or address , namely finding players who might have a comparative advantage in a certain week versus an absolute advantage throughout the season . preferably , wherein the first user competes against a house user and the user with the highest award points wins the fantasy game . another aspect of the invention relates to systems or methods where one or more users compete against “ the house ” ( e . g , “ vegas model ”). for example , according to the “ vegas model ”, each week ( for football season ) or game ( for baseball , basketball , hockey , etc . ), a user bets against the house “ utopian ” score . the utopian score is calculated by the highest projected totals for each fantasy position . in order to win , presumably “ even money ,” the user would have to + 1 the house score . one aspect of the invention relates to methods and systems for conducting a game comprising : generating a house fantasy team including predicted highest scoring players for each fantasy team position for a specified playing period and aggregating the predicted scores for said predicted highest scoring players for said specified playing period thereby forming a utopian score ; receiving assignments of a plurality of players for each fantasy team position from a first user forming a first user fantasy team for said specified playing period ; receiving real - world player scores for said specified playing period ; calculating a real - world first user fantasy team score by aggregating the real - world scores for said plurality of players for said specified playing period ; and awarding said first user if said real - world first user fantasy team score is greater than said utopian score . according to one preferred embodiment , the first user competes alongside one or more other users . preferably , the user with the highest calculated award points wins the fantasy game . preferably , the first user competes alongside a specified number of other users and wherein the user with the highest calculated award points wins the fantasy game . another aspect of the invention relates to systems and methods for conducting a game comprising : generating a house fantasy team including predicted highest scoring players for each fantasy team position for a specified playing period and aggregating the predicted scores for said predicted highest scoring players for said specified playing period thereby forming a utopian score ; receiving assignments of a plurality of players for each fantasy team position from a first user forming a first user fantasy team for said specified playing period ; receiving real - world player scores for said specified playing period ; calculating a real - world house fantasy team score by aggregating the real - world scores for said predicted highest scoring players for said specified playing period ; calculating a real - world first user fantasy team score by aggregating the real - world scores for said plurality of players for said specified playing period ; and awarding said first user if said real - world first user fantasy team score is greater than said real - world house fantasy team score . accordingly , aspects of the invention include “ open competition ” and “ vegas ” game methods and systems . according to preferred embodiments , awarding according to the fantasy game is performed after a predetermined timed interval . preferably , the awarding is performed after a predetermined number of real - world events . preferably , the fantasy game lasts one day , one week , one month , one season or one year . preferably , the players are assigned salary information and a user is allocated fantasy money for forming the user &# 39 ; s fantasy team within specified salary caps . according to preferred embodiments , the players are professional sports players , college players or olympic players . preferably , professional players selected from football , baseball , basketball , hockey , soccer , cricket , cycling , racing , tennis , or rugby . preferably , the players are professional players selected from nfl , mlb , nhl , nba , pga , or mls . according to preferred embodiments , the players are baseball players and the one or more playing metrics including one or more metrics selected from the group consisting of : hits , hr , rbi , sb , ba , avg , slg %, ops , ob %, w , whip , k / 9 , tb and ibb . according to preferred embodiments , the players are football players and the one or more playing metrics including one or more metrics selected from the group consisting of those listed in table a . according to preferred embodiments , users would either have an appropriated amount of funds ( salary - cap ) to create a fantasy team or would draft a finite amount of players ( e . g . in fantasy football , a standardized lineup 1 qb , 2 rb , 3 wr , 1 te , 1 k , 1 d , 6 bench ). for vegas game model , the salary cap is essentially the utopian vegas score . for example , on a random monday , it may be deduced that the top mlb utopian lineup is 145 points . ergo , according to preferred embodiments , a user &# 39 ; s salary allotment cannot go over 145 projected points because it is impossible ( cannot go over the utopian amount ). in short , according to preferred embodiments , a user can procure any players as long as they fit into the user &# 39 ; s lineup with their positions . the fantasy games according to the invention can be applied to the nba , mlb , nfl , pga , etc . for each and every sporting event , individual players ( athletes ) would preferably designated their own fantasy line . the methods and system of the invention include a variety of method for users to generate their fantasy team lineup . for example , procuring players to fill out one &# 39 ; s lineup according to preferred embodiments , there would be three possible scenarios : a .) “ draft ” b .) “ appropriation of funds / salary cap ” c .) “ free for all pick &# 39 ; em ”: this would be applicable to the vegas embodiments , users would fill out a standard fantasy lineup and wager their players would score higher than vegas high prediction for the day . in options a + b , there would be a finite amount of users / players in a league . again , being risk - averse might entail the league lasting at least two weeks . in option c the user would be merely playing against the house . for example , a user can walk into the mirage and bet the miami heat spread versus the new york knicks . instead , according to the invention , the user would have the same ability to construct a fantasy roster that that the user thinks would beat the house score . preferably , pursuant to the cumulative difference games according to preferred embodiments , the underlying purpose is to have your players with a higher differential versus their predicted performance than your opponent . you would just have to pick “ surprise ” players that you believe will far exceed their expectations . this creates an egalitarian platform where the miami dolphins backup running back might be as important and picked by a user over peyton manning . other embodiments of the invention relate to the above - described methods adapted or configured to incorporate the theme or concept of “ confidence points ”. for example , with respect to fantasy line ( s ), “ confidence points ” would be used to give weight to each line in a given week . succinctly , a fantasy football starting lineup generally consists of 10 - 12 nfl players . ( i . e . 1 qb , 2 rb , 3 wr , 1 te , 1 wr / rb / te , 1 k , 1 d ). confidence point selections will be paired with their respective fantasy line to create a novel game ( see example 5 below ). the term “ confidence points ” can be described as the higher the confidence you assign to a fantasy line , the more points you will earn if you have selected the winning team . each line will have a different confidence value assigned to it , such as , ranging from 1 ( least confident ) to 10 ( most confident ). for example , if you assign 9 points to calvin johnson scoring 15 fantasy points vs . the vikings ( because you are very confident in him exceeding that total ) and he actually totals 17 points , your entry will receive 9 points for the correct selection . if johnson scores under 15 fantasy points , you will receive 0 confidence points . another aspect of the invention relates to a computer based system capable of performing the game methods of the invention comprising a processor coupled to a memory , the memory having computer readable code , which when executed by the processor causes the computer system to perform the methods described above . according to preferred embodiments , the methods are performed using an algorithmic logic engine . existing systems and methods can be modified and used to implement the current invention . see , us 201200115585 to goldman et al . ; us20120264503 to lisen , u . s . pat . no . 8 , 360 , 835 to strause et al ., u . s . pat . no . 8 , 292 , 725 to wikander ; u . s . pat . no . 8 , 177 , 644 to andersen , et al ., us20100279774 braig et al ., us 20130018492 to trdinich , et al ., us 20130005422 to callery et al ., us20060237905 to mitenberger , et al , hereby incorporated by reference , specifically the computer based methods and systems described in the detailed description of each document and each of the figures and figure description . on week 1 of the 2013 nfl season , a sports lines maker projects that that the highest - scoring “ utopian ” lineup for the line maker &# 39 ; s fantasy team would yield 112 points . this number would be computed by adding the projected lines of the highest rated players for line maker &# 39 ; s designated fantasy team positions ( e . g ., 1 qb , 2 rb , 3 wr , 1 te , 1 k , and 1 d ). accordingly , for a user to beat the sport - line generated utopian score , the user would need to score greater than 112 points ( e . g . + 1 over the utopian score ). similar to example 1 , in a rotisserie - style vegas game applied to professional baseball sporting events , a user would have to outscore the sports - line on a number of metrics ( i . e . hits , hr , avg , slg %, ops , ob %, w , whip , k / 9 ). the fantasy game period could last a day , a week , or throughout the duration of the 182 - game baseball season . a user challenges vegas to their week 3 fantasy challenge . each week , a fantasy linesmaker would prognosticate the highest scoring players from each position . the aggregate scores from these positions ( 1 qb , 2 rb , 3 wr , 1 te , 1 k , 1 d ) would comprise the utopian score of the week . down below , tom brady is projected to be the highest rated qb for week 3 , thereby his 35 projected points are included in the house utopian score . additionally , adrian peterson and frank gore are projected to be the two highest scoring rb &# 39 ; s and their projected total &# 39 ; s are also included in the utopian score . this will subsequently done for the 3 wr , 1 te , 1 k , and 1 d a user walks into the bellagio on wednesday , october 13th . he decides to challenge the house in their weekly fantasy challenge . the user has the option of picking any player from every game ( tr - m ) to fill out his lineup prior to the first game played every week . otherwise , the pool of players becomes more narrow and dilutes this as less of a game of skill and more of a game of gambling . the numbers on the left indicate confidence point selections whereas the numbers on the right are the players fantasy line . for instance , in week 2 of the nfl season , tom brady is projected to score at least 10 fantasy points . out of all the players on the roster above , i am the most confident tom brady will achieve at or above his fantasy line designation . therefore , i ascribed 10 confidence points to him . if tom scores under his fantasy line projection ( 10 )— i do not receive my ( 10 ) confidence points . whereas , if brady had a scintillating fantasy day and had well over 10 fantasy points , i would thereby gain the ( 10 ) confidence points . individual golf scores are computed by taking the cumulative difference from the actual scores of each golfer ( from their respective rounds ) you would need to fill out a fantasy golf lineup so this game is not misconstrued as a prop bet . for instance , there may be fantasy golf tiers to which players you can procure . for the twenty golfers with the lowest projected scores , perhaps you are only allowed to obtain 3 of them . this can be said for each set of twenty , until the field is exhausted . nascar : same scoring system as golf . the cumulative difference of their projected finish ( s ). you would add the projected finishes of your drivers ( a finite amount ) and find the difference for their actual finish . the systems and methods may be provided on many different types of computer - readable media including computer storage mechanisms ( e . g ., cd - rom , diskette , ram , flash memory , computer &# 39 ; s hard drive , etc .) that contain instructions for use in execution by a processor to perform the methods &# 39 ; operations and implement the systems described herein . with respect to the appended claims , unless stated otherwise , the term “ first ” does not , by itself , require that there also be a “ second ”. moreover , reference to only “ a first ” and “ a second ” does not exclude additional items ( e . g ., sensors ). while the particular computer - based systems and methods described herein and described in detail are fully capable of attaining the above - described objects and advantages of the invention , it is to be understood that these are the presently preferred embodiments of the invention and are thus representative of the subject matter which is broadly contemplated by the present invention , that the scope of the present invention fully encompasses other embodiments which may become obvious to those skilled in the art , and that the scope of the present invention is accordingly to be limited by nothing other than the appended claims , in which reference to an element in the singular means “ one or more ” and not “ one and only one ”, unless otherwise so recited in the claim . although the invention has been described relative to specific embodiments thereof , there are numerous variations and modifications that will be readily apparent to those skilled in the art in light of the above teachings . it is therefore to be understood that , within the scope of the appended claims , the invention may be practiced other than as specifically described .

US-201414200276-A

the ottoman recliner chair includes a pair of opposed side panels , a seat coupled between the side panels , and a back pivotably coupled to the seat . the back is pivotable between a stowed , horizontal position and a generally vertical position . a footrest is coupled to the side panels and seat with a footrest linkage . the footrest is movable between a stowed and extended position wherein the ottoman recliner chair is movable between a stowed ottoman position with the back in the horizontal position and the footrest in stowed position , and a reclined position with the back in the generally vertical extended position and the footrest in extended position .

referring to the drawings in greater detail and initially to fig1 , an ottoman recliner is shown and designated generally by the numeral 10 . ottoman recliner 10 includes a top cushion 12 , a pair of side panels 14 , 16 and a front footrest portion 18 . fig1 illustrates the ottoman recliner 10 in the ottoman position . in this position , ottoman recliner 10 looks similar to existing ottomans . fig2 illustrates ottoman recliner 10 in a recliner position with the top cushion 12 now functioning as a backrest , with the front footrest 18 in the extended position , and with a seat cushion 20 , now exposed . as can be seen , the top cushion 12 serves both as a seat cushion and as a backrest depending on the position of ottoman 10 . the front portion 18 serves as both a front panel and as a footrest depending of the position of ottoman 10 . as best seen in fig3 , the top cushion 12 and seat 20 are angled so as to provide an ergonomically suitable unit that also folds as desired . the internal linkages of ottoman 10 are best seen in fig3 - 5 . as best seen in fig3 - 5 the ottoman recliner linkages broadly include a stationary bracket 22 , a recliner mechanism 24 , and a footrest mechanism 26 . as best seen in fig6 , it will be appreciated that the above referenced items contain mirror - image replicas on each side of the ottoman recliner . as best illustrated in fig6 , ottoman recliner 10 broadly includes a plurality of cross - support members 27 , 29 , and 31 . base support members 27 are fixably coupled to side member 14 at one end and fixably coupled to side member 16 at the other end . stationary bracket 22 is fixably coupled to side panel 16 . any suitable attachment mechanism could be used for coupling stationary bracket 22 to side panel 16 , such as screws , bolts , pins or the like . recliner mechanism 24 is rotatably coupled to stationary bracket 22 . footrest mechanism 26 is rotatably coupled to stationary bracket 22 and recliner mechanism 24 . thus stationary bracket 22 serves to interconnect recliner mechanism 24 to footrest mechanism 26 , and is the point about which the linkages , described below , move . with reference to fig3 - 6 , recliner mechanism 24 broadly includes the seat 20 , a seat support 28 , support members 29 , an l - shaped link 30 , and a back link 32 , which are further described below . seat 20 is fixably coupled to seat support 28 . seat support 28 is located under seat 20 and provides support when the user is seated . while not shown , seat 20 may include additional support such as resilient foam , springs or the like , as would be understood by one skilled in the art . seat support 28 is a generally elongated rectangular block member and can be made from any suitable material such as wood . support members 29 are fixably coupled to seat supports 28 to provide additional support . seat support 28 includes a mounting bracket 34 located on its lower portion . mounting bracket 34 contains a plurality of apertures 36 used for attachment to support 28 . mounting bracket 34 further includes a stop 37 . stop 37 serves to cease rearward movement of recliner linkage 24 , as will be discussed further below . l - shaped link 30 includes a lower leg 38 and an upper leg 40 . lower leg 38 contains a number of apertures 42 used to fixably couple it to seat support 28 at its lower leg 38 . again , any suitable attachment mechanism could be used , such as screws , bolts , pins or the like . upper leg 40 contains a mounting aperture 44 and an arcuate slot 46 . it will be appreciated from fig3 - 5 that slot 46 serves to allow a controlled rotation of approximately ninety degrees . l - shaped link 30 is coupled to back link 32 at its upper leg 40 using aperture 44 and slot 46 . again , any suitable attachment mechanism could be used , such as screws , bolts , pins or the like . back link 32 contains a plurality of apertures 48 and a protrusion 50 . protrusion 50 is generally cylindrical in nature and extends outwardly from back link 32 . protrusion 50 is received in slot 46 contained in l - shaped link 30 . link 32 is also pivotably coupled to link 30 about the connection point 44 . as best seen in fig6 , back link 32 is fixably coupled to internal framework 49 , 51 of backrest 12 , using aperture 44 and apertures 48 . back support members 31 are coupled to internal framework 49 , 51 to provide additional support . as can best be seen by comparing fig3 and 4 , when the front of backrest 12 is moved upwardly , the backrest rotates about mounting aperture 44 through a defined angle of approximately ninety degrees , defined by arcuate slot 46 . recliner mechanism 24 is coupled to stationary bracket 22 through bracket 34 and an activator link 52 and a connector link 54 . thus , activator link 52 and connector link 54 attach recliner mechanism 24 to stationary bracket 22 . again , any suitable attachment mechanism could be used , such as screws , bolts , pins or the like . activator link 52 is generally l - shaped and includes an attaching end 56 , a link pivot 58 , and a drive end 60 . activator link 52 is rotatably coupled to mounting bracket 34 on recliner mechanism 24 at attaching end 56 . attaching end 56 has a hole therethrough , which facilitates fastening activator link 52 to mounting bracket 34 . activator link 52 is also rotatably coupled to stationary bracket 22 at link pivot 58 . connector link 54 is rotatably coupled to mounting bracket 34 on recliner mechanism 24 on its upper end and to stationary bracket 22 on its lower end . connector link 54 has holes located at its ends for facilitating attachment to mounting bracket 34 and stationary bracket 22 . with continued reference to fig3 - 5 , the footrest mechanism 26 will be described in more detail . footrest mechanism 26 includes a drive link 62 , a straight link 64 , an up link 66 , a bracket 68 , and footrest 18 . drive link 62 is generally l - shaped and includes a drive end 70 , a pivot 72 , and an upper end 74 . as best seen in fig3 drive link 62 is rotatably coupled to activator link 52 at drive end 70 and is coupled to bracket 68 at upper end 74 . straight link 64 includes an upper end 76 , a pivot point 72 , a lower end 78 , and a stop 80 . straight link 64 is rotatably coupled to mounting bracket 34 at upper end 76 and rotatably coupled to up link 66 at lower end 78 . straight link 64 is pivotably coupled to drive link 62 at pivot 72 and thus forms a scissor linkage with drive link 62 . stop 80 on link 64 serves to cease rotation of footrest mechanism 26 . opposite the connection of up link 66 to straight link 64 , up link 66 is coupled to bracket 68 . bracket 68 is generally rectangular and contains a plurality of apertures 82 for fastening the various links to footrest 18 . bracket 68 is fixably coupled to footrest 18 . the conversion of the ottoman to the recliner 10 is best described with reference to fig3 - 5 . fig3 represents the ottoman recliner 10 in the closed ottoman position , position one . fig4 represents the ottoman recliner 10 in the open chair position , position two . fig5 represents the ottoman recliner 10 in the open recliner position , position three . in use , if the occupant desires to convert from position one to position two , the user rotates the top cushion 12 rearwardly . the seat 20 is located under the top cushion / backrest 12 . the top cushion 12 rotates about mounting aperture 44 . the amount of rearward rotation is limited by the slot 46 and protrusion 50 configuration . it will be appreciated from fig3 - 5 that the amount of rotation is limited to approximately ninety degrees . as the top cushion 12 begins to pivot rearwardly about the mounting aperture 44 , the relative positions of the seat 20 and footrest 18 remain fixed . when the top cushion 12 reaches its rotational limit , as defined by slot 46 and protrusion 50 , the ottoman recliner is in position two as illustrated in fig4 . to move from position two to position three , additional force is applied to side panels 14 , 16 . the forward force in direction 84 on the side panels 14 , 16 , shown in fig5 , causes the seat portion 20 to move rearwardly as shown by reference numeral 86 . as the seat 20 begins to move rearwardly , the recliner mechanism 24 rotates clockwise about the stationary bracket 22 . this clockwise movement causes interconnected links 54 , 52 , and 64 to rotate clockwise about the stationary bracket 22 . the clockwise motion engages acitvator link 52 and straight link 64 . consequently , the activator link 52 pivots clockwise about pivots 56 , 58 and straight link 64 pivots clockwise about pivot 76 . this action in turn causes links 52 and 64 to push upwardly on links 62 , 66 thereby beginning the extension of the footrest 26 from its tucked position underneath the seat 20 . continued rearward motion of the recliner mechanism 24 causes links 62 , 66 to move upwardly . rearward motion ceases when the connector link 54 and drive link 62 contact stops 37 and 80 respectively which serve to lock the footrest 18 in its fully extended position , position three , as shown in fig5 . footrest mechanism 26 is closed in the conventional method by applying a downward force . the present invention has been described in relation to particular embodiments , which are intended in all respects to be illustrative rather than restrictive . alternative embodiments will become apparent to those skilled in the art to which the present invention pertains without departing from its scope . it will be seen from the foregoing that this invention is one well adapted to attain the ends and objects set forth above , and to attain other advantages , which are obvious and inherent in the device . it will be understood that certain features and subcombinations are of utility and may be employed without reference to other features and subcombinations . this is contemplated by and within the scope of the claims . it will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove . rather , all matter herein set forth or shown in the accompanying drawings is to be interpreted as illustrative and not limiting .

US-89517104-A

the present invention relates to controlled release pharmaceutical compositions comprising budesonide . the invention also relates to processes for the preparation of such compositions and using those compositions in the treatment of inflammatory bowel disease and irritable bowel syndrome including mild to moderate ulcerative colitis .

the present invention provides a controlled release pharmaceutical composition of budesonide for oral administration comprising budesonide as an active ingredient , wherein the active ingredient is released from the composition at a controlled rate along a pre - determined release profile , and wherein the controlled release budesonide composition comprises a tablet core comprising an amphiphilic excipient , a hydrophilic excipient , one or more pharmaceutically acceptable excipients and a gastro - resistant film coating . it has now surprisingly been found that a budesonide composition comprising hydrophilic excipient and an amphiphilic excipient can be prepared , thus avoiding the use of a lipophilic matrix forming excipient . for the purposes of this invention , the term “ budesonide ” includes budesonide or any pharmaceutically acceptable salts or derivatives thereof , including polymorphs , hydrates , solvates or amorphous forms . the term “ controlled release ” as used herein can be used synonymously with extended release , sustained release , modified release , delayed release or pulsatile release . as used herein , unless otherwise noted , “ rate of release ” or “ release rate ” of a drug refers to the quantity of drug released from a dosage form per unit time , e . g ., milligrams of drug released per hour ( mg / hr ) or a percentage of a total drug dose released per hour . drug release rates for dosage forms are typically measured as an in vitro rate of drug release i . e ., a quantity of drug released from the dosage form per unit time measured under appropriate conditions and in a suitable fluid . the release rates referred to herein are determined by performing dissolution test by introducing individual tablets in a rotating basket type dissolution apparatus containing from 500 to 1000 ml of a buffered solution set to different ph conditions ( ph 1 and 7 . 2 are the ph condition generally used in this test application ), so that the ph conditions , from stomach to large intestine , should be reproduced . to simulate the human body conditions , the test is carried out at a temperature of 37 ° c .± 2 ° c . and at predetermined time periods samples of the dissolution medium are withdrawn to detect the percentage of active ingredient dissolved over time . the term “ gastro resistant ”, as used herein can be used synonymously with delayed release . one embodiment discloses a controlled release composition comprising up to 20 % budesonide by total weight of the composition . another embodiment discloses a matrix based controlled release composition comprising up to 20 % budesonide by total weight of the composition . yet another embodiment discloses a controlled release budesonide composition wherein the composition releases not more than about 80 % of budesonide within about 8 hours . yet another embodiment discloses controlled release composition , wherein the composition is in the form of a tablet , minitablets , pellets , a capsule , a caplet , a sachet , beads or granules . the amphiphilic excipients which can be used according to the invention may include one or more of polar lipids of type i or ii ( lecithin , phosphatidylcholine , phosphatidylethanolamine ), ceramides , glycol alkyl ethers such as diethylene glycol monomethyl ether . the hydrophilic excipients include excipients known as hydrogels , i . e . substances which when passing from the dry state to the hydrated one , undergo the so - called “ molecular relaxation ”, namely a remarkable increase in mass and weight following the coordination of a large number of water molecules by the polar groups present in the polymeric chains of the excipients themselves . suitable hydrogels which can be used according to the invention may include one or more of acrylic or methacrylic acid polymers or copolymers , alkylvinyl polymers , hydroxyalkyl celluloses , carboxyalkyl celluloses , polysaccharides , dextrins , pectins , starches and derivatives , natural or synthetic gums , alginic acid . the use of polyalcohols such as xylitol , maltitol and mannitol can also be advantageous in case of taste masking . suitable fillers which can be used according to the invention may include one or more of dextrose , sucrose , maltose , and lactose , sugar - alcohols , which include mannitol , sorbitol , maltitol , xylitol , starch hydrolysates , which include dextrins , and maltodextrins , microcrystalline cellulose or other cellulosic derivatives , dicalcium phosphate , tricalcium phosphate , and mixtures thereof and the like . suitable binders may include one or more of starch , microcrystalline cellulose , highly dispersed silica , mannitol , lactose , polyvinylpyrrolidone , crosslinked polyvinylpyrrolidone , polymethacrylic acid derivatives , ethyl cellulose , methyl cellulose , hydroxyethyl cellulose cross - linked carboxymethylcellulose , hydroxypropylcellulose , hydroxypropyl methylcellulose and natural and synthetic gums , carbomers , dextrin , zein , gelatin , polymethacrylates , polyvinylpyrrolidone , pregelatinized starch , sodium alginate , gums , synthetic resins and the like . suitable disintegrants may include one or more of starch or modified starches , particularly sodium starch glycolate , cornstarch , potato starch or pre - gelatinated starch , clays , particularly bentonite , montmorillonite or veegum ; celluloses , particularly microcrystalline cellulose like l - hydroxypropylcellulose or carboxymethylcellulose ; alginates , particularly sodium alginate or alginic acid ; crosslinked celluloses , particularly croscarmellose sodium ; gums , particularly guar gum or xanthan gum ; crosslinked polymers , particularly crospovidone and the like . suitable lubricants , glidants and antiadherents may include one or more of talc , colloidal silicon dioxide , finely divided silicon dioxide , powdered cellulose , starch , sodium stearyl fumarate , mineral oil , kaolin and the like . suitable solubilizers for the purpose of the present invention may include one or more of solubility enhancing agents , dissolution enhancing agents , absorption enhancing agents , penetration enhancing agents , surface active agents and stabilizing agents . the representative , but non - limiting examples of these compounds are vitamin e tpgs , amino acids such as glutamic acid and glycine , sorbitol , mannose , amylose , maltose , mannitol , lactose , sucrose , glucose , xylitose , dextrins such as maltodextrin , sodium lauryl sulfate , tween 80 ( polyoxyethylene sorbitan monooleate ), benzyl alcohol , poloxamer 407 , polyethylene glycols , such as peg3350 ; polyvinylpyrrolidones such as pvp k25 , polyvinylalcohols , polyalcohols , crospovidone , sodium starch glycolate , croscarmellose sodium , carboxymethylcellulose , starch , pregelatinized starch , hpmc , substituted hydroxypropyl cellulose , microcrystalline cellulose , sodium bicarbonate , calcium citrate and menthol , among others . suitable taste - masking agents include , but are not limited to , one or more of polymers , surfactants , sweeteners and flavors . examples of polymers include one or more of cellulose acetate , polymethacrylates , hydroxypropylmethyl cellulose , hydroxypropyl cellulose , hydroxylethyl cellulose ; and the like . suitable sweeteners include , but are not limited to , saccharides such as aspartame , sucrose , dextrose , glucose , maltose , dextrins , d - tagatose , trehalose , dried invert sugar , fructose , levulose , galactose , corn syrup solids , and the like , alone or in combination . other examples of sweeteners comprise sodium saccharin ; aspartame ; sugarless sweeteners including polyhydric alcohols such as sorbitol , mannitol , xylitol , glycerol , hydrogenated starch hydrolysates , maltitol , isomaltitol , erythritol , lactitol and the like , alone or in combination . suitable flavors include , but are not limited to citric acid , cinnamon , wintergreen , eucalyptus , spearmint , peppermint , menthol , anise as well as fruit flavors such as apple , pear , peach , vanilla , strawberry , cherry , apricot , orange , watermelon , banana and the like ; bean - derived flavors , such as coffee , cocoa and the like or mixtures thereof . the composition according to the invention may be subjected to known coating processes with a gastro - resistant film which may comprise one or more of acrylic and methacrylic acids polymers ( eudragit ( r )) or copolymer or cellulose derivatives , such as cellulose acetophthalate which include cellulose acetate trimelliate ; hydroxypropyl methylcellulose phthalate ; hydroxypropyl methylcellulose acetate succinate ; polyvinyl acetate phthalate and the like . the pharmaceutical compositions as described herein may be prepared by processes known to the person having ordinary skill in the art of pharmaceutical technology such as direct compression , wet granulation , dry granulation , melt granulation . in another embodiment , the method includes a process for providing a controlled release composition , wherein the process includes the steps of : b ) determining specific amounts of budesonide , an amphiphilic excipient , a hydrophilic excipient and one or more pharmaceutically acceptable excipients necessary to produce the pre - determined release profile , and in one more embodiment , the method comprises a step for providing a controlled release composition , wherein the composition may be prepared by sifting the amphiphilic and hydrophilic excipients with one or more pharmaceutically acceptable excipients followed by mixing with an active ingredient . the obtained mixture may be granulated using a solvent . the granules may be dried and then milled . the dried granules may be blended with one or more pharmaceutically acceptable excipients , lubricated and compressed to obtain final composition , which can further be coated with a delayed release coat . in another embodiment , the method comprises a step for providing a controlled release composition , wherein the composition may be prepared by sifting an amphiphilic excipient with one or more pharmaceutically acceptable excipients followed by mixing with budesonide . the obtained mixture may be granulated using a solvent . the granules may be dried and then milled . the dried granules may be blended with hydrophilic excipient and other pharmaceutically acceptable excipients , lubricated and compressed to obtain final composition , which can further be coated with a delayed release coat . in another embodiment , the method comprises a step for providing a controlled release composition , wherein the composition may be prepared by sifting the hydrophilic excipient with other pharmaceutically acceptable excipients followed by mixing with budesonide . the obtained mixture may be granulated using a solvent . the granules may be dried and then milled . the dried granules may be blended with an amphiphilic excipient and one or more pharmaceutically acceptable excipients , lubricated and compressed to obtain final composition , which can further be coated with a delayed release coat . for the purposes of the present invention , the coating step of the process can be carried out using spraying techniques known in the art or compression coating . the term “ coat ” as used herein is defined to mean a coating substantially surrounding a core which provides desirable properties to the dosage form . as is clear to the person of skill in the art , the coat can serve several purposes , including but not limited to protecting the dosage form from environmental conditions , such as light or moisture , providing esthetic or taste - masking properties to the dosage form , making the dosage form easier to swallow or to handle during the production process , or modifying the release properties of the dosage form , such that pharmaceutically active ingredient is released at a different rate from the coated core than from the uncoated core . one or more than one coat , with the same or different functions or properties , can be applied to a core . the term “ coat ” includes , but is not limited to , modified release coats and non - functional soluble coats . in another embodiment , the controlled release composition of the present invention may be prepared by the steps comprising : a ) mixing budesonide , an amphiphilic excipient , a hydrophilic excipient and one or more pharmaceutically acceptable excipients , in another embodiment , the composition of the present invention comprising budesonide exhibits bioequivalence to a reference composition of budesonide or a pharmaceutically acceptable salt thereof . as used herein , a “ reference composition ” is intended to mean a composition of budesonide or a pharmaceutically acceptable salt thereof which is currently approved for marketing and which may be used as a reference for a new drug application ( nda ) or an abbreviated new drug application ( anda ) under the federal food drug & amp ; cosmetic act . another embodiment discloses a method for the treatment of inflammatory bowel disease or irritable bowel syndrome , comprising administering the controlled release composition of the present invention to a patient in need of such treatment . the bioequivalence studies were carried out between uceris ® extended release tablets ( reference ) and compositions of the invention ( test ) in fasted and fed state . the study was monitored in terms of c max and auc achieved with the test product and the reference product ( uceris ®). the invention is further illustrated by the following example which is provided to be exemplary of the invention and does not limit the scope of the invention . while the present invention has been described in terms of its specific embodiments , certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention . budesonide , soy lecithin powder , lactose monohydrate , microcrystalline cellulose and hydroxypropyl cellulose were sifted and mixed . the mixture was granulated using purified water as solvent . the granules were dried and then milled . the dried granules were blended with soy lecithin powder , lactose monohydrate and microcrystalline cellulose . the blend was lubricated using colloidal silicon dioxide and sodium stearyl fumarate and compressed into tablets using suitable tooling . the tablets obtained were coated with a solution of methacrylic acid copolymers . the dissolution performance was measured using a usp - i rotating basket apparatus . release times were measured by placing the tablet in a small wire basket placed on the end of a rod spinning at 100 rpm . aliquots were withdrawn from 0 . 1 n hcl for 2 hour followed by phosphate buffer ph 7 . 2 up to 12 hour . budesonide , soy lecithin powder , microcrystalline cellulose and hydroxypropyl cellulose were sifted and mixed . the mixture was granulated using purified water as solvent . the granules were dried and then milled . the dried granules were blended with hydroxypropyl cellulose grades , lactose monohydrate and microcrystalline cellulose . the blend was lubricated using colloidal silicon dioxide and sodium stearyl fumarate and compressed into tablets using suitable tooling . the tablets obtained were coated with a solution of methacrylic acid copolymers . the dissolution performance was measured using a usp - i rotating basket apparatus . release times were measured by placing the tablet in a small wire basket placed on the end of a rod spinning at 100 rpm . aliquots were withdrawn from 0 . 1 n hcl for 2 hour followed by phosphate buffer ph 7 . 2 up to 12 hour . in - vivo study was conducted in healthy human volunteers to assess bioavailability of budesonide controlled release tablets ( test — composition of the invention as per example 2 ) and uceris ® ( reference ). while the invention has been described in terms of its specific embodiments , certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the invention .

US-201414520634-A

a rotational action needle driver that comprises an cumbersome ergonomically designed handle , rotational mechanism and an integrated locking / unlocking system that permits surgeons to perform the surgical suturing procedure in a less complicated and more secure way by allowing more control over the suturing needle and the area to be stitched , even when the suturing area is small , deep , and / or restricted .

turning to the diagram , fig1 shows the device 1 of the present disclosure comprises a first elongated element 2 , a second elongated element 3 , an actuator 4 and rotational transfer element 6 and at least an elastic member 7 . the first elongated element 3 , as shown in fig2 a - 3b , includes a first elongated body 33 , a first tip 61 at a distal end and a round contour including a first socket 30 at the proximal end . the second elongated element 2 , as shown in fig2 b , includes a second elongated body 23 , a second tip 62 at a distal end and a round contour including a second socket 20 at the proximal end . the rounded contour of the first elongated element 3 and second elongated element 2 are ergonomically designed to rest against surgeon &# 39 ; s palm his hand , permitting its proper use to right and left handed surgeons , therefore a resting palm wall 21 is provided coupled to the first socket 20 at the proximal end . the surgeon will maintain the handle fixed to the palm his hand by using his thumb . the present device comprises several features presented from fig1 through fig1 b . for example , an object of the present disclosure is to perform safest and simplest suturing procedures . the present suturing device 1 comprises a suturing mechanism including an actuator 4 , wherein said actuator 4 initiates the rotational mechanism during the suturing procedure using the present device 1 . in accordance with the principles of the current disclosure the actuator 4 is mechanically coupled to the first elongated element 3 at a first pivot point , as shown in 2 a through 3 b . the actuator 4 is mechanically coupled to the first elongated body 33 by a pin 8 , wherein said pin 8 permits rotational movement or displacement of said actuator 4 with respects to said first pivot point . the actuator 4 comprises a platform 4 a , mainly extended away from the first elongated body 33 , configured or shaped to receive a thumb and be driven by said thumb , base on the present exemplary embodiment the actuator is driven by the thumb , wherein said thumb pushes said platform 4 a towards the first elongated body 33 moving the actuator from a first position , as shown in fig2 a - 2b , to a second position , as shown in fig3 a - 3b . it is important to understand that the movement of the actuator 4 is a radial displacement wherein the center said radial displacement is provided by the first pivot point or pin 8 . further the actuator 4 comprises a linear actuator mechanism fixed to said platform 4 a , wherein said linear actuator comprises a rack 51 , which moves mainly vertical toward the first elongated body 33 . the rack 51 is configured or designed to interact with the rotational bar 6 , more particularly with the pinion 600 at a distal end of said rotational bar 6 , as shown in fig2 a through 3b . the interaction of the rack and pinion converts the radial displacement of the actuator 4 into a rotational movement of the rotational bar 6 . the rotational bar 6 structures is explained in more details below . another object of the present disclosure is to provide different direction of the rotation of said rotational bar 6 while using the actuator 4 . fig4 a is directed to show the displacement of the actuator with respects to the pin 8 . as shown the pin 8 comprises a length longer than the actuator length x 2 with respect to the pin 8 . for example the pin comprises a total length x 3 , and the actuator comprises an attachment portion 71 connected to the pin 8 comprising a second length x 2 . the difference between the lengths provides a space x 1 for the displacement of the attachment portion 71 . the displacement of said attachment portion 71 is enough to move the rack 51 from providing a rotational direction of the pinion to another direction ( i . e . from counterclockwise to clockwise ). for example , the space x ′ 1 provided on fig2 a is positioned at a portion of the pin 8 different from the one showed in fig4 a . in fact the position of the rack 51 in fig2 a will provide clockwise motion of the pinion 600 and counterclockwise motion of the pinion 600 in fig4 a . it is important to understand that the movement of the actuator 4 , more particularly the displacement of the attachment portion 71 is accomplish when the actuator is in the first position . the actuator 4 further comprises an elastic or resilient member 7 coupled to the platform 4 a . the elastic member 7 is configured to be compress from the first position to the second position . subsequently as soon the platform 4 a is release returns to its original position or first position . the elastic member 7 in the exemplary embodiment is a spring configured to recoil the platform to the first position . it is important to understand that any other resilient member can be used as long assists to recoil the platform 4 a . further the first elongated body 33 extends from said first socket 30 towards said first tip 61 . the first elongated body 33 comprises at least a set of walls 331 , 332 forming a clearance between each other , as shown in fig4 a . the clearance between the walls is enough to provide space for the rotational bar 6 and a portion of the second elongated body 23 to be located between them while the suturing device 1 is in use . in the instant case the suturing device is considered in use when the tips 61 , 62 are grasping the needle n or in close contact . in addition the second elongated element 2 , as mentioned , includes a second elongated body 23 , a second tip 62 at a distal end and a round contour including a second socket 20 at the proximal end . further the elongated body 23 comprises a rotational bar support s . the rotational bar support s hold the rotational bar 6 in position with respect to the second elongated body 23 while provide bearing for the rotational movement of said rotational bar 6 when the actuator 4 interacts with the pinion 600 . the rotational bar is mechanical coupled to the second tip 62 , therefore the rotational movement generated at the pinion is transferred to the second tip 62 . the first elongated element 2 and the second elongated member 3 are joint together at the box joint p . the box joint p serves as an intersection or pivot point between the first elongated element 3 and the second elongated element 2 . as shown in fig5 through fig7 , the second tip 62 and first tip 61 extends away from the box joint p . fig5 through fig9 shows the grasping portion created by first tip 61 and second tip 62 . in accordance with the exemplary embodiment the grasping force is preferred to be in an oblique manner , however the contact between tips 61 , 62 maybe provided in other angles . each tip 61 , 62 is removable and comprises at least a distal end gear 60 . in accordance with the principles of the present disclosure the gear is intended to assists to transmit the rotational movement of the second tip 62 connected to the rotational bar 6 to the first tip during the suturing procedures . it is important to understand that the gear serves as a rotation transmitting element for assisting to transferring the rotational motion from second tip 62 to the first tip 61 , therefore any other rotation transmitting element could be used . also each tip 62 , 62 comprises at least contact distal end 620 , 621 including grooves . the grooves or recess assists the increases the grasping force at the contact distal end 620 , 621 . the recess area may vary in order to assists to grasp different sizes of needles n . further the tip 61 , 62 may vary in length . the tip 61 , 62 are made of any selected material capable to perform at least the functions herein mentioned . the selection of the material depends on the field the device is going to be employed . also the contact distal end 620 , 621 is preferred to have a surface that assist the performed action . for example , while using the device in a suturing process is preferred to have a distal end or contact distal end surface cover with a material , such as but not limited to silicon or rubber , that provide some friction over the needle in order to keep a constant displacement of said needle . further the tips may include a layer of antibiotic or any other medical substance that assist the suturing and healing process of the patient . as mentioned before , the tips are removable and securely installed at the distal end of said elongated elements 2 , 3 . it is important to understand that the tips 61 , 62 are removable and / or replaceable due to the need of grooves sizes for specific needles n or / and due to wear and tear problems , such as losing grasping force and / or avoiding particles losses due to friction . a locking mechanism 200 is located between the first elongated body 33 and second elongated body 23 , as shown in fig1 a and 11b . each elongated body comprises a extended member with teeth interlocking with each other , in the form of a ratchet , assisting to hold the position between elongated bodies and consequently the distance between the first tips 62 and second tip 61 . further from said extended member 200 , 201 comprise protrusion 22 a , 22 b . it is important to understand that the current device is usually on an open stage wherein the locking mechanism is not providing a constant distance between the first elongated element 3 and said second elongated element 2 . while using the device 1 the user desires to close the gap between the elongated elements 2 , 3 in order to provide a constant distance between these two parts , consequently the first tip 62 and second tip 61 are in close contact grasping the needle n . another advantage of the present suturing device 1 is the unlocking mechanism , shown in fig1 a and fig1 b . the actuator 4 , as previously disclosed , comprises a linear actuator including rack 51 and a flange 50 . the flange 50 comprises at least two bumps 50 a , 50 b . the bump 50 a , 50 b are intended to assists with the unlocking mechanism by pushing up protrusions 22 b , 22 a . the protrusion 22 b , 22 a extends from the locking mechanism 200 , 201 . the bumps 50 a , 50 b are preferably located closer to the platform 4 a . the purpose of providing the bumps 50 a , 50 b closer to the platform is to provide enough displacement of the rack 51 to rotate the pinion 600 before the bumps 50 a , 50 b interacts with the protrusions 22 a , 22 b . therefore , when the actuator 4 is close to the second position the bumps 50 a , 50 b push up the protrusion 22 a , 22 b unlocking the rackets or locking mechanism 200 , 201 . the disclosure is not limited to the precise configuration described above . while the disclosure has been described as having a preferred design , it is understood that many changes , modifications , variations and other uses and applications of the subject invention will , however , become apparent to those skilled in the art without materially departing from the novel teachings and advantages of this invention after considering this specification together with the accompanying drawings . accordingly , all such changes , modifications , variations and other uses and applications which do not depart from the spirit and scope of the invention are deemed to be covered by this invention as defined in the following claims and their legal equivalents . in the claims , means - plus - function clauses , if any , are intended to cover the structures described herein as performing the recited function and not only structural equivalents but also equivalent structures . all of the patents , patent applications , and publications recited herein , and in the declaration attached hereto , if any , are hereby incorporated by reference as if set forth in their entirety herein . all , or substantially all , the components disclosed in such patents may be used in the embodiments of the present invention , as well as equivalents thereof . the details in the patents , patent applications , and publications incorporated by reference herein may be considered to be incorporable at applicant &# 39 ; s option , into the claims during prosecution as further limitations in the claims to patentable distinguish any amended claims from any applied prior art .

US-201514949877-A

the present invention is a novel approach in combining wired and wireless ecg monitoring . an ecg wireless plug is inserted between the trunk cable and the leadwire cable , so as to both pass the ecg to the host monitor and to intercept the signal for processing and wireless transmission . when the wplug is inserted and the host monitor is active , the signal transmitted to the telemetry receiver can be identified as belonging to the same patient as on the host monitor .

fig1 illustrates the basic embodiment the invention ; here the wplug in shown inserted between the trunk cable and the leadwire cable . the wplug can communicate directly to a telemetry receiver , which can be a computer behind a wi - fi access point , a host monitor , or a smartphone close to the patient . when communicating locally within a short distance from the host monitor , the preferred communication could be bluetooth low energy ( ble ) or body area network ( ban , [ 4 ]). for extended patient mobility , the preferred communication is wi - fi or traditional telemetry channels ( e . g . wtms in the us ). as it is desirable to have a display at the patient side , a patient dedicated smartphone is preferred ; the wplug communicates ble to the smartphone , which processes the ecg and displays and alarms locally in addition to transmitting to the telemetry receiver over the hospital wi - fi network . having the processing close to the patient is advantageous , as the effects of communication disturbances are minimized . fig2 shows a basic wplug design for wide compatibility with legacy host monitors . the wplug has connectors that match the trunk cable and the leadwire cable . it passes the ecg signals through and captures them for its own processing . the detailed design of “ eavesdropping ” on the signals from the patient to the host is crucial . the wplug must show high impedance in all eavesdropping connections so as not to reduce ecg performance of the host monitor . note that the host monitor typically has defibrillation protection resistors in its front end , which means that during defibrillation the voltage between any leads can rise to 5000 volts . also , the host monitor may use impedance respiration , meaning it feeds 30 - 100 khz current to the patient and measures chest impedance variations . none of this can be disturbed by the wplug . special attention must be given to the right leg drive ( rld ), a standard way of reducing noise in an ecg monitor , as it involves active feedback from the ecg amplifier system into the patient . the wplug rld must be very weak or switchable to off when the host is connected . host connection can be detected by the wplug in various ways : by using the standard leads off mechanism , where a small current is injected into the electrodes to measure dc or ac impedance , or by detecting the presence of the shield connections ( rash , lash . . . ) which the host connects to floating ground . fortunately the need for rld in wireless mode is much smaller than in standard host monitor mode , as the leakage current through the host monitor ecg floating front end is essentially missing . the preferred design is weak rld by using a large value for the defibrillation resistor rdef . also the leads off mechanism should be flexible and adapt to the host monitor leads off mechanism when connected . otherwise the mechanisms will interfere . the basic design has a replaceable battery ( alkaline , lithium , rechargeable ) or a built in battery . in the case of a replaceable battery , it is desirable to have a super capacitor as internal backup , as it enables operation during the time the battery is removed from the wplug . with good industrial design battery replacement takes less than one minute , which a 1 farad super capacitor can easily support . if the wplug is replaced with a second device while the first one is removed for charging , the pairing needs to be re - performed . the wireless receiver detects the break in operation , and automatically performs or requests a re - pairing . small variations in the connectors are included in the invention . examples of these are the use of 6 lead ecg connectors instead of 5 leads ( 6 leads adds c2 to the standards 5 lead connector . also a unified 3 - 5 - 6 - 12 lead connector can be used [ 2 ]. a 3 lead cable can be used on the patient side , but the host port must use at least a 5 lead connector that has a dedicated n pin . fig3 shows an extended capability design with battery charging and possible wired digital communication . the extended design can be achieved in several ways . the simplest way of enabling wplug battery charging or battery saving when host connected , is to use a dedicated trunk cable with two connectors at the host monitor end . one goes to a legacy host monitor and the other forks to a battery or floating power supply that is used to feed the wplug battery charging power . it is obviously much more elegant to have host monitor support for power . in case of a host monitor that is supportive of the wplug , it is useful to add a direct wired communication modality to the wplug , e . g . usb . this can be used for several purposes , e . g . making the pairing faster and less dependent on correlating ecg waveforms . again , the easiest way of doing this is using the redundant “ t ” and “ l ” connector shield ground pins . fig4 shows a possible use of the host monitor side of the wplug when in non - host connected mode , where the connector is unused . a version of the wplug can support full 12 lead ecg by utilizing the host port connector as a chest lead connector . it is also possible to allow usage of standard 5 + 5 pin leadwire sets by adding a “ t ”-“ t ” adapter on the host port . normally this allows 12 l ecg only when in non - host mode , but it is obvious that a multiport adapter is easy to design , which would allow all modalities to be used simultaneously . the wplug can also be used for other physiological monitoring , e . g . a pulse oximeter . in addition to dedicated connector for this , a host port that is redundant when not connected to a host monitor , can be used to connect an oximeter or an oximeter probe . u . s . pat . no . 7 , 403 , 808 b2 rud istvan et . al . 17 jul . 2001 4 ] sana ullah , henry higgins , bart braem , benoit latre , chris blondia , ingrid moerman , shahnaz saleem , ziaur rahman and kyung sup kwak , a comprehensive survey of wireless body area networks : on phy , mac , and network layers solutions , journal of medical systems ( springer ), 2010 . doi : 10 . 1007 / s10916 - 010 - 9571 - 3 .

US-201514658142-A

a combination of a bicycle and a display rack therefor , the bicycle has a frame and a plurality of wheels on the frame . the rack having a frame , a mount portion of the frame arranged to be coupled to a ceiling of a building , a linkage having a hanger such that the bicycle can be coupled to the hanger and wherein the linkage is moveable between a first raised position for display and a second lowered position for providing access to the hanger and a cylinder and piston within the mounting portion for retracting the linkage from the second position to the first position .

referring to the accompanying drawings , there is illustrated a bicycle display 1 having a first section , indicated by reference numeral 3 , and a second section 5 . each section 3 , 5 can be utilised with the entire bicycle display 1 as shown or can be set up individually for different applications . the first section 3 , as shown in fig2 to 6 , has an upright frame 7 which supports a plurality of moveable hangers 9 . the hangers are positioned side by side in rows 11 . as illustrated , there are three rows positioned one on top of the other on the frame , but the number of rows can be increased to four or decreased to two if desirable depending upon the space available the and the size of the articles to be displayed . each hanger is moveable on a respective support arrangement defined by a rail 13 such that each hanger can be moved away from a storage position at the frame to a display position i front of the frame and in front of the remaining hangers in the storage position for access to the hanger . each hanger is arranged to support either a single bicycle or more preferably two bicycles 15 as is illustrated . the hanger supports the bicycle with wheel holsters 17 which are arranged to cradle a front wheel 19 of a bicycle , as illustrated in fig4 . the rear wheel 21 is supported by an elongate cradle 23 having a length arranged such that different sized bicycles can be supported thereon . a wheel support lever 25 is pivotally mounted to a frame 27 of the hanger to engage the front wheel for holding the wheel and thus the bicycle in position on the holster 17 . the bike mounts on the hanger are located on respective sides of the hanger frame and are staggered such that the holsters , support lever and cradle are all slightly offset so that one bike is mounted thereon slightly in front of and slightly above the other . the frame 27 includes a horizontal top bar 271 , vertical main support 272 , a horizontal bottom bar 273 and braces 274 and 275 . the holsters 17 and cradles 23 are suspended by support bars passing across the bottom bar 273 . the levers 25 include an inverted u - shaped holder 251 for the wheel attached to a rearwardly extending arm 252 pivoted on a bracket 253 attached to the vertical bar 272 . the frame has guide wheels 29 on the top bar 271 thereof which are arranged to fit within the rail for movement therein . the rail is arranged such that the hanger can sway to allow side to side movement of the hanger . the side to side movement can be used by manual manipulation of the frame as the frame is manually pulled forwardly to release the bikes on the hangers from engagement with bikes on other hangers such that the hangers can be relatively close to each other . a lowering arrangement 31 utilized by the third or higher rows is arranged to provide a user with access to the top row or rows in that the third row is moved downwardly to the height of the second row when pulled manually forwardly to the display position . the lowering arrangement carries the rail 13 on a pair of vertical posts 311 and 312 which guides the rail 13 and its respective hanger downwards such that the top hanger is lowered to be accessed by a user . a first embodiment of the lowering arrangement , as illustrated in fig2 and 4 , is arranged such that the rail 13 lowers with the hanger . an inner end 33 of the rail 13 is mounted within the vertical post 311 and a second vertical support post 312 is mounted in front of the vertical post 311 arranged to provide horizontal support for the rail 13 . the rail 13 slides along the posts and is raised and lowered manually or electrically using a winch 313 . a second embodiment of the lowering arrangement , as illustrated in fig5 comprises a mount beam 37 which has a guide wheel 39 for riding on the rail 13 . in this arrangement , the rail 13 remains at a constant height and the movement of the hanger is effected by a linkage between the rail and the hanger . the arrangement has a linkage 41 which is moveable upwards and downwards . the linkage is a four bar linkage which is retracted by a cylinder and piston , not shown , which controls the movement of the linkage as well as providing assistance in raising and lowering . the linkage described above is described in u . s . pat . no . 6 , 302 , 278 ( dueck ), the disclosure of which is incorporated herein by reference . at the bottom of the linkage 41 is provided a hook 411 to which is attached a hanging frame 412 with the same holsters and cradles as previously described for supporting the bicycle or bicycles . each cradle is connected by a latching mechanism 43 which prohibits movement of a cradle if another cradle is pulled out . this specifically is important for safety reasons such that the cradles in the upper rows can only be pulled out one at a time which provides balance to the first section . the weight of the bicycles is not overly heavy but with larger built sections , holding a large number of bicycles , the weight of more than one cradle at a time may cause the section to tilt forwards . as illustrated in fig1 there are two sections 3 and 5 which are arranged face to face that is so that each co - operates with a central display position 4 between the two sections 3 and 5 which is dimensioned so that it can receive for display the bicycles from one row of one of the sections . thus the area 4 between the sections is dimensioned so as to just receive the length of the bicycle together with additional space in front and rear of the bicycle to allow a sales person to show the features of the bicycle while the customer can also view the bicycle . a bicycle can therefore be displayed from any one of the three rows of each of the two sections . the bottom row displays the bicycles at floor level while the top two rows display the bicycle at a raised elevation approximately equal to the height of the second row . in addition , the sections can perform a part of a further display system which utilizes the space above the sections to store yet further bicycles . thus the top of the sections 3 and 5 supports a frame structure generally indicated at 50 defining a pair of parallel raised main rails 51 supported above a floor section 52 . the main beams are carried on braces 53 . the structure of the frame is shown only schematically since the frame structure will be apparent to one skilled in the art . the pair of main rails 51 are spaced across the width of the sections 3 and 5 so as to provide two guide rails each for receiving a respective end of a transverse support beam 53 which extends across the structure and includes a winch 54 for raising and lowering cables 55 . the cables are spaced apart across the width of the structure and carry a suspended frame 56 which has a plurality of attachment holders by which a series of bicycles are attached to the frame 56 . the frame 56 can thus be raised and lowered on the cables 55 by operation of the electric winch 54 . as shown there are five support beams 53 and co - operating frames 56 and these can be moved along the beams 51 so that each in turn can be moved to a position above the display area 4 . while the frame 56 are in the retracted or raised position , the support beam and the associated frame can be moved to a position adjacent one end of the rails 51 into a storage area above the floor structure 52 . the beams 53 are movable along the rails 51 on suitable guides ( not shown ) and are moved by motors provided on the beams 53 which drive the beams to the required position either in the storage location or above the display area 4 . the frames of the sections thus provide posts 7 which support the superstructure for the additional above floor storage and additional posts 71 can be provided at the front of the sections together with braces 72 which render the structure more stable . the frames 56 are rectangular horizontal elements . the details of the mounting arrangement of the bicycles on the frames 56 by which the saddle attaches to a rear support and the handle bars attach to a front support are well known to one skilled in the art and therefore do not need to be shown . while one embodiment of the present invention has been described in the foregoing , it is to be understood that other embodiments are possible within the scope of the invention . the invention is to be considered limited solely by the scope of the appended claims .

US-5805902-A

a blood flow measuring apparatus includes : a module which is configured to emit radiation to an object to be measured and receive reflection of the radiation , to detect movement of the object to be measured based on a doppler effect ; a reflective holding member which internally hold the module with a gap from an abutment surface that is to be butted against a skin , and which includes a reflective member covering the module and configured to reflect the radiation ; and a process circuit which is configured to receive an output from the module , and which is configured to perform at least a process related to a blood flow speed .

fig1 a and 1b show the configuration of a blood flow measurement probe 2 in an embodiment of the presently disclosed subject matter . fig1 a is a plan view , and fig1 b is a side sectional view . a reflective holding member 4 which is made of a plastic material , and which has a truncated pyramidal shape has a hollowed interior . the lower surface of the reflective holding member 4 is opened . the lower portion of the reflective holding member 4 functions as a skin abutment surface 4 a . the inner surface of the reflective holding member 4 is plated with aluminum 6 . a microwave doppler sensor 8 is fixed to the inner side of the upper plate of the reflective holding member 4 . power input and signal output from the microwave doppler sensor 8 are performed through a line 10 . fig2 is a block diagram of the whole blood flow measuring apparatus using the blood flow measurement probe 2 of fig1 a and 1b . a transmission section 8 a of the microwave doppler sensor 8 a causes a microwave ( electromagnetic wave of , for example , 4 . 2 ghz ) to be radiated from an antenna 8 b . the microwave reaches the blood vessel to be measured , through the skin of the subject , and reflects from the object to be measured ( blood flow ). the reflection is received by a reception section 8 c via the antenna 8 b . a control section 8 d controls the reception section 8 c , and detects the phase difference between the transmitted and received waves , thereby calculating and outputting the speed of the object ( blood flow ). the output speed signal is sent to a process circuit 12 via the line 10 . the process circuit 12 performs a graph displaying process and pulsation detection based on the received speed signal . fig3 shows a state in the case where the blood flow measurement probe 2 is butted against the human body and the blood flow is measured . as shown in the figure , the antenna 8 b is disposed on the lower surface of the microwave doppler sensor 8 . the abutment surface 4 a of the reflective holding member 4 is butted against the measurement portion of the human body 20 . preferably , the measurement portion is a portion ( the abdominal aorta ) of the descending aorta or the like which does not overlap with the heart , because a large amount of blood flows in the heart and the measurement is hardly performed , and further because a change in the blood flow speed does not remarkably appear in a blood vessel which is largely separated from the heart . in the embodiment , since the inner surface of the reflective holding member 4 is plated with the aluminum 6 , there is no possibility of receiving a reflected wave ( noises ) from a moving object other than the blood flow which is the object to be measured . this is because , since the microwave is reflected by the aluminum 6 , the microwave is not radiated to a direction other than the desired direction ( the direction toward the human body ), and a microwave from a direction other than the desired direction is not received . even when the palm is moved in the periphery of the probe during the measurement , for example , noises due to this are not received ( even when such noises are received , the level is very low ). furthermore , the measurement is performed in a non - contact manner with respect to the blood flow , and therefore it is not affected by the contact impedance and polarization . according to an aspect of the presently disclosed subject matter , an influence of disturbance is eliminated , and the blood flow can be measured more correctly . fig4 a and 4b show the configuration of a blood flow measurement probe 22 in a second embodiment . fig4 a is a plan view , and fig4 b is a side sectional view . the portions corresponding to those of the blood flow measurement probe 2 of fig1 a and 1b are denoted by the same reference numerals . the embodiment is configured in a similar manner as the first embodiment , but largely different in that the shape of the inner surface which is plated with the aluminum 6 constitutes a part of an ellipsoidal body . the microwave doppler sensor 8 is held to the reflective holding member 4 by a rod - like stay 9 . the microwave doppler sensor 8 is held so that the antenna 8 b is located at one focal point f 1 of the ellipsoidal body formed by the shape of the inner surface . on the other hand , the shape of the ellipsoidal body is designed so that the other focal point f 2 of the ellipsoidal body is located at the position of the descending aorta 24 which is the object to be measured . according to the configuration , external noises are prevented from entering , and moreover the microwave emitted in any direction reaches the descending aorta which is the object to be measured , as indicated by α , β , and γ in fig4 b . similarly , all reflected waves which are reflected from the descending aorta in a predetermined angular range are received by the antenna 8 b of the microwave doppler sensor 8 . therefore , the measurement accuracy can be enhanced . according to as aspect of the presently disclosed subject matter , the sensitivity can be further enhanced . ( 1 ) in the above - described embodiments , the inner surface of the plastic member is plated with the aluminum 6 . the inner surface may be plated with any material other than aluminum as far as the material reflects a microwave . alternatively , vapor deposition or pasting may be performed in place of plating . these materials may be disposed on the outer surface or intermediate portion of the reflective holding member 4 . alternatively , the reflective holding member 4 itself may be configured by a material which reflects a microwave , such as aluminum . ( 2 ) in the embodiments , the measurement is performed while radiating a microwave . alternatively , an electromagnetic wave of another frequency , an ultrasonic wave , or light may be radiated . in the alternative , a reflective material which is adapted to the kind of radiation is preferably used . ( 3 ) in the embodiments , it is assumed that the distance from the human body to the microwave doppler sensor 8 is predetermined . alternatively , the position of the focal point may be changeable depending on the object to be measured . as shown in fig5 , for example , a second reflective holding member 42 which can be vertically slidably adjusted with respect to a first reflective holding member 40 may be disposed , and these members may configure the reflective holding member . when the second reflective holding member 42 is vertically adjusted , the focal point can be moved so as to be adapted to the object to be measured . alternatively , the diameter may be changed in place of the length . according to an aspect of the presently disclosed subject matter , the focal point can be changed in accordance with the object to be measured , and a more sensitive measurement can be performed . ( 4 ) as shown in fig6 , parts 5 a , 5 b , 5 c of a plurality of ellipsoidal bodies which share the one focal point f 1 may be combined with one another to configure the reflective holding member 4 . according to the configuration , objects to be measured which are located respectively at three positions f 21 , f 22 , f 23 can be measured . according to an aspect of the presently disclosed subject matter , a measurement can be performed with a high sensitivity on all of objects to be measured which are at different positions . ( 5 ) in the embodiments , the reflective holding member 4 is configured by dividing an ellipsoidal body in a substantially middle thereof in parallel to the minor axis . as shown in fig7 , alternatively , the reflective holding member 4 may be configured by dividing an ellipsoidal body by a plane which forms a certain angle with respect to the minor axis . according to the configuration , the directionality can be inclinedly provided , so that the measurement is enabled even in the case where a portion which reflects a microwave exists immediately above the object to be measured . the process circuit 12 receives the speed signal from the microwave doppler sensor 8 , and can perform various processes . hereinafter , some examples of the processes will be shown . according to the blood flow measuring apparatus of the presently disclosed subject matter , it is possible to check the existence or non - existence of a blood flow , and to determine the necessity for cardiac massage , or the like . in this case , the process circuit 12 produces a graph showing the temporal transition of the blood flow speed , and displays it on a display device or the like . fig8 a and 8b show display examples . as compared to the case where there , as shown in fig8 a , are large changes ( pulsations ) in the blood flow speed and the blood is properly ejected from the heart , in the case where the flow speed is low and constant as shown in fig8 b , it is possible to determine that the blood is not ejected . therefore , the doctor can know that a treatment such as cardiac massage is necessary . this can be known also by monitoring an electrocardiogram . however , there is a case where , despite that the heart operates , the blood is not ejected ( because the heart improperly operates ). therefore , it is preferable to directly monitor the blood flow . moreover , it is possible also to measure the degree of excitation . in this case , the process circuit 12 calculates the pulsation intervals based on the temporal change of the blood flow speed . in the case of fig8 a , for example , intervals between adjacent peaks t 1 , t 2 , t 3 , . . . are pulsation intervals . the degree of excitation can be obtained from the degree of fluctuation of the pulsation intervals . specifically , when the following process is executed by a cpu of the process circuit 12 in accordance with a program , it is possible to obtain the degree of excitation . according to an aspect of the presently disclosed subject matter , the degree of excitation of the subject can be easily acquired . first , the cpu calculates the temporal change of the pulsation intervals and plots them ( see fig9 a ). the time intervals of the plot with respect to the abscissa is made corresponding to the actual one pulsation period . the temporal change of the pulsation intervals is a discrete value for each pulsation . as shown in fig9 a , therefore , they are connected to one another with a smooth curve by spline interpolation . as a result , the waveform of the pulsation interval variation can be obtained . next , the cpu performs resampling at time intervals ( for example , several tens of ms ) which is shorter than one pulsation , based on the produced waveform of the pulsation interval variation , thereby obtaining time - series data of the pulsation intervals . the time - series data are frequency analyzed , and values for respective frequency components are calculated . the value obtained by the frequency analysis is calculated for each unit time interval of the resampling . fig9 b shows the waveform of the thus obtained frequency analysis . the ordinate indicates the power spectral density ( the unit : msec 2 · hz ), and the abscissa indicates the frequency ( the unit : hz ). the wave having a peak which appears in a low frequency is called vlf , that having the next peak is called lf , and that having the further next peak is called hf . then , the cpu calculates the hf value in the following manner . first , the maximum value in the range of 0 . 15 hz to 0 . 4 hz ( alternatively , the range may be extended to 2 hz ) is found ( see p 1 in fig9 b ). as shown in fig9 c , then , the waveform in the 0 . 15 hz zone around the maximum value is extracted , and its area is calculated while the minimum value is set as the baseline . the area is divided by the frequency width ( 0 . 3 hz ) to calculate the average value . the average value is the value of the pulsation interval hf . the cpu calculates and records a 5 - second average value of the values of the pulsation interval hf which are calculated for respective unit time intervals of the resampling . the cpu calculates also the value of the pulsation interval lf in a similar manner as described above . the cpu calculates pulsation interval lf / pulsation interval hf , whereby the degree of excitation can be obtained . when the thus calculated degree of excitation is given as information to a game machine or the like , for example , it is possible to realize a game machine or the like in which the story line is changed depending on the degree of excitation . according to the presently disclosed subject matter , an advantage is provided that , without requiring adhesion of electrodes or the like , the blood flow speed can be measured simply by butting the blood flow measurement probe against the human body . moreover , the presently disclosed subject matter can be applied to a sleep preventing system for a driver of a vehicle or the like by using a phenomenon that hf is lowered during sleep . when the measurement is performed while the depth of the other focal point is gradually change ( for example , by using the blood flow measurement probe 22 having a structure such as shown in fig5 ), furthermore , a stereoscopic image of the blood flow can be reconstructed . an experiment was conducted in order to show that the blood flow speed can be measured by using the microwave doppler sensor 8 . a cannula in which one end was inserted into the hip artery of an anesthetized rat was outward derived , and the other end was inserted into the cervical artery . therefore , a blood flow is produced in the cannula . a polyethylene tube having a strength at which physical deformation is not caused by the blood pressure was used in the cannula in order to prevent a physical change of the cannula itself from being measured . fig1 a shows a temporal change of the output of the microwave doppler sensor 8 in the case where the blood flow measurement probe 22 was approached toward the cannula . it is seen that the pulsation was able to be recognized and the blood flow speed was measured . fig1 b shows a temporal change of the output of the microwave doppler sensor 8 in the case where the cannula was removed away from the above - described configuration . an experiment on the influence of disturbance was conducted by using the blood flow measurement probe 22 shown in fig4 a and 4b ( a probe same as that of experiment 1 was used as the microwave doppler sensor 8 ). the reflective holding member 4 having a height of about 20 cm and a diameter of about 15 cm was used . the reflective holding member 4 which itself is formed by a metal was used . the object to be measured was the descending aorta , and a measurement was performed while the blood flow measurement probe 22 was butted against an abdominal portion . fig1 a and 11b show measurement results , and fig1 c shows a measurement result in the case where the microwave doppler sensor 8 was not covered by the reflective holding member 4 so as to be exposed to the exterior . in the measurements of fig1 b and 11c , a person other than the subject moved the hand in front of the blood flow measurement probe 22 ( i . e ., in rear of the subject ) during a period from timing t 10 to the end of the graph . as apparent from comparison of the graphs , it is clear that the case where the sensor is covered by the reflective holding member 4 is more insusceptible to large disturbance in which the hand is moved . moreover , it is obvious that the measurement was not affected by disturbance also in the state where distinct disturbance in which the hand was moved was not produced ( see the region ε ). in the measurement of fig1 a , a person other than the subject moved the hand in rear of the blood flow measurement probe 22 ( in front of the subject ) during the period from timing t 10 to the end of the graph . also in this case , an influence of disturbance was not caused because the sensor was covered by the reflective holding member 4 .

US-201313778830-A

a method of playing a casino table wagering game with at least two players comprises wagering on an underlying game where players may receive a bonus for obtaining a player hand of at least a predetermined rank ; placing a side bet that at least one player of the at least two players will obtain a player hand of at least a predetermined rank ; playing a hand of the casino table wagering game to conclusion ; determining if at least one of the at least two players has obtained a player hand of said at least a predetermined rank ; if a player has not obtained a player hand of at least a predetermined rank , but that player has placed the side bet that at least one player of the at least two players will obtain a player hand of at least a predetermined rank , and if another player has obtained a player hand of at least a predetermined rank , awarding that player a predetermined proportional share of the bonus for obtaining a player hand of at least a predetermined rank .

referring to fig1 , the apparatus for the wagering game of the present invention includes a typical casino gambling or gaming table 10 . the table 10 has a curved side 12 for accommodating up to seven players and a straight side 14 for accommodating the dealer . the table 10 has a flat surface 16 covered with felt or other appropriate material . although seven playing positions or locations 18 a - g for individual players are provided , it is not essential to the game that exactly seven persons play and as many as sixteen players may participate . for casino play , a maximum of seven players provides for a game that is easily manageable by the dealer and house , and one in which the individual players feel more involved . a house dealer position 20 , including an area suitable for displaying the dealer &# 39 ; s cards 21 , is provided . each of the playing positions 18 a - g includes a wagering zone 22 , comprising four separate and distinct wagering or betting areas 22 a , b , c , d . a separate wagering area 22 e may be provided for placing of a bonus or jackpot ( e . g ., progressive jackpot ) wager . each position 18 a - g also includes a card area 19 a - g for receiving and displaying cards dealt to the player occupying the position . the wagering areas 22 a , b , c , d are designed to receive appropriate wagering indicators or settling means such as chips ( not shown ). at one side of the dealer station 20 , the apparatus for practicing the method of the present invention may include a microprocessor or computer controlled shuffling machine 32 supported by a table extension 34 . the shuffling machine 32 may be of the type disclosed in u . s . pat . no . 4 , 807 , 884 or any other single deck or multideck shuffling apparatus manufactured by shuffle master gaming , inc ., the disclosure of which patent is incorporated herein by reference . the shuffling machine 32 may include a dealing module for automatically and sequentially dealing cards and also may include a display means for displaying wager amounts , the identity of winning players , or other game related information . referring to the flow diagram of fig2 , the initial step in playing the game of the present invention is preparing or shuffling a deck of cards , represented at block 40 , by activating the shuffling machine 32 or by hand - shuffling a deck to provide a shuffled deck . next , the players place the initial wager , block 42 , by putting equal amounts in each of the four betting areas 22 a , b , c , d . two of the parts of this initial wager , the parts placed in wagering area 22 a and 22 b are retrievable at the option of the player . the third portion placed in area 22 c is a wager that is forfeited if the second wager at 22 b is withdrawn . the fourth part 22 d of the four part wager is a nonwithdrawable bet . after the placing of the wager by each player , the cards are dealt , block 44 , preferably three cards being dealt down to each player and preferably two cards are dealt down in front of the dealer . the players inspect or “ sweat ” their cards in preparation for reaching decision block 46 . at decision block 46 , the players are queried by the dealer about whether the first part of the initial wager , the part placed in wagering area 22 a , should be left or whether the player wishes to withdraw that portion of the bet . each player makes the decision at decision block 46 on the basis of the three cards forming the player &# 39 ; s incomplete hand at this point . once each player has been queried and has decided whether or not to let the first portion of the bet ride , and those bets the player chooses to retrieve or remove are physically removed from area 22 a and returned to the player , the dealer shows one of the down common cards , block 48 . now , each player has four cards to consider , the three cards dealt to that player originally and the single common card showing on the table . each player must then decide whether to let the second part of the initial wager ride or whether to withdraw it from the game . as noted , if the second part of the wager is withdrawn , the third part of the wager is forfeit and is collected by the house . after each player is queried and decides what to do with regard to the second part of the bet , and those bets to be withdrawn are physically removed from area 22 b ( and 22 c if the third part is forfeit ) and returned to the player , the dealer reveals the second common down card , as represented at block 52 . each player now has a five card hand comprised of the three cards each player was originally dealt plus the two revealed common cards . the third bet , the bet placed at wagering area 22 d , is a nonretrievable portion of the initial bet and the flow of the game proceeds to block 54 wherein the players show or reveal their three cards to the dealer . the dealer resolves each player &# 39 ; s bet ( which includes all three parts , the second and third part or only the third part , depending on the player &# 39 ; s choices during play of the hand ) based on the five card hand at block 56 and determines what payout , if any , the player is entitled to receive according to the payout schedule at the particular gaming table or casino . bets on non - winning hands are collected by the dealer or house . the hand is then over and the flow of the game returns to block 40 , preparing and shuffling the deck for a new hand . the award or payoff is given for each of the optional bets that were allowed to ride to the end of the hand and for the non - withdrawable part of the bet . a typical pay table would be as follows : pair , sixes or better 1 - 1 ( even money ) two pairs 2 - 1 three of a kind 3 - 1 straight 5 - 1 flush 8 - 1 full house 11 - 1 four of a kind 50 - 1 straight flush 200 - 1 royal flush 1 , 000 - 1 the method of the present invention is not limited to five card poker games , but may be applied or used in other appropriate games such as seven card poker , as described elsewhere herein . the method of the present invention does not require a shuffling machine 32 , dealing module 33 or a display means 36 . however , these facilitate and expedite the play of the game as well as add interest to the game . while the initial wager of the present invention is preferably comprised of four equal bets , the bets do not necessarily have to be equal . the second and third parts should be equal , or the third part may be smaller than or greater than the second part . similarly , the first , second , third and fourth parts may be of different values , but the fourth bet must be at least equal to a table minimum and may be required to be at least equal to or greater than any other wager part . while equal bets are highly preferred for casino play , unequal bets may be used in home play , if desired . the wagering game of the present invention might be played live in casinos with a dealer , or in casinos or homes in interactive electronic or video form with automatic coin or betting means receptacles and payout capability , wherein appropriate symbols for cards , wagers or score keeping would be displayed electronically . a “ board - type game ” suitable for home , club or casino use may also be provided for practicing the method of the present invention . in combination with or separate from the play of dakota stud ™ casino table poker , a new wagering structure resulting in different bonus structures may be used . the pure wagering structure described above , where the third part of the wager is tied to the election made by the player on the separate part of the wager is itself novel . the use of that wagering structure in combination with certain pseudo - pooling payout outcomes at the table is a further advance in the structure of wagering and play at casino table card games . an example of the additional wagering structure and alternative payout structures include the use of excess retention by the house because of the unique wagering structure described above in the four - part wager ( e . g ., retaining a pair of 10 &# 39 ; s or other rank higher than 6 &# 39 ; s , 7 &# 39 ; s , 8 &# 39 ; s , or 9 &# 39 ; s as the winning hand ) or by providing the option of a side bet to enter the additional award structure described below . once the player is entered into the additional award structure ( either automatically or with the optional or required side bet ), the payout can be altered as follows . those players that are entered into play of the additional award structure can participate in winning awards at the table , even where the awards occur in different hands , that is , hands of other players . in present table gaming with bonuses or jackpots with side wagers , only the player receiving the hand is paid on the achievement of the bonus hand of at least a predetermined rank . in some poker clubs , certain events are paid both to players at the table and to the winning player from a pool when certain unusual events occur . for example , house rake may be partially deposited in a pool account where when the event occurs , the pool is paid to the table where it occurs and the money in the pool is distributed proportionally . such a situation would occur where , for example , the winning event in a pool was where a losing hand at a card table was at least a full house with at least three aces and two 10 &# 39 ; s as the losing hand . the pool is distributed among the players and the sometimes the dealer at the table as , for example ( 70 % to the winning hand , 10 % to the losing hand and 20 % to the remaining players at the table ; or 70 % to the winning hand , 15 % to the second place hand , 20 % to the remaining players at the table , and 5 % to the dealer ). the pool is a form of progressive jackpot which is incremented according to discretionary rules of the poker club or casino . all players at the table partake of the pool winnings if they anted in the play of the hand where the winning event occurred . no distinct side wager or particular wagering element is required to enter into the chance to win the pool , which occurs with only a single specific event occurring , as described . in the practice of the present invention , accruing take from the third wager ( automatically entering the player in the bonus event during the game ) or preferably requiring a separate side wager to enter the bonus payout event is used to enable a player to enter the bonus event . the player is either required to place a side bet or has the option of placing a side bet to enter the bonus event . the bonus event is played against a pay table , whereby whenever any player at the table achieves a hand of predetermined rank , all players that are entered into the bonus event ( either automatically or by placing the side bet ) partakes of the bonus award for the predetermined hand . the rules may vary , so that a ) only players that made the side bet wager can participate in the bonus , b ) only players that made the side bet wager and remain in the game at the end of the hand can participate in the bonus , c ) only players that made the side bet wager and have a qualifying hand can participate in the bonus , or d ) only players that made the side bet wager and have a hand that beats the dealer &# 39 ; s hand can participate in the bonus . the preferred method of play is a ). the play of this bonus event with side bet can even be extended to include multiple tables . for example , certain progressive jackpot games link tables for the jackpot or bonus awards taken out of the jackpot pool . the tables can be linked by having players who had made the side bet wager at a distal table in the last hand before the bonus event was won at a proximal table . this is not a preferred embodiment ( because of potential complexities in synchronization of play or debating when hands were played relative to distal side bets ), but is within the skill of play and design . additionally , the bonus may be paid either when any hand at the table achieves the predetermined hand rank , or only when a player that has made a side bet achieves a hand of the predetermined rank . the second format is preferred to stimulate more persons at the table to make the wager . an aspect of this pay structure is to increase the frequency of bonus events at a table . with more players at a table , there are more hands per game at the table , and the hit frequency of bonus hands increases . even though the actual size of individual awards per player decreases , the increased frequency improves the overall ambiance of the game . for example , if there are six players at a table , the frequency of bonus hands statistically increases to six times what the frequency was with a single player at the table . the payouts for each player will necessarily vary according to the number of players that are in the game and / or have made the side bonus bet . the house may require a minimum number of players to engage play of this side bet bonus event , primarily to limit the number of pay tables that must be displayed it is also possible to have a display device ( e . g ., screen , monitor led , liquid crystal display , plasma screen , etc .) that is fed by data from a computer or microprocessor or other image source to show the applicable pay table for the number of players involved in the payout for the hands . for example , the display may show separate screen for 2 player , 3 player , 4 player , 5 player , 6 player and 7 player bonus events , each screen having different odds and payouts . automated equipment indicating the number of wagers placed , the number of players entered , the rank of the hand , and other factors can be provided . for example , camera , scanners , digital readers , and software interpreting the data such as that provided in u . s . pat . nos . 6 , 313 , 871 ; 6 , 460 , 848 ; 6 , 126 , 166 ; 5 , 941 , 769 ; and the like could be used to assist in automating the reading of cards , ranks , wagers , and the number of players . it is also possible for players to elect to play a “ double bonus .” in this format , rather than a typical one dollar side bet being placed , two separate one dollar wagers or a single two dollar wager may be placed to enter the player in both an individual bonus payout event and the shared bonus event discussed above . except where the bonus was a progressive bonus , this system could be highly attractive to players . the rules must be clear in the event that a progressive jackpot is used , so that it would be understood that a 100 % jackpot win by a player with both side bets placed would win 50 % of the total jackpot for him / herself , and the remaining 50 % would be split among players in the bonus event , including the winning player . with a fixed bonus pay table , one of five players at a table with both side bets having been placed ( the individual bonus and the shared bonus or group bonus wager ) would receive a payment of the fixed amount for obtaining a predetermined rank hand and ⅕ th of the award for the group award on the ranked hand . for example , if the ranked hand were a straight flush with a $ 2 , 000 fixed award , the player with that hand would win $ 2 , 400 -$ 2 , 000 for the individual bonus side bet and ⅕ th of $ 2 , 000 ($ 400 ) for the group bonus wager . the side bets may be made on sensing systems or by placing tokens , chips or money on the table that remain on the table at appropriate locations until conclusion of the game . typical sensing devices include coin drops , photooptical sensors , proximity detectors , cameras , scales , and the like . the format of this game is particularly compatible with any poker - type games where bonus awards are provided from a pay table , such as let it ride ® stud poker , three card ™ poker , four card poker , 3 - 5 - 7 ™ poker table game , and the like . it is also useful in games where progressive jackpots are used , alone or in combination with pay tables , such as with certain formats of caribbean stud ™ poker . the wager could also be used in games where there are special bonuses given to players who obtain unique hands . for example , in pai gow poker , there may be special awards for perfect pai gow hands ( e . g ., 9 , 8 , 7 , 5 , 4 , 3 and 2 ) or uniquely ranked hands ( e . g ., a front pair of aces and at least four - of - a - kind on the rear hand ). the payouts could be made to all players participating in the wager ( e . g ., on a proportional basis ), rather than just to the player who obtains the hand . the bonus wager could also be doubled so that a player could receive both the individual award and the group award for the hand . the present invention may be embodied in other specific forms without departing from the essential attributes thereof . it is desired that the embodiments described above may be considered in all respects as illustrative , not restrictive , reference being made to the appended claims to indicate the scope of the invention .

US-19655005-A

a closure for bottles having twist - type closure provision . the closure includes an inner member with a disk - like portion and a depending peripheral lip having an interior adapted to match the particular closure provision of the bottle . a neck projecting from the disk portion terminates in a closed flange having a slightly greater diameter than the neck . an outer member , rotatable with respect to the inner member , has a disk - like portion and a depending peripheral lip equally spaced from that of the inner member and has a central opening of a diameter intermediate that of the neck and the flange to permit snapping the flange through the opening to assemble the closure . a spring between the disk portions of the members normally maintain these portions separated but allows movement toward each other when pressure is applied to the outer member . cooperating opening tabs between the members , when aligned and engaged by pressure upon the outer member , permit the outer member and the inner member to be turned counterclockwise in unison to effect removal of the closure from the bottle . arrow indicia on the top surfaces of the flange and the outer member indicate the proper alignment of the opening tabs . cooperating closure tabs carried by the members effect the clockwise turning of the components is unison to tighten the closure . optionally , numerals are equally spaced about the opening in the outer member to provide information as to the time of the next dosage of a medicine , for example .

this invention relates generally to closures for bottles and similar objects having an opening provided with external threads or other twist type provision , and more particularly to closures for medicine bottles and the like for indicating the time for the next dosage , the closure being child - proof . considerable background for this invention is set forth in my u . s . pat . no . 4 , 501 , 370 , issued on feb . 26 , 1985 . briefly , it is a common problem with many persons , especially the elderly , to forget the time to take the next dosage of a medicine . the prescription may indicate &# 34 ; every four hours &# 34 ;, but often the time of the last dosage cannot be remembered . thus , it is desirable to indicate the next dosage time when a dose is taken . while there are devices for this indication , most are difficult to manufacture . yet another problem with many closures for medicine bottles is the difficulty of opening them when the design is such as to make the bottle &# 34 ; child - proof &# 34 ;. in fact , many of such closures are also referred to as being &# 34 ; adult - proof .&# 34 ; the closure of my above - identified patent was an improvement upon what was available . it has certain disadvantages , however , including the necessity of squeezing the closure to remove the same from a bottle ( the child - proof feature ) or to replace the closure . some persons afflicted with arthritis have difficulty in this operation because of the soreness in the fingers or wrists , for example . accordingly , it is a primary object of the present invention to provide a bottle closure that can be used for medicine bottles which provides a &# 34 ; child - proof &# 34 ; feature that does not require a squeezing action for either opening or closing the bottle . it is another object of the present invention to couple the improved child proof construction with an indicator for giving information as to the time of the next dosage . other objects and advantages of the present invention will become apparent upon a consideration of the drawings and the detailed description that follows . in accordance with the present invention , there is provided a two - piece closure for medicine bottles and the like having a top or neck provided with external threads or other twist - type surface . an inner member is provided with internal threads or other surface to mate with that of the bottle for sealing the bottle . the second piece or outer member , which generally surrounds the inner member , has a central aperture to receive an upstanding dial - like portion of the inner member , with a snap fit between the pieces at this aperture . spring - like lift tabs are positioned between top flat surfaces of both the inner member and the outer member to urge them apart but to yield under pressure applied to the top of the outer member . both the top surface of the dial - like portion of the inner member and the top surface of the outer member carry arrows or like signs that , when aligned , permit the closure to be removed if downward pressure is applied to the outer member . this is achieved through the use of a tab carried by one of the members that is inserted between two tabs in the other member when this pressure is applied . thus , both of the members can be turned in unison counter - clockwise to remove the closure . a second set of tabs are provided upon the members that are engaged whenever the closure is turned in a clockwise direction , thus assuring tightening of the closure upon the bottle . in one embodiment , the top surface of the outer member also carries numbers ( which may be raised ) indicating the hours so that a specific time of day can be selected for the next dosage . fig1 is a cross - sectional view of one embodiment of the present invention taken at 1 -- 1 of fig2 and 5 when the components shown in those figures are combined . fig2 is a top view of the inner member of the embodiment of fig1 showing the indicator arrow , the lift tabs and the opening and closing tabs carried by that portion of the present invention . fig3 is a side view , taken from the rear side , of the inner member of fig2 showing an elevation of the opening tabs carried by that inner member . fig4 is a side view , taken from the front side , of the inner member of fig2 showing an elevation of the closing tab carried by that inner member . fig5 is a top view of the outer member of the embodiment of fig1 showing the indicator arrow , the time numerals , and the opening tab and the closing tab carried by that portion of the present invention . fig6 is a side view , taken from the rear side , of the outer member of fig5 showing the elevation of the opening tab carried thereby . fig7 is a side view taken from the front side of the outer member of fig5 showing the elevation of the closing tab carried by that outer member . fig8 is a schematic drawing illustrating the operation of the opening tabs of the present invention . fig9 is a schematic drawing illustrating the operation of the closing tabs of the present invention . fig1 is a cross - sectional view of another embodiment of the present invention as taken at 10 -- 10 of fig1 and 12 when the components of those figures are assembled together . fig1 is a top view of a modified inner member of the present invention showing the opening tabs positioned upon the top surface of that member . fig1 is a top view of a modified outer member of the present invention showing the position of the opening tab thereon . referring now to fig1 shown therein at 14 is one embodiment of the present invention . it is fabricated of two components : an inner member 16 and an outer member 18 . the inner member 16 is generally cupped shaped , with a flat top or disk portion 20 and a depending lip 22 . the interior surface of the lip 22 is provided with threads 24 to mate with threads on a bottle ( not shown ) that is to be closed . it will be understood that if the bottle has another type of twist type closure provision , the interior surface of the lip 22 will have a corresponding configuration . a neck portion 26 is upstanding from the disk portion 20 , and terminates in a closed flange - like portion 28 that has a diameter slightly greater than that of the neck 26 . this flange 28 optionally carries a raised arrow 30 ( see fig2 ). the exterior surface of the lip 22 carries opening tabs 32 and a closing tab 34 that are more clearly seen in fig2 . the outer member 18 is also generally cupped shaped , with a flat disk - like upper portion 36 and a depending lip 38 . the interior of the outer member 18 is dimensioned to encompass the exterior of the inner member 16 , and the upper portion 36 is provided with a central aperture 40 to closely embrace the neck 26 of the inner member 16 . the interior 42 of the lip portion 38 is provided , near the upper portion , with an opening tab 44 ; and , near the lower edge , with a closing tab 46 . these are illustrated more clearly in fig5 . interposed between the flat surfaces of the inner member 16 and the outer member 18 , as shown , are a pair of spring - like members or lift tabs 48 , 50 , that urge these surfaces apart but allow them to be pressed toward each other . a top view of the inner member 16 is shown in fig2 . this view illustrates the arrow 30 on the flange 28 as well as the opening tabs 32a , 32b , and the closing tab 34 . it can be seen , for example , that the closing tab 34 is cantilevered from the outer surface of the lip 22 in a direction whereby a cooperating tab on the outer member engages the same so as to cause tightening the closure upon a bottle . this tab 34 , however , has sufficient flexibility such that the cooperating tab on the outer member can pass by when the outer member is turned in a counter - closkwise direction . furthermore , the lift tabs 48 , 50 are shown as being attached at one end each to the flat disk portion 20 . these lift tabs 48 , 50 are essentially cantilevered spring units . the opening tabs 32 associated with the inner member 16 are more clearly illustrated in fig3 . as also shown in fig2 there are two portions 32a and 32b . portion 32a has a raised portion 52 of uniform height with a flat face 54 and an angled face 56 . ( the purpose of these faces , and those of tab 32b will be described in connection with fig8 ). tab portion 32b has a central portion 58 of uniform height and angled faces 60 , 62 . by referring to both fig2 and 3 , it can be seen that all of the angled faces of both the opening tab units 32a and 32b slope in two directions in this embodiment . fig4 is another side view of the inner member 16 . more clearly seen therein is the cantilevered closing tab 34 located at substantially the lower edge of the lip 22 . also , shown therein more clearly is the length of the neck 26 between the disk portion 20 of the inner member 16 and the flange 28 . this length of the neck is selected to accommodate the thickness of the disk portion of the outer member 18 plus the movement necessary to engage the various components of the opening tabs . typically the distance of this movement is about 1 / 16 inch . the top surface 36 of the outer member 18 is shown in fig5 . the central aperture 40 can be seen ; this aperture accepts the neck of the inner member 16 as shown in fig1 . also , the opening tab 44 and the closing tab 46 are indicated so as to show their relative positions to the cooperating tabs of the inner member 16 . this top is provided with an arrow 64 and , optionally , the word &# 34 ; open &# 34 ; within the arrow . around the periphery of the aperture 40 are twelve positions other than at the arrow ; these optionally can have numerals 64 to indicate the hours for dosage . the numerals can , optionally , be raised ( e . g ., embossed ) above the surface 36 . in order to give instructions to a user of the bottle , brief instructions 66 can be imprinted on the top ; these also optionally can be embossed on the surface . when the outer member is pushed down , as indicated by the instructions , counter - clockwise turning will open the bottle and clockwise turning will tighten the closure on the bottle . when no pressure is applied , counter - clockwise rotation will not effect any rotation of the inner member and clockwise rotation will tighten the closure . side or edge views of the outer member 18 are shown in fig6 and 7 . in fig6 the elevation of the opening tab 44 on the inside is shown , and in fig7 is shown the closing tab 46 . the external surface of the lip portion 38 can , optionally , be provided with ridges 68 to facilitate grasp during the turning of the outer member 18 . fig8 schematically illustrates the operation of the opening tabs of the present invention . when no pressure is applied to the top surface 36 of outer member 18 , the opening tab 44 attached thereto is in the position indicated by solid lines . it can be seen that if the outer member is turned in either direction , there is no interaction between the tab 44 and the opening tabs 32a and 32b on the inner member 16 . however , when pressure is applied , movement to positon 70 occurs whereby , in dashed lines , it can be seen that the tab 44 is placed between tab 32a and tab 32b with flat surfaces in contact . then when the outer member 18 is turned in the direction indicated by the arrow 72 , this direction being counter - clockwise , the inner member will also be turned and thus the bottle will be opened . however , if the outer member 18 is turned in the direction indicated by the arrow 74 , which is clockwise , the tab 44 will slip over tab 32b and the inner member 16 will not be turned . a schematic drawing of the closing tabs 34 and 46 is shown in fig9 . as in fig8 the solid lines indicate the positions when no pressusre is applied to the top 36 of outer member 18 . when pressure is applied , the tab 46 moves to the position indicated by the dashed lines 76 . rotation of the outer member 18 in the direction indicated by the arrow 78 ( clockwise ) brings the tab 46 on the outer member 18 into contact with the end of tab 34 on the inner member 16 . this is the position to cause tightening of the closure on the bottle . rotation in the opposite direction , as indicated by the arrow 80 , causes the tab 46 to move past the tab 34 by nature of the sloped surface 82 . these relative movements of the tabs 34 and 46 occur in either position of the outer member 18 ; up with no pressure , or down with pressure . the present invention can be fabricated with various changes that do not change the principles of operation . another embodiment that includes several of the types of changes that can be made is illustrated in the cross - sectional view of fig1 at 14 &# 39 ;. components that are identical with those of the prior embodiment carry the same number designations , and those that are changed utilize the same number with a prime . as in the prior embodiment , there is an inner member 16 &# 39 ; which has a neck portion 26 that penetrates and snaps in a central aperture 30 of an outer member 18 &# 39 ;. this inner member is provided with internal threads 24 to engage threads of a bottle upon which the present closure is to be used . the lip portion 22 &# 39 ; has been modified at a bottom edge to provide a radially extending flange 84 . the outer member 18 &# 39 ; has been similarly modified to provide an inwardly directed ridge 86 , with the flange 84 and the ridge 86 having complimentary curved configurations such that the outer member 18 &# 39 ; can be snapped over the inner member 16 &# 39 ; in a manner similar to that shown in fig3 of my above - referenced patent . a further change illustrated in this embodiment can be seen by referring to fig1 and 12 . it can be seen that the opening tabs 32a &# 39 ; and 32b &# 39 ; have been moved to the top surface of disk portion 20 &# 39 ; of the inner member 16 &# 39 ;. correspondingly , the tab 44 &# 39 ; is moved to the underside of the top 36 &# 39 ; of the outer member 18 &# 39 ; at the same radius . in these positions , the opening tabs still function in the same manner as illustrated in fig8 . a minor modification illustrated in these fig1 through 12 is the removal of the word &# 34 ; open &# 34 ; from the arrow 62 &# 39 ;, and the removal of numbers from the positions 64 &# 39 ;. as indicated , these are optional variations . this second embodiment shown in fig1 utilizes the same lifting tabs 48 , 60 as in the prior embodiment . it will be understood that these lifting tabs could be attached to the underside of the top 36 of outer member 18 &# 39 ; rather than to the inner member 16 &# 39 ;. the invention is not limited to this particular type of biasing means , however . for example , an annular wave - type spring encircling the neck 26 could be used to accomplish the biasing apart of the inner member 16 ( or 16 &# 39 ;) and the outer member 18 ( or 18 &# 39 ;). such a spring would also permit the movement of the outer member 18 toward the inner member 16 whereby the opening tab 44 ( or 44 &# 39 ;) will engage the tabs 32a and 32b ( or 32a &# 39 ; and 32b &# 39 ;). other variations would include the reversal of the tab components : tabs 32a and 32b on the outer member 18 , and tab 44 on the inner member . the closing tabs 34 and 46 can also be reversed in position on the two components as long as the correct direction of rotation is followed . although the operation of the present invention has been generally discussed hereinabove , the following will provide a more complete description . with regard to the embodiment of fig1 through 9 , the present invention is assembled by snapping the neck 26 of the inner member 16 through the aperture 40 in the outer member 18 . thereafter , the closure can be applied to a bottle by turning the outer member 18 in a clockwise direction . the tab 46 will bear against the end of the tab 34 causing the inner member 16 to be screwed upon the bottle threads until tight . the outer member 18 , with the pressure removed , can then be turned in a counter - clockwise direction by a user until one of the numerals 64 is aligned with the arrow 30 ; this giving , for example , the time for the next dosage of medicine . when a dosage is to be taken , the outer member is turned until the arrow 30 and the arrow 62 are aligned . with the arrows in this position , downward pressure upon the outer member 18 causes the opening tab 44 to be interlocked between tabs 32a and 32b . with continued pressure , the outer member is turned counter - clockwise and the closure is removed from the bottle . during this rotation , the closure tab 46 slips over the tab 34 . to close the bottle , the above - cited closure procedure is followed . during closure , if pressure is applied to the outer member 18 , the opening tab 44 will slip over the tabs 32a and 32b . while only two embodiments have been shown and described , it will be understood that there is no intent to limit the invention by such disclosure . rather , it is intended to cover all modifications and all constructions falling within the spirit and scope of the present invention as defined in the appended claims and their equivalents .

US-78454285-A

a micropower dc / dc conversion system providing a stabilized voltage output at a predetermined voltage higher than that of the energy source . the system is powered by one or more primary cells in parallel or by a suitable battery , and the system is of special use with systems requiring low power at stabilized voltage which is substantially independent of the energy source impedance and load variations . according to the preferred embodiment of the system the output voltage stabilization is controlled by voltage detection circuit based on c - mos inverters which allows extremely low power drain . the system is of special value for use with electronic implantable devices such as cardiac pacemakers .

as illustrated with reference to fig1 the components of the dc / dc converter system of the present invention , which provides a stabilized voltage output , comprise in combination a power source 4 , such as lithium primary cell , connected via pulse driver 5 and switching means 7 , inductor 8 , catch diode 10 , an output capacitor 11 being in parallel with voltage divider resistors 12 and 13 , and output voltage terminals 15 and 16 . further components of the system are the pulse generators means 1 and the pulse driver means 5 . the voltage conversion is effected by means of switching device 7 , the inductor 8 , the catch diode 10 and the output capacitor 11 and the energy source being the primary cell 4 . switching device 7 commutates inductor 8 first across energy source 4 for charge and after this in series with energy source 4 , catch diode 10 and capacitor 11 for discharge . the charge - discharge sequence of the inductor 8 results in an energy transfer from the power source 4 to the capacitor 11 . thus , the output voltage at 15 increases as long as such commutation continues . the main part of the loop is controlled by voltage detection circuit 9 and the and - gate 3 . the voltage regulation is achieved by application of a sample of output voltage 14 to the voltage detection circuit 9 , the output of which ( generally being a digital output ) is applied as signal 2 to and - gate 3 . a logic zero on the control signal 2 signifies that the voltage is of the predetermined voltage whereas a logic one means a drop of output voltage and thus a voltage value below the predetermined value . the and - gate 3 passes driving pulses from pulse generator 1 as long as the control signal 2 is in logic one , i . e . as long as the output voltage is lower than desired . the pulses activate the switching device 7 via pulse driver means 5 , resulting in a commutation of the inductor 8 for charge / discharge , resulting in an increase of the output voltage until the predetermined value is attained , changing the control signal 2 to logic zero , thus closing the regulation loop providing the desired voltage output at 15 - 16 . fig3 illustrates waveforms associated with the system . a typical pulse generator output waveform is shown as clock ( a ). a typical waveform of control signal of fig1 is shown as waveform ( b ). the resulting combined output waveform of the and - gate 3 is shown as waveform ( c ). the waveform at the inductor 8 , catch diode 10 and switching device 7 output junction is shown as waveform ( d ). the switching means 7 connects inductor 8 to the common potential of the energy source 4 during the switching pulse period ( 52 ), and at the end of this switching period , the energy accumulated in inductor 8 maintains the current and thus the voltage increases abruptly to ( 53 ) where conduction of catch diode 10 occurs . this is indicated by the positive deflections to ( 53 ) on the waveform ( d ), transferring the energy stored in inductor 8 to capacitor 11 , whereupon the voltage drops to ( 54 ), i . e . v in . a typical output waveform is shown as ( e ). the maximum ripple is generally within 2 % of the predetermined output voltage . according to one possible embodiment , shown in fig2 the switching device 33 is a bipolar transistor with base limited current , resistor 31 being used as current limiting device . a current source incorporated within the pulse driving device such as c - mos and gate 27 can be used to substitute resistor 31 . the bipolar transistor 32 in 33 can be replaced by a suitable mos - fet device as shown in fig2 c . the c - mos inverters 44 and 42 combine to act as a voltage detector for sensing the voltage from the divider 45 , 46 . inverter 41 acts to buffer the output signal of inverter 42 . resistor 43 provides regenerative feedback for the voltage detector to allow negative slope of the inverter 44 threshold versus output voltage 48 as shown on fig5 a . the resistor 43 supplies regeneration feedback only during the transition periods and therefore eliminating current drain all other time . in addition , the resistor 43 acts as a current limiter during transition periods thus , decreasing further the current consumption of the voltage detector circuit . the output of 41 is characterized by a sharp rectangular wave for controlling the and - gate 27 or monostable via line 29 shown in fig2 b . capacitor 47 is used as a high pass filter of the output variations to the comparator input . fig5 is a detailed description of the voltage detector circuit comprised of c - mos inverter devices such as 4007 drained by common resistor 43 . fig5 a in a graphical representation of the threshold behaviour versus v dd which is an output voltage of the system . a further embodiment of pulse generating circuitry is shown in fig2 a . a series of c - mos inverters 17 , and 21 are used for the oscillator circuitry . resistors 18 and 20 with capacitor 19 comprise the time constant circuit for the oscillator . a combination of the resistors 18 and 20 establishes the duty cycle and the desired pulse width . inverter 25 is used as a buffer between oscillator and driving gate 27 . fig2 b illustrates another pulse generator circuit . here the oscillator generates square waveform and triggers a monostable circuit for generating sharp narrow pulses required for the switching device . it is clear that the same oscillator can be used in common with other parts of the powered system and therefore its current consumption could be subtracted from that of the conversion system in efficiency calculations . fig4 is a graphical representation of the output voltage versus energy source voltage at three representative load values . this graph was obtained from a prototype converter circuit , loaded by a pacemaker with energy supplied by a lithium - iodine cell . the pulse generator rate was dependent on cell voltage . thus , decrease of 10 % in rate occurred at 2 v cell . the output voltage fall indicates current limiting properties of the prototype converter . according to a preferred embodiment there are used single primary cells having a voltage of more than 1 v and an internal impedance of less than about 100kω . suitable cells are primary cells of the lithium / iodine or lithium chlorine type . it is preferred that the pulse generator is an assymetrical multivibrator based on c - mos devices . yet a further pulse generator type is a c - mos monostable multivibrator driven by c - mos square wave multivibrator or by an external pulse generator providing pulses of predetermined duration and rate . the pulse generator is advantageously provided with means for adjusting the rate of pulses supplied as well as the pulse width so as to make possible telemetric measurements of the parameters of the energy source . the pulse driver is advantageously provided with means for controlling the length of pulse trains . it is preferred to use a bipolar npn or pnp high speed switching transistor or p - channel or n - channel high speed mos - fet device as switching means . the inductor used as energy transfer device is preferably wound on a soft ferrite core of toroid shape , or on a pot core , or use is made of an air coil , wherein the storage of energy is according to ## equ1 ## where the device is advantageously provided with a switching diode 39 of fig2 which serves as a catch diode and which passes the current in case of absence of oscillations or when another fault occurs in the conversion system . the diode 39 is advantageously one with low leakage , low voltage drop and of high speed . the system is optionally provided with a diode 50 of the conventional type which allows passage of current from the energy source to the load when output voltage becomes lower than input voltage . the capacitor 40 can be of the electrolytic or dielectric type , with a very low leakage current . the voltage divider preferably comprises linear resistors of high resistance , and preferably of a resistance in the range of 10 to 50 mω . it is clear that the above description is by way of illustration only and that various changes and modifications in the nature and arrangement of the components may be resorted to without departing from the scope and spirit of the use present invention .

US-37933882-A

the invention is a system and method in which a plurality of consumer products is organized into “ use ” groups , and these groups are conveyed to a consumer through color - coding and icons situated on an information layout . the information layout is provided on the product packaging , or proximally located near the actual products in a store or pictures of the products on an electronic display . in a particular embodiment , the products are footwear - related products , such as socks , insoles , shoes , and shoe - care products , and the “ use ” groups are “ comfort ”, “ performance ”, and “ outdoor ”.

referring now to the figures , the present invention uses product information and icons to classify goods and aid consumers in the purchase of one or more products based on the consumers &# 39 ; desired “ use ” of the products . fig1 illustrates an example of a product packaging label 1 for a “ comfort ” use group product , specifically , a shoe insole . a label such as this is readily affixed to the outside of the product packaging . the product packaging label 1 includes a circular icon 2 , product information 3 , and packaging graphics 4 . a packaging background 5 includes a specific color , depending on which “ use ” group the product belongs to , and packaging graphics 4 which illustrate some of the activities that individuals purchasing this product may use the product for . in this case , as illustrated on fig1 , the insole is a “ comfort ” product , and the packaging graphics 4 correspond to activities that may require comfortable shoe insoles , e . g . golf and running . the product packaging label 1 also contains reference to the “ fit system ” 6 of product classification of which this product is a part . as illustrated on fig1 , icon 2 is an example of the type of icon on a product packaging label 1 that makes up part of the fit system . in the case of the examples provided on fig1 through 3 , the icon 2 contains a graphic of a human foot 7 which partially overlays a solid circle 9 . the foot graphic 7 and solid circle 9 are in turn surrounded by two semi - circular graphics 10 and 11 , which contain backgrounds of solid - color and overlays of text . portions of the solid - color background and of the text together convey to a consumer which of the several use groups the product belongs to . for example , referring to fig1 , the icon 2 in this instance has a lower semi - circular graphic 10 containing the text “ comfort ” 12 and a solid - color background 13 . the solid color of the background 13 is of a color which appears only on labels , displays , or guides which refer to the “ comfort ” use group . still referring to fig1 , the icon 2 further has an upper semi - circular graphic 11 , which contains the text “ sof - sole ” 14 and a solid - color background 15 , of a color distinct from that of the lower semi - circular graphic 13 . alternatively , solid - color background 15 may be the same color as background color 13 of the upper semi - circular graphic 11 . fig2 shows an icon 2 for the comfort use group in more detail . in this alternate embodiment a numeral 35 , in this case “ 2 ”, acts as an additional indicator of the particular use group , in addition to the text 12 , and colors of the icon background 13 and packaging background 5 . to further enhance use group identification , the numeral 35 optionally has a solid - color filling 36 , the solid color being the same as the colors of the icon background 13 and packaging background 5 . the use of numbers as part of the fit system classification method of the present invention makes it even easier for consumers to identify and associate products based on use group and to purchase multiple goods in that group . it will be understood by those of skill in the art that the scope of the graphics contemplated for each use group icon in accordance with the present invention is not limited in any way by the icon 2 as illustrated for the use groups in fig1 - 6 . for example , icon 2 may be a triangular shaped graphic containing text , color , and additional graphics that represent the particular use group in question . according to another embodiment , icon 2 may contain only human foot graphic 7 and solid circle 9 . the graphics provided in fig1 and fig2 are therefore mere examples of that which may form a part of a “ comfort ” use group icon . according to one embodiment of the present invention , the packaging background 5 , as illustrated on fig1 , and 5 , includes color which may be the same as the color or colors used in the icon 2 associated with the use group for that product — exemplified in fig1 by the color of the background 13 in the lower semi circular graphic 10 . coordinating the packaging background 5 color with one or more of the colors used in the icon 2 ( shown on fig1 - 6 ) for a particular use group reinforces the association of that color with the particular use category for that product and enhances a consumer &# 39 ; s recognition of , and desire to purchase , multiple products within a particular use group . importantly , a different color is used for each use group icon 2 and each corresponding packaging background 5 such that consumers are able to distinguish between the use groups . for example , referring to fig1 , the “ comfort ” group may be distinguished by the color blue as part of the graphics that make up the “ comfort ” use group icon 2 and the packaging background 5 , while red may be used for the “ performance ” use group , and green may be used for the “ outdoor ” use group . it should be understood that the scope of the present invention is not limited to these particular colors or the use of color at all as part of the icon 2 graphics and packaging background 5 . fig3 illustrates a product packaging label 1 for a shoe insole which contains an icon 2 , product information 3 , packaging graphics 4 , and a packaging background 5 of a particular color . alternatively , the packaging background 5 can be white , or no color . icon 2 according to this example has a specific “ performance ” background color 13 , and the text “ performance ” 26 as part of a lower semi - circular graphic 10 . also present is the text “ sof sole ” 14 as part of an upper semi - circular graphic 11 . fig4 shows an alternate embodiment for the “ performance ” use group icon , including the numeral 37 identifying the use group , in this case the numeral “ 1 ”. as illustrated on fig5 , one example of product packaging label 1 for an “ outdoor ” use group shoe insole is similar to those shown on fig1 and 3 for other use groups . the text “ outdoor ” 32 as part of the lower semi - circular graphic 10 indicates the “ outdoor ” use group . fig6 shows an alternate embodiment of the icon for the “ outdoor ” use group icon , including the numeral 38 identifying the use group , in this case the numeral “ 3 ”. in addition to providing product information 3 on product packaging label 1 ( see fig1 ), the present invention includes one or more information guides provided on or near a point - of - sale display . one possible embodiment of such a guide and point - of - sale display is shown in fig7 as a rack 24 that holds and / or displays the consumer products . attached to the rack 24 are a main information guide 16 and other information panels 18 . the main information guide 16 optimally includes an icon 2 for each use group , and optionally includes product graphics 25 and other product information . for example , as illustrated on fig7 , a main information guide 16 providing an icon 2 for each use group , product graphics 25 of human feet with socks on them , with the “ sof sole ” logo 17 . information panels 18 provide additional information about the consumer products . such information can be product sizes , product qualities , prices , etc . it will be understood by those of skill in the art that a main information display 16 , information panels 18 , and other forms of information displays located at or near the products being offered for sale are not limited to the types or styles of information displays illustrated in fig7 and are not limited by the types of information listed herein . according to the example provided on fig7 , display rack 14 holds products that are spatially grouped by product type , namely socks 19 and insoles 20 . within each product type , articles are further spatially located based on use group . for example , those insoles 20 in the use group “ comfort ” are located together in product rows 21 , all those in the use group “ performance ” are located together in product rows 22 , and all those in the “ outdoor ” use group are located together in product rows 23 . the socks 19 are similarly separated spatially according to the same use groups . as explained previously , both the insoles 20 and the socks 19 belonging to a given use group are labeled with a common color and a common icon 2 , and this color and icon 2 match those in the corresponding part of main information guide 16 . thereby , a consumer can quickly pick out and remove from the rack 24 both an insole and socks which together provide the optimum combination for a particular use , thus benefiting the consumer and providing additional sales for the merchant . according to the example provided in fig7 , display rack 14 is a moveable rack that provides for horizontal rods on which products are hung , for example , using hangers or hooks attached to the rods themselves , or attached to the actual product packaging 1 of each product . options for displaying the products on the rack 14 are many , including shelves , hooks , rods , hangers , velcro , and tape and any combination of these , that supports and displays the consumer products that are sold as part of the fit system . preferably , the fit system consumer products are displayed on a moveable display rack 14 , as illustrated in fig7 , where the product packaging 1 for each product has a built in hanger or “ holder ” which allows the product to be hung on horizontal rods for display . this one embodiment of the present invention is illustrated in fig4 . alternatively , products are situated throughout a bricks and mortar store , or images of products are provided for consumer purchase through computerized methods such as on a web site . in these cases , the appropriate icon 2 for the use group that each product belongs to is situated on the product packaging label 1 so that consumers are able to match different products in the same use group . optionally , additional information guides are provided on product packaging label 1 , or in opportune locations throughout the store or web site , so that information about each product is available to the consumer , and the product can be matched according to use category using icon 2 . for example , according to one embodiment , a web site lists and offers for sale products advertised as part of the sof sole fit system . consumers use the web site to purchase socks , insoles , and other footwear - related products belonging to the “ performance ” use group . referring to fig3 , using the icon 2 that is associated with the “ performance ” group , the consumer will be able to select socks and insoles belonging to that group . additional product information is available for review on the web page or web pages selected by the consumer . additionally , the consumer is able to view the product packaging 1 that may include additional product information 3 , packaging graphics 4 and packaging background 5 of a particular color that matches a color or colors in the icon 2 . numerous use groups are contemplated according to the present invention . such groups are based on desired use and performance of the groupings of consumer products . “ sub - groups ” within each group are also contemplated as part of the present invention . for example , “ comfort cushion ”, “ comfort light ”, “ performance cushion ”, “ performance light ”, “ outdoor cushion ” and “ outdoor light ”. these groups and sub - groups illustrate some of the “ use ” diversity of consumer products such as socks , insoles , and other footwear - related products . it will be understood by one of ordinary skill that the scope of the present invention is not limited to these categories and that many different uses are contemplated for the current system and method of classifying consumer goods by use and desired performance . the foregoing description provides only an exemplary embodiment of the present invention for the purposes of illustration and not limitation . it will be readily apparent to those skilled in the art that the embodiments described herein may be modified or revised in various ways without departing from the spirit and scope of the invention . the scope of the invention is to be measured by the appended claims .

US-62854703-A

an insect trap having an entrapment chamber comprising one or more compartments , a tapered guide extending into each compartment , and an entry structure providing insect access to each compartment . the tapered guides optionally include a plurality of projections defining a crown structure for discouraging insect egress from the trap . the entry structures each define a plurality of entry apertures or entryways that are physically separated such that interactions between insects at different entryways is reduced or eliminated .

aspects of insect traps in accordance with the present invention will now be illustrated by showing currently preferred embodiments of insect traps , and with reference to the figures , wherein like numbers indicate like part . fig1 shows a perspective view of an insect trap 100 that is suitable for trapping flying insects . refer also to fig2 , which shows an exploded view of the insect trap 100 . the insect trap 100 has an entrapment chamber 110 that is closed at the top 112 , and open at the bottom 114 . an entry structure 120 is removably attached to the entrapment chamber 110 . in a current embodiment , the entry structure 120 threadably engages the lower end 114 of the entrapment chamber 110 . however , it will be apparent that other attachment means are possible as are known in the art , for example utilizing a friction fit , tab and slot arrangements , external attachment members , or the like . although not required for the present invention , in the preferred embodiment the entrapment chamber 110 is formed generally as a transparent or translucent , circular cylinder . the color and translucence of the entrapment chamber 110 may be selected , for example , to attract a particular target insect , to deter pests or other animals that are not target insects , or to accommodate aesthetic considerations . a hanging nib 116 defining a through - aperture 118 is shown at the top of the entrapment chamber 110 , to facilitate hanging the trap 100 . a tapered guide 130 extends into the entrapment chamber 110 from the open bottom end 114 , and is retained therein by the entry structure 120 . the tapered guide 130 is shaped generally as a truncated cone , having a smaller open top end 132 , and a larger open bottom end 134 . in this embodiment , the guide 130 includes a lower , generally cylindrical portion 135 sized to fit snugly in the entrapment chamber 110 , and an outwardly extending annular rim 136 that abuts the bottom of the entrapment chamber 110 . the tapered guide 130 includes a plurality of apertures 137 therethrough , which in this embodiment are generally elongate , rectangular slots . the apertures 137 , which are preferably disposed near an upper end of the tapered guide 130 , allow light to pass through , such that in suitable lighting the upper portion of the guide will be better illuminated , providing a sense of openness , and encouraging target insects to proceed into the tapered guide 130 . the apertures 137 also provide a perch for such insects . fig3 shows a fragmentary view of the insect trap 100 , showing details of the tapered guide 130 . a novel aspect of the tapered guide 130 is a crown structure 138 disposed at the open top end 132 . the crown structure 138 comprises a plurality of upward extensions ( eight shown ) spaced circumferentially about the open top end 132 . the crown structure 138 tends to discourage or inhibit insects that have entered the entrapment chamber 110 through the tapered guide 130 , from re - entering the tapered guide 130 and exiting the entrapment chamber 110 . fig4 a is a perspective view of the entry structure 120 , and fig4 b shows a bottom view of the entry structure 120 . the entry structure 120 attaches to the entrapment chamber 110 , e . g ., after the tapered guide 130 has been inserted into the open lower end 114 . the entry structure 120 defines a central recess 121 , which may be used , for example , to support or retain an attractant ( not shown ) for attracting one or more targeted insects . the attractant may be in liquid or solid form , and may be as simple as water , or a more complex organic or chemical attractant . a plurality of entryways 122 are defined in the entry structure 120 . in this embodiment the entryways 122 comprise apertures 123 defined by upright tubular members . a plurality of slots 124 are spaced about the perimeter of the entry structure 120 . the slots 124 provide an opening that allows attractant to exit the trap 100 to form a plume . the attractant may exit the trap 100 by diffusion , by pressure driven outflow resulting from changes in temperature in the entrapment chamber 110 , and / or by convection or airflow initiated by external air entering the trap 100 from one or more of the slots 124 . of course , attractant may also exit the entryway apertures 123 , wherein attractant from an entryway aperture 123 and slot 124 may cooperatively form the plume . the attractant plume tends to urge the target insects toward the trap 100 , and specifically toward the trap entryways 122 . as seen most clearly from comparing fig4 a and fig4 b , the bottom of the entry structure 120 defines a plurality of panels or fins 125 comprising radially oriented walls extending from the central recess structure 121 to the periphery of the entry structure 120 . the fins 125 define a plurality of converging channels , each channel leading to one of the entryway apertures 123 . the fins 125 are substantially planar , upright walls , although other configurations are clearly possible . the fins 125 provide several advantages . for example , the fins 125 separate neighboring entryway apertures 123 , thereby reducing the opportunity for multiple insects arriving at the same time from interacting with each other . this allows the entryway apertures 123 to be located closer together without increasing insect interference . the fins 125 also guide the insects toward the aperture 123 , thereby tending to encourage target insects to enter the trap through the entry aperture 123 . also , the fins 125 tend to guide and retain the attractant plume , to better entice the target insects into the trap 100 . a second embodiment of an insect trap 200 in accordance with the present invention is shown in fig5 - 7 . fig5 shows a perspective view of the insect trap 200 , fig6 shows an exploded view of the insect trap 200 , and fig7 shows a detail view showing a second entry structure 240 . certain aspects of this embodiment of the trap 200 are similar to corresponding aspects of trap 100 discussed above with reference to fig1 - 4b . generally , where similar elements are shown , the identifiers are the same . similar aspects will not be described again for clarity and brevity . also , the insect trap 200 shares many aspects with the insect traps disclosed and illustrated in the applicant &# 39 ; s co - pending u . s . patent application ser . no . 12 / 200820 filed on aug . 28 , 2008 , which is hereby incorporated by reference in its entirety . as shown in fig5 and 6 , the insect trap 200 includes an entrapment chamber 210 having multiple , separate compartments . in this embodiment a lower first compartment 211 is separated from a second compartment 213 by a transverse wall 215 . it is contemplated by the present invention that more than two compartments may alternatively be provided . the entrapment chamber 210 is preferably transparent or semi - transparent , although it is contemplated that for some target species an opaque entrapment chamber may be preferred . a first entry structure 120 is removably attached to a lower end 214 of the entrapment chamber 210 , providing insect access to the first compartment 211 . the first entry structure 120 is discussed above . in particular , the first entry structure 120 includes a plurality of entryways 122 providing access to the first compartment 211 , a central recess 121 that may be used to retain an attractant , a plurality of circumferential slots 124 , and a plurality of fins 125 that in the current embodiment are generally radially oriented to define converging channels leading to a corresponding entryway 122 . a tapered guide 130 is removably disposed in the first compartment 211 . the tapered guide 130 is described above , and includes an open top end 132 with a crown structure 138 to deter insect egress , an open bottom end 134 , and a plurality of apertures 137 through a conical portion of the tapered guide 130 . the entrapment chamber transverse wall 215 is located above and spaced away from the top end of the tapered guide 130 . the entrapment chamber 210 has a second open end 212 that provides access to the second compartment 213 , and is adapted or configured to receive a second entry structure 240 . the second entry structure 240 includes an attachment fixture 242 , an annular lid 250 , and a tapered guide 260 . a detail , partially cutaway view showing the second entry structure is shown in fig7 . the lid 250 releasably engages the upper end 212 of the entrapment chamber 210 , for example by threadable engagement , friction fit or any other suitable attachment . the lid 250 , which may be at least partially transparent to allow ambient light into the trap 200 , includes a center aperture 252 and a plurality of short , radial slots 254 . in this embodiment , the aperture 252 is defined by a downwardly curving lip portion 256 , to further facilitate target insects entering the trap 200 . the attachment fixture 242 includes an upper cap 244 having an optional hanging nib 245 to facilitate hanging the trap 200 . a divider 246 extends downwardly from the cap 244 defining a plurality of radial panels ( three shown ) that are sized and positioned to slidably engage the short slots 254 in the lid 250 . as seen most clearly in fig6 , the divider 246 includes a plurality of tabs 247 that engage corresponding apertures 269 in the tapered guide 260 . to assemble the second entry structure , the divider 246 extends through the slits 254 in the lid 250 , and the tabs 247 engage apertures 269 in the tapered guide 260 . as seen most clearly in fig7 , the tapered guide 260 includes a truncated conic portion 261 having a smaller open end 262 , a larger open end 264 , and a plurality of spaced apertures 267 . the larger open end 264 of the guide 260 is sized to fit around or receive a portion of the curved lip 256 of the lid 250 . wing members 266 extend from near the top of the tapered guide 260 , defining a plurality of apertures or openings 268 . the openings 268 may be used to hold vials of attractant ( not shown ), or the like . the divider 246 includes a distal portion that extends a distance into the conic portion 261 , and is shaped to approximately conform to the inner surface of the conic portion . the divider 246 and tapered guide 260 , therefore , cooperatively define three entryways into the second compartment 213 that are effectively isolated from each other . the separate entryways separate target insects arriving at different entryways , such that the insects are unlikely to interact or interfere with each other . of course , the particular number of entryways is a matter of design choice , and fewer than three , or more than three entryways are contemplated . it is contemplated that in use , one or more attractants may be retained by the wing members 266 , producing one or more plumes of attractant that emanate from the second entry structure 240 . it is believed that at a distance the plumes from the second entry structure 240 are likely to merge , producing a relatively strong plume to attract target insects . near the second entry structure 240 , the plumes should remain separated , such that target insects will be attracted to one of the entryways , thereby allowing multiple insects to access the trap 200 without substantially interfering with each other . similarly , an attractant may be provided in the first entry structure 120 , such that plural insects may simultaneously be trapped in the first compartment 211 without , or with minimal , mutual interference . by improving the efficiency of the insect traps the number of traps required to achieve a desired level of efficacy will be reduced . in the present embodiment , the attachment fixture 242 and tapered guide 260 are attached to each other and slidably engage the lid 250 . this conveniently allows the second entry structure 240 to be closed by sliding the attachment fixture downwardly such that the cap portion 244 closes the lid center aperture 252 . this facilitates packaging and shipping of the trap 200 , for example . it will be appreciated , and it is contemplated herein , that a crown structure may be provided on the smaller open end 262 of the tapered guide 260 , similar to the crown structure 138 described above , to discourage insect egress from the second compartment 213 . while illustrative embodiments have been illustrated and described , it will be appreciated that various changes can be made therein without departing from the spirit and scope of the invention .

US-35091109-A

a shower door assembly with linkage control comprising a stationary frame , a movable frame and an adjustment assembly disposed between the stationary frame and the movable frame . the adjustment assembly comprises at least two adjustment devices and locking devices for locking each of the adjustment devices . each of the locking devices comprises a locking element and a guiding device along which the locking element can slide . an actuating arm is provided to release and lock adjustment devices all at once . therefore , it is unnecessary to adjust each of the adjustment devices separately , facilitating the operation of adjustment .

the invention will be described in more detail by the following examples in reference to the accompanied drawings . fig1 shows a locking device according to one example of the invention . the locking device comprises a locking element 30 and guiding devices 31 , 32 , which are cooperated to lock an adjustment element 10 . in the example , the locking element 30 comprises a upper locking portion 35 and a lower locking portion 36 , with each of the locking portions comprises a first through hole 351 , 361 and a second through hole 352 , 362 in communication with the first through hole . the first through hole 351 , 352 has a dimension greater than or equal to that of an end surface 102 of the adjustment element 10 . the second through hole 352 , 362 has a dimension less than that of the end surface 102 . therefore , the adjustment element 10 , which is disposed on a carrier element 20 , can pass through the first through hole 351 , 352 , but not the second through hole 352 , 362 . the locking element 30 further comprises an upper securing portion 354 at the upper locking portion 35 , a lower securing portion 364 at the lower locking portion 36 , an actuating arm 40 ( fig1 ) passing through the upper securing portion 354 , and a fixing element 329 ( fig5 ) passing through the lower securing portion 364 . in the example , the upper and lower locking portions 35 , 36 are detachably connected by a linkage element 33 . the detachable connection can be achieved by a number of methods known in the art . in the present example , linkage holes 356 , 366 are respectively provided to the upper and lower locking portions 35 , 36 , and are connected to hooks 331 provided at both ends of the linkage element 33 , such that the upper and lower locking portions 35 , 36 are connected . in other examples , the upper and lower locking portions 35 , 36 are form in a single piece , as shown in fig7 . in this situation , no linkage element 33 is necessary . with reference again to fig1 , the guiding device comprises an upper guiding element 31 and a lower guiding element 32 . as shown in more detail in fig2 and 3 , the upper guiding element 31 comprises a first guiding slot 314 along which the locking element 30 is able to slide ; a supportive platform 313 for supporting the actuating arm 40 ; a first cavity 312 for receiving one of the adjustment elements 10 ; and a carrying platform 319 for carrying the upper securing portion 354 of the locking element 30 . in the example , the first guiding slot 314 is interrupted between the supportive platform 313 and the carrying platform 319 . in another example , the first guiding slot 314 is continuous as long as the guiding elements provide a passage for the actuating arm to pass through and to abut against the supportive platform 313 . in the example , see fig4 and 5 , the lower guiding element 32 comprises a second guiding slot 324 . the locking element 30 is able to slide along the first guiding slot 314 and enters into the second guiding slot 324 and slides therein . the lower guiding element 32 further comprises a second cavity 322 for receiving other of the adjustment element 10 , an elastic element 321 for providing elastic force when in contact with the lower securing portion 364 , and a third cavity 323 located below the second cavity 322 and having the elastic element 321 received therein . the fixing element 329 passes through the lower securing portion 364 and also the elastic element 321 and is fixed to an upper wall 325 of the third cavity 322 . in the example , the elastic element 321 is a spring . the upper and lower guiding elements 31 , 32 are connected to the stationary frame by suitable methods . in the example , see fig2 to 5 , the upper and lower guiding elements 31 , 32 each has linkage elements 316 , 318 and 326 , 328 respectively . a plurality of threaded holes are provided at bottom side of the stationary frame 60 , wherein a threaded hole 62 is position in corresponding to the linkage elements such as 316 , 318 , such that the guiding elements 31 , 32 are connected to a space 63 of the stationary frame 60 by fasteners . in another example , with reference to fig1 - 19 , the upper guiding element 31 has an extension 310 where at least one locking recess 311 is provided . between the extension 310 and the carrying platform 319 and also on the supportive platform 313 are formed with locking slots 315 , with the locking recess 311 adjacent the path of the locking slots 315 . similarly , the lower guiding element 32 has an extension 320 where at least one locking recess 327 is provided . on the lower guiding element 32 is formed with a locking slot 380 , with the locking recess 327 adjacent the path of the locking slot 380 . the stationary frame 60 has a guiding groove 66 defined by two ridges 65 which are able to insert into the locking slots 315 , 380 , such that the upper and lower guiding elements 31 , 32 can slide along the stationary frame 60 . when the guiding elements 31 , 32 is suitably positioned , the ridges 65 will be pressed by a tool ( such as a screw driver ) in alignment with the recesses 311 , 327 , so that the ridges will be deformed and forced into the recesses . the guiding elements 31 , 32 will then be prevented from sliding and connected to the stationary frame 60 . the stationary frame 60 can be attached to a suitable surface , such as a wall surface , by suitable methods . in the example , threaded holes 61 are provided at the bottom side of the frame 60 such that the frame can be attached to the wall surface by fasteners . the person skilled in the art will know other ways to achieve the attachment . with reference again to fig1 and 7 , in the example , the locking element 30 further comprises one or more intermediate locking portions 34 , each comprises a first through hole 341 and a second through hole 342 in communication therewith . the first through hole 341 has a dimension greater than or equal to that of the end surface 102 of the adjustment element 10 . the second through hole 342 has a dimension less than that of the end surface 102 . correspondingly , the guiding device further comprises one or more intermediate guiding elements 37 , each preferably having same structures as the upper guiding element 31 . for purpose of standardization , each of the upper locking portion 35 , lower locking portion 36 and possibly existed intermediate locking portions 34 further comprises a third through hole 353 , 343 or 363 which is in communication with the first through hole 351 , 341 , 361 and symmetrically positioned with respect to the second through hole 352 , 342 , 362 about the first through hole 351 , 341 , 361 . the third through hole 353 , 343 , 363 has a dimension less than that of the end surface 102 and preferably same as that of the second through hole 352 , 342 , 362 . in the example , the upper guiding element 31 has a spacer 317 arranged between the supportive platform 313 and the carrying platform 319 , such that the upper guiding element 31 has a height matching with that of the locking element 30 . with reference to fig8 , it is shown an exemplary adjustment device which comprises the adjustment element 10 and a carrier element 20 carrying the element 10 . the adjustment element 10 has a smooth side surface 104 , exposed when loaded on the carrier element 20 . the adjustment element 10 has end surfaces 102 , a top surface 106 and a bottom surface ( not shown ). in the example , at least one of the top surface and the bottom surface is provided with a sliding groove 11 . in other examples , the sliding groove can also be absent . the carrier element 20 comprises connection wings 12 for connecting to a movable frame 50 ( fig1 ), an upper loading frame 14 connecting to the connection wings 12 , a lower loading frame 13 in parallel with the upper loading frame 14 and in connection with the connection wings 12 , and an opening 17 which , together with the upper and lower loading frames 14 , 13 , defines a space 16 for receiving the adjustment element 10 . in the example , a portion of at least one of the upper and lower frames 14 , 13 forms a guiding rail for engaging within the sliding groove 11 such that the adjustment element 10 can be stably received within the space 16 . in other examples , when the adjustment element 10 is not provided with the sliding groove 11 , the adjustment element 10 has a height slightly greater than that of the opening 17 , such that the adjustment element 10 can be received in the space 16 by virtue of its flexibility . in the example , the adjustment element 10 has a length equal to that of the space 16 . in other examples , the adjustment element 10 has a length slightly smaller / greater than that of the space 16 . in the example , the carrier element 20 further comprises a front blocking plate 15 connecting with the free ends of the upper and lower loading frames 14 , 13 , respectively , in order to prevent the adjustment element 10 from moving outside the space 16 . when the adjustment element 10 is received in the space 16 , one of the end surfaces 102 is in contact with the front blocking plate 15 . in other examples , the front blocking plate 15 may be absent . with reference to fig9 , it is shown the adjustment element 10 and the carrier element 20 when assembled . as shown , when the adjustment element 10 is loaded on the carrier element 20 , the two side surfaces 104 of the adjustment element 10 are exposed outside . the top surface 106 is in contact with the top loading frame 14 , and one of the end surfaces 102 abuts against the front blocking plate 15 , and the other end surface 102 is accommodated in the opening 17 . fig1 shows the assembly of the adjustment device with an exemplary movable frame 50 . the movable frame 50 is provided with a receiving groove 51 into which the wings 12 can be inserted so that the whole adjustment device can be attached to the movable frame 50 and slide along the groove 51 . fig1 shows the assembly of one adjustment device , the upper locking portion 35 and the upper guiding element 31 . as shown , the adjustment device passes through the first through hole 351 and into the first cavity 312 of the upper guiding element 31 . the upper locking portion 35 is inserted into the first guiding slot 314 . the actuating arm 40 ( a threaded rod in this example ) passes through the upper securing portion 354 and the through hole 316 of the carrying platform 319 and then abuts against the supportive platform 313 . in the state as shown , the adjustment device can pass through the first through hole 351 and the first cavity 312 freely , so the position and angle of the movable frame 50 can be adjusted freely in relative to the stationary frame 60 . fig1 shows that the adjustment device is forced into the second through hole 352 such that it is locked . specifically , when the position of the movable frame 50 in relation to the stationary frame 60 is determined , by rotation of the actuating arm 40 , the upper locking portion 35 will move upward due to counterforce , because the actuating arm 40 has one terminal end abutting against the supportive platform 313 and thus cannot move downward . however , the first cavity 312 is not able to move upward , the adjustment device therefore will be forced into the second through hole 352 . in the present invention , the adjustment element 10 is generally made from flexible materials , such as rubbers , pu or modified pu , while the locking device is generally made of rigid materials , for example engineered plastics such as polyformaldehyde or nylon 66 , or zinc alloy . therefore , the adjustment element 10 can be forced into the second through hole 352 by application of forces . when forced into the second through hole 352 , the adjustment device will be unable to move in relative to the stationary frame 60 . therefore , relative position between the movable frame 50 and the stationary frame 60 is fixed . fig1 and 14 show the assembly of an adjustment device with an intermediate locking portion 34 and an intermediate guiding element 37 . the locking of the adjustment device by the locking portion 34 is similar to that as shown in fig1 and 12 , except that the intermediate locking portion 34 does not need additional actuating arm 40 , but instead , is moved upward by virtue of the linkage element 33 or along with the upper locking portion 35 when formed into one piece therewith . fig1 and 16 show the assembly of an adjustment device with the lower locking portion 36 and the lower guiding element 32 . in fig1 , the adjustment device can pass the first through hole 361 and the second cavity 322 freely , so that the position and angle of the movable frame 50 can be freely adjusted in relation to the stationary frame 60 . as shown , the elastic element 321 is in its relaxed or slightly compressed state . by similar principle as that shown in fig1 and 12 , the adjustment device is locked by the lower locking portion 36 , except that the lower locking portion 36 does not need additional actuating arm 40 , but instead , is moved upward by virtue of the linkage element 33 or along with the upper locking portion 35 when formed into one piece therewith . in the locked state , the elastic element 321 is in its compressed state due to the upward movement of the lower locking portion 36 . when the relative position between the movable frame 50 and the stationary frame 60 needs to be changed , by contrarotation of the actuating arm 40 , the whole locking device is pushed to move downward along the first and second guiding slots 314 , 324 due to the elastic force of the elastic element 321 , such that the adjustment device is released from the second through hole 352 , 342 , 362 and returns back to the first through hole 351 , 341 , 361 where the adjustment device can freely move again . it should be understood that various example embodiments have been described with reference to the accompanying drawings in which only some example embodiments are shown . the present invention , however , may be embodied in many alternate forms and should not be construed as limited to only the example embodiments set forth herein .

US-201414252113-A

a system for enhancing and improving the transcutaneous or transdermal delivery of topical chemicals or drugs . a disposable container contains a substantially sterile unit dose of an active agent adapted for a single use in a medical treatment . the unit dose is formulated to enhance transport of the active agent through mammalian skin when the active agent is applied to the skin and the skin is exposed to light and / or ultrasound defined by at least one specific parameter .

the following detailed description is of the best presently contemplated mode of carrying out the invention . this description is not to be taken in a limiting sense , but is made merely for the purpose of illustrating the general principles of the invention . the scope of the invention is best defined by the appended claims . in a preferred embodiment , each active agent may be specially formulated to achieve a desired result using ultrasound . at present , many drugs are formulated to achieve a desired result using topical penetration , but the inventor is unaware of any drug that is specially formulated to achieve a desired or optimal result using ultrasound . at present , a coupling agent must typically be useful to enable effective transmission using ultrasound . in a preferred embodiment each active agent may be provided in a single dose container or packet . the packet may preferably contain only a pure active agent , at an optimal strength and / or at an optimal concentration for a specific use . the active agent may be dissolved in an appropriate vehicle medium , such as a gel or a liquid . all other contaminants ( including , for example , preservatives , fragrances , etc .) are preferably absent or removed from the packet . the need to include , with the active agent , additives for prolonging shelf life , improving stability , preventing spoilage , improving texture , etc ., is thereby eliminated . in a preferred embodiment of the invention everything is removed from the active agent formulation which does not have a desired effect . each packet is preferably packaged in a sterile manner , by radiation sterilization or other means . additionally , the parameters of the collimated ultrasound are preferably selected for maximum safety . preferably , exposure times are confined to intervals of five , ten , fifteen or twenty minutes . in this preferred embodiment a layer of the active agent may first be placed on the skin . the ultrasound equipment may be adjusted to the optimize the ultrasound parameters , including the exposure time , and then turned on . the ultrasound wand may be moved gently over the skin for the duration of the selected exposure time . the treatment is essentially complete at the end of the selected exposure time . any active agent residue left on the skin may be cleansed with a gentle cleansing agent , so that no active agent is left to irritate the skin . treatment may be repeated at periodic intervals . in another embodiment of the invention an ultrasound gel or similar substance may be put on the skin first . the skin may then be exposed to ultrasound . the gel may be removed and the active agent may be placed on the skin . the active agent may be allowed to sit on the skin for a period of time , preferably between about five and twenty minutes . this tends to provide a short “ burst ” of the active agent at a higher penetration . the residue may then be wiped off , so that no active agent is left to irritate the skin . another option would be to apply the active agent in a ‘ delivery device ’ such as a biomembrane , dressing or band - aid , liposome - polymer complex , aerosol spray dressing which functions as a delivery device , but also provides a barrier function . in this option , the active agent would be left on the skin for a period of hours or perhaps overnight . it appears that , at least in this embodiment , the increased barrier spreading on the cells and / or permeability may last for up to one or two days . a topical agent , aerosol agent , dressing , or delivery device may be applied to help protect during this time or to help restore the barrier function . a preferred formulation could be a lipid mixture such as cholesterol , ceramides , free fatty acids , linoleic acid . another option would be a lipid or liposome — polymer mixture or aerosol polymer coating . consequently , the skin may be relatively absorbent and it may be preferable to provide some associated aftercare , such as avoiding sunburn , retin - a or aftershave . treatment with a topical agent specifically formulated to “ restore ” or improve barrier function may be used . such a topical agent may also be packaged as described above . in another embodiment of the invention an outer layer of skin may be removed before the skin is exposed to an active agent or ultrasound . this tends to enable the active agent to penetrate better and / or deeper . this may be achieved , for example , by first wiping the skin with acetone to strip the oils out . an enzyme may then be useful to selectively remove and / or kill only dead skin cells . pretreatment with heat , skin hydrating preparations and preparations to alter ( and optimize for treatment ) the skin ph may also be utilized . chemicals , abraders and lasers may also be used for this purpose , although they tend to be less discriminate . an active agent may then be placed on the skin and exposed to ultrasound , or the skin may be exposed to ultrasound prior to placing an active agent on the skin . the active agent may then be wiped off . the barrier function of the outer skin layer tends to return within a few hours or days . it has been found that removing impediments to the introduction of an active agent to the skin tends to have at least one of the following three effects : ( 1 ) increasing the amount of active agent which enters the skin , ( 2 ) shortening the time during which the skin must be exposed , and / or ( 3 ) increasing the penetration depth of the active agent . precision , uniformity and safety may be improved by reducing variations in the material actually placed on the skin and having the ultrasound beam as uniformly distributed as possible . treatment in accordance with the present invention tends to be relatively safe , relatively inexpensive , does not necessarily need to be performed by a physician , has a recovery time which is relatively short ( and in many cases non - existent ), and can be done repeatedly with virtually no cumulative adverse effects but with cumulative beneficial effects . the present invention may provide a safe , effective delivery mechanism for a wide variety of active agents , including bleaching cremes , vitamin c , the vitamin a family , and topical anesthetics . in some cases the present invention may allow topical anesthetics to be administered in sufficient strength that scalpel work may be performed without needles . the present invention may be used for the treatment of leg ulcers , where the known effects of ultrasound alone may be useful to stimulate wound healing and treatment in accordance with the present invention may be useful to drive one or more new agents which enhance , speed or stimulate wound healing in to greater depths , producing results that are better and / or faster . the packets may be provided in different sizes . for example , the size of one packet may be configured so that there is sufficient active agent in the packet to treat the average face . as another example , packet size may be configured so that there is sufficient active agent in the packet to treat the arms and / or legs . the packet may be configured for unit dose delivery , and the active agent may be optimized both for its vehicle and its percentage . if two or three active agents are used in combination , or if some of the active agents are dissolved in micro spheres or synthetic devices , then the penetration ratio may be affected by the coefficients of diffusion and characteristics that are unique for each active agent , including molecular size and shape . if two or more active agents are used in combination , then each active agent may not necessarily be driven into the skin at the same ratio because each molecule may be driven in at a different rate . when several active agents are used in combination , some active agents may be driven in to higher strengths than others based on factors including their weight , their volume , their size , their shape and other properties . these factors may be optimized to achieve the desired treatment effect . the active agent may be useful to stimulate biological systems , and from a disease therapeutic standpoint the active agent may also be useful to inhibit or turn off certain biological functions . in other words , the present invention may be useful to provide an active agent concentration of sufficient magnitude that it may cause a feedback inhibition . for example , if a concentration of 2 % in the skin provides stimulation and a concentration of 4 % is considered optimal , then it is possible that a concentration of 10 % may provide less effect than 4 % and at 15 % the reverse effect may occur . it is therefore possible to have an active agent formulation ( and / or time period and / or set of parameters ) optimized so that the treatment does not merely restore biological function but actually treats disease . the embodiment illustrated in figure iv is primarily as a ‘ biostimulating ’ process and not a destructive or ablative process , such as commonly used in today &# 39 ; s art . using laser therapy or ultrasound ( or both ) to produce heat at a subnecrotic damage or injury threshold is another possible embodiment . ( an example might be trying to achieve a dermal temperature that affects collagen — perhaps beginning around 55 - 60 ° c .). fig . iv illustrates an example of an embodiment using low energy laser therapy to stimulate ( directly or indirectly ) the production , proliferation , activation , or inhibition of the activity , structure or function of various biochemical or photochemical or biological processes so as to result ( directly or indirectly ) in effects that are beneficial to the structure , function or appearance of the skin and / or subcutaneous tissues or which results in the “ rejuvenation ” of photoaged , environmentally damaged or disease or drug / therapy altered skin or subcutaneous tissue . the present invention , in a preferred embodiment , may be used either as a pretreatment followed by topical application of a desired agent or used in a coupling media vehicle to directly deliver the desired agent . at present , topical pharmaceutical products are not generally formulated in such a way as to optimize their efficiency as ultrasound couplants . a preferred formulation for an “ active ” coupling agent is one which would best meet the criteria described for the optimal active agent alone , and yet would still provide an effective coupling function for an ultrasound transducer head . the present invention , in a preferred embodiment , formulates these topical agents in concentrations and vehicles so as to be optimally effective when used in conjunction with sonophoresis . these specifications may vary with molecular size as well as diffusion and partition coefficients and other factors and may be uniquely formulated for each agent . the preferred embodiment for many may be a gel . also preferred is individual single use sterile dose packets , thereby avoiding the need for preservatives and other additives that may cause undesirable effects or side effects . the goal in many cases may be to maximize percutaneous transmission of the active agent . the following principles may be useful in selecting these formulations , except in some situations where a milder or submaximal effect or transmission may be desired for a given agent or situation . in such case , the formulation may be shifted or modified to have reduced effect . also , certain complex or synthetic delivery systems may follow different principles , such as lipid bilayers ( liposomes ) or synthetic polymers ( microsponges ). however , for many situations the preferred formulation may be based upon the desire to approach , but not quite reach , a saturated solution of the active agent ( s ). thus , the rate of release of active agent or drug may be greater in vehicles in which it exhibits poorest solubility . this may be more important than the total concentration , so as to maximize bioavailability and release . in a preferred formulation , it may be desirable to select a vehicle which poorly solubizes the active agent and which preferably may evaporate at such a rate that the concentration of the active agent increases to offset the release into and through the stratum corneum . however , it may also be important that it not evaporate so quickly as to precipitate out on the skin , since this may decrease or even stop transport ( situations where stable , supersaturated solutions form may be acceptable ). thus , it may be desirable to have sufficient non - volatile vehicle to avoid precipitation from occurring during the time the active agent may be applied to the skin . since the transport rate may be affected by various factors , such as those described herein , the optimal vehicle may vary not only with each specific active agent , but also with the specific technique parameters ( or disease state ) since the barrier function ( and thus transport depletion of concentration of active agent in vehicle ) may vary . preferred ultrasound parameters may be determined in accordance with both efficacy and safety requirements . for example , one preferred range for lower frequency ultrasound may be between about 25 khz and about 3 mhz at about 0 . 5 - 2 . 0 w / cm 2 ( either continuous or pulsed , using about a 20 - 25 % duty cycle if pulsed ). a preferred setting within this range may be at about 1 . 0 mhz at about 2 . 0 w / cm 2 , with a continuous wave beam and a treatment time of between about five and ten minutes . a preferred setting within this range for non - continuous beam ( i . e . pulsed delivery ) may be at about 1 . 0 mhz at about 0 . 2 - 0 . 5 w / cm 2 with a 20 - 25 % duty cycle with around a 2 . 0 - 20 . 0 msec “ on ” cycle and a treatment time of about five and ten minutes . one preferred range for higher frequency ultrasound may be between about 3 mhz and about 16 mhz at about 0 . 2 - 1 . 0 w / cm 2 ( either continuous or pulsed , using about a 20 % duty cycle if pulses ), with a treatment time of between about one and twenty minutes . a preferred setting within this range may be at about 10 mhz at about 0 . 2 w / cm 2 , with a continuous treatment time of between about five and twenty minutes . in a preferred embodiment the beam profile may be a collimated beam with precise control of output . in an alternative embodiment a focused beam may also be suitable . a preferred embodiment may provide a feedback warning if the operator loses contact with the skin , thus ensuring optimal treatment technique . further adjuncts to the process which increase permeability of skin or decrease skin barrier function may be helpful with optimizing the present invention . options for this include , but are not limited to , stripping , removing , thinning or diminishing the structure , function , thickness or permeability of the stratum corneum by various mechanical , abrasive , photo acoustical , ablative , thermal , chemical , abrasive or enzymatic methods . examples of these could include solvent or tape stripping , scrubbing , laser ablation or vaporization , chemical peeling , micro dermabrasion , enzyme peeling , or laser treatment using high peak power , short pulse duration lasers . a preferred embodiment may be enzyme peel , which is formulated to specifically remove only the dead stratum corneum cells . in another embodiment of the invention sonophoresis may be used alone , without a topical agent , to produce a thermal effect ( rather than to drive drugs in ) to stimulate the skin ( e . g . make fibroblasts , produce new collagen , elastin , etc .). examples of the active agent might include any of the following , either alone or in combination : vitamin c ; vitamin e ; vitamin a ; vitamin k ; vitamin f ; any of the various chemical forms and analogs ; of these vitamins ; retin a ( tretinoin ); adapalene ; retinol ; hydroquinone ; kojic acid ; various growth factors ; echinacea ; antibiotics ; antifungals ; antivirals ; bleaching agents ; alpha hydroxy acids ; beta hydroxy acids ; salicylic acid ; antioxidant triad compound ( with or without tretinoin or vitamin a derivatives ); seaweed and salt water derived products antioxidants , phytuanthocyanims , phytonutrients , botanical and herbaceous products , hormones ( including insulin ), enzymes , minerals , growth factors , genetically engineered substances , cofactors or catalysts for various biological pathways and other antiaging substances , antibiotics , antifungals , and antivirals . the active agents used in accordance with the present invention may be characterized by one or more of a variety of properties . optimization of the active agents for use in accordance with the present invention may be achieved by the modifying one or more of these properties . the following are examples of some of the properties which may be modified , alone or in combination , to optimize active agents for use in accordance with the present invention : solubility — a sufficient concentration of active agent should preferably be dissolved in the selected delivery system vehicle or coupling agent for the desired treatment . stability — some active agents may be unstable and may rapidly degrade after being dissolved in a vehicle or coupling agent . therefore , in one preferred embodiment the active agent may be in the form of a powder ( such as a freeze dried powder or lyophilized powder , for example ) that is not mixed until treatment is imminent . other instabilities may be related to oxidation from atmospheric oxygen or exposure to ultraviolet light or sunlight . thus , in one preferred embodiment the active agent may be packaged under vacuum or nitrogen or another inert gas and may be packaged in a manner that protects the active agent from light . molecular size — the active agent should preferably have a molecular size which enables it to penetrate the skin at the time of maximum permeability , and then should preferably be in a form which is either “ active ” or may become “ activated ” in the skin . for example , in the case of vitamin c treatments , l - ascorbic acid has stability problems but is the active form in the skin and is a small molecule which enables penetration . in contrast , magnesium ascorbyl phosphate is very stable but is a much larger molecule and does not penetrate easily with current delivery systems . guy & amp ; potts have shown that the permeability of human ( and mouse ) stratum corneum may be determined by the molecular volume ( weight ) and the partition coefficient log poor . ph — the activity of an active agent may frequently depend on an appropriate ph level . it is also important for skin to be at an optimal ph level . there is good evidence that the stratum corneum is much more permeable to neutral molecules than the salts of the weak acids or bases . furthermore , skin enzymes and other processes may operate optimally at certain ph levels and poorly at others . for example , an enzyme preparation useful to remove stratum corneum may operate effectively at a ph level of 8 . 5 . the skin may preferably be “ pretreated ” with a topical agent that increases the ph of the skin to this level . at the end of the treatment it may be advantageous to add another topical buffering solution or agent to “ readjust ” the skin back down to a normal skin ph level of 5 . 5 . pka — the pka tends to affect the amount of free acid and base in equilibrium , and thus has an impact on both the beneficial and adverse clinical effects of the active agent . a recent study by the fda has shown that there may be considerable variation in the beneficial clinical effects ( as well as the adverse and undesirable clinical side effects ) of glycolic acid , even when the glycolic acid concentrations are the identical percentage . for example , if the ph of the glycolic acid preparation is adjusted to around 4 . 4 ( approximately equal to the pka of glycolic acid ), then the ratio of beneficial to adverse side effects is much better than when the ph is lower than the pka ( and more free acid is available in the equilibrium ). the pka may vary for different compounds and thus may effect the choice of formulation . purity , sterility , absence of nonactive ingredients — the presence of an impurity ( including chemical contaminants , preservatives , additives , fragrances , or micro - organisms , for example ) may also potentially have enhanced penetration and thus produce undesired adverse or toxic effects . lipid bi - layer and ionization — these may determine the “ distribution ” of the active agent , either in the lipid phase or in the ionized chemical form . these may affect diffusion and delivery of the active agent . lipophillic and lipophobic — the choice of the delivery vehicle or coupling agent for the active drug may be effected by these properties of the active agent . diffusion coefficient — one of the dominant factors in determining the transfer of the active agent into the skin , the diffusion coefficient measures the use of movement across the stratum corneum and the difference in concentration or percentage of active agent and also the thickness of the stratum corneum . partition coefficient — one of the dominant factors in determining the percentage transfer of the active agent into the skin , the partition coefficient refers to the tendency for the active agent to leave its vehicle and enter the stratum corneum . the amount of material that moves across the units representative of stratum corneum and a given unit of time tends to be directly proportional to the partition coefficient as well as the diffusion coefficient . in a preferred embodiment the invention may be provided in the form of a “ treatment kit ” prepackaged to contain all the appropriate topical agents , drugs , supplies , etc . needed for a specific treatment . the kit may be divided into compartments or zones . each compartment may be coded by color , number or letter ( for example ), so that the compartments follow a “ step system ” that guides the treatment provider ( i . e ., the nurse , esthetician , physician , etc .) through the treatment process . within each color coded zone , individual products that are color coded to match that step color would be provided so that they would not be easily confused . each kit may be produced specifically for a certain active agent . each kit may be produced specifically for a certain usage , based on disorder being treated , anatomic area , etc . treatment regimen cards may be included in the kit . the treatment cards may become a part of the patient record or chart . the treatment cards may enable the treatment provider to chart multiple , serial treatments . such treatment cards may be useful to record basic information such as date of treatment , anatomic location , disorder , patient name , comments , etc . the treatment cards may also provide information regarding suggested treatment intervals , numbers of treatments , incremental increases in treatment parameters , incremental increases in active agent application time or strength . several different treatment cards may be included in a kit for a treatment provider to select . for example , a single kit may include different treatment cards for sensitive skin , regular skin , and post surgical skin treatment . these different treatment cards may have , as their distinguishing characteristics , differences in one or more of at least the following : percentage dilution of active agents , amount of time various agents or treatment are applied , or ultrasound or light source parameters , etc . different treatment cards may be provided for different anatomic areas , such as the face , the arms or the legs , where these parameters may also be varied . different treatment cards may be provided for different treatment options , for example gentle treatment for mild sun damage vs . aggressive treatment for severe sun damage . the treatment cards may be color coded to indicate the time period for equipment parameters directly on the card . the treatment cards may also cross reference for percent concentration to the kit itself ( in essence within each step of the kit ) which may be color coded ( for example pale blue background ). for example , there may be three levels of dilution or strength ( mild , intermediate , maximal ) which may be identified by a color code on the treatment card . for example , at one step of the treatment the active agent may be mixed from a dry powder . the mixing instructions may be imprinted on the box for the dilution , and the treatment card may also indicate the recommended dilution . for example , a patient with sensitive skin receiving a series of six treatments may start at the most mild of the three dilution strengths for the first three treatments and then go to the intermediate for the last three . in contrast , a person with average skin might have the first two treatments performed at the mild strength , the third and fourth treatments at the intermediate strength , and the fifth and sixth treatments at the maximum strength . in that case weeks one and two of the treatment card may be one color to match the mild bar and the one background color , weeks three and four may be a different color to match the intermediate bar , and weeks five and six may be a third background color to match the maximum bar . another option may be to have colors , letters or numbers ( for example 1 . 0 , 2 . 0 , 3 . 0 , etc .) for the strengths of the kits where a dilution was not involved ( for example cream or lotion that does not require mixing from a powder ). in such a case , the patient treatment card background colors may correspond to the strength or color of the kit , rather than an individual dilution or compound of the kit . in such a case the cream may be in separate packages outside the kit , but still color coded . likewise , different color bars may be useful to indicate the duration of the treatment in minutes , or the treatment parameters to be used on the ultrasound or laser . colors may be also used in color code to link or “ intertwine ” ultrasound / topical treatments and light or laser light treatments into a predetermined sequence and at the appropriate time interval . in a preferred embodiment of the invention , for example , step one of the kit may include the following items : a tear and wipe prepackaged skin pad impregnated with a skin cleanser . a sterile unpreserved unit dose package , vial , twist off plastic , tear packet , etc . type of container which contains a solution that adjusts the ph of the skin to ph 8 . 5 a vial of dry enzyme powder ( which requires ph 8 . 5 to properly function ). a small vial of an appropriate amount of sterile distilled unpreserved h 2 o to add to the dry powder . a small plastic cup and plastic spatula to mix these in . all of the items in step one of the kit may be coded with the same identifying number , letter and / or color . step two of the kit may include a set of instructions to use the coupling gel and ultrasound as per the patient treatment card parameters . step three may include the active agent itself , in a sterile single use package , with any additional ancillary items needed for that particular agent . step 4 may include the post treatment skin protective regimen which may include the following : a buffering solution to restore the skin to ph 5 . 5 ( if necessary for a given process or active agent ). an environmental protection lotion which may be specially formulated to help protect the skin until it has regained its own barrier function . a possible nonirritating sun block to use on top of the environmental protective cream . the present invention has numerous potential beneficial uses . for example , the present invention , in a preferred embodiment , may be useful to directly or indirectly produce beneficial effects by biochemical stimulation of tissue or cells ( or thermal events without the use of topical agents ) including such activities as stimulating fibroblast production of new collagen or elastic fibers . the present invention , in a preferred embodiment , may be useful to lighten uneven or extra pigment ( including melanin ) in the epidermis or dermis . the present invention may be useful to add , augment or supplement antioxidants , vitamins , phytonutrients , trace elements , minerals , or naturally occurring , synthetic or generically engineered substances which may alter or improve the structure , health or function of the skin or subcutaneous tissue . the present invention , in a preferred embodiment , may be useful to : deliver agents which enhance , speed or promote wound healing ; deliver anesthetic agents to the skin and subcutaneous tissues ; improve skin tone and “ tighten ” loose skin ; to reduce the appearance of cellulite ; reduce wrinkles or scars ; deliver drugs for the purpose of producing a non - local , systemic effect ( such as insulin ); deliver agents in their pure or neat form of in vehicles such as gels , creams , ointments , emulsions , micropolymer beads ( or sponges , etc . ), liposomes or other natural or synthetic “ transport device ” used with or without a coupling media . the present invention provides the possibility for the non - surgical rejuvenation of skin , improved wound healing , better anesthetic for cutaneous surgery without needles , delivery of drugs that currently are ineffective or poorly tolerated by topical delivery . in other words , the present invention may be useful for improving the absorption of drugs or other substance which were previously inefficiently absorbed , and for allowing the absorption of drugs or other substances which were previously not absorbable at all . as used herein , the term “ light therapy in accordance with the present invention ” includes , but is not limited to , laser light therapy and low energy laser light therapy ( also occasionally referred to as “ low light therapy ” or “ llt ”). in general , laser light may be characterized as “ coherent ” light , whereas non - laser light may be characterized as “ non - coherent ” light . the present invention encompasses therapeutic uses of both “ coherent ” and “ non - coherent ” light . as used herein , the term “ cell ” or “ cells ” includes , but is not limited to , cells of virtually any living organism , including human cells , mammalian animal cells , non - mammalian animal cells and plant cells . the present invention , in a preferred embodiment , may be useful to biostimulate cells or fibroblasts ( including fetal fibroblasts ). although the precise mechanism by which such biostimulation occurs is not fully understood , it appears that some part of the energy producing portion of the cells may be stimulated by light . using different wavelengths , different energy parameters , etc ., for different cell types . the present invention , in a preferred embodiment , may be useful to stimulate , or inhibit , many different living cells ( not just human cells and not just human fibroblasts ). possible “ targets ” within the cell itself might include , for example : mitochondria , cytochrome system , ferrodoxin absorption ( redox reactions ). biostimulation of fibroblasts ( including fetal fibroblasts ) may affect production of atp for cell energy , may work on other cells with mitochondria , and may be able to inhibit certain cell functions ( e . g . decrease production of scar tissue , slow growth of cancer or tumor cells , etc ) as well as stimulate . light therapy in accordance with the present invention probably produces biostimulation in an energy range of from about 0 . 01 to about 5 . 0 joules / cm 2 and perhaps up to about 10 joules / cm 2 . inhibition probably extends from about 5 . 0 to about 10 . 0 joules / cm 2 or perhaps higher in some cases . the present invention , in a preferred embodiment , may be useful to specifically stimulate ( or inhibit ) the growth of hair or other skin appendages ( such as nails , etc ). the present invention , in a preferred embodiment , may also be useful to stimulate the growth , or re - growth , of fine vellus or dormant or inactive hairs ( e . g . to treat hair loss , for example ). for example , the present invention may be useful to enhance the effectiveness of rogaine or similar drugs used in the treatment of male pattern baldness . the present invention , in a preferred embodiment , may be useful to stimulate ( or inhibit ) the growth of other cells . various laser parameters may be matched to those effective for the particular cells being treated . these laser parameters may include wavelength , energy fluence , pulse duration , time of exposure , frequency of exposure , etc . the present invention , in a preferred embodiment , may be useful to stimulate cell activity , such as stimulating fibroblasts ( including fetal fibroblasts ) to produce collagen and elastin , for example . the present invention , in a preferred embodiment , may be useful to stimulate cell proliferation or multiplication , such as stimulating native , transplanted , foreign or bioengineered fibroblasts , for example . the present invention may further be useful to stimulate simultaneously both cell activity and cell proliferation . the present invention , in a preferred embodiment , may be useful to affect abnormal cells , such as benign or malignant cells , by inhibiting ( or stimulating ) tumor growth . the stimulation may be achieved either directly or indirectly , through interaction with an added substance . such added substances might include , for example , chemicals , dyes , hormones , genetically engineered substances , plant derived materials , synthetic human materials ( such as synthetic melanin ), etc . the added substances may be effective inside or outside the cell , and may be incorporated into cells or structures by various methods . the present invention , in a preferred embodiment , may also be useful to affect organ regeneration . the present invention , in a preferred embodiment , may be useful to affect or modify cells which have been manipulated or altered ( by genetic engineering or other cell modification technology ) so that the cells may be stimulated or inhibited . cells may be made more or less productive , active , to multiply , to die , etc ., so that the cells respond more favorably than normal or native cells to any of the processes described herein . this could make subcellular components , systems , or organelles behave in like manner as described above ( e . g . could make the cell “ energy factories ”— the mitochondria — more productive or photoactive , etc ., or make changes to cellular dna and / or rna that would alter response to treatments described herein ). changes in the telomere may alter the cellular division “ limit ” or remove limits on the functioning or multiplication capabilities of selected cells or cell lines . the present invention , in a preferred embodiment , may be useful to insert , inject , or otherwise place fibroblasts ( including fetal , autologous , donor , or genetically engineered fibroblasts ) into the skin ( or into wounds , etc ), associated with a collagen ( including fetal collagen ), synthetic or bioengineered matrix . light therapy , ultrasound therapy , topicals , or a combination of these may be useful to stimulate the treated area . current commercially available materials that may be used for this purpose may include , for example , appligraf , dermologen , isolagen , zyderm , zyplast , and other similar products or mixtures thereof . for example , the present invention may be useful to treat chronic skin ulcers . such skin ulcers may be pretreated in accordance with the present invention to prepare or stimulate the wound bed . appligraf may then be applied . the ulcers may be postreated in accordance with the present invention to stimulate or activate fibroblasts ( including fetal fibroblasts ) and to enhance wound healing . meanwhile , the treatment may be supplemented by providing precursor substance intravenously . the present invention , in a preferred embodiment , may be useful to add “ precursor substances ” in appropriate concentrations , forms , etc . that may enhance or facilitate appropriate metabolic pathways . the precursor substances may be added prior to , during , after , or at any time relative to the time of treatment ( s ) to maximize the effects of stimulation ( or inhibition ) by light therapy or ultrasound therapy ( or both , since ultrasound therapy may help enhance permeability for large molecules ). the maximum effectiveness of a product may thereby be obtained from the stimulation ( inhibition ). such precursor substances may include , but are not limited to , chemicals , enzymes , cofactors , etc . ( for example , for collagen ( including fetal collagen ) synthesis the precursor substances may include : ascorbic acid , iron , proline , hydroxyproline , etc .). such precursor substances could also be oral or parenteral ( e . g ., delivered intravenously for wound healing ). it is also possible to add ( any route , not just skin ) inhibitors of breakdown of the substance whose increased production is desired ( e . g . for elastin could use substances which inhibit elastase enzyme . for collagen ( including fetal collagen ) could use inhibitors of metalloproteinases also formerly known as collagenases ). these inhibitors could be direct or could work in an indirect manner to either increase activity / quantity of other native or exogenously added inhibitors or to decrease activity / quantity of the substance that produces the breakdown . the present invention , in a preferred embodiment , may be useful to stimulate or activate new skin substitutes , wound healing agents or dressings that contain fibroblasts ( e . g . appligraf ). the present invention , in a preferred embodiment , may be useful to directly stimulate ( or inhibit ) the hair follicle itself or to deliver stimulating to the follicle or perifollicular support structures , including follicle vascular supply . for example , the present invention may be useful to enhance the healing of transplanted hair and / or to stimulate the growth of transplanted hairs . similarly , the present invention may be useful to enhance the survival of and / or improve the healing of skin grafts and tissue transfers . the present invention , in a preferred embodiment , may be useful to stimulate or inhibit ( through the eye or through the skin , perhaps via blood vessels close to skin surface ) endogenous hormone activities ( e . g . melatonin production ) or drugs in order to affect , alter , adjust sleep cycles , jet lag , insomnia , and perhaps seasonal affective disorder or even depression . for example , a small electronic unit in accordance with the present invention and containing a fiber optic device or led could be strapped to a travelers arm or leg before , during and / or after jet travel to help reduce or eliminate the effects of jet lag . the present invention , in a preferred embodiment , may be useful to affect certain infectious processes where the organisms may be reachable by these techniques and also where the organisms may be susceptible to being reduced or killed by light stimulation or simply by heat itself from either of these modalities ( e . g ., nail fungal infections , chronic wounds , venous or diabetic ulcers , etc .). the present invention , in a preferred embodiment , may also be delivered by using , whether serially or simultaneously , different wavelengths of light or multiple wavelengths of light ( with either same or different parameters ). the present invention , in a preferred embodiment , may be useful in targeting amino acids in the hair shaft . for example , the present invention could be used to facilitate the destruction of hairs ( hair removal ) or to stimulate hair activity ( growth or regrowth of hair ) or to affect the cosmetic appearance or style of hair . the present invention may be useful in altering the amino acids in hair to change the color and / or the curliness or straightness of the hair . the present invention , in a preferred embodiment , may be useful in delaying aging , or at least delaying the outward appearance or cosmetic manifestations of aging in skin and other cells and tissues . preventing or diminishing the production or activity of skin matrix metalloproteinases ( mmp ) may help to prevent or diminish the degradation of existing or newly formed collagen and skin dermal matrix . the present invention may be useful as periodic treatment to counter the adverse effects of photaging . various processes and events produce or promote their activities . for example , ultraviolet light exposure produces photoaging of the skin and solar scarring of the skin . if the objective is to stimulate the production of new collagen , or to inject or implant fibroblasts ( or cover a wound with them ) with or without being kept on a latticework or matrix of some type of already formed collagen , then premature degradation is undesirable . likewise , degradation of the newly formed collagen is undesirable . the presently disclosed embodiments are to be considered in all respects as illustrative and not restrictive , the scope of the invention being indicated by the appended claims , rather than the foregoing description , and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein .

US-16868398-A

the device is implantable in the living body for attachment and augmentation of tendons and / or reinforcement of bones . it comprises a substantially flat membrane having a rounded outer shape and at least two perforations . the membrane contains resorbable or degradable polymeric and / or polymeric - ceramic material , having a young &# 39 ; s modulus in the range of 1 to 50 gpa and a tensile strength in the range of 0 . 1 to 20 . 0 gpa . it allows a more secure fixation of transosseous sutures .

fig1 shows a device according to the invention consisting of a substantially flat membrane 1 having a rounded outer shape , with the approximate dimensions of 5 . 0 × 10 . 0 × 1 . 4 mm , having two pairs of lateral holes 2 , 3 and 4 , 5 with diameters in the range of 0 . 2 to 2 . 5 mm , and preferably 1 mm , to house the suture . all edges of the device are rounded to prevent irritation of the tissue and diminish the chance of suture damage due to friction . the surface 6 of the device which faces the tendon has 0 . 5 mm long spikes 7 to prevent slippage of the device on the tendon . the opposite surface 8 of the flat membrane 1 of the device is strengthened by incorporation of three bars 9 of the same material as the membrane 1 . fig2 a , 2b and 2c show a tendon augmentation device according to the invention which has a circular shape in the form of a disk 10 . the diameter of the disk 10 is about 8 mm and its thickness about 2 mm . the disk 10 has two or three 0 . 5 mm thick reinforcing bars 11 of the same material as the disk to support the suture and two holes 12 with a diameter of 0 . 5 to 1 . 3 mm to house the suture and two cuts 13 at the edges of disk 10 to protect against slippage of the suture over the device . the surface 14 of the device facing the tendon has rounded edges 15 to diminish irritation and 0 . 5 to 1 . 0 mm long spikes 16 to prevent slippage of the device on the tendon . as illustrated in fig3 the tendon augmentation device 1 according to fig1 is used for repairing and augmenting a disrupted tendon in a living body . the surgical method comprises the following steps : a . placing the augmentation device 1 intraoperatively on the surface 17 of the tendon 18 . b . pulling proximally , along the tendon direction , the suture 19 from the cut end of tendon 18 , towards its outer surface . c . pulling the suture 19 through the tendon 18 and one pair of two lateral holes 3 , 2 and towards the outer surface of the tendon 18 . d . pulling the suture 19 back through the tendon 18 and the other pair of lateral holes 4 , 5 towards its outer surface . e . pulling the suture 19 longitudinally through the tendon 18 to its distal cut end . once fixed to the tendon the membrane 1 prevents the suture 19 from cutting through the tendon 18 at the point of highest stress ( pulley ). the same operative technique is illustrated in fig4 when a pair of disk - shaped devices 10 according to fig2 are used . the operative method comprises : a . placing a first device 10 according to claim 5 on the surface 17 of the tendon 18 . b . pulling proximally , along the tendon direction , a suture 19 from the cut end 20 of tendon 18 towards the device 10 and through one of its holes 12 to its outer surface . c . pulling the suture 19 through one of the cuts 13 into the tendon 18 towards to outer surface of the tendon 18 . d . pulling the suture 19 back into the tendon 18 through the other cut 13 and the other hole 12 and again into the tendon 18 . e . pulling the suture 19 longitudinally through the tendon 18 to its distal cut end . f . placing a second device 10 according to claim 5 on the surface 17 of the tendon 18 and performing steps b to e . in vitro tests showed that the use of resorbable tendon augmentation devices according to the invention for the augmentation of the supraspinatus tendon , increased the pull out strength up to 469n ( 126 %), as compared with the nonaugmented suture technique ( with a tensile strength of 371n only ). fig5 shows a bone augmentation device consisting of a membrane 20 similar to the one used for the tendon augmentation device according to fig1 . it is fashioned into a rectangle , preferably with dimensions of 5 . 0 × 10 . 0 × 1 . 4 mm , with rounded edges to prevent irritation of the surrounding tissue and diminish friction between the suture and the device . the membrane 20 has two holes 21 , 22 and three reinforcing bars 23 . intraoperatively the device according to fig5 is placed onto the osteoporotic bone of e . g . the humeral head . the suture is pulled through the holes 21 , 22 while the device acts as a washer . in vivo tests in the sheep with the resorbable device according to fig5 to augment the bone showed to increase its holding power to 398n ( 520 %), as compared with 76n for the nonaugmented cancellous bone . it allows therefore a more secure fixation of transosseous sutures to the bone . a similar surgical technique is used for the bone augmentation device but care should be taken that the holes drilled into the bone have identical distances between them as in the device to be secured to it in order to prevent cutting the bone by the suture material and diastasis which can be formed when the bone is cut . to achieve a high accuracy which is desirable it is recommended to use a special drill guide 22 as shown in fig6 with guiding holes 21 corresponding exactly to the holes 12 of the device 10 to be secured to the bone . the use of both , the tendon and the bone augmentation devices according to the invention have several advantages as compared with existing repair techniques . thus , it reduces diastasis between the tendon and the bone being the main problem in the rotator cuff tear repair , it protects against tendon strangulation and cutting through the tendon and the osteoporotic bone at the place of fixation . the use of resorbable augmentation devices according to the invention has also additional advantages , i . e . once the device is resorbed , it no longer affects the already critical blood supply . the tendon and bone augmentation device according to the invention can be prepared using one of the common techniques applied to polymer processing , e . g . injection - moulding , extrusion , compression - molding , solution - casting , etc . the devices can be produced as a composite device consisting of a resorbable polymer reinforced with resorbable polymeric and / or glass fibres . i . a nonporous membrane with dimensions of 5 . 0 × 10 . 0 × 1 . 4 mm was prepared by casting from 10 wt .-% solution of poly ( l - lactide ) in chloroform at room temperature . poly ( l - lactide ) with viscosity - average molecular weight of 350 . 000 daltons used for preparation of the membrane was purified twice by dissolution in chloroform followed by precipitation with a methanol / water mixture . membranes were dried to constant weight in vacuum oven at 70 °. augmentation devices of the required size were cut out from the membranes using a steel stamp . when used to augment the supraspinatus tendon they increased the pull out strength of the tendon to 470n as compared with 370n for nonaugmented tendons . ii . a nonporous membrane with dimensions of 5 . 0 × 10 . 0 × 0 . 7 mm was prepared by casting from 7 weight - percent solution of poly ( l - lactide ) with a viscosity - average molecular weight of 350 . 000 daltons in chloroform . when used to augment osteoporotic bone it increased the holding strength of the bone from 70n to 270n . iii . a nonporous membrane with dimensions of 5 . 0 × 10 . 0 × 1 . 4 mm was prepared by injection molding of highly purified poly ( l - lactide ) with a viscosity - average molecular weight of 340 . 000 daltons . the polymer was dried and kept under vacuum prior to injection - moulding to diminish thermomechanical degradation . the augmentation device placed on osteoporotic bone of the humeral head increased the holding strength of the bone from 75n to 400n . iv . a porous membrane with porosity in the range in the range of 0 . 5 to 1 . 0 μm and dimensions of 5 . 0 × 10 . 0 × 2 . 0 mm was prepared by solution casting from poly ( l - lactide ) with molecular weight of 240 . 000 daltons . the augmentation device was cut out from the membrane using a steel stamp with a suitable shape . reinforcing bars pressed in the microporous device using a suitable mould / hydraulic press system . the augmentation device placed on osteoporotic bone of the humeral head increased the holding strength of the bone from 80 to 310n . v . several manufacturing processes can be used to include reinforcing bars into the augmentation devices : the mould used for preparation of the augmentation device has a shape which allows formation of the reinforcing bars in one injection - molding operation ; the polymer ribbon is extruded through a nozzle having a shape of a device with the reinforcing bars . the final device is cut out from the ribbon using a suitable stamp . a membrane is prepared by solution casting . next the membrane is placed in a mould with a suitable shape and subsequently compression moulded at temperatures in the range of 80 ° to 110 ° c .

US-29797594-A

modified anterior or posterior fusion plates and interbody fusion devices have been developed that contain slots to allow the use of pins to position and to guide the placement of the plate while the screws are being secured , reducing the likelihood of improper placement and localization of the plate and screws . this reduces the amount of time required for the operative procedure , and prevents inadvertent introduction of the screws for the plate into the former pin holes . this system allows the surgeon to carefully identify the geometry of the vertebral bodies at the outset of the case , when there is no significant bleeding , and when the field is clearly visualized , to determine the placement of the distracting pins . then , the careful placement of the distracting pins serves as the guide and basis for placement of the plate and screws .

placement of a distraction pin early in the course of an anterior cervical spine operation is commonly done to allow accurate distraction of the disc space and promote a thorough decompression of the spinal cord and nerve roots . the distraction pins are generally placed in the midline of the vertebral body at a 90 degree angle to the vertebra . this position is ideal for reference throughout the operation . because the distraction pins are placed early in the operation , prior to distortion of the anatomy by surgical dissection , they represent the most accurate reference site for placement of an anterior cervical plate . an anterior cervical plating system has been designed to reference the size and location of the cervical plate from the distraction pins in the vertebral body . the distraction pins serve several functions besides vertebral distraction during decompression , allowing correct sizing of the plate , compression of the bone graft during plating and provisionally securing the plate during drilling of the screw holes and application of the screws . in this way , the surgeon can move immediately from the decompression to grafting and plating without the need of removal of the distraction pins . the distraction pins provide rapid and accurate information on the size of the plate and allow graft compression and provisional plate fixation . a series of complex surgical steps is simplified into a simple exercise using the distraction pins in this way . the plate incorporates a series of other features designed to promote ease of application and flexibility of use during anterior cervical plating . these features included “ windows ” in the plate to allow visualization of the bone graft , variable angled screws , a simple screw locking mechanism ( requiring no additional steps ), a sliding segment to allow fixation of intervening vertebral bodies and a reference guide for drilling screw holes that allows accurate placement of the screws based on the position of the distraction pins . distraction pins are inserted into the vertebral body , but contain a mechanism to capture the anterior cervical plate . the pins are designed with a “ stop ” ( expanded portion to prevent over drilling of the pin ) and a second “ lip ” under which the plate is captured and provisionally held during plating . the distractor pins currently in use have a broad flange that prevents their removal if a plate is placed on top of the flange . this problem is obviated by the design of the pins described herein to allow placement of the plate with the distractor pin positioned within the veterbral body but still capable of being easily removed . the anterior cervical plate has an adaptation at each end to allow the ends of the plate to be secured by the distraction pins . the adaptation is an indention in the plate at each end with a thin portion that can be captured under the “ lip ” of the distraction pin . alternatively , the plate can have holes in each end allowing it to slide over the distraction pins . the anterior cervical plate also contains “ windows ” over the edges of the bone graft so that the graft / vertebra junction can be visualized accurately during plating . the anterior cervical plate has a mechanism to allow variable angulation of the screw while allowing the screws to be attached to the plate without the need for separate steps . this consists of “ expandable bushings ” that can rotate in desired directions within the plate . these bushings are internally threaded to allow screws to be placed through the bushings . the screws can thus be angled in a desired direction . the screws are designed with a screw head that expands the bushing during terminal seating of the screw so that the bushing is expanded and fixed in position to the hole in the plate . in addition , the screw head has a shape that prevents it from loosening or backing out once it is well seated into the expandable bushing . the anterior cervical plate may also contain a sliding segment or segments to allow fixation of intervening vertebral bodies with screws . this consists of cross member ( s ) that can be attached to the lateral structures of the plate . these cross member ( s ) have screw holes with expandable bushings to allow the placement of vertebral screws . the cross members can be adjusted in position towards the top of bottom of the plate such that they are optimally positioned over an intervening vertebral body . the slots allow for positioning of the plates after placement of the pins but prior to removal . the pins may include a sleeve to enhance retention of the pin in the slot during placement . alternatively , the slot may be ridged or beveled to retain the pin within the slot during placement . the drill guide for screw placement is designed so that accurate angulation of the drill holes can be referenced from the distraction pins . the pins can be used to introduce hemostatic agents , such as bone wax , to prevent bleeding once they are removed . these plates , pins and drill guides , and method for installing this system upon a patient &# 39 ; s spine , overcome the drawbacks of the prior art by allowing a desired level of compression to be applied to the adjacent vertebrae surrounding the site of a corpectomy or discectomy , prior to , and during , the anchoring of the fusion plate . furthermore , the fusion plate system and method results in the fusion plate being properly centered upon a patient &# 39 ; s spine , so that an aesthetically pleasing , as well as functional , surgical result is achieved . the system and method uses distractor pins to properly guide the fusion plate to a centered positioning upon a patient &# 39 ; s spine . once guided onto the spine , the fusion plate is anchored with bone screws . the distractor pins are centered on the spine using anatomical landmarks such as the longis colli muscles or uncinate processes . plates and pins are preferably made of surgical stainless steel or titanium . most other materials lack sufficient strength under stress . as shown in fig1 , the plate 10 has holes 12 a , 12 b , 12 c , 12 d , 12 e , and 12 f , for screws to secure the plate 10 to the vertebrae . the plate has slots 14 a and 14 b for placement of distractor pins 16 , shown in fig2 a , 2 b and 2 c . the slots 14 a , 14 b allow placement , manipulation , and removal of pins after insertion of screws through holes 12 a - 1 f . another embodiment of the plates is shown in fig3 a - 3d . these plates 18 have fully enclosed slots 19 for pin placement . the plates will typically be provided in several sizes , typically ranging from 20 to 70 mm . these are used to accommodate different sized bones . a pin 20 is shown in fig4 . the pin has a threaded bone entry end 22 , a sleeve 24 , and a multi - faceted tool fitting 26 . the pins are used to distract the discs and to place the plate . these guide the plate as well as secure the plate until the screws are positioned . unlike conventional plates , the pins are not removed until after the plates are secured with the screws . the pins allow compression across the plate before attaching the screws , thereby enhancing the likelihood of a successful fusion . the sleeve , typically formed of an elastomer or polymeric material such as polypropylene , or formed of a ridged metal as an integral part of the slot , holds the pin in place within the slot in the plate as it is screwed in . this makes it possible to position the pins using only one hand , instead of requiring one hand to turn the pin and one hand to hold the pin in the plate . unique features of the pins include that they can be pushed apart , the plates put into position , then used to compress the opening prior to securing the screws . in contrast , current systems require removal of the pins prior to placement of the plate and positioning of the screws . this is achieved through the use of the slots at each end of the plates . with conventional plates , some of the compression is lost during the interval between placement of the screws and removal of the pins . this system also allows more bone graft to be used . typically , the hole left by removal of the pins will be filled with bone wax or other sealant to prevent bleeding . plates , screws and pins are typically provided in a sterile kit or kits . the kit may also include tool ( s ) for placement of the pins and / or screws such as drills , taps , and drivers . the physician will select the appropriately - sized plate for fixation to the vertebral bodies . a properly sized plate will bridge the affected segments without overhanging into adjacent disc space . the pins are inserted into the placement tool and screwed into the vertebral bodies . the plate is then positioned with the pins holding the plate in place . screw holes are drilled and then the screws inserted . the screws may be self - drilling or self - tapping screws , with cutting or blunt tips . the pins are then removed after the screws are secured . in the preferred embodiment , the method of using the plates and pins described herein is as follows : use distractor system used to push pins apart ( i . e ., distract ) to expand the disc space ; select appropriately sized plate that is defined by the space between the pins ; modifications and variations of the claimed pins and plates and methods of use thereof will be obvious to those skilled in the art and are intended to come within the scope of the appended claims .

US-97368510-A

a supply device for the operation of at least one medical instrument , in particular an electrosurgical instrument and / or a cryosurgical instrument and / or a water jet surgical instrument . the supply device includes a control unit for the control of the at least one medical instrument and a memory unit for the storage of configuration data which describe a state device with a plurality of states . the control unit is designed such that it reads in configuration data and converts the state device into a control program and controls the at least one medical instrument according to the control program . this ensures efficient control of medical instruments because the control programs used can be more efficiently checked for their correctness and updated accordingly .

fig1 shows a supply device 30 which is connected via a first hf line 31 to an electrosurgical instrument 20 . a second hf line 31 ′ leads to a neutral electrode 21 . the instrument 20 has a further electrode for the application of an hf voltage u which is provided by the supply device 30 . thus , the hf voltage u can be applied between the neutral electrode 21 and the further electrode . as shown in fig1 , the neutral electrode 21 and the further electrode of the electrosurgical instrument 20 can be used to introduce an hf current i into a biological tissue . fig1 shows a torso 1 to which the self - adhesive neutral electrode 21 is attached . the further electrode of the electrosurgical instrument 20 is used to cut or coagulate the tissue on the other side of the torso 1 . as shown in fig2 , the supply device 30 has a control unit 40 and an hf generator 50 . the hf generator 50 serves to provide a suitable hf voltage u for the electrosurgical instrument 20 and the neutral electrode 21 . the control unit 40 controls the hf generator 50 by sending control signals to the hf generator 50 and receiving sensor signals from the hf generator 50 , which provide information about the state of the hf generator 50 as well as the applied hf current i and the hf voltage u . the sensor signals received can also provide information on tissue impedance r , an hf power p or a power factor cos φ . the control unit 40 is preferably designed to provide a plurality of different operating modes which , for example , have an effect on the hf voltage u or hf power p . thus , the control unit 40 can offer a mode for coagulation and another mode for cutting tissue . in addition , further modes can be provided for different electrosurgical instruments 20 ( for example , for monopolar or bipolar instruments ) or for different types of tissue ( liver or muscle tissue ). the supply device 30 has an input unit 70 , which makes it possible to receive inputs from a user of the electrosurgical instrument 20 . the user can thus select a certain operating mode using the input unit 70 and activate the control unit 40 such that the hf generator 50 , and thus the electrosurgical instrument 20 , are operated in this operating mode . to make the selection of a particular operating mode easier , and to display status information relating to the hf generator 50 and / or the control unit 40 and / or the electrosurgical instrument 20 , the supply device 30 further has an output unit 80 . the output unit 80 has a screen for displaying information . the control unit 40 is further in communicative connection with a memory unit 60 , which has an interface 63 via which configuration data can be loaded into the memory unit 60 . the control unit 40 has a time capture unit 44 , which issues sensor signals in the form of time signals that allow the capture of predetermined time intervals . in accordance with an embodiment of the invention , the memory unit 60 has a framework program that is executed by the control unit 40 . this framework program causes the control unit 40 to load configuration data from the memory unit 60 and to generate a control program , which enables the control of the instrument 20 connected to the supply device 30 . a table - controlled switching mechanism is preferably implemented here , which has a plurality of states z 0 to z 4 , the individual states z 0 to z 4 being adopted depending on specified boundary conditions . the configuration data stored in the memory unit 60 can here model a state machine 10 in a tabular manner . a corresponding state machine 10 is shown in fig3 . it includes the states z 0 to z 4 , the start state z 0 , for example , being adopted after the selection of a certain coagulation mode . starting from the initial state z 0 , the state machine switches to a first state z 1 . the state machine 10 has a plurality of transitions , trans 13 , trans 14 , trans 21 , trans 32 , which model transition to further states , namely to a second state z 2 , to a third state z 3 , to a fourth state z 4 . the transition trans 13 , for example , describes a transition from the first state z 1 into the third state z 3 . each of these transitions trans 13 , trans 14 , trans 21 , trans 32 is assigned a transition rule reg 13 / reg 14 / reg 21 / reg 32 respectively . the transition rule reg 13 belongs to the transition trans 13 and contains two conditions which , if satisfied , results in the control unit 40 switching from a control mode according to the first state z 1 into a control mode according to the third state z 3 . in the embodiment described in fig3 , the transition trans 13 is carried out when the impedance r is greater than 80 ohms or if the power factor cos φ is greater than 0 . 5 . transition rules reg 13 , reg 14 , reg 21 , reg 32 are conceivable in which a condition must be maintained over a specified time period . for example , it is conceivable that the transition trans 13 is only carried out if the power factor cos φ is greater than 0 . 5 for more than 5 milliseconds . starting from the first state z 1 , further transitions trans 13 , trans 14 , trans 21 , trans 32 are possible . a further transition trans 14 leads from the first state to the fourth state . the transition rule reg 14 is assigned to the transition trans 14 . the transition trans 14 is carried out in accordance with the transition rule reg 14 , when the control unit 40 has remained in the control mode according to the first state z 1 for longer than 1000 milliseconds ( dwell time t v is greater than 1000 milliseconds ). the transition trans 32 leads from the third state z 3 to the second state z 2 and is carried out according to the transition rule reg 32 when the hf power p is greater than 50 watts . the transition trans 21 leads from the second state z 2 to the third state z 3 and takes place after the second state z 2 has been adopted for a period longer than 1 , 000 milliseconds ( exemplary condition : dwell time t v greater than 1000 milliseconds ). this exemplary condition is given by the transition rule reg 21 . overall , the state machine 10 models a closed control algorithm which leads the control unit 40 from a start state z 0 through several intermediate states z 1 , z 2 , z 3 to a final state , namely the fourth state z 4 . each of the states z 1 to z 4 is preferably assigned setpoints in tabular form : an exemplary setpoint set for state zi is : u = 200 v ; i = 3 a ; and p = 120 w . an exemplary setpoint set for state z 2 is : u = 350 v ; i = 1 a ; and p = 300 w . an exemplary setpoint set for state z 3 is : u = 500 v ; i = 1 a ; and p = 120 w . an exemplary setpoint set for state z 4 is : u = 250 v ; i = 3 a ; and p = 90 w . the control unit 40 may be configured such that the individual setpoints are set as the control values . for example , the control unit 40 can emit control signals to the hf generator 50 , which set it so that the setpoints are met . it is frequently the case , however , that operation of the supply device 30 at the given setpoints is not possible . for these cases , the control unit 40 is configured to establish operating points at which settings or measured values are achieved that are as close as possible to the specified setpoints . in the aforementioned embodiment , a plurality of transitions , namely the transitions trans 13 and trans 14 , result from the first state z 1 . it is possible to assign priorities to the individual transitions trans 13 , trans 14 so that they are checked by the control unit 40 in a given order . for example , the transition trans 13 can be checked before the transition trans 14 . if , therefore , the conditions according to the transition rule reg 13 are satisfied at a given time at which the control unit 40 is in a control mode according to the first state z 1 , then the control unit will immediately switch to a control mode according to the third state z 3 . the transition rule reg 14 is checked only if the conditions of the transition rule reg 13 are not satisfied . in general , a control machine / state machine ( i . e ., device ) in accordance with an embodiment of the invention can be parameterized through a control table , which may include : ( 1 ) start setting : for example , with a setpoint for the start state z 0 ; ( 2 ) further states as resulting states : for example , the states zi to z 4 ; ( 3 ) transitions : exemplary transitions trans 13 , trans 14 , trans 21 , trans 32 ; and ( 4 ) transition conditions : exemplary transition rules reg 13 , reg 14 , reg 21 , reg 32 . the transition conditions can relate to thresholds or changes of slope of measured variables or to absolute values ( for example , r greater than 200 ohms ) or to relative values ( for example , r greater than 10 % of the last value measured ). alternatively , frequencies ( for example , in how many measurements was r greater than 200 ohms ) or time interval ( for example , dwell time t v = 300 milliseconds ) can be taken into account . the transition conditions can also include combinations of transition conditions ( for example , logical and / or operations ). an example of a control table for the instrument 20 is shown below , which essentially corresponds to the configuration of fig3 . the time frame of the jump conditions = i00 μs . jump 1a : if rload & gt ;= 80 ohms once , then switch to state 3 jump 1b & gt ;& gt ;& gt ; cos phi & lt ; 0 . 5 (= lf 16384 ) & lt ;& lt ;& lt ; jump 1b : when lf & lt ; 16384 fifty times , then switch to state 3 jump 3a : if p_hf & gt ; 50 w once , then switch to state 2 in the preceding embodiments , control programs for electrosurgical instruments were described to illustrate the invention . however , it should be apparent to a person skilled in the art how the invention can be used to control cryosurgical instruments and / or water jet surgical instruments . in this context , it must also be noted that the setpoints may also relate to mechanical activities , such as activation and deactivation of a valve . for example , a setpoint may relate to the opening or closing of a valve . furthermore , it is conceivable that a setpoint relates to a position in a three - dimensional coordinate system to which a device , for example a robot arm , is to move . the setpoint can also indicate that the tip of an electrosurgical instrument is extended or retracted . thus , the individual states can be linked to a plurality of mechanical activities which are carried out by the electrosurgical instrument or the supply device .

US-201013497108-A

a method of testing the integrity of a membrane of at least one filter located along a dialysis solution circuit . the method includes the steps of wetting the test membrane with an aqueous solution , expelling the aqueous solution from the filter , filling a fill chamber of the filter with a given quantity of gas after closing the gas flow lines from the fill chamber , and detecting gas flow through the membrane , which bounds the fill chamber .

fig1 is a schematic view of portions of a dialysis machine 1 in accordance with one embodiment of the present invention . as shown in fig1 , the dialysis machine 1 comprises a known haemodialysis filter 2 ( not described in detail ), an artery line 3 for feeding blood from a patient p to filter 2 , a pump 3 a fitted to artery line 3 to ensure blood flow , a vein line 4 for feeding blood from filter 2 to patient p , a drip chamber 5 located along vein line 4 , and a dialysis solution circuit 6 . in the illustrated embodiment , the dialysis solution circuit 6 comprises a preparation device 7 , an inflow branch 8 for feeding dialysis solution to filter 2 , a first sterile filter 9 along inflow branch 8 , a substitution - fluid line 10 for feeding substitution fluid from first sterile filter 9 to drip chamber 5 , a second sterile filter 11 along substitution - fluid line 10 , a pump 12 located along substitution - fluid line 10 , downstream from second sterile filter 11 , a dialysis solution outflow branch 13 from filter 2 , and a flow gauge 14 through which inflow branch 8 and outflow branch 13 extend . inflow branch 8 and outflow branch 13 are fitted with respective pumps 15 and 16 . as shown , the first and second sterile filters 9 , 11 each comprise a pair of chambers 9 a , 9 b and 11 a , 11 b , with each pair separated by a hydrophilic membrane 9 c , 11 c , respectively . in various embodiments , the membranes 9 c , 11 c are configured to prevent bacteria or endotoxins in the dialysis solution from passing from the chambers 9 a , 11 a to the chambers 9 b , 11 b , respectively , of the filters 9 , 11 . inflow branch 8 comprises a first bypass solenoid valve 17 for bypassing the chamber 9 a of first sterile filter 9 and connecting inflow branch 8 , by means of a connecting line 10 a , to chamber 9 b of the first sterile filter and , hence , to substitution - fluid line 10 , which , in the example shown , extends from chamber 9 b of filter 9 . inflow branch 8 also comprises a second bypass solenoid valve 18 for bypassing haemodialysis filter 2 and connecting inflow branch 8 directly to outflow branch 13 , either upstream or downstream from a solenoid valve 18 a , depending on the operating mode employed . dialysis machine 1 comprises a first drain line 19 connecting chamber 9 a of first sterile filter 9 to outflow branch 13 , and a second drain line 20 connecting chamber 11 a of second sterile filter 11 to outlet branch 13 . drain lines 19 , 20 are fitted with respective solenoid spill valves 19 a , 20 a , which are opened periodically to wash the membranes of filters 9 and 11 and prevent accumulated bacteria and endotoxins from impairing operation of the filters . dialysis machine 1 also comprises a test line 21 connecting substitution - fluid line 10 , downstream from second sterile filter 11 , to outflow branch 13 . finally , in the illustrated embodiment , the dialysis machine 1 comprises an antibacterial filter 22 for filtering outside air , a solenoid valve 23 for switching the fluid source of inflow branch 8 from preparation device 7 to antibacterial filter 22 , and an air sensor 24 located along outflow branch 13 , downstream from the connections to drain lines 19 , 20 and test line 21 . the sensor 24 can be of any type suitable for detecting fluid flow through the outflow branch 13 . in one embodiment , the sensor 24 may be an ultrasound sensor . in one embodiment , the sensor 24 may be an optical sensor . in various embodiments , the sensor 24 may be a continuous - reading type sensor . in other embodiments , other types of sensors may be utilized . in actual use , once dialysis treatment is completed , the dialysis machine 1 is switched from dialysis mode to wash / test mode . after dialysis solution circuit 6 has been flushed with an aqueous solution , e . g . the dialysis solution itself , solenoid valve 23 is switched to antibacterial filter 22 to feed circuit 6 with air from antibacterial filter 22 as opposed to the dialysis solution from preparation device 7 . at the same time , the outlet of chamber 9 b of first filter 9 is closed by closing solenoid valve 18 a and switching bypass solenoid valve 18 to the circuit portion upstream from solenoid valve 18 a , the outlet of chamber 11 a of second filter 11 is closed by closing solenoid valve 20 a . in addition , the solenoid valve 17 is set to connect inflow branch 8 directly to substitution - fluid line 10 , so that the air pumped by pump 15 is fed into chamber 9 b of first sterile filter 9 and into chamber 11 a of second sterile filter 11 to expel the liquid from the filters . in the event of damage to either one of membranes 9 c , 11 c separating chambers 9 a and 9 b and chambers 11 a and 11 b respectively , air flows along drain line 19 or test line 21 , and is detected by sensor 24 . more specifically , comparison of the information from sensor 24 with a reference threshold determines the integrity or not of membranes 9 c and 11 c and , hence , of filters 9 and 11 . moreover , by acting on solenoid valve 19 a , the integrity first of membrane 11 c and then of membrane 9 c can be tested separately . fig2 is a schematic view of portions of a dialysis machine 30 according to another embodiment of the present invention . parts identical to those of dialysis machine 1 are indicated using the same reference numbers , with no further description . as can be seen in fig2 , the dialysis machine 30 differs from dialysis machine 1 by comprising one three - chamber filter 31 as opposed to two sterile filters 9 and 11 ( see fig1 ), which means integrity testing of machine 30 applies to filter 31 and , more specifically , to the two membranes 32 and 33 dividing filter 31 into three chambers 31 a , 31 b , 31 c . as shown , dialysis machine 30 comprises a dialysis solution circuit 34 connected selectively to chamber 31 a or chamber 31 b of filter 31 , and a substitution - fluid line 36 connecting chamber 31 c of filter 31 to drip chamber 5 . in the illustrated embodiment , the inflow branch 35 comprises a bypass solenoid valve 37 which , in test mode , bypasses chamber 31 a of filter 31 to connect inflow branch 35 directly , along a connecting line 39 , to chamber 31 b . in normal operating mode , solenoid valve 37 connects inflow branch 35 to chamber 31 a of filter 31 , spill valve 38 a . as further shown , the dialysis machine 30 also comprises a drain line 40 connecting chamber 31 a directly to outflow branch 13 , and which is fitted with a solenoid spill valve 40 a . in actual use , once dialysis treatment is completed , dialysis machine 30 is switched from dialysis mode to wash / test mode . after dialysis solution circuit 34 has been flushed with an aqueous solution , e . g . the dialysis solution itself , solenoid valve 23 is switched to antibacterial filter 22 to feed circuit 34 with air from antibacterial filter 22 as opposed to the dialysis solution from preparation device 7 . at the same time , the outlet of chamber 31 b of filter 31 is closed by closing solenoid valve 18 a and switching bypass solenoid valve 18 to the circuit portion upstream from solenoid valve 18 a , and solenoid valve 37 is set to connect inflow branch 35 directly to chamber 31 b of filter 31 , so that the air pumped by pump 15 is fed into chamber 31 b of filter 31 to expel the liquid from the filter . in the event of damage to either one of membranes 32 , 33 , air flows along drain line 40 or test line 21 , and is detected by sensor 24 . as in dialysis machine 1 , comparison of the information from sensor 24 with a reference threshold determines the integrity or not of membranes 32 and 33 and , hence , of filter 31 . fig3 is a schematic view of portions of a dialysis machine 41 according to a third embodiment of the present invention . parts identical to those of dialysis machine 1 are indicated using the same reference numbers , with no further description . as can be seen in fig3 , the dialysis machine 41 differs from dialysis machine 1 by having no sensor 24 , and by comprising a solenoid valve 42 located between preparation device 7 and solenoid valve 23 to completely cut off inflow branch 8 when solenoid valve 23 is switched to preparation device 7 . in actual use , once dialysis treatment is completed , dialysis machine 41 is switched from dialysis mode to wash / test mode . after dialysis solution circuit 6 has been flushed with an aqueous solution , e . g . the dialysis solution itself , solenoid valve 23 is switched to antibacterial filter 22 to feed air into respective chambers 9 b and 11 a of filters 9 and 11 , in the same way as described for machine 1 . once chamber 9 b of filter 9 and chamber 11 a of filter 11 are filled with air , solenoid valve 23 is switched to preparation device 7 , and branch 8 is fed with a sufficient amount of fluid to further compress the air inside chambers 9 b and 11 a . at this point , solenoid valve 42 is closed , and flow along branch 8 is measured by differential flow gauge 14 . in other words , any damage to either one of membranes 9 c , 11 c would result in air flow and , consequently , flow of the fluid compressing the air , thus giving a flow reading of other than zero along branch 8 . as will be apparent to anyone skilled in the art , the test method and relative unit according to the present invention are controlled by a known central control unit not described or illustrated .

US-85043107-A

antiviral compounds and the water - soluble salts thereof have formula , wherein n is from 1 to 8 ; r 1 is selected from the group consisting of , wherein m is zero , 1 , 2 or 3 ; and , wherein q is from 1 to 20 ; r 2 is independently selected from the group consisting of oxygen and sulfur ; r 3 is independently selected from the group consisting of hydrogen and hydroxyl ; and r 4 is selected from the group consisting of hydrogen , hydroxyl and ; r 5 is selected from the group consisting of hydroxyl and ; r 6 is selected from the group consisting of , et , wherein x is from 1 to 20 ; provided that one of r 1 , r 4 and r 5 is wherein r 6 is defined as above ; or water soluble salt thereof .

according to the present invention , an aminoalkanoyl linkage serves as a biodegradable ester - bound spacer between a 2 ′- 5 ′- oligoadenylate molecule , or derivative thereof , and a ligand which promotes cellular uptake . the spacer is cleaved by intercellular esterases , thereby releasing the oligomer from the ligand . the 2 ′- 5a derivative conjugates of formula i may be prepared by attaching one of the following three cell uptake - promoting moieties to the 2 ′- or 5 ′- terminal nucleoside of a 2 ′, 5 ′- phosphodiester , 2 ′, 5 ′- phosphorothioate or a 2 ′, 5 ′- mixed phosphorothioate / phosphodiester oligonucleotide . the preparation of the 2 ′, 5 ′- phosphorothioates , including fully resolved enantiomers thereof , is disclosed in u . s . pat . no . 4 , 924 , 624 and is incorporated herein by reference . the substitution of sulfur for oxygen in the 2 ′, 5 ′- phosphodiester backbone referenced above , introduces chirality into the molecules and introduces a new chemistry of the backbone . the core 2 ′, 5 ′- phosphorothioates exhibit increased resistance to phosphodiesterase and phosphatases and new biological activities compared to authentic 2 - 5a cores . a mixture of phosphorothioate and phosphodiester linkages is possible in the same oligomer , providing molecules with a mixed phosphodiester / phosphorothioate backbone , as described in pct / us95 / 10683 , the entire disclosure of which is incorporated by reference . while the preparation and examples that follow are directed to conjugates of oligocordycepin derivatives , the conjugation described is equally applicable to the manufacture of oligomers comprising a chain of adenosine residues , or a mixed chain of cordycepin and adenosine residues as described in u . s . pat . no . 4 , 859 , 768 , the entire disclosure of which is incorporated by reference . the synthesis of cordycepin [ 21 ], its protected derivatives 4 and 5 [ 8 ], and the cordycepin - trimer derivative 27 [ 20 ] have already been described in the literature . for the protection of the spacer , 6 - aminohexanoic acid ( 1 ) was blocked at the amino function by reaction with n -{[( 9h - fluoren - 9 - yl ) methoxy ] carbonyl } oxysuccinimide ( 2 ) in a 9 % aqueous na 2 co 3 solution and dmf to give compound 3 in 78 % yield ( scheme 1 ). esterification of the cordycepin derivatives 4 and 5 with 3 worked well with the carbodiimide method applying n -[ 3 -( dimethylamino ) propyl ]- n - ethylcarbodiimide hydrochloride ( edc ) and 4 -( dimethylamino ) pyridine ( dmap ) as condensing agents to form the monomeric educts 6 and 7 in 90 and 80 % yield , respectively . the 2 ′- o - conjugates 8 and 9 were prepared first by cleavage of the ( 9h - fluoren - 9 - yl ) methoxycarbonyl ( fmoc ) protecting group from 6 with 3 % piperidine in dry dmf , followed by acylation with myristic and cholic acid , respectively , in the presence of o -{[ cyano ( ethoxycarbonyl )- methyliden ]- amino }- 1 , 1 , 3 , 3 - tetramethyluronium tetrafluoroborate ( totu ) and n - methylmorpholine . detritiylation to 10 and 11 proceeded in good yields ( 88 and 87 %), and subsequent elimination of the [ 2 -( 4 - nitrophenyl ) ethoxy [ carbonyl ( npeoc ) group resulted in 86 % yield of the myristic - acid conjugate 12 and in 78 % yield of the cholic - acid conjugate 13 . the structural analogues conjugated at 5 ′- o - position were synthesized in a similar manner first by deblocking the amino function in compound 7 and then by totu - activated amidation with myristic and cholic acid , respectively , to give 14 in 70 % and 15 in 76 % yield . deprotection with 1 , 8 - diazabicylo [ 5 . 4 . 0 ] undec - 7 - ene ( dbu ) gave 16 in 86 % and 17 in 67 % yield , respectively . starting material for the trimeric 2 ′- o - conjugates was compound 18 , which was prepared by acid treatment of 6 . stepwise condensation with 3 ′- deoxy - 5 ′- o -( monomethoxytrityl )- n 6 [ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenosine 2 ′-[ 2 -( 4 - nitrophenyl ) ethyl diisopropylphosphoramidite ] [ 22 ] gave , on subsequent oxidation of the intermediary phosphite triester , the fully protected dimer 19 in 89 % yield ( scheme 2 ). quantitative detritylation to the dimer 20 and further condensation and oxidation generated the trimer 21 in 94 % yield . similarly to the one - pot reaction of the monomers , the fmoc group in compound 21 was cleaved off by treatment with 3 % piperidine in dry dmf , and subsequent reaction with myristic or cholic acid by totu activation proceeded to the fully protected trimer conjugates 22 and 23 in 73 and 69 % yield , respectively . treatment with 2 % tsoh in ch 2 cl 2 / meoh 4 : 1 and further β - elimination of the npe / npeoc groups with dbu in dry pyridine gave the desired cordycepin - trimer conjugates 24 ( 78 %) and 25 ( 80 %). synthesis of the corresponding 5 ′- o - conjugates of cordycepin trimer was achieved by carbodiimide - activated esterification of the trimeric educt 27 [ 20 ] with the fmoc - protected amino acid 3 to give compound 28 in 79 % yield ( scheme 3 ). subsequent deblocking of the amino group and acylation with myristic and cholic acid gave conjugates 29 and 30 in 69 and 75 % yield , respectively . β - elimination of the npe and npeoc groups by dbu treatment generated the deblocked cordycepin - trimer 5 ′- o - conjugates 31 and 32 in 95 and 96 % yield , respectively . the approach to the folic - acid conjugates 26 and 33 did not allow to isolate the intermediary products due to their unusual and inconvenient physical properties . both trimeric educts , compound 21 and 28 , respectively , were treated in the first step with 3 % piperidine in dry dmf and then successively condensed with 6 equiv . of edc - activated folic acid . after evaporation , the crude product was treated with et 2 o and ch 2 cl 2 and then deprotected by dbu in dry pyridine . finally , the mixture was neutralized with acoh and evaporated , and the residue treated with mecn , and subsequently with 80 % acoh / h 2 0 , and centrifuged . the supernatant was evaporated and submitted to final hplc purification providing the desired conjugates 26 and 33 in relatively low yields . the compounds of the present invention may be combined with appropriate pharmaceutical or agricultural carriers to form an antiviral composition . for pharmaceutical use , the compounds of the invention may be taken up in pharmaceutically acceptable carriers , such as , solutions , suspensions , tablets , capsules , ointments , elixirs and injectable composition and the like . they are administered to subjects suffering from viral infection . the dosage administered depends upon the nature and severity of the infection , the disease stage , and , when administered systematically , the size and weight of the infected subject . the compounds are generally administered in the form of water - soluble salts . pharmaceutically acceptable water soluble salts include , for example , the sodium , potassium or ammonium salts of the active compounds . they are readily dissolved in water or saline solution . thus , the preferred formulation for pharmacological use comprises a saline solution of the desired compound in salt form . the formulation may further contain an agent , such as a sugar or protein , to maintain osmotic balance . the salt form of the compound is preferred owing to the relatively high acidity ( about ph 3 ) of the acid form of the compounds . the compounds of the invention may be used as a treatment for humans and animals from viral infectives such as herpes simplex , rhinovirus , hepatitis and other infections of the hepatitis virus family , epstein barr virus , measles virus , multiple sclerosis ( which may be caused by a viral agent ) and the various human immunodeficiency viruses (“ hiv ”), such as hiv - 1 , which causes cutaneous t cell lymphoma , hiv - 2 , which causes sezary lymphoma , and hiv - 3 , which is responsible for acquired immune deficiency syndrome (“ aids ”). the compounds of the invention inhibit hiv - 1 induced syncytia formation . the compounds may be applied topically to treat skin cancers caused by radiation , carcinogens or viral agents . such skin cancers include cutaneous t - cell lymphoma , sezary lymphoma , xeroderma pigmentosium , ataxia telangiectasia and bloom &# 39 ; s syndrome . a sufficient amount of a preparation containing a compound of the invention is applied to cover the lesion or affected area . an effective concentration of active agent is between about 10 − 3 m and 10 − 5 m , with 10 − 4 m being preferred . the compounds of the present invention may also be used to treat plant - infecting virus , particularly tobacco mosaic virus , and other viruses which cause necrosis in turnips , cucumbers , orchids and in other plants . such viruses include , but are not limited to , tobacco vein mottling virus , vesicular stomatitis virus , vaccinia virus , turnip necrosis virus , and cymbidium orchid virus . the compounds may be administered effectively to plants by topical application by abrasion of the leaf surface , aerosol spray , treatment of the soil , spraying , or dusting . an effective antiviral composition may be formed by combining one or more of the compounds of the invention with a carrier material suitable for agricultural use . the active compound may also be administered by spraying insect vectors such as aphids , thrips and whiteflies which carry virus to plants . the dosage administered depends upon the severity of the infection . the compounds of the invention may be applied to plant seeds prior to germination to control viruses contained in the germ plasm . the seeds may be soaked in a solution of polyethylene glycol (“ peg ”) containing one or more of the compounds . peg brings the seeds to physiological activity and arrest . the relative concentration of active compound to peg depends upon the type of seed under treatment . plants may be effectively treated with an aqueous formulation containing from about 10 − 1 to about 10 − 2 m concentration of active ingredient . the compounds of the invention may be applied at very low concentrations . an effective amount of active ingredient on the plant surface is from about 10 − 8 to about 10 − 12 mole per cm 2 of plant surface area , with about 10 − 10 mole to about 10 − 12 mole per cm 2 being preferred . for the typical tobacco plant , 10 − 5 m of compound is effective . at this rate , one pound of active ingredient is sufficient to treat 2 × 10 − 8 tobacco plants . for agricultural application , the compounds are advantageously administered in the form of water - soluble salts , e . g . ammonium or potassium salts . sodium salts are generally avoided in treating edible plants . the compounds of the invention are readily dissolved in water , particularly at such low concentrations . aqueous formulations for agricultural use may optionally contain a sticker and / or a uv - stabilizer . such agents are well - known to those skilled in the art . fatty acids ( 1 %) are useful as spreader sticker agents . effective uv - stabilizers include , for example , p - aminobenzoic acid . for antiviral use in mammals , the compounds of the invention are administered parenterally , such as intravenously , intraarterially , intramuscularly , subcutaneously or when administered as an anti - cancer agent , intratumorally . the preferred route of administration for antiviral therapy is intravenous injection . the compounds of the invention may be administered to mammals at very low concentrations . the actual dosage administered may take into account the size and weight of the patient , whether the nature of the treatment is prophylactic or therapeutic in nature , the age , health and sex of the patient , the route of administration , the nature and stage of the affliction , and other factors . an effective daily dosage of active ingredient , based upon in vivo studies involving other 2 - 5a analogues , is from about 0 . 25 g per 70 kg of body weight ( approximately 152 lbs ) to about 2 . 5 g per 70 kg of body weight . the preferred daily dosage is about 0 . 5 g per 70 kg of body weight . those skilled in the art should readily be able to derive appropriate dosages and schedules of administration to suit the specific circumstance and needs of the patient . it is expected that an effective treatment regimen includes administration of the daily dosage for two days . treatment is continued at least until the disease condition is substantially abated . preferably , the therapeutic end point is determined by testing for the continued presence of viral dna . such testing can be done by polymerase chain reaction ( pcr ) in which the presence of viral dna is assayed according to conventional pcr . pcr primers of appropriate nucleotide sequences for amplification of viral dna can be prepared from known viral nucleotide sequences . to obtain dna for testing , patient peripheral blood mononuclear cells are lysed with an appropriate lysing agent , such as np - 40 . alternatively , testing for the continued presence of the virus can be performed by an antigen - antibody assay using any of the known monoclonal or polyclonal antisera against a protein antigen of the target virus protein coat . for example , an antigen - antibody assay may be employed to detect any of the protein antigen in the virus hiv protein coat , for example , the gp120 , p17 or p24 . moreover , the target antigen is not limited merely to coat protein antigens . antisera can be targeted against a suitable non - coat protein antigen , such as the hiv reverse transcriptase ( rt ) molecule . monoclonal antibodies to hiv rt are known . sobol et al ., biochemistry 1991 , 30 , 10623 . additionally , testing for the presence of the infecting virus during or post - treatment could be accomplished by an assay which assesses the viral load in the patient &# 39 ; s blood stream . this can be done by determining syncytia formation . see procedure outlined in henderson et al ., virology , 1991 , 182 , 186 . in addition to administration with conventional carriers , the compounds of the present invention may be administered by a variety of specialized oligonucleotide or nucleic acid delivery techniques . 2 - 5a and its analogues have been successfully encapsulated in various encapsulating materials , such as in unilamellar liposomes and delivered with the aid of monoclonal antibodies to cells , bayard et al ., eur . j . biochem ., 1985 , 151 , 319 . reconstituted sendai virus envelopes have been successfully used to deliver rna and dna to cells , arad et al ., biochem . biophys . acta . 1986 , 859 , 88 . moreover , the virus envelope is not limited to sendai virus , but could include encapsulation in any retroviral amphotrophic particle . for example , an hiv envelope could be formed from any part or all of the outer protein coat of a non - infectious hiv particle . such particles as gp 120 can be cloned by known recombinant techniques . these techniques may be utilized for introduction of the present 2 - 5a oligoadenylate derivatives into cells . three studies were performed to determine the antiviral activity of the ( 2 ′- 5 ′) oligonucleotide derivatives of the present invention : ( i ) inhibition of hiv - 1 - replication , ( ii ) inhibition of hiv - 1 reverse - transcriptase ( rt ) activity , and ( iii ) activation of recombinant human gst - rnase l . the concentration of compound in the replication and rt assays was 300 μm , and 10μm in the gst - rnase l activation assay . the compounds tested were the cordycepin trimer folate conjugates 26 and 33 . cordycepin and the 2 ′, 5 ′- cordycepin trimer core (“ ccc ”) were also tested for comparison . the infected centers assay as described by henderson et al ., virology 1991 , 182 , 186 , was used to measure the ability of the conjugated trimer core compounds of the invention to inhibit hiv - 1 induced syncytia formation , an indicator of hiv - 1 replication in t cells . freshly isolated peripheral blood lymphocytes ( pbl ) were treated with cordycepin trimer core - folate conjugate 26 or 33 ( 300 μm ) for 2 hours and infected with hiv - 1 strain iiib at a multiplicity of infection of approximately 0 . 1 . the infected pbl were maintained in rpmi - 1640 medium supplemented with 10 % ( v / v ) heat - inactivated fetal calf serum at 37 ° c . in a humidified 5 % co 2 in air atmosphere . after 48 hours , the cells were washed twice in hank &# 39 ; s balanced salt solution , serially diluted and seeded into multiple wells of a 96 - well microtiter plate . immediately , 2 × 105 exponentially growing sup t1 cells were added to each well ; sup t1 cells readily form a syncytium with a cell which is productively infected with hiv - 1 . the wells were examined daily for the presence of syncytia , using a tissue culture microscope . the first signs of syncytia formation can be seen in 12 hours , with some complete syncytia developing by 24 hours . final results were read at 72 hours . each syncytium was counted as a single infected cell . the number of syncytia per seeded cell was determined and expressed as an infected center per infected cell . the number of syncytia per 104 cells was 144 for the control sup t1 cells . the data is shown in table 1 . the mean of triplicate determinations is shown ; variance did not exceed 5 - 10 %. sup t1 cells were treated with cordycepin trimer core - folate conjugate 26 or 33 ( 300 μm ) for 6 hours and then infected with hiv - 1 at a multiplicity of infection of approximately 0 . 1 . at 96 hours post - infection , culture supernatant was removed and hiv - 1 rt activity was assayed in triplicate as described by henderson et al ., virology 1991 , 182 , 186 . briefly in this method , 25 μl of culture supernatant was added to a 50 μl cocktail containing 50 mm tris ( ph 8 . 0 ), 20 mm dithiothreitol , 10 mm mgcl 2 , 60 mm nacl , 0 . 05 % nonidet p - 40 , 5 μg / ml oligodeoxythymidylic acid , 10 μg / ml polyriboadenylic acid , 10 μm deoxythymidine triphosphate and 1mci [ α 32 p ] thymidine 5 ′- triphosphate . the mixture was incubated at 37 ° c . for 2 hours . fifty microliters of the cocktail were then spotted onto diethylaminoethyl ( deae ) paper , dried , washed with 2 × ssc solution ( three times for 10 minutes each time ) and 95 % ethanol ( two times for 5 minutes each time ), dried and exposed to radiographic film for 18 to 24 hours at − 80 ° c . the filters were cut and final quantitation was determined by scintillation spectrometry . the data for the hiv - 1 rt activity is shown in table 1 as a percent of rt activity . control values for rt activity ranged from 24 , 000 to 33 , 000 dpm [ 32 p ] incorporated . the mean of duplicate determinations is shown in table 1 . variance did not exceed 5 - 10 %. human recombinant rnase l was expressed in e . coli ( dh5α ) as a fusion protein of glutathione - s - transferase ( gst ). activation of human recombinant gst - rnase l was measured as the percent of poly ( u )[ 32 p ] pcp hydrolyzed in the presence of cordycepin trimer core - folate conjugate 26 or 33 ( 10 μm ) as described by sobol et al ., j . biol . chem . 1995 , 270 , 5963 . the data is shown in table 1 as the mean of duplicate determinations . variance did not exceed 5 - 10 %. a inhibition of hiv - 1 replication was determined by hiv - 1 induced syncytia formation ( fold reduction in infection ) for each cordycepin - trimer folate derivative of 2 - 5a ( 300 μm ). the number of syncytia / 10 4 cells was 144 for the control sup t1 cells . the mean of triplicate determinations is shown ; variance did not exceed 5 - 10 %. b percent inhibition of hiv - 1 reverse transcriptase ( hiv - 1 rt ) activity was measured for each cordycepin - trimer folate derivative of 2 - 5a at 300 μm . control values for hiv - 1 rt activity ranged from 24 , 000 to 33 , 000 dpm incorporated . the mean of duplicate determinations is shown ; variance did not exceed 5 - 10 %. c the activation of recombinant human rnase l was measured as the percent hydrolysis of poly ( u )- 3 ′-[ 32 p ] pcp in the presence of the cordycepin - trimer folate derivative of 2 - 5a ( 10 μm ). the mean of a duplicate determination is shown ; variance did not exceed 5 - 10 %. inhibition of hiv - 1 rt activity with 26 and 33 was 45 and 81 %, respectively , compared to 96 and 13 % inhibition of hiv - 1 rt activity by the 2 ′- 5 ′- oligocordycepin trimer core and cordycepin , respectively . when folic acid is covalently linked to c ( 2 ′) at the 2 ′- terminus of the cordycepin trimer core as in 26 , gst - rnase l is not activated ; however , covalent linkage to c ( 5 ′) at the 5 ′- terminus as in 33 activates gst - rnase l by 35 %. these data suggest that the inhibition of hiv - 1 replication by 26 is due to inhibition of hiv - 1 rt . however , the 7 . 5 - fold reduction in syncytia formation by 33 is in part attributed to the inhibition of hiv - 1 rt activity and the activation of rnase l . the synthesis of the unphosphorlyated compounds of the present invention is illustrated by the following non - limiting examples . general . tlc : precoated silica gel tlc sheets f1500 ls 254 from schleicher & amp ; schüll . prep . tlc : silica gel 60 pf 254 ( merck ). prep . column flash chromatography ( fc ): silica gel for flash chromatography ( baker ). hplc : merck - hitachi l - 6200 , l - 3000 photo diode array ; detector ; column rp18 . 125 × 4 mm , 5 μm , merck ; flow rate 1 ml / min . uv / vis : perkin elmer lambda 5 ; λ max in nm ( log ε ). 1 h - nmr : bruker ac 250 , δ in ppm rel . to dmso . to a solution (“ soln .”) of 6 - aminohexanoic acid ( 1 ; 144 mg , 1 . 1 mmol ) in 9 % aq . na 2 co 3 soln . ( 2 . 4 ml ) was added a soln . of ( 9h - fluoren - 9 - yl ) methyl succinimidyl carbonate ( 2 ; 337 mg , 1 mmol ) in dmf ( 2 . 5 ml ). after stirring for 1 h at room temperature (“ r . t .”), the mixture was diluted with h 2 o ( 50 ml ) and extracted twice with et 2 o ( 2 × 20 ml ). then , the h 2 o phase was acified with conc . hcl soln . to ph 2 and extracted with acoet ( 5 × 30 ml ). the organic (“ org .”) layer was dried ( mgso 4 ) and evaporated . the residue was crystallized in chcl 3 / petroleum ether : 306 mg ( 86 %) of 3 . colorless crystals . m . p . 116 °. 1 h - nmr ( cdcl 3 ): 7 . 80 - 7 . 55 ( 2m , h — c ( 1 )( fmoc ), h — c ( 4 )( fmoc ), h — c ( 5 ) fmoc , h — c ( 8 )( fmoc ); 7 . 45 - 7 . 25 ( m , h — c ( 2 )( fmoc ), h — c ( 3 )( fmoc ), h — c ( 6 )( fmoc ), h — c ( 7 )( fmoc ); 4 . 45 ( m , ch 2 o )( fmoc )); 4 . 2 ( m , h — c ( 9 )( fmoc )); 3 . 25 - 3 . 0 , 2 . 4 , 1 . 8 - 1 . 3 ( 3m , nh ( ch 2 ) 5 co ). anal . calc . for c 21 h 23 no 4 ( 353 . 42 ): c 71 . 37 , h 6 . 56 , n 3 . 96 ; found : c 71 . 35 , h 6 . 65 , n 3 . 93 . a mixture of 3 ′- deoxy - 5 ′- o -( monomethoxytrityl )- n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenosine ( 4 ; 215 mg , 0 . 3 mmol ) [ 8 ], 3 ( 120 mg , 0 . 3 mmol ), n -[ 3 -( dimethylamino ) propyl ]- n ′- ethylcarbodiimide hydrochloride ( edc ; 58 mg , 0 . 3 mmol ), and 4 -( dimethylamino ) pyridine ( dmap ; 37 mg , 0 . 3 mmol ) in dry ch 2 cl 2 ( 4 ml ) was stirred at r . t . for 3 h , diluted with ch 2 cl 2 ( 60 ml ), and washed with sat . nahco 3 / naco 3 soln . ( 25 ml ). the aqueous (“ aq .”) phase was reextracted with ch 2 cl 2 ( 40 ml ), the combined org . layer extracted with 10 % citric acid soln ., the acid phase reextracted with ch 2 cl 2 , the combined org . layer dried ( mgso 4 ) and evaporated , and the residue purified by fc ( silica gel , 14 . 5 × 2 cm , toluene / acoet 1 : 1 then 1 : 1 + 3 % meoh ): 292 mg ( ca . 93 %) of 6 which was already contaminated with amino acid . a pure sample of 6 , was obtained by prep . tlc ( silica gel , 20 × 40 cm , chcl 3 + 4 % meoh ) of 138 mg of the crude product : 117 mg of 6 . uv ( ch 2 cl 2 ): 300 ( 4 . 00 ), 286 ( sh , 4 . 14 ), 272 ( sh , 4 . 58 ), 266 ( 4 . 66 ), 237 ( sh , 4 . 36 ). 1 h - nmr ( cdcl 3 ): 8 . 61 , 8 . 58 , 8 . 17 - 8 . 13 ( 3s , d , h — c ( 8 ), h — c ( 2 ), nh , 2 h o to no 2 ); 7 . 76 - 7 . 16 ( m , 8 h of fmoc . 2 h m to no 2 , 12 h of meotr ); 6 . 78 ( d , 2 h o to meo ); 6 . 13 ( d , h — c ( 1 ′)); 5 . 73 ( m , h — c ( 2 ′)); 4 . 89 - 4 . 15 ( m , nh ( ch 2 ) 5 co ), h ′ c ( 4 ′), och 2 ch 2 , h — c ( 9 )( fmoc ), ch 2 o ( fmoc )); 3 . 76 ( s , meo ); 3 . 5 - 3 . 35 ( m , 2h — c ( 5 ′)); 3 . 35 - 3 . 15 ( m , och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 65 ( m , h — c ( 3 ′)); 2 . 39 ( t , 1 ch 2 of nh ( ch 2 ) 5 co ); 1 . 7 - 1 . 2 ( m , 3 ch 2 of nh ( ch 2 ) 5 co ). anal . calc . for c 60 h 57 n 7 o 11 ( 1052 . 15 ): c 68 . 49 , h 5 . 46 , n 9 . 32 ; found : c 68 . 56 , h 5 . 67 , n 9 . 12 . as described in preparation 2 , with 3 ′- deoxy - n 6 , 2 ′- o - bis [ 2 -(- nitrophenyl ) ethoxy - carbonyl ] adenosine ( 5 ; 1 . 912 g , 3 mmol ) [ 8 ], 3 ( 1 . 166 g , 3 . 3 mmol ), edc ( 633 mg , 3 . 3 mmol ), dmap ( 403 mg , 3 . 3 mmol ), and anh . ch 2 cl 2 ( 10 ml ; 3 . 5 h ). workup with ch 2 cl 2 ( 150 ml ), nahco 3 soln . and 10 % citric acid soln . ( 80 ml ) and purification by fc ( silica gel . 7 . 5 × 4 . 5 cm , toluene / acoet 1 : 1 , then 1 : 1 + 2 % meoh ) gave 2 . 35 g ( 80 %) of 7 . amorphous solid . uv ( ch 2 ch 2 ): 297 ( 4 . 12 ), 286 ( sh , 4 . 31 ), 272 ( sh , 4 . 66 ), 266 ( 4 . 71 ). 1 h - nmr ( cdcl 3 ): 9 . 3 - 8 . 0 ( m , h — c ( 8 ), h — c ( 2 ), nh , 4 h o to no 2 ); 7 . 75 - 7 . 3 ( m , 8 h of fmoc , 4 h m to no 2 ); 6 . 12 ( s , h — c ( 1 ′)); 5 . 71 ( m , h — c ( 2 ′)); 5 . 18 ( t , nh ( ch 2 ) 5 co ); 4 . 65 - 4 . 15 ( m h — c ( 4 ′), 2 och 2 ch 2 , h — c ( 9 )( fmoc ), ch 2 o ( fmoc ), 2 h — c ( 5 ′)); 3 . 2 - 3 . 0 ( m , 2 och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 65 ( m , h — c ( 3 ′)); 2 . 25 ( m , h — c ( 3 ′), 1 ch 2 of nh ( ch 2 ) 5 co ); 1 . 65 - 1 . 15 ( m , 3 ch 2 of nh ( ch 2 ) 5 co ). anal . calc . for c 49 h 48 n 8 o 14 ( 972 . 97 ): c 60 . 49 , h 4 . 97 , n 11 . 52 ; found : c 60 . 83 , h 5 . 08 , n 11 . 15 . for acid activation , a mixture of tetradecanoic acid ( 128 mg , 0 . 56 mmol ), totu ( 184 mg , 0 . 56 mmol ), and n - methylmorpholine ( 57 mg , 0 . 56 mmol ) in absolute (“ abs .”) dmf ( 4 ml ) was kept at r . t . for 1 . 5 h . then 6 ( 490 mg , 0 . 466 mmol ) was treated with 3 % piperidine in abs . dmf ( 7 ml ; 10 min ) and evaporated . the above - mentioned soln . was added and the mixture stirred for 3 h at r . t . and evaporated . the residue was diluted with acoet ( 180 ml ), washed with nahco , soln . ( 2 × 80 ml ), the aq . phase reextracted with acoet ( 80 ml ), the combined org . layer dried ( mgso 4 ) and evaporated , and the residue purified by fc ( silica gel , 11 × 2 cm , toluene / acoet 1 : 1 + 2 % meoh , 1 : 1 + 3 % meoh ): 408 mg ( 84 %) of 8 . amorphous solid . uv ( ch 2 cl 2 ): 272 ( sh , 4 . 39 ); 267 ( 4 . 44 ), 237 ( sh , 4 . 30 ). 1 h - nmr ( cdcl 3 ): 8 . 38 , 8 . 18 ( 2s , m , h — c ( 8 ), h — c ( 2 ), 2 h o to no 2 , nh ( ade )); 7 . 45 - 7 . 20 ( m , 2h m to no 2 , 12h of meotr ); 6 . 79 ( d , 2 h o to meo ); 6 . 14 ( d , h — c ( 1 ′)); 5 . 73 ( m , h — c ( 2 ′)): 5 . 50 ( t , nh ( ch 2 ) 5 co ); 4 . 55 ( m , t , h — c ( 4 ′), och 2 ch 2 ); 3 . 78 ( s , meo ); 3 . 41 ( m , 2 h — c ( 5 ′)); 3 . 20 ( q , 1 ch 2 of nh ( ch 2 ) 5 co ); 3 . 15 ( t , och 2 ch 2 ); 2 . 6 , 2 . 2 ( 2m , h — c ( 3 ′)); 2 . 39 , 2 . 14 ( 2m , 2 ch 2 of nh ( ch 2 ) 5 co , 2 h of me ( ch 2 ) 12 co ); 1 . 7 - 1 . 15 ( m , 28 h 2 ch 2 of nh ( ch 2 ) 5 co , me ( ch 2 ) 12 co ); 0 . 87 ( t , me ( ch 2 ) 2 co ). anal . calc . for c 59 h 73 n 7 o 10 ½ h 2 o ( 1040 . 27 ): c 67 . 52 , h 7 . 06 , n 9 . 34 ; found : c 67 . 25 , h 7 . 20 , n 9 . 33 . as described in preparation 4 , with cholic acid ( 450 mg , 1 . 1 mmol ) and totu ( 361 mg , 1 . 1 mmol ) in abs . dmf ( 5 ml ; lh ). deblocking of 6 ( 1 . 052 g , 1 mmol ) with 3 % piperidine in abs . dmf ( 15 ml ; 10 min ) and addition of the above - mentioned soln . ( r . t ., 1 . 5 h ). workup with acoet ( 200 ml ) and nahco 3 soln . ( 2 × 100 ml ), reextraction , and purification by fc ( silica gel , 14 × 3 . 5 cm , chcl 3 , then chcl 3 / meoh 98 : 2 , 96 : 4 , 93 . 7 , 90 : 10 ) gave 944 mg ( 77 %) of 9 . amorphous solid . uv ( ch 2 cl 2 ): 272 ( sh , 4 . 42 ), 267 ( 4 . 47 ), 237 ( sh , 4 . 31 ). 1 h - nmr ( cdcl 3 ): 9 . 12 ( br ., nh ( ade )); 8 . 68 - 8 . 11 ( 2s , d , h — c ( 8 ), h — c ( 2 ), 2 h o to no 2 ); 7 . 48 - 7 . 12 ( m , 2 h m to no 2 , meotr ); 6 . 8 ( d , 2 h o to meo ); 6 . 1 ( s , h — c ( 1 ′)); 5 . 88 ( t , nh ( ch 2 ) 5 co ); 5 . 63 ( m , h — c ( 2 ′)); 4 . 6 ( m , h — c ( 4 ′)); 4 . 51 ( t , och 2 ch 2 ); 3 . 98 - 3 . 7 ( s , m , meo , 2h of chol ); 3 . 55 - 3 . 1 ( m , 8h , 2h — c ( 5 ′), och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 c ) 1 2 h of chol . ); 2 . 65 - 0 . 6 ( m , 2h — c ( 3 ′), 4ch 2 of nh ( ch 2 ) 5 co ), 33 h of chol .). anal . calc . for c 69 h 85 n 7 o 13 ( 1220 . 47 ): c 67 . 90 , h 7 . 02 , n 8 . 03 ; found c 67 . 74 , h 7 . 26 , n . 7 . 65 compound 8 ( 330 mg , 0 . 317 mmol ) was stirred at r . t . in ch 2 cl 2 / meoh 4 : 1 ( 6 ml ) containing 2 % of tsoh . h 2 o for 15 min . then the mixture was diluted with ch 2 cl 2 ( 70 ml ) and washed with sat . nahco 3 soln . ( 2 × 40 ml ), the aq . phase reextracted with ch 2 cl 2 , the combined org . layer dried ( mgso 4 ) and evaporated , and the residue purified by fc ( silica gel , 12 × 2 cm , chcl 3 , chcl 3 + 5 % meoh ). the obtained oily substance was treated with small amounts of et 2 o / mecn 2 : 1 to give 215 mg ( 88 %) of 10 . amorphous solid . uv ( ch 2 cl 2 ); 272 ( sh , 4 . 36 ), 267 ( 4 . 41 ). 1 h - nmr ( cdcl 3 ): 8 . 71 , 8 . 21 - 8 . 15 ( 2m , h — c ( 8 ), h — c ( 2 ), 2 h o to no 2 , nh ( ade )); 7 . 45 ( d , 2 h m to no 2 ); 6 . 03 ( d , h — c ( 1 ′)); 5 . 58 ( m , h — c ( 2 ′)); 5 . 55 ( br ., nh ( ch 2 ) 5 co ); 5 . 0 ( br ., oh — c ( 5 ′)); 4 . 65 - 4 . 50 ( m , t , h — c ( 4 ′), och 2 ch 2 ); 4 . 12 , 3 , 75 ( 2m , 2 h — c ( 5 ′)); 3 . 25 ( q , 1 ch 2 of nh ( ch 2 ) 5 co ); 3 . 15 ( t , och 2 ch 2 ); 2 . 9 , 2 . 25 ( 2m , 2 h — c ( 3 ′)); 2 . 35 , 2 . 15 ( 2t , 2 ch 2 of nh ( ch 2 ) 5 co ), 2 h of me ( ch 2 ) 12 co ); 1 . 7 - 1 . 15 ( m , 28 h , 2 ch 2 of nh ( ch 2 ) 5 co , me ( ch 2 ) 12 co ); 0 . 87 ( t , me ( ch 2 ) 12 co ) 12 anal . calc . for c 39 h 57 n 7 o 9 ½ h 2 o ( 782 . 02 ): c 59 . 90 , h 7 . 41 , n 12 . 54 ; found : c 60 . 27 , h 7 . 66 , n 12 . 06 . as described in preparation 6 , with 9 ( 860 mg , 0 . 705 mmol ) and ch 2 cl 2 / meoh 4 : 1 ( 14 ml ) containing 2 % of tsoh h 2 0 ( 15 min ). workup with ch 2 cl 2 ( 70 ml ) and sat . nahco 3 soln . ( 2 × 40 ml ), and reextraction , and purification by precipitation of the crude product in et 2 o ( 100 ml ) gave 578 mg ( 87 %) of 11 . uv ( meoh ): 272 ( sh , 4 . 39 ), 267 ( 4 . 43 ). 1 h - nmr ( cdcl 3 ): 9 . 70 ( s , nh ( ade )); 8 . 73 , 8 . 44 ( 2s , h — c ( 8 )), h — c ( 2 )); 8 . 17 ( d , 2 h o to no 2 ); 7 . 45 ( d h m to no 2 ); 6 . 18 ( m , nh ( ch 2 ) 4 co ); 6 . 10 ( d , h — c ( 1 ′)); 5 . 57 ( m , h — c ( 2 ′)); 5 . 05 ( br . oh — c ( 5 ′)); 4 . 55 - 4 . 45 ( m , h — c ( 4 ′), och 2 ch 2 ); 4 . 1 - 3 . 65 ( m , 2 h of chol ., 2 h — c ( 5 ′)); 3 . 5 - 2 . 7 ( m , 4 h of chol ., och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ), h — c ( 3 ′)); 2 . 45 - 0 . 6 ( m , h — c ( 3 ′), 4 ch 2 of nh ( ch 2 ) 5 co ), 33 h of chol .). anal calc . for c 49 h 69 n 7 o 12 ( 948 . 13 ): c 62 . 07 , h 7 . 34 , n 10 . 34 ; found : c 61 . 54 , h 7 . 41 , n 9 . 92 . compound 10 ( 160 mg , 0 . 208 mol ) was co - evaporated twice with abs . pyridine and then dissolved in abs . pyridine ( 2 ml ). dbu ( 158 mg , 1 . 04 mmol ) was added , the mixture kept at r . t . for 18 h , then acoh ( 62 mg , 1 . 04 mmol ) added , and the soln . evaporated . the residue was diluted with chcl 3 ( 80 ml ) and washed with a 10 % citric acid soln . ( 2 × 50 ml ), the aq . phase reextracted with chcl 3 , the combined org . layer dried ( mgso 4 ), evaporated , and co - evaporated with toluene , and the residue precipitated by meoh and washed with et 2 o : 103 mg ( 86 %) of 12 . uv ( ch 2 cl 2 : 259 ( 4 . 16 ). 1 h - nmr (( d 6 ) dmso ): 8 . 33 , 8 . 13 ( 2s , h — c ( 8 ), h — c ( 2 )); 7 . 68 ( t , nh ( ch 2 ) 5 co ); 7 . 25 ( s , nh 2 ); 6 . 05 ( d , h — c ( 1 ′)); 5 . 60 ( m , h — c ( 2 ′)); 5 . 11 ( t , oh — c ( 5 ′)); 4 . 32 ( m , h — c ( 4 ′)); 3 . 65 , 3 . 47 ( 2m , 2 h — c ( 5 ′)); 2 . 95 ( q , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 6 , 2 . 15 ( 2m , 2 h — c ( 3 ′)); 2 . 34 , 2 . 00 ( 2t , 2 ch 2 of nh ( ch 2 ) 5 co , 2 h of me ( ch 2 ) 12 co ); 1 . 65 - 1 . 15 ( m , 28 h , 2 ch 2 of nh ( ch 2 ) 5 co , me ( ch 2 ) 12 co ); 0 . 83 ( t , me ( ch 2 ) 12 co ). anal . calc . for c 30 h 50 n 6 o 5 ½ h 2 o ( 583 . 76 ): c 61 . 72 , h 8 . 81 , n . 14 . 39 ; found c 62 . 04 , h 9 . 07 , n 13 . 85 . as described in preparation 8 , with 11 ( 430 mg . 0 . 454 mmol ), 0 . 5m dbu in abs . pyridine ( 6 . 7 ml ; 20 h ), and acoh ( 250 mg , 4 . 16 mmol ). workup with chcl 3 ( 200 ml ) including a small amount of meoh , h 2 o ( 60 ml ), and sat . nahco 3 soln . ( 80 ml ), reextraction , purification by fc ( silica gel , 4 × 3 cm , chcl 3 / meoh 9 : 1 , then 4 : 1 ), and precipitation of the product in petroleum ether gave 269 mg of 13 ( 78 %). uv ( meoh ): 259 ( 4 . 16 ). 1 h - nmr (( d 6 ) dmso ): 8 . 33 , 8 . 13 ( 2s , h — c ( 8 ), h — c ( 2 )); 7 . 71 ( t , nh ( ch 2 ) 5 co ); 7 . 31 ( s , nh 2 ( ade )); 6 . 05 ( d , h — c ( 1 ′)); 5 . 60 ( m , h — c ( 2 ′)); 5 . 12 ( t , oh — c ( 5 ′)); 4 . 31 ( m , h — c ( 4 ′), oh - chol . ); 4 . 07 ( d , oh - chol . ); 3 . 98 ( d , oh - chol . ); 3 . 77 , 3 . 55 , 3 . 15 ( 3m , 3 h of chol . ); 3 . 65 , 3 . 47 ( m , 2 h — c ( 5 ′)); 2 . 98 ( m , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 6 - 0 . 55 ( m , 2 h — c ( 3 ′), 4 ch 2 of nh ( ch 2 ) 5 co ), 33 h of chol .). anal . calc . for c 40 h 62 n 6 o 8 . ½ h 2 o ( 763 . 98 ): c 62 . 89 , h 8 . 31 , n 11 . 00 ; found : c 62 . 63 , 8 . 28 , n 11 . 26 . as described in preparation 4 , with tetradecanoic acid ( 151 mg , 0 . 66 mmol ), totu ( 67 mg , 0 . 66 mmol ), and n - methylmorpholine ( 67 , 0 . 66 mmol ) in abs . dmf ( 3 ml ; 1 h ). deblocking of 7 ( 584 mg , 0 . 6 mmol ) with 3 % piperidine in abs . dmf ( 6 ml ; 10 min ) and addition of above - mentioned soln . ( r . t ., 2 . 5 h ). workup with chcl 3 ( 150 ml ) and nahco 3 soln . ( 2 × 70 ml ) and reextraction . purification by fc ( silica gel , 12 × 3 cm , chcl 3 , then chcl 3 / meoh 98 : 2 , 95 : 5 ): 405 mg ( 70 %) of 14 . colorless oil . 1 h - nmr ( cdcl 3 ): 8 . 73 - 8 . 15 ( m , h — c ( 8 ), h — c ( 2 ), 4 h o to no 2 , nh ( ade )); 7 . 47 - 7 . 38 ( m , 4h m to no 2 ); 6 . 12 ( d , h — c ( 1 ′)); 5 . 73 ( m , h — c ( 2 ′)); 5 . 57 ( t , nh ( ch 2 ) 5 co ); 4 . 68 ( m , h — c ( 4 ′)); 4 . 54 , 4 . 43 ( 2t , 2 och 2 ch 2 ); 4 . 4 - 4 . 2 ( m , 2 h — c ( 5 ′)); 3 . 7 - 3 . 5 ( m , 1 ch 2 of nh ( ch 2 ) 5 co ); 3 . 25 - 3 . 1 ( m , 2 och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 65 , 2 . 25 ( 2m , 2 h — c ( 3 ′)); 2 . 27 , 2 . 15 ( 2t , 2 ch 2 of nh ( ch 2 ) 5 co ), 1 ch 2 of me ( ch 2 ) 12 co ); 1 . 7 - 1 . 15 ( m , 3 ch 2 of nh ( ch 2 ) 5 co ), 11 ch 2 of me ( ch 2 ) 12 co ); 0 . 87 ( t , me ( ch 2 ) 12 co ). as described in preparation 8 , with crude 14 ( 392 mg . 0 . 408 mmol ), 0 . 5m dbu in abs . pyridine ( 12ml ; 20 h ), and acoh ( 400 mg , 6 . 66 mmol ). workup with ch 2 cl 2 ( 120 ml ) and h 2 o ( 2 × 60 ml ), reextraction , co - evaporation of the residue with toluene , and purification by precipitation of the product in petroleum ether gave 202 mg of 16 ( 86 %). colorless powder . uv ( meoh ): 259 ( 4 . 16 ). 1 h - nmr ( cdcl 3 ): 8 . 22 , 8 . 13 ( 2s , h — c ( 8 ), h — c ( 2 )); 7 . 68 ( br ., nh ( ch 2 ) 5 co ); 7 . 26 ( br ., nh 2 ( ade )); 5 . 90 ( s , h — c ( 1 ′)); 5 . 76 ( br ., oh — c ( 2 ′)); 4 . 69 ( m , h — c ( 2 ′)); 4 . 53 ( m , h — c ( 4 ′)); 4 . 3 - 4 . 1 ( m , 2 h — c ( 5 ′)); 3 . 0 ( m , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 35 - 2 . 0 ( 2m , 2t , 2 h — c ( 3 ′), 1 ch 2 of nh ( ch 2 ) 5 co , 1 ch 2 of me ( ch 2 ) 12 co ; 1 . 5 - 1 . 1 ( m , 3 ch 2 of nh ( ch 2 ) 5 co . 11 ch 2 of me ( ch 2 ) 12 co ); 0 . 83 ( t , me ( ch 2 ) 12 co ). anal . calc . for c 30 h 50 n 6 o 5 ( 574 . 76 ): c 62 . 69 , h 8 . 77 , n 14 . 62 ; found : c 62 . 32 , h 8 . 68 , n 14 . 55 . as described in preparation 4 , with cholic acid ( 270 mg , 0 . 66 mmol ), totu ( 67 mg , 0 . 66 mmol ). and n - methylmorpholine ( 67 mg , 0 . 66 mmol ) in abs . dmf ( 3 ml ; 1 h ). deblocking of 7 ( 584 mg , 0 . 6 mmol ) with 3 % piperidine in abs . dmf ( 6 ml ; 10 min ) and addition of the above - mentioned soln . ( r . t ., 1 . 5 h ). workup with chcl 3 ( 200 ml ) and nahco 3 soln . ( 2 × 100 ml ), reextraction , and purification by fc ( silica gel , 8 × 3 cm , chcl3 / meoh 95 : 5 , 93 : 7 gave 518 mg ( ca . 76 %) of 15 . amorphous solid . contaminated with cholic acid . 1 h - nmr ( cdcl 3 ): 9 . 35 ( br ., nh ( ade )); 8 . 73 , 8 . 3 - 8 . 15 ( s , m , h — c ( 8 ), h — c ( 2 ), 4 h o to no 2 ); 7 . 47 - 740 ( m , 4 h m to no 2 ); 6 . 15 ( s , h — c ( 1 ′)); 5 . 92 ( t , nh ( ch 2 ) 5 co ); 5 . 75 ( m , h — c ( 2 ′)); 4 . 63 ( m , h — c ( 4 ′)); 4 . 6 - 4 . 2 ( m , 2 och 2 ch 2 , 2 h — c ( 5 ′)); 4 . 0 - 3 . 25 ( m , 6 h of chol . ); 3 . 22 - 3 . 1 m , 2 och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5co ); 2 . 7 , 2 . 5 - 0 . 65 ( m , 2 h — c ( 3 ′), 4 ch 2 of nh ( ch 2 ) 5 co , 33 h of chol .). as described in preparation 8 , with crude 15 ( 447 mg , 0 . 392 mmol ), 0 . 5m dbu in abs . pyridine ( 11 . 5 ml ; 20 h ), and acoh ( 380 mg , 6 . 32 mmol ). workup with chcl 3 ( 200 ml ) including a small amount of meoh , h 2 o ( 60 ml ), and sat . nahco 3 soln ., reextraction , co - evaporation of the residue with toluene , purification by fc ( silica gel , 4 × 3 cm , chcl 3 , then chcl 3 / meoh 9 : 1 , 8 : 2 ), and precipitation of the product in petroleum ether : 197 mg of 17 ( 67 %). colorless powder . uv ( meoh ): 259 ( 4 . 16 ). 1 h - nmr (( d 6 ) dmso ): 8 . 22 , 8 . 13 ( 2s , h — c ( 8 ), h — c ( 2 )); 7 . 70 ( 1 , nh ( ch 2 ) 5 co ); 7 . 28 ( s , nh 2 ( ade )); 5 . 90 ( d , h — c ( 1 ′)); 5 . 72 ( m , oh — c ( 2 ′)); 4 . 67 ( br ., h — c ( 2 ′); 4 . 50 ( m , h — c ( 4 ′)); 4 . 29 , 4 . 07 , 3 . 99 ( 3m , 3 oh - chol . ); 4 . 25 - 4 . 17 ( m , 2 h — c ( 5 ′)); 3 . 77 , 3 . 59 , 3 . 17 ( 3m , 3h of chol . ); 3 . 0 ( q , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 3 - 0 . 55 ( m , 2 h — c ( 3 ′), 4 ch 2 of nh ( ch 2 ) 5 co ), 33 h of chol .). anal . calc . for c 40 h 62 n 6 o 8 . h 2 o ( 763 . 98 ): c 62 . 15 , h 8 . 35 , n 10 . 87 ; found : c 62 . 36 , h 8 . 27 , n 10 . 65 . to a soln . of 6 ( 1 . 052 g , 1 mmol ) in abs . ch 2 cl 2 ( 20 ml ) was added cf 3 cooh ( 0 . 4 ml ) and stirred at r . t . for 1 h . then , meoh ( 5 ml ) was added , the mixture evaporated and co - evaporated with toluene / meoh , and the residue purified by fc ( silica gel , 14 . 5 × 3 . 5 cm , ch 2 cl 2 , then ch 2 cl 2 / meoh 98 : 2 , 97 : 3 , 95 : 5 , 90 : 10 , 85 : 15 ): 535 mg ( 69 %) of 18 . amorphous solid . uv ( ch 2 cl 2 ): 299 ( 4 . 00 ), 2 . 86 ( sh , 4 . 10 ), 272 ( sh , 4 . 55 ), 2 . 66 ( 4 . 62 ). 1 h - nmr ( cdcl 3 ): 8 . 72 - 8 . 10 ( 3s , d , h — c ( 8 ), h — c ( 2 ), nh , 2 h o to no 2 ); 7 . 77 - 7 . 27 ( m , 8 h of fmoc , 2 h m to no 2 ); 5 . 96 ( d , h — c ( 1 ′)); 5 . 65 ( m , h —( 2 ′)); 4 . 90 - 4 . 80 ( m , nh ( ch 2 ) 5 co , oh — c ( 5 ′)); 4 . 56 - 4 . 22 ( m , h — c ( 4 ′), och 2 ch 2 , h — c ( 9 )( fmoc ), ch 2 o ( fmoc )); 4 . 15 , 3 . 72 ( 2m , 2 h — c ( 5 ′)); 3 . 25 - 3 . 05 ( m , och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 90 , 2 . 30 ( 2m , 2 h — c ( 3 ′)); 2 . 36 ( t , 1 ch 2 of nh ( ch 2 ) 5 co ); 1 . 9 - 1 . 35 ( m , 1 ch 2 of nh ( ch 2 ) 5 co ). anal . calc . for c 40 h 41 n 7 o 10 ( 779 . 81 ): c 61 . 61 , h 5 . 30 , n 12 . 57 found : c 61 . 65 , h 5 . 37 , n 12 . 53 . a mixture of 18 ( 1 . 46 g , 1 . 87 mmol ), 3 ′- deoxy - 5 ′- o -( monomethoxytrityl )- n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenosine 2 ′-[ 2 -( 4 - nitrophenyl ) ethyl diisopropylphosphoramidite ][ 22 ( 2 . 28 g , 2 . 25 mmol ) and 1h - tetrazole ( 656 mg , 9 . 36 mmol ) was stirred in dry mecn ( 7 ml ) and a few drops of dry ch 2 cl 2 under n 2 at r . t . for 2 . 5 h . then it was oxidized with a i 2 soln . ( i 2 ( 500 mg ) in pyridine ( 3 ml ), ch 2 cl 2 ( 1 ml ), and h 2 o ( 1 ml )) until no change of color was detected . the mixture was stirred for 15 min . diluted with chcl 3 ( 200 ml ), and washed with na 2 s 2 o 3 / nacl soln . ( 100 ml ) and sat . nahco 3 soln ., the aq . phase reextracted with chcl 3 , the combined org . layer dried ( mgso 4 ), evaporated , and co - evaporated with toluene , and the residue purified by fc ( silica gel , 16 × 3 cm , ch 2 cl 2 , ch 2 cl 2 / meoh 98 : 2 , 97 : 3 , 96 : 4 ). purification had to be repeated for contaminated fractions : 2 . 858 g ( 89 %) of 19 . amorphous solid . uv ( ch 2 cl 2 ): 299 ( 4 . 26 ), 286 ( sh , 4 . 47 ), 272 ( sh , 4 . 83 ), 266 ( 4 . 89 ), 239 ( sh , 4 . 52 ). 1 h - nmr ( cdcl 3 ): 8 . 69 - 8 . 10 ( m , 2 h — c ( 8 ), 2 h — c ( 2 ), 2 nh , 6 h o to no 2 ); 7 . 76 - 7 . 20 ( m . 8 h of fmoc , 6 h m to no 2 , 12 h of meotr ); 6 . 80 ( d , 2 h o to meo ); 6 . 19 , 6 . 02 ( d , s , 2 h — c ( 1 ′)); 5 . 66 , 5 . 5 - 5 . 3 ( 2m , 2 h — c ( 2 ′)); 4 . 95 ( m , nh ( ch 2 ) 5 co ); 4 . 55 - 4 . 15 ( m , 2 h — c ( 4 ′), 3 och 2 ch 2 , h — c ( 9 )( fmoc ), ch 2 o ( fmoc ), 2 h — c ( 5 ′)); 3 . 77 ( s , meo ); 3 . 5 - 3 . 25 ( 2m , 2 h — c ( 5 ′)); 3 . 19 - 3 . 00 ( m , 3 och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 8 - 2 . 15 ( m , 4 h — c ( 3 ′), 1 ch 2 of nh ( ch 2 ) 5 co ); 1 . 85 - 1 . 3 ( m , 3 ch 2 of nh ( ch 2 ) 5 co ). anal . calc . for c 87 h 83 n 14 o 22 p ( 1707 . 67 ): c 61 . 19 , h 4 . 90 , n 11 . 48 : found : c 60 . 99 , h 4 . 98 , n 11 . 20 . as described in preparation 6 , with 19 ( 2 . 36 g , 1 . 38 mmol ) and ch 2 cl 2 / meoh 4 : 1 ( 28 ml ) containing 2 % of tsoh · h 2 o ( 45 min ). workup with chcl 3 ( 150 ml ) and sat . nahco 3 soln . ( 100 ml ), reextraction , and purification by fc ( silica gel , 14 × 3 . 5 cm , chcl 3 , then chcl 3 / meoh 96 : 4 , 95 : 5 , 94 : 6 , 92 : 8 ) gave 1 . 995 g ( quant .) of 20 . amorphous solid . uv ( ch 2 cl 2 ): 299 ( 4 . 25 ), 286 ( sh , 4 . 48 ), 272 ( sh , 4 . 83 ), 266 ( 4 . 88 ). 1 h - nmr (( d 6 ) dmso ): 10 . 61 ( s , 2 nh ); 8 . 62 - 8 . 53 ( m , 2 h — c ( 8 ), 2 h — c ( 2 ); 8 . 15 - 7 . 23 ( m , 6 h o to no 2 , 8 h of fmoc , 6 h m to no 2 ); 6 . 19 - 6 . 11 ( m , 2 h — c ( 1 ′)); 5 . 69 , 5 . 15 ( 2m , 2 h — c ( 2 ′)); 5 . 10 ( t , oh — c ( 5 ′)); 4 . 45 - 4 . 05 ( m , nh ( ch 2 ) 5 co , 2 h — c ( 4 ′), 3 och 2 ch 2 , h — c ( 9 )( fmoc ), ch 2 o ( fmoc ), 2 h — c ( 5 ′)); 3 . 65 - 3 . 45 ( 2m , 2 h — c ( 5 ′)); 3 . 25 - 2 . 85 ( m , 3 och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 8 - 2 . 0 h — c ( 3 ′), 1 ch 2 of nh ( ch 2 ) 5 co ); 1 . 7 - 1 . 25 ( m , 3 ch 2 of nh ( ch 2 ) 5 co ). anal . calc . for c 67 h 66 n 14 o 21 p ( 1434 . 32 ): c 56 . 11 , h 4 . 64 , n 13 . 67 ; found : c 55 . 99 , h 4 . 75 , n 13 . 34 . as described in preparation 13 , with 20 ( 2 . 0 g , 1 . 39 mmol ), 3 ′- deoxy - 5 ′- o -( monomethoxytrityl )- n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenosine 2 ′-[ 2 -( 4 - nitrophenyl ) ethyl diisopropylphosphoramidite ][ 22 ]( 1 . 766 g , 1 . 74 mmol ), 1 h - tetrazole ( 478 mg , 6 . 95 mmol ), anh . mecn ( 7 ml ; 2h ), and i 2 soln . workup with chcl 3 ( 150 ml ) and na 2 s 2 o 3 / nacl soln . ( 2 × 80 ml ), reextraction , and purification by fc ( silica gel , 7 × 4 . 5 cm , chcl 3 , then chcl 3 / meoh 97 : 3 , 96 : 4 gave 3 . 092 g ( 94 %) of 21 . amorphous solid . uv ( ch 2 cl 2 ): 297 ( 4 . 45 ), 286 ( sh , 4 . 67 ), 272 ( sh , 5 . 01 ), 266 ( 5 . 05 ). 1 h - nmr (( d 6 ) dmso ): 9 . 1 - 8 . 0 ( m , 3 nh , 3 h — c ( 8 ), 3 h — c ( 2 ), 10 h o to no 2 ); 7 . 75 - 7 . 15 ( m , 8 h of fmoc , 10 h m to no 2 , 12 h of meotr ); 6 . 78 ( d , 2 h o to meo ); 6 . 19 - 6 . 01 ( m , 3 h — c ( 1 ′)); 5 . 73 , 5 . 45 , 5 . 32 ( m , 3 h — c ( 2 ′)); 5 . 0 ( m , nh ( ch 2 ) 5 co ); 4 . 6 - 4 . 1 ( m , 3 h — c ( 4 ′), 5 och 2 ch 2 , h — c ( 9 )( fmoc ), ch 2 o ( fmoc ), 4 h — c ( 5 ′)); 3 . 76 ( s , meo ); 3 . 45 , 3 . 3 ( 2m , 2 h — c ( 5 ′)); 3 . 25 - 2 . 95 ( m , 5 och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 8 - 1 . 9 ( m , 6 h — c ( 3 ′), 1 ch 2 of nh ( ch 2 ) 5 co ); 1 . 7 - 1 . 3 ( m , 3 of nh ( ch 2 ) 5 co ). anal . calc . for c 114 h 109 n 21 o 33 p 2 ( 2363 . 19 ): c 57 . 94 , h 4 . 65 , n 12 . 44 ; found : c 57 . 71 , h 4 . 69 , n 12 . 27 . as described in preparation 4 , with tetradecanoic acid ( 38 mg , 0 . 165 mmol ), totu ( 54 mg , 0 . 165 mmol ), and n - methylmorpholine ( 17 mg , 0 . 165 mmol ) in abs . dmf ( 1 . 5 ml ; 1 h ). deblocking of 21 ( 354 mg , 0 . 15 mmol ) with 3 % piperidine in abs . dmf ( 2 ml ; 10 min ) and addition of the above - mentioned soln . ( r . t ., 3 h ), more preactivated tetradecanoic acid ( 38 mg , 0 . 165 mmol ), totu ( 54 mg , 0 . 165 mmol ), and n - methylmorpholine ( 17 mg , 0 . 165 mmol ) in abs . dmf ( 1 . 5 ml ; 1 . 5 h ). workup with acoet ( 100 ml ) and nahco 3 soln . ( 2 × 50 ml ), reextraction , and purification by fc ( 2 ×, silica gel , 12 × 3 cm , chcl 3 , then chcl 3 / meoh 98 : 2 , 97 : 3 , 96 : 4 , 95 : 5 ) gave 257 mg ( 73 %) of 22 . amorphous solid . uv ( ch 2 cl 2 ): 272 ( sh , 4 . 92 ), 267 ( 4 . 95 ), 239 ( sh , 4 . 60 ). 1 h - nmr ( cdcl 3 ): 8 . 65 - 8 . 0 ( m , 3 h — c ( 8 ), 3 h — c ( 2 ), 10 h o to no 2 ); 7 . 5 - 7 . 15 ( m , 10 h m to no 2 , 12 h of meotr ); 6 . 78 ( d , 2 h o to meo ); 6 . 21 - 5 . 98 ( m , 3 h — c ( 1 ′)); 5 . 75 - 5 . 25 ( m , 3 h — c ( 2 ′)); 4 . 65 - 4 . 1 ( m , 3 h — c ( 4 ′), 5 och 2 ch 2 , 4 h — c ( 5 ′), nh ( ch 2 ) 5 co ); 3 . 78 ( s , meo ); 3 . 7 - 0 . 85 ( m , 2 h — c ( 5 ′), 5 och 2 ch 2 , nh ( ch 2 ) 5 co , 6 h — c ( 3 ′), me ( ch 2 ) 12 co ). anal . calc . for c 113 h 125 n 21 o 32 p 2 ( 2351 . 31 ): c 57 . 72 , h 5 . 36 , n 12 . 51 ; found : c 57 . 58 , h 5 . 43 , n 12 . 51 . as described in preparation 4 , with cholic acid ( 67 mg , 0 . 165 mmol ), totu ( 54 mg , 0 . 165 mmol ) and n - methylmorpholine ( 17 mg , 0 . 165 mmol ) in abs . dmf ( 1 . 5 ml ; 1 h ). deblocking of 21 ( 354 mg , 0 . 15 mmol ) with 3 % piperidine in abs . dmf ( 2 ml ; 10 min ) and addition of the above - mentioned soln . ( r . t ., 3h ), more pre - activated cholic acid ( 34 mg , 82 . 5 μmol ), totu ( 27 mg , 82 . 5 μmol ), and n - methylmorpholine ( 9 mg , 82 . 5 μmol ) in abs . dmf ( 1 ml ; 1 . 5 h ). workup with chcl 3 ( 100 ml ) and nahco 3 soln . ( 50 ml ), reextraction and purification by fc ( several times , silica gel , chcl 3 , then chcl 3 / meoh 98 : 2 , 93 : 7 , 90 : 10 , 85 : 15 ) gave 260 mg ( 69 %) of 23 . amorphous solid . uv ( ch 2 cl 2 ): 272 ( sh , 4 . 90 ), 267 ( 4 . 94 ) 240 ( sh . 4 . 58 ). anal . calc . for c 123 h 137 n 21 o 35 p 2 ( 2531 . 51 ): c 58 . 36 , h 5 . 45 , n 11 . 62 ; found : c 58 . 35 , h 5 . 7 , n 10 . 91 . a mixture of 22 ( 80 mg , 34 μmol ) in ch 2 cl 2 / meoh 4 : 1 ( 4 ml ) containing 2 % tsoh . h 2 o was stirred at r . t . for 20 min . then the mixture was diluted with chcl 3 ( 30 ml ) and washed with sat . nahco 3 soln . ( 2 × 10 ml ), the aq . phase reextracted with chcl 3 , and the combined org . layer dried ( mgso 4 ) and evaporated . the crude product was diluted with a small amount of chcl 3 and precipitated from et 2 o ( 15 ml ), centrifugated , and dried . for further deblocking , the precipitate was co - evaporated twice with abs . pyridine , then 0 . 5 m dbu in abs . pyridine was added and the mixture stirred at r . t . for 2 d . then acoh ( 60 mg , 1 mmol ) was added , the mixture evaporated and co - evaporated with abs . dioxane , and the product precipitated from dioxane / et 2 o 1 : 3 , washed , and centrifugated several times with dioxane / et 2 o : 35 mg of 24 ( 882 oc ). colorless powder . hplc ( 0 - 100 % mecn ( 0 - 20 min ) in 0 . 1m ( et 3 nh ) oac buffer ( ph 7 )); t r 14 . 94 min . as described in example 2 with 23 ( 90 mg , 36 μmol ) and ch 2 cl / meoh 4 : 1 containing 2 % tsoh h 2 o ( 4 ml ; 20 min ). workup with chcl 3 ( 30 ml ) and sat . nahco 3 soln . ( 2 × 10 ml ), reextraction , and precipitation from et 2 o ( 15 ml ) gave a colorless powder . treatment with 0 . 5m dbu in abs . pyridine ( 1 ml ; 2d ) and acoh ( 60 mg , 1 mmol ), workup with abs . dioxane , and precipitation with abs . mecn / et 2 o gave 45 mg of 25 ( 965 od ). colorless powder . hplc ( 0 - 100 % mecn ( 0 - 20 min ) in 0 . 1m ( et 3 nh ) oac buffer ( ph 7 )); t r 11 . 81 min . for acid - activation , a mixture of folic acid ( 3 × 44 mg , 0 . 1 mmol ), edc ( 3 × 23 mg , 0 . 12 mmol ), and dmap ( 3 × 15 mg , 0 . 12 mmol ) in abs . dmf ( 3 × 2 . 5 ml ) was kept at r . t . for 3 h . trimer 21 ( 115 mg , 0 . 05 mmol ) was treated with a soln . of 3 % piperidine in abs . dmf ( 2 ml ; 15 min ) and then evaporated . the above - mentioned soln . was added in 3 portions within 3 h and further stirred for 1 h at r . t ., then the mixture was evaporated . the residue was treated with et 2 o / ch 2 cl 2 and the yellow residue washed and centrifugated with ch 2 cl 2 and et 2 o . then the residue was co - evaporated with abs . pyridine and dissolved in abs . pyridine ( 5 ml ). dbu ( 380 mg , 2 . 5 mmol ) was added and the mixture stirred at r . t . for 18 h . then acoh ( 300 mg , 5 mmol ) was added , the mixture evaporated and the residue treated with 80 % acoh / h 2 o ( 10 ml , 17 h ). the mixture was centrifugated , the supernatant evaporated , and the residue treated with mecn . the obtained yellow crude product ( 27 mg ) was purified by prep . hplc ( lichrospher 100 rp 18 , 10 μm , 25 × 2 cm , 10 % mecn ( 0 - 5 min ), 10 - 35 % mecn ( 5 - 40 ), 35 - 50 % ( 40 - 45 min ), 50 % mecn ( 45 - 50 min ) in 0 . 1 m ( et 3 nh ) oac buffer ( ph 7 ), 7 ml / min ): 9 mg ( 228 od ) of 26 . yellow powder . hplc ( 0 - 50 % mecn ( 2 - 32 min ) in 0 . 1 m ( et 3 nh ) oac buffer ( ph 7 )): t r 16 . 00 min . fab - ms ( matrix glycerol / 3 - nitrobenzyl alcohol 1 : 1 ): ( mh + ; calc . 1414 . 5 ). as described in preparation 2 , with 3 ′- deoxy - n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenylyl -{ 2 ′} o p -[ 2 -( 4 - nitrophenyl ) ethyl ]}→ 5 ′} 3 ′- deoxy - n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenylyl -{ 2 ′-{ o p -[ 2 -( 4 - nitrophenyl ) ethyl ]} 5 ′}- 3 ′- deoxy - n 6 , 2 ′- o - bis [ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenosine ( 27 ; 2 . 533 g , 1 . 3 mmol ) [ 20 ], 3 ( 505 mg , 1 . 43 mmol ), edc ( 274 mg , 1 . 43 mmol ), dmap ( 175 mg , 1 . 43 mmol ), and ch 2 cl 2 ( 18 ml ; 2 . 5 h ), then more 3 ( 124 mg , 0 . 35 mmol ), ecd ( 67 mg , 0 . 35 mmol ), and dmap ( 43 mg , 0 . 35 mmol ; 3 h ). workup with ch 2 cl 2 ( 200 ml ) and 10 % citric acid soln . ( 100 ml ), reextraction , sat . nahco 3 soln . ( 100 ml ), reextraction and purification by fc ( silica gel , chcl 3 + 3 % meoh gave 2 . 347 g ( 79 %) of 28 . amorphous solid . uv ( ch 2 cl 2 ): 298 ( sh , 4 . 46 ), 285 ( sh , 4 . 71 ), 272 ( sh , 5 . 01 ), 267 ( 5 . 06 ). 1 h - nmr ( cdcl 3 ): 8 : 65 - 8 . 0 ( m , 3 h — c ( 8 ), 3 h — c ( 2 ), 12 h o to no 2 ); 7 . 75 - 7 . 2 ( m , 8 h of fmoc , 12 h m to no 2 ); 6 . 15 - 5 . 98 ( m , 3 h —( 1 ′)); 5 . 7 - 5 . 15 ( m , 3 h — c ( 2 ′)); 4 . 65 - 4 . 05 ( m , nh ( ch 2 ) 5 co , 3 h — c ( 4 ′), 6 och 2 ch 2 , h — c ( 9 )( fmoc ), ch 2 o ( fmoc ), 6 h — c ( 5 ′)); 3 . 2 - 2 . 9 ( m , 6 och 2 ch 2 , 1 ch 2 of nh ( ch 2 ) 5 co ); 2 . 7 ( m , h — c ( 3 ′)); 2 . 4 - 2 . 1 ( m , 5 h — c ( 3 ′), 1 ch 2 of nh ( ch 2 ) 5 co ); 1 . 65 - 1 . 25 ( m , 3 ch 2 of nh ( ch 2 ) 5 co ). anal . calc . for c 103 h 100 n 22 o 36 p 2 ( 2284 . 00 ): c 54 . 17 , h 4 . 41 , n 13 . 49 ; found : c 54 . 25 , h 4 . 53 , n 13 . 03 . 3 ′- deoxy - n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ]- 5 ′- o -[ 6 -( tetradecanoylamino ) hexanoyl ] adenylyl - 2 ′-{ o p -[ 2 -( 4 - nitrophenyl ) ethyl )}→ 5 ′} 3 ′- deoxy - n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenylyl -{ 2 ′-{ o p -[ 2 -( 4 - nitrophenyl ) ethyl }→ 5 ′}- 3 ′- deoxy - n 6 , 2 ′- o - bis [ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenosine ( 29 ). as described in preparation 4 , with tetradecanoic acid ( 40 mg , 0 . 176 mmol ), totu ( 56 mg , 0 . 176 mmol ), and n - methylmorpholine ( 18 mg , 0 . 176 mmol ) in abs . dmf ( 1 . 5 ml ; 1 h ). deblocking of 28 ( 265 mg , 0 . 16 mmol ) with 3 % piperidine in abs . dmf ( 4 ml ; 15 min ) and addition of the above - mentioned soln . ( r . t ., 1 . 5 h ), more pre - activated tetradecanoic acid ( 40 mg , 0 . 176 mmol ), totu ( 58 mg , 0 . 176 mmol ), and n - methylmorpholine ( 18 mg , 0 . 176 mmol ) in abs . dmf ( 1 . 5 ml ; 1 . 5 h ). workup with chcl 3 ( 100 ml ) and nahco 2 soln . ( 50 ml ), reextraction , and purification by fc ( 2 ×, silica gel , 13 . 5 × 2 cm , chcl 3 , then chcl 3 / meoh 96 : 4 , 94 : 6 ) gave 272 mg ( 75 %) of 29 . amorphous solid . uv ( ch 2 cl 2 ): 272 ( sh , 4 . 96 ), 267 ( 4 . 99 ). 1 h - nmr ( cdcl 3 ): 9 . 15 - 8 . 05 ( m , 3 nh ( ade ), 3 h — c ( 8 ), 3 h — c ( 2 ), 12 h o to no 2 ); 7 . 5 - 7 . 2 ( m , 12 h m to no 2 ); 6 . 15 - 5 . 95 ( m , 3 h — c ( 1 ′)); 5 . 7 - 5 . 25 ( m , 3 h ( 2 ′)); 4 . 65 - 4 . 1 ( m , 3 h — c ( 4 ′), 6 och 2 ch 2 , 6 h — c ( 5 ′), nh ( ch 2 ) 5 co ); 3 . 3 - 3 . 0 ( m , 6 och 2 ch 2 , 4 ch 2 of nh ( ch 2 ) 5co ); 3 . 0 - 2 . 0 ( m , 6 h — c ( 3 ′), 1 ch 2 of me ( ch 2 ) 12 co ); 1 . 7 - 1 . 2 ( m , 3 ch 2 of nh ( ch 2 ) 5 co , 10 ch 2 of me ( ch 2 ) 12 co ); 0 . 87 ( t , me ( ch 2 ) 12 co ). anal . calc . for c 102 h 116 n 22 o 35 p 2 ( 2272 . 12 ): c 53 . 92 , h 5 . 15 , n 13 . 56 ; found : c 53 . 72 , h 5 . 19 , n 13 . 41 . 3 ′- dexoy - n 6 -[ 2 ( 4 - nitrophenyl ) ethoxycarbonyl ]- 5 ′- o -{ 6 -[( 3α , 7α , 12α - trihydrox - 5β - cholan - 24 - oyl ) amino ]- hexanoyl } adenylyl -{ 2 ′-{ o p [ 2 -( 4 - nitrophenyl ) ethyl ]}→ 5 ′}- 3 ′- deoxy - n 6 -[ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenylyl -{ 2 ′- o p -[ 2 -( 4 - nitrophenyl ) ethyl ]}→ 5 ′}- 3 ′- deoxy - n 6 , 2 ′- o - bis [ 2 -( 4 - nitrophenyl ) ethoxycarbonyl ] adenosine ( 30 ). as described in preparation 4 , with cholic acid ( 54 mg , 0 . 132 mmol ), totu ( 43 mg , 0 . 132 mmol ), and n - methylmorpholine ( 14 mg , 0 . 132 mmol ) in abs . dmf ( 1 . 5 ml ; 1 h ). deblocking of 28 ( 275 mg . 0 . 12 ( mmol ) with 3 % piperidine in abs . dmf ( 2 ml ; 20 min ) and addition of the above - mentioned soln . ( r . t ., 1 . 5 h ), more preactivated cholic acid ( 54 mg , 0 . 132 mmol ), totu ( 43 mg ; 0 . 132 mmol ), and n - methylmorpholine ( 14 mg , 0 . 132 mmol ) in abs . dmf ( 1 ml ; 1 . 5 h ). workup with chcl 3 ( 100 ml ) and nahco 3 soln . ( 50 ml ), reextraction , and purification by fc ( several times , silica gel , chcl 3 , then chcl 3 / meoh 95 : 5 , 90 : 5 , 85 : 15 ) gave 195 mg ( 69 %) of 30 . amorphous solid . uv ( ch 2 cl 2 ): 272 ( sh , 4 . 96 ), 268 ( 4 . 99 ). anal . calc . for c 112 h 128 n 22 o 38 p 2 ( 2452 . 32 ): c 54 . 68 , h 5 . 26 , n 12 . 57 ; found : c 55 . 17 , h 5 . 51 , n 11 . 86 . trimer 29 ( 85 mg , 37 μmol ) was first co - evaporated with abs . pyridine . then 0 . 5 m dbu in abs . pyridine ( 1 . 3 ml ) was added and the mixture stirred at r . t . for 2 d . then acoh ( 80 mg , 1 . 3 mmol ) was added , the mixture evaporated and co - evaporated with abs . dioxane , and the product precipitated from dioxane / et 2 o 1 : 3 , washed , and centrifugated with dioxane / et 2 o : 45 mg of 31 ( 1166 od ). colorless powder . hplc ( 0 - 100 % mecn ( 0 - 20 min ) in 0 . 1 m ( et 3 nh ) oac buffer ( ph 7 )): t r 14 . 98 min . as described in example 4 , with 30 ( 50 mg , 20 , mol ), 0 . 5 m dbu in abs . pyridine ( 0 . 8 ml ; r . t . ; 2 d ), and acoh ( 60 mg , 1 mmol ). workup with abs . dioxane , precipitation with abs . mecn , and washing with abs . mecn and et 2 o : 32 mg of 32 ( 639 od ). colorless powder . hplc ( 0 - 100 % mecn ( 0 - 20 min ) in 0 . 1 m ( et 3 nh ) oac buffer ( ph 7 )); t r 11 . 75 min . as described in example 3 , with folic acid ( 3 × 44 mg , 0 . 1 mmol ). ecd ( 3 × 23 mg , 0 . 12 mmol ), and dmap ( 3 × 15 mg , 0 . 12 mmol ) in abs . dmf ( 3 × 2 . 5 ml ; r . t ., 3 h ). deblocking of trimer 28 ( 111 mg , 0 . 05 mmol ) with 3 % piperidine in abs . dmf ( 2 ml ; 15 min ) and addition of the above - mentioned soln . ( 3 portions within 4 h ). workup with et 2 o / ch 2 cl 2 , then washing and centrifugation with ch 2 cl 2 and et 2 o , further deblocking by dbu treatment ( 380 mg , 2 . 5 mmol ) in abs . pyridine ( 5 ml ; 18 h ), addition of acoh ( 300 mg , 5 mmol ), evaporation , and treatment with 80 % acoh / h 2 o ( 10 ml , 17 h ). the mixture was centrifugated and the supernatant evaporated and treated with mecn : yellow powder ( 19 mg ). purification by prep . hplc ( lichrospher 100 rp18 , 10 μm , 25 × 2 cm , 10 % mecn ( 0 - 5 min ), 10 - 35 % mecn ( 5 - 40 min ), 35 - 50 % mecn ( 40 - 45 min ), 50 % mecn ( 45 - 50 min ) in 0 . 1 m ( et 3 nh ) oac buffer ( ph 7 ), 7 ml / min ): 43 od of 33 . yellow amorphous solid . hplc ( 0 - 50 % mecn ( 0 - 20 min ), 50 - 75 % mecn ( 20 - 25 min ) in 0 . 1 m ( et 3 nh ) oac buffer ( ph 7 )): t r 11 . 86 min . fab - ms ( matrix glycerol / 3 - nitrobenzyl alcohol 1 : 1 ): 1414 ( mh + ; calc . 1414 . 5 ). the core compounds of the present invention may be 5 ′- monophosphorylated according to the procedure of sambrook et al ., molecular cloning — a laboratory manual , 2 ed ., cold spring harbor laboratory press , pp . 5 . 68 - 5 . 71 ( 1989 ) with atp with t4 polynucleotide kinase . 5 ′- monophosphorylation may be determined by reverse - phase hplc analysis and confirmed by the subsequent hydrolysis of each 5 ′- monophosphate derivative by 5 ′- nucleotidase . yields of phosphorylation range from 15 % to 60 %. in the case where the r 2 groups of all internucleotide bonds ( formula i ) of the molecule comprise oxygen , i . e ., the linkages comprise phosphodiester bonds , the 5 ′- monophosphates are readily prepared by reacting the corresponding unphosphorylated core compound with pocl 3 . the 5 ′- diphosphate and 5 ′- triphosphate of the core compounds of the invention may be prepared by following the procedure of example 7 . all reactions are performed in glassware oven - dried at 125 ° c . for 18 - 24 hr . core compound ( 400 od units at 260 run ) is dissolved in 500 microliters of dry dimethylformamide (“ dmf ”) and dried in vacuo in a 10 ml conical flask at 35 ° c . this process is repeated three times . to the dry residue , 50 micromoles of triphenylphosphine , 100 micromoles of imidazole and 50 micromoles of dipyridinyl disulfide are added . the mixture is dissolved in 500 microliters dry dmf plus 50 microliters of dry dimethylsulfoxide . the solution is stirred with a stirring bar for 2 hr at room temperature . after 2 hr the solution is homogeneous ( after 30 minutes , the solution begins to change to yellow ). the solution is transferred dropwise to 10 ml of a 1 % nai / dry acetone ( w / v ) solution . the clear colorless precipitate which forms is the sodium salt of the 5 ′- phosphoroimidazolidate . the precipitate is centrifuged at room temperature , the supernatant is decanted , and the precipitate is washed three times with 10 ml dry acetone . the centrifuging is repeated . the precipitate is dried over p 2 o 5 in vacuo for 2 hr . the precipitate is dissolved in 200 microliters of freshly prepared 0 . 5 m tributylammonium pyrophosphate in dry dmf . the solution is maintained at room temperature for 18 hr after which time the dmf is removed in vacuo . the residue is dissolved in 0 . 25 m triethylammonium bicarbonate buffer (“ teab ”) ( ph 7 . 5 ). the 5 ′- di and 5 ′- triphosphate products are separated using a deae - sephadex a25 column ( hco 3 - form ; 1 × 20 cm ) with a linear gradient of 0 . 25 m to 0 . 75 m teab . fractions ( 10 ml ) are collected . the product is observed by ultraviolet spectroscopy at 254 nm . the fractions containing the 5 ′- di and 5 ′- triphosphates are separately pooled and dried in vacuo . the teab is removed by repeated addition of water followed by lyophilization . the yield of the 5 ′- diphosphate is about 5 %; the yield of the 5 ′- triphosphate is about 60 %. all references cited with respect to synthetic , preparative and analytical procedures are incorporated by reference . the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof and , accordingly , reference should be made to the appended claims , rather than to the foregoing specification , as indication the scope of the invention . c . hörndler , r . j . suhadolnik , n . f . muto , e . e . henderson , m . x . guan , w . pfleiderer , helv . chim . acta 1997 , 80 , in press . b . r . g . williams , r . r . golger , r . e . brown , c . s . gilbert , i . m . kerr , nature 1979 , 282 , 582 . a . g . hovanessian , j . interferon res . 1991 , 11 , 199 . h . c . schröder , r . j . suhadolnik , w . pfleiderer , r . charubala , w . e . g . müller , int . j . biochem . 1992 , 24 , 55 . [ 61 b . a . hassell , a . zhon , r . h . silverman , cell 1993 , 72 , 753 . r . charubala , w . pfleiderer , tetrahedron lett . 1980 , 21 , 4077 . p . w . doetsch et al ., proc . natl . acad . sci . usa 78 : 6699 ( 1981 ) h . sawai et al ., j . biol . chem . 258 : 1671 ( 1983 ) progress in molecular and subcellular biology , biological response modifiers — interferons , doublestranded rna and 2 ′- 5 ′- oligoadenylates , eds . w . e . g . müller et al ., springer verlag , berlin , 1994 , vol . 14 . k . renneisen et al ., j . biol . chem . 265 : 16337 ( 1990 ) j . goodchild et al ., bioconjugate chem . 1 : 165 ( 1990 ) and ref . cit . therein . c . p . leamon et al ., proc . natl . acad . sci . usa 88 : 5572 ( 1991 )

US-44555999-A

an electrode holding device is described using a headset having a neutral curvature with a radius smaller than a human skull . the headset adapted to provide spring load force against the human skull at the first and the second ends where first and second respective electrode holding panels are attached . the electrode holding panels conform to the human above the ears . the electrode panels are adapted to pivot about pivot points on the ends of the headset . the panels are adapted to contact the human skull under pressure from spring load force generated from the headset bent beyond the neutral curvature of the headset . the headset can in certain examples be further adapted in certain to accommodate an arm having an a third electrode panel that possesses a third electrode assembly , the third electrode assembly adapted to be spring loaded against and in contact with the human forehead .

initially , this disclosure is by way of example only , not by limitation . thus , although the instrumentalities described herein are for the convenience of explanation , shown and described with respect to exemplary embodiments , it will be appreciated that the principles herein may be applied equally in other types of situations involving an electrode supporting headset . to illustrate an exemplary environment in which preferred embodiments of the present invention can be practiced , fig1 depicts a ¾ view of an embodiment of an electrode holding headset 100 in accordance with embodiments of the present invention . as shown , the headset / headband 100 defines a first end 105 and a second end 107 and conforms at least partially to a human skull . the first end 105 and the second end 107 provides spring load force against the human skull . a left electrode supporting panel 110 and a right electrode supporting panel 111 are pivotally attached to the headset 100 at pivot locations 108 essentially at the first and second ends . this embodiment depicts the electrode supporting panels 110 and 111 as curved to conform to the shape of a human head / skull , not shown . the headband 102 is a semi - rigid curved member that spring loads the electrode supporting panels 110 and 111 against a wearer &# 39 ; s scalp , skull , or other parts of their head . certain embodiments contemplate the electrodes 110 and 111 positioned just above the ears ( not shown ) of the wearer ( on a human skull ). the headband 102 is adjustable along varied circumferences of a head or head sizes via extension members 106 . locking members 104 lock the extension members 106 in place when the desired location of the electrode supporting panels 110 and 111 are found . the headband 102 provides a wider headband region 112 that rests over the apex of a skull for comfort and stability . in this embodiment , power is provided to the electrodes 101 via a battery 113 disposed on the outer portion of the wider headband region 112 to actively sense or provide electrical or electromagnetic current to the brain . certain embodiments contemplate battery power and wireless transmitting device 115 ( via a transmitter , controller , memory ,) adapted to transmit stimulating input to the brain / skull or receive sensing output from the brain / skull that is then sent to a wirelessly connected computer hub , not shown . other embodiments contemplate one or more wireline &# 39 ; s running along the headset 100 and connected to the electrodes . the wireline adapted to transmit stimulating input to the brain / skull or receive sensing output from the brain / skull to a physically connected computer hub . fig2 illustratively shows a side view of the electrode supporting headset 100 depicted in fig1 without the battery and wireless device consistent with embodiments of the present invention . the left side is displayed showing the wider headband region 112 that rests over the apex of a skull that narrows to the spring - loaded headband 102 . as discussed above , the headband is extendable via an extension member 106 and locked into place via a locking member 104 . the left electrode supporting panel 110 is shown for reference . fig3 depicts the top view of the electrode holding headset 100 without the battery and wireless device consistent with embodiments of the present invention . prominently shown in the middle of the headset 102 is the wider headband region 112 that rest of the apex of the skull . the left electrode supporting panel 110 , the right electrode supporting panel 111 and the two locking members 104 are shown from the top view . fig4 illustratively depicts a front view of the embodiment depicted in fig1 without the battery and wireless device cooperating with the human skull 210 consistent with embodiments of the present invention . the electrode holding headset 100 is shown cooperating with the human skull 210 . as illustratively shown , the electrode supporting panels 110 and 111 are spring - loaded against the human skull 210 as shown by the arrows pointing towards the center of the human skull 210 . the electrode supporting panels 110 and 111 are adapted to pivot about pivot points 108 to conform to the human skull 210 . the extension member 106 is shown partially extended with the locking members 104 engaged ( pointing down ) to lock the extension members 106 in position . embodiments of the present invention contemplate one or more electrodes located on one or more of the electrode supporting panels 110 and 111 . embodiments contemplate that the electrodes can be active or passive electrodes that can be placed on the scalp , ear , forehead , or other reasonable places on a human head . a passive system is envisioned to hold a plurality of electrodes in place on the scalp , ear or forehead , for example , to passively detect current from the brain either which itself can be active , quiet or experiencing induced input such as auditory , visual , tactile as well as other energy sources , such as photon or chemical modulation . certain embodiments contemplate active electrodes adapted to either stimulate the scalp or brain using a variety of forms of electrical or electromagnetic current in varied frequencies and frequency profiles ( e . g . waveforms , signal intensity / amplitude , etc . direct current can be continuous or interrupted . stimulation can also be alternating current called tes or transcranial electrical stimulation and there is transcranial magnetic stimulation — all working on the brain , placed in the appropriate locations over various parts of the brain . embodiments of a passive electrode system envision a plurality of electrodes in place on the scalp , ear , forehead , or other regional places on human head to passively detect current from the brain either which itself can be active , quiet , or experiencing induced input such as auditory , visual , tactile as well as other energy sources such as photon or chemical modulation . embodiments contemplate the electrode holding headset 100 applied to the lateral sides of a human skull 210 in contact with the scalp above the ear using and attachment system for the frontal plane over the top of the skull 210 or secondarily posterior , inferior or anterior and a combination thereof , for example . while other embodiments contemplate the electrodes contacting the ears via the panels . certain embodiments contemplate one or more electrodes integrated with the left electrode supporting panel 110 providing a reverse polarity to the one or more electrodes integrated with the right electrode supporting panel 111 . in other words , the electrodes on the left electrode supporting panel 110 possesses an opposite polarity to the right electrode supporting panel 111 . other embodiments contemplate one or more electrodes of opposite polarity over the frontal scalp or forehead relative to paired electrodes ( one or more ) in contact with another port of the scalp , skull , or over a body part on the other side or even ipsilateral side of the body . this embodiment could include one electrode held in place with the electrode supporting headset 100 over the frontal scalp and / or forehead and the opposite electrode over the contralateral scalp overlying the frontal motor , sensory , temporal or parietal regions of the brain ( see fig5 ). the contralateral or opposite polarity electrode could also be over the opposite side of the neck , upper back or in some cases further down the body on either side . certain embodiments contemplate one electrode or set of electrodes on the scalp and the other electrode on the neck or upper neck of the person . this can be accomplished by extending an arm 510 from the electrode supporting headset 500 . such as that depicted in capital fig5 which illustratively depicts an electrode supporting headset 500 with an arm 510 extending from the wider headband region 112 . the arm 510 possesses a pivotable electrode supporting panel 512 ( pivotable about pivot point 514 ) that conforms to the forehead or neck of a person using the elector supporting headset 500 . other embodiments contemplate at least one other electrode attached to the human body and connected to the headset 100 . embodiments of the electrode supporting headsets 100 and 500 contemplate the headset being capable and adapted to be self - administered with only one hand . in other words , a user ( or person using ) electrode supporting headsets can put the electrode supporting headset on their head and adjust the electrode supporting panels to be placed in the appropriate parts of their skull , forehead , neck , or upper body with one hand . embodiments of the electrode supporting headset 100 contemplates supporting a small magnetic coil ( not shown ) to stimulate the brain , such as a transcranial magnetic stimulator . other embodiments contemplate a first electrode supporting panel possessing a plurality of electrodes with a relatively negative charge thereon and a second electrode supporting panel possessing a plurality of electrodes with a relatively positive charge thereon . optionally , a first electrode supporting panel is envisioned to possess a plurality of electrodes with a negative charge thereon in contact with a person forehead while a second electrode supporting panel 612 possessing a plurality of electrodes with positive charge thereon on the opposite side of the scalp near or over the occipital portion of the skull ( overlaying the frontal motor , sensory , temp oral or parietal regions of the brain ), fig6 , or over an ipsilateral part of the body ( in the same line with the occipital portion along the person &# 39 ; s neck or back ) or even ipsilateral side of the body . fig7 shows yet another embodiment illustrating a plurality of electrodes 704 disposed along a semi - rigid curved headset 700 . here , there is a top panel 702 that is pivotally adjustable about a pivot point 708 over the top of a human skull . the arrows indicate the pressure direction of the panels 110 , 111 and 702 over the human head . an optional embodiment contemplates more panels , less panels or no panels with the electrodes traversing the curved headset 700 adapted to contact a human skull . in this arrangement , the electrodes 704 contact the human head along the path of the headset 700 from the left ear to the right ear . certain embodiments contemplate a plurality of electrodes that contact a human skull via the headset 100 or 700 . the plurality of electrodes includes a first group of electrodes and a second group of electrodes . the first group of electrodes possessing a negative polarity charge and the second group possessing positive polarity , relative to the first group . a method for using the headset 100 is further contemplated whereby the headset , as previously discussed , is semi - rigid with a curvature smaller than a human skull , the headset having a first end supporting a first electrode arrangement and a second end supporting a second electrode arrangement . a person will bend the headset in an open direction by spacing apart the first end 105 from the second end 107 in a direction that opens up the curvature of the headset 100 . while in the open position , place the headset 100 over the human skull while the headset is spaced apart . in this way , the curvature of the headset is a bit greater than the human skull allowing the panels 110 and 111 to unobstructively be placed over the skull . when in position over the skull , release the headset 100 allowing the first electrode arrangement and the second electrode arrangement to move towards one another in a closed position that compresses the electrodes against the human skull . the first electrode arrangement on a first panel 110 and the second electrode arrangement on a second panel 111 , the panels pivoting to conform to the human skull . positioning the first electrode arrangement on the human skull above a left ear and the second electrode arrangement on the human skull above a right ear is done to place the electrodes in the right positions over the brain . the panels 110 and 111 can then be locked into position with the latches 104 . the electrodes can be dampened to improve contact with the human head , the electrodes can protrude to penetrate through hair on the head , or can have adhesive if the head is shaved . when the electrodes are in contact and pressing against the skin of the person &# 39 ; s head , the electrodes can be energized via a power supply ( wireline or via a battery ) to produce stimulation or to receive signals from the brain . some embodiments contemplate passively sensing signals from the brain by the energy produced by the brain transmitted through the skull . it is to be understood that even though numerous characteristics and advantages of various embodiments of the present invention have been set forth in the foregoing description , together with the details of the structure and function of various embodiments of the invention , this disclosure is illustrative only , and changes may be made in detail , especially in matters of structure and arrangement of parts within the principles of the present invention to the full extent indicated by the broad general meaning of the terms in which the summary is expressed . for example , additional electrode supporting panels can be used in a consistent manner with embodiments of the present invention while still maintaining substantially the same functionality without departing from the scope and spirit of the present invention . another example can include various linked arms with electrode supporting panels were multiple electrode supporting panels along a single arm , or various lines emanating from the headset / headband that can adhere to various parts of the body without departing from the scope and spirit of the present invention . it will be clear that the present invention is well adapted to attain the ends and advantages mentioned as well as those inherent therein . while presently preferred embodiments have been described for purposes of this disclosure , numerous changes may be made which readily suggest themselves to those skilled in the art and which are encompassed in the spirit of the invention disclosed and presented in the appended claims .

US-201615183589-A

the present invention relates to a process for the isolation of artemisinin , an antimalarial agent from the herb of the artemisia annua plant , comprising of extracting the herb with ethanol , partitioning of the extract between water and hexane , followed by evaporative crystallization of artemisinin from hexane phase to produce substantially pure artemisinin .

in accordance with the method of the invention , dried pulverized leaves of artemisia annua , may be extracted by continuous percolation over a period of four to six hours using five to ten fold volume of the non - aqueous solvent selected from ethanol or methanol . the said extraction process may be repeated three to five times using same solvent ratios to ensure maximum extraction of artemisinin from the herb . the resulting extract can be concentrated to 1 to 5 % of the original volume by distillation under vacuum . the recovered solvent may be used again in the extraction process . the excess of water ( four times of the reduced volume of ethanol extract ) to be added to the concentrated to make it 80 % aqueous followed by partitioning of the contents between water and hexane . for partitioning the aqueous content and hexane may be used in a ratio of 1 : 1 or 2 : 1 v / v . partitioning of aqueous content with non - polar solvent may be repeated three to five times using the same solvent ratio in order to ensure maximum transfer of artemisinin to hexane fraction . the combined hexane fractions may be pooled together before they are distilled under vacuum ( to recover the solvent for using again ) to obtain 1 - 5 % of its original volume . the concentrated liquid may be a light to dark green oily liquid . ethyl acetate ( 10 - 20 % v / v ) is added to it . to remove the green pigmentation this liquid is treated with 1 - 3 % w / v of any colour absorbing substance activated charcoal . the yellowish liquid obtained after removal of activete charcoal ( by filtration ) may be subjected to the evaporative crystallization yielding substantially pure artemisinin without using chromatography . as an embodiment in the present invention the extraction of dry , pulverized leaves with non - aqueous ethanol may have several advantages over the previously used hexane or di - ethyl ether solvents . besides extraction being rapid , ethanol will extract less amount of fatty material , which are considered as an obstacle in the purification and crystallization steps . as an embodiment of the present invention the extract is partitioned between water and hexane in order to enrich the extract with respect to the artemsinin and remove as many impurities as possible from the concentrate to facilitate the crystallization of artemisinin . according to another embodiment of the present invention , partitioning of the ethanol extract is carried out using water and hexane in a ratio ranging from ( 1 : 1 or 2 : 1 ), the process of partitioning can be repeated 3 - 5 times to ensure maximum transfer of artemisinin to hexane layer . the partitioning step results in a substantially exclusive transfer of the artemisinin into the hexane layer with concomitant reduction in the amount of material , i . e . only 30 to 35 % weight of the original extract is transferred in to hexane layer . according to yet another embodiment of the invention hexane fraction can directly be used for crystallization by slow evaporation after concentrating the hexane fraction and mixing 10 - 20 % ( v / v ) of ethyl acetate . in the prior art artemisinin is obtained through a hot extraction in hexane , petroleum ether , which takes more time for extraction . hot extraction of plant leaves with the above solvent is hazardous and extract more colouring substances and fatty material , which are proved obstacle in purification . whereas , the extraction with ethanol at room temperature is relatively rapid and obviates the co - extraction of colouring and fatty substances . partitioning of the hexane extract between hexane and 20 % aqueous acetonitrile results in transfer of artemisinin in to aqueous acetonitrile layer . water is separated from aqueous acetonitrile layer by addition of sodium chloride to saturation prior to chromatography . for partitioning step acetonitrile being relatively costly raises the cost of production of artemisinin . water and hexane combination , which has been used for liquid : liquid partitioning results in two distinct layers easily due to higher density differences . this will also be a preferable solvent system for partitioning of artemisinin on economic ground as compared to hexane and acetonitrile of the prior art . as a result of partitioning only 30 to 35 % fraction of the extract remained in hexane thus enriching the extract in artemisinin . wherefrom artemisinin could be directly crystallized using evaporative crystallization without going for chromatography , while it is not possible with acetonitrile layer , which consist of artemisinin after partitioning in methods described earlier . the present invention further described with reference to the following examples which are given by way of illustration and therefore , should not be construed to limit the scope of the present invention in any manner . to select an efficient solvent for extraction of artemisinin different solvents systems were tested . for this 10 g of dry powdered leaves of artemisia annua were extracted with methanol , 20 % aqueous methanol , ethanol , 20 % aqueous ethanol or hexane as a solvent individually in separate tubes . 10 ml of the solvent was taken out of the tube at 2 , 4 and 6 h of incubation . the fraction was evaporated to dryness on a water bath , extract was solubilized in 2 . 0 ml solvent and spots ( 5 μl ) were loaded on a tlc plate along with pure artemisinin dissolved in the respective solvent @ 1 mg / ml taken as controls . the tlc was carried out in a glass tlc tank saturated with the mobile phase hexane : diethyl ether ( 1 : 1 ), plates were developed to a height of 15 cm . later plates were dried and spots were visualized by immersing the plates in a developing reagent ( glacial acetic acid : sulfuric acid : anisaldehyde , 50 : 1 : 0 . 5 ), followed by heating the plate at 110 ° c . for 15 minutes or until pink spots of artemisinin appeared . for quantification , tlc spots corresponding to artemisinin were scanned at 540 and 610 nm dual wavelength mode of tlc scanner . the results obtained are presented in the form of % artemisinin extracted in to the solvent and are summarized in table - 1 . it is clear from the table that pure ethanol and methanol rapidly extract the artemisinin as compared to hexane , however after a certain period of time concentration of artemisinin starts diminishing in methanol and ethanol extracts in contrast to hexane extract possibly because of decomposition or transformation of artemisinin into another unknown compound . mixing of water in methanol caused a severe decay of artemisinin extraction . ethanol was more efficient for extracting more artemisinin in less time period as compared to methanol and hexane both . on the basis of lower cost and rapid extraction efficiency ethanol will be a suitable solvent . pure artemisinin ( 0 . 2 g ) was dissolved in different test tubes containing 1 : 1 ( v / v ) mixture of two non - miscible solvents , hexane and aqueous ethanol ( i . e . ethanol mixed in water ), where concentration of ethanol varied from 20 to 80 %. after completely solubilizing the artemisinin in the mixture , two layers of hexane and ethanol were separated with the help of a separating funnel . the individual layer from different test tube was tested for the presence of artemisinin content by tlc as in example 1 . the results showing the % fraction of artemisinin partitioned between the hexane and aqueous ethanolic layers separated from each tube are given in the table - 2 . this example suggests that artemisisnin can be selectively transferred from ethatnolic extract of artemisia annua in to hexane by maintaining the above ratios . from hexane fraction , artemisinin can be crystallized directly using known methods of evaporative crystallization . dry pulverized leaves of artemisia annua ( 100 g ) was extracted by continuous percolation over a period of four hours using 600 ml of ethanol at 30 ° c . temperature . the process of extraction was repeated four times using same solvent ratios . the combined extract was concentrated under vacuum to reduce the volume to 50 ml , volume was made up to 250 ml by adding water to it . the resulting mixture was partitioned with 250 - ml hexane four times . the combined hexane layer was reduced under vacuum ( to recover hexane ) to 5 % of its original volume to result in dark green oily liquid . a 20 % v / v ethyl acetate was mixed to this liquid followed by treating this with 1 % w / v activated charcoal . the liquid was filtered through a whatman 3 mm filter paper to remove the activated charcoal . after filtration the resulting dark yellow liquid was subjected to evaporative crystallization . the resulting white , needle shaped crystals were separated out by vacuum filtration device and weighed . the total crystals yielded were 603 mg . dry pulverized leaves of artemisia annua ( 100 g ) was extracted by continuous percolation over a period of four hours using 1 . 0 litre of ethanol at 30 ° c . temperature . the process of extraction was repeated four times using same solvent ratios . the combined extract was concentrated under vacuum to reduce the volume to 80 ml , volume was made up to 400 ml by adding water to it . the resulting mixture was partitioned with 400 - ml hexane four times . the combined hexane layer was reduced under vacuum to 50 ml volume to result in dark green oily liquid . a 20 % v / v ethyl acetate was mixed to this liquid followed by treating this with 1 % w / v activated charcoal . the liquid was filtered as in example 3 and subjected to evaporative crystallization . the artemisinin crystals obtained were weighed to be 605 mg . dried pulverized leaves of artemisia annua ( 100 g ) were extracted as in example 3 . the concentrated extract 50 ml was made up to 250 ml by adding water to it . the resulting mixture was partitioned with 125 ml hexane five times . the combined hexane layer was reduced under vacuum to 50 ml dark green oily liquid . a 20 % v / v ethyl acetate was mixed to this liquid followed by treating this with 1 % w / v activated charcoal . the liquid was filtered through a whatman filter to remove the activated charcoal . after filtration the resulting dark yellow liquid was subjected to evaporative crystallization . the resulting white , needle shaped crystals were separated and weighed . the total artemisinin yield was 601 mg . extraction of artemisia annua leaves was performed as described in example 3 but under varied temperatures 20 , 30 , 40 and 50 ° c . conditions in separate vials . the concentrated extracts 50 ml each obtained after was concentrating under vacuum were made to 250 ml by adding water to them separately . the resulting mixtures were partitioned with 250 - ml hexane three times individualy . the hexane layers were reduced under vacuum to 5 % of their original volumes , the dark green oily liquids . a 20 % v / v ethyl acetate was mixed to each liquid followed by treating them with 1 % w / v activated charcoal . the liquids were filtered and resulting dark yellow liquids were subjected to evaporative crystallization individualy in separate vials . the resulting artemisinin crystals were separated and weighed . the crystal yields were 410 , 603 , 600 and 550 mg at temperatures 20 , 30 , 40 and 50 ° c . respectively . dried pulverized leaves of artemisia annua ( 1 . 0 kg ) were extracted by continuous percolation over a period of four hours using 6 litres of ethanol at 30 ° c . temperature . the process of extraction was repeated four times using same solvent ratios . the combined extract was concentrated under vacuum to reduce the volume to 400 ml , volume was made up to 2 . 0 liters by adding water to it . the resulting mixture was partitioned with 2 . 0 liters hexane three times . the combined hexane layer was reduced under vacuum ( to recover hexane for using again ) to 300 ml dark green oily liquid . a 60 ml ethyl acetate was mixed to this liquid followed by treating this with 1 % w / v activated charcoal ( for removal of the green pigmentation ). the resulting dark yellow liquid after filtration was subjected to evaporative crystallization . the artemisinin crystals were separated and weighed . a total of 5 . 95 g artemisinin crystals were obtained . dried pulverized leaves of artemisia annua ( 100 g ) were extracted by continuous percolation over a period of four hours using 600 ml of methanol at 30 ° c . temperature . the process of extraction was repeated four times using same solvent ratios . the combined extract was concentrated under vacuum to reduce the volume to 50 ml , volume was made up to 250 ml by adding water to it . the resulting mixture was partitioned with 250 - ml hexane three times . the combined hexane layer was reduced 5 % of its original volume to result in dark green oily liquid . a 20 % v / v ethyl acetate was mixed to this liquid followed by treating this with 1 % w / v activated charcoal . the liquid was filtered through a whatman filter to remove the activated charcoal . after filtration the resulting dark yellow liquid was subjected to evaporative crystallization . the resulting white , needle shaped crystals were separated out by vacuum filtration device and weighed . the artemisinin crystals obtained were 320 mg . the improved process of production of artemisinin , the subject matter of this patent offered a number of advantages such as 1 . extraction with ethanol is rapid and thus less time consuming . 2 . extraction is energy saver as heating is not required during the process . 3 . partitioning of extract between water and hexane to obtain artemisinin is a better option as compared to acetonitrile and hexane because of being economical . 4 . the hexane layer obtained after partitioning can be used for crystallization of artemisinin without chromatography . 5 . overall process offers 30 to 40 % reduction of production costs of artemisinin over prior art . 6 . any possible contamination of toxic chemicals in artemisinin due to using the commercial grade hexane during extraction may be avoided . 7 . setting up costly devise for liquefying the carbon dioxide is not required . 8 . since method does not need very large infra structure , the extraction of artemisinin can be easily planned in rural areas . 9 . overall process is efficient and economical as solvents used in the process are being recovered and reused .

US-11207002-A

disclosed is an apparatus for examining the field of vision , having a scanning device , which is provided with beam deflecting and beam imaging elements , via which the illumination light beam from an illumination light source is guided onto the region of the fundus oculi to be imaged and , if need be , the light reflected from the fundus oculi is guided to a detector device , from the time - sequential output signal of which an evaluation and synchronization unit generates an image of the scanned section by points , and having a control unit , which controls the intensity of the illumination light beam scanning the fundus oculi in such a manner that marks , respectively patterns , are projected onto a predeterminable region of the fundus oculi with predeterminable brightness , which the person under examination perceives , respectively does not perceive in the event of defects in the field of vision . the present invention is distinguished by the fact that in order to set a specific value of brightness of the marks , respectively of the patterns , the control unit switches the illumination light beam within the time span , during which the illumination light beam illuminates a scanning point , from a first intensity value to at least a second intensity value for a specific fraction of this time span .

the present invention relates to an apparatus for examining the field of vision . the devices presently commercially available for field of view examinations have a hemispherical dish in which spots of light of adjustable brightness , also referred to as stimuli , which are distributed over the field of vision light up alternately . these spots of light of adjustable brightness are generated by light diodes attached to the hemispherical dish or by a projection system . by pressing a button , by way of illustration , the person under examination focussing on a so - called fixation mark , signals &# 34 ; seen &# 34 ; or &# 34 ; not seen &# 34 ;. a control registers the response given allocating location and brightness of the lit spot of light . the result , which is usually represented in a graph , presents a &# 34 ; map &# 34 ; of the absolute o relative field view defects . these state of the art instruments , however , have a number of disadvantages : although the brightness of a spot of light can be adjusted , the value of the adjusted brightness is in no strict correlation to the intensity of light actually reaching the fundus oculi as this not only depends on the brightness value of the lit spot of light , but also on the size of the pupil , etc . furthermore , in the state of the art devices , it must be insured that the patient focusses on the fixation mark and &# 34 ; does not let his eye wander around the hemispherical dish &# 34 ; otherwise his response &# 34 ; seen &# 34 ; gives no valid information about the lack of view field defects . in particular , with the state of the art apparatuses it is not possible to directly correlate between the point of the lit spot of light and perhaps the pronounced , respectively pathological , structures as the person examining is unable to observe the fundus oculi directly during the field of vision examination . above all , the afore mentioned known instruments for examining the field of view are dependent on the &# 34 ; assistance &# 34 ; of the person under examination . i . e . they do not permit a so - called objective visus examination . in the so - called objective visus determination , the visus , that is the faculty of sight of a test person , is to be ascertained without requiring the cooperation of the person under examination . typical applications of an objective visus determination would be the exposure of malingers for expert opinions for the courts or the visus examination of infants and pre - school children . in scientific literature , it has been proposed to induce so - called opto - kinetic nystagmus in order to determine the visus objectively . by this is meant that the person under examination is presented a lively pattern , respectively a mark as a stimulus . if the pattern is perceived , i . e . if the structures in the pattern are large enough to be resolved by the eye , the stimulated movement causes consequent characteristic , involuntary eye movements , so - called opto - kinetic nystagmus . hitherto , however , there is no state of the art device with which it would be possible to determine the visus obtectively in practice . the reason for this is that especially malingerers repeatedly succeed in intentionally looking passed the stimulus and thereby in deceiving the examining person . furthermore , an instrument for examining the view field has been suggested , in which a so - called scanning laser ophthalmoscope is utilized in which the intensity of the scanning light for generating the marks , respectively the stimuli , is modulated . such devices are , by way of illustration , described in the article &# 34 ; scanning laser ophthalmoscopy &# 34 ;, ophthalmology , vol . 89 , no . 7 july 1982 , pp . 852 - 857 or in the article &# 34 ; reading with a mascular scotoma &# 34 ;, in investigative ophthalmology and visual science , july 1986 , vol . 27 , pp . 1137 - 1147 , to which , moreover , express reference is made with regard to the explanation of all details not made more apparent herein . the use of a so - called scanning laser ophthalmoscope for examining the field of vision has the advantage that the view field examination can occur under the visual observation of the examining person as the amount of light required for generating the image of the fundus oculi is so minimal that it virtually is not disturbing as &# 34 ; background brightness &# 34 ;. furthermore , the scanning laser ophthalmosopes have , especially if they employ &# 34 ; pupil separation &# 34 ; between the entry pupil for the illumination beam of light and the exit pupil for the light reflected from the fundus oculi described in the u . s . pat . no . 4 , 213 , 678 , the advantage that the illumination beam of light passes through a small , central section of the pupil of the eye in such a manner that the illuminant reaching the fundus oculi does not depend on the size of the pupil . moreover , the stimuli may not only be spots of light , but also complicated patterns , such as by way of illustration landolt rings . in the case of the known apparatuses from the afore - cited publications , an acousto - optical modulator is used to control the intensity of the illumination light beam , which -- depending whether only an image from the fundus oculi or a &# 34 ; stimulus &# 34 ; pattern is to be generated -- permits a more or less large portion of the illumination light beam to pass through . the intensity of the illumination beam of light can be varied approximately by the factor 100 with known acousto - optical modulators . such a variation of intensity is , however , insufficient for an apparatus for field of vision examination as it is necessary to vary the light intensity physiologically by about 40 to 50 db , by way of illustration , in order to discover the so - called relative field of vision defects , i . e . points in the view field at which bright spots of light , but not dark spots of light are still perceived . moreover , it is practically not possible to project a pattern with varying brightness . this state of the art instrument also does not permit objective visus examination , but is dependent on the cooperation of the person under examination . the object of the present intention is to improve an apparatus for examining the field of vision in such a manner that the intensity of the illumination beam of light can be varied at least by 40 db or more . another object of the present invention is to provide a device for an objective examination of the field of vision , respectively for an objective visus determination , with which , in particular , the visus of people who want to deceive the examining person about their faculty of sight can be objectively ascertained . a solution to the first object in accordance with the present solution is characterized in setting a specific brightness value for the marks ( pattern ), respectively stimuli , the control unit switches the illumination beam of light at least once from a first intensity value to a second intensity value within a time span , during which the illumination beam of light scans a scanning point . this second intensity value may , in particular , have the value zero , i . e . the control unit switches the illumination beam of light off at least once for a specific fraction of this time span . according to the present invention , thus the intensity of the illumination beam of light is not constant during the illumination of a &# 34 ; scanning point &# 34 ; as is the case in the state of the art devices . as on the other hand , the duration of the illumination of a scanning point -- depending on the number of &# 34 ; pixel &# 34 ; taken -- is approx . 100 ns , this switching of the illumination light beam , which inevitably results in &# 34 ; pulse durations &# 34 ; of less than 100 ns for the individual intensity values , is not noticed by the person under examination . but rather the retina of the person under examination registers a mean value of brightness corresponding to the temporal integral over the incident light intensity . by means of this invented measure , the brightness of the marks inscribed by the illumination beam of light can be varied within a substantially greater framework than is the case with the state of the art apparatuses , in which the transmission factor of the acousto - optical modulator is varied between a minimum and a maximum value with the transmission factor of the acouto - optical modulator not changing during the &# 34 ; scanning of a point &# 34 ;. in particular , marks can also be generated in this way &# 34 ; containing a series of scanning points &# 34 ; and in which brightness is varied in such a manner that the variation is resolved by the human eye . this can , by way of illustration , be advantageous in examining so - called receptive fields . furthermore , in accordance with the present invention , the visus of a person under examination can he determined while simultaneously controlling fixation . an element of the present invention is that , by switching the light beam from the illumination light source of such scanning ophthalmoscopes between at least two degrees of brightness , patterns are projected onto the fundus oculi thereby triggering an opto - kinetic nystagmus and that at the same time the involuntary eye movements caused by projecting the patterns are tracked . in this case , it is especially advantageous if the &# 34 ; normal &# 34 ; brightness of the scanning light beam in a scanning opthalmoscope may be so small that it can remain below the &# 34 ; stimulus threshold &# 34 ;. that is to say that the person under examination does not perceive the projected patterns on a &# 34 ; very high level of brightness &# 34 ; as would , by way of illustration , be required if the fundus oculi were examined with a conventional fundus camera with an areal illumination light source during the projection of the pattern . furthermore , it is advantageous if , random patterns can be easily generated by the modulated illumination light beam , whereby the patterns can be moved without difficulty over predetermined regions of the fundus oculi . the reaction of the person under examination can , by way of illustration , be visually controlled by the examining person on a monitor , on which an image of the fundus oculi is represented . however , it is particularly advantageous if with the invented development , with which the projection of the patterns is simultaneous with the representation of the fundus oculi , the control and evaluation unit registers the movements of the eye and correlates them to the point on the fundus oculi , onto which the pattern or patterns were projected . in addition , according to claim 6 hereto , the voluntary eye movements can be compensated via so - called &# 34 ; fundus tracking &# 34 ; as is known in principle in the field of ophthalmology . as the invented apparatus automatically recognizes if the shown structure is seen by the person under examination , moreover , by varying the brightness of the light beam more than two degrees or by continually varying it , automatic visus threshold value measuring can also be carried out , in which the structure when recognized is successively reduced in brightness , respectively the size of the structure is successively decreased , until the so - called opto - kinetic nystagmus is no longer triggered . naturally , the invented apparatus can also be operated in the conventional manner so that the person under examination responds &# 34 ; seen &# 34 ; or &# 34 ; not seen &# 34 ;, by way of illustration , by pushing a button . the control unit , which by way of illustration , may be provided with a conventional micro - computer , stores the response of the person under examination in correlation to the position , the size and the brightness of the respective pattern , respectively mark . in order to keep irritation of the person under examination by the &# 34 ; normal illumination light &# 34 ; to a minimum , it is in addition also possible with the invented apparatus to work with two wavelengths , thus , by way of illustration , to conduct the normal fundus examination with infrared light , which the person under examination does not perceive , and only to fade in visible light in order to project the pattern , respectively the marks . naturally , the control unit can also vary the intensity of the illumination light beam . this can , by way of illustration , occur in the event a light diode or a laser diode is utilized as the illumination light source , by varying the operational voltage of the diode . the switching , respectively switching off and subsequently switching on , may , of course , occur in the most varied ways , by way of illustration , by switching the illumination light source on and off accordingly . furthermore , the control unit can be provided with an acousto - optic modulator arranged in the path of the illumination beam . this acousto - optical modulator may in this case serve to adjust the intensity value of the illumination light source or it can be triggered with high - frequency in such a manner that , while the images are being generated , it blocks the light path &# 34 ; most of the time &# 34 ; at those points at which only the fundus oculi is to be imaged and thereby only lets a small part of the illumination light beam pass , whereas with a scanning device , in which the marks are to be inscribed , it opens the path of the illumination light a bigger fraction of the scanning time and thereby permits a larger part of the illumination light to pass . moreover , an additional light source is provided , which generates the background brightness so that the field of vision examination takes place &# 34 ; on a specific level of ambient brightness &# 34 ;. it is expressly pointed out that the desired &# 34 ; ambient brightness &# 34 ; can also be adjusted by the scanning illumination light beam , which also can generate &# 34 ; on the average &# 34 ; a certain &# 34 ; background brightness &# 34 ;. apparatuses for examining the view field have , compared to other field of vision examination devices , in which light diodes are provided for generating the marks , the advantage that &# 34 ; stimuli &# 34 ; can be generated at any points in the field of vision of freely predetermined shape . for this reason , the control unit is preferably provided with a so - called ( image ) memory , in which the position , shape and brightness of the marks are stored , which are to be presented consecutively to the person under examination and which possibly stores the response of the person under examination allocating it to the position and size , respectively brightness , of the respective mark , respectively &# 34 ; involuntary &# 34 ; movements of the eye that might occur . it is evident that in this case certain procedures in presenting the individual marks may be followed as may be known from the patent literature or from devices of the present applicant . in particular , information can first be elicited from marks which are roughly distributed over the field of vision ; the detected defects can subsequently be &# 34 ; picked - up &# 34 ; more closely . the invented apparatus has the special advantage that the individual data of the marks can be stored allocating them to the image recorded , respectively of the pronounced points of the fundus : in order to do this , an image is made of the fundus under examination by raster projection , respectively mark projection and the position of a pronounced fundus structure is simultaneously analyzed . for this purpose , such a fundus structure ( templet ) is selected prior to starting the examination . with all the images subsequently made during each raster projection , how far the marked structure has shifted from the position of the structure in the original or the preceding image is examined . this can occur automatically via so - called fundus tracking or semi - automatically via marking the pronounced structure . the shifts respectively detected are utilized to compensate for the movements of the fundus during the examination , respectively to subsequently correct the raster position . this tracking permits for the first time an examination of field of vision sensitiveness in conformance to the position . the digital storage of the position , size and brightness of the individual marks as provided for in accordance with the present invention is advantageously further improved by the brightness of the marks is stored , by way of illustration , as an 8 - bit value . as only a scale of two and a half can be represented with 8 bits , in accordance with the present invention the stored 8 - bit value is allocated non - linearly to a specific brightness value . this can , by way of illustration occur by first converting the 8 - bit value stored in the image memory digitally / analogously and the analogously converted value is transformed by at least one logarithmic amplifier with fixed or programmable amplification into a grey value , i . e . a value of brightness . the present invention is made more apparent by way of illustration in the following section without the intention of limiting the overall scope of the inventive concept using preferred embodiments with reference to the accompanying drawing , to which , moreover , express reference is made with regard to the disclosure of all the invented details not made more apparent herein : fig3 shows the invented variation of brightness in conjunction with the additional variation of intensity . the invented apparatus can , by way of illustration , be realized with a laser scanning ophthalmoscope in the manner described in wo 88 / 033 96 . this apparatus has an illumination light source 1 , which in the case of the depicted preferred embodiment is composed of two lasers 1 &# 39 ; and 1 &# 34 ; operating with different wavelengths and by means of a mirror 2 alternately or jointly generate an illumination light beam 3 . in the case of the depicted preferred embodiment , both the illumination light beam 3 and the light beam 4 coming from the fundus oculi &# 34 ; pass &# 34 ; via the deflection device , which is made more apparent in the following . the light beam 3 from the illumination light source 1 is deflected in a horizontal direction by a horizontal scanner , which in the case of the depicted preferred embodiment is a rotating polygonal mirror 5 . the beam thus fanned out in the horizontal plane passes mirror system 6 and 7 and strikes a vertical scanner , which in the case of the preferred embodiment is an oscillating mirror , respectively a galvanometer mirror 8 . behind mirror 8 , the bundle of beams has a &# 34 ; rectangular &# 34 ; cross - section . following the deflection on a plane mirror 9 , it is imaged upon the eye under examination 11 by a concave mirror 10 . the beam of light 4 reflected at the fundus oculi passes the afore - mentioned elements in reverse order and is indicated behind the horizontal deflection element 5 by a detector unit 12 following prior separation of the paths of the illumination and examination light by means of a mirror 13 . combining the mirrors as imaging elements yields a number of advantages , such as minimal imaging errors , no reflexes , achromaticity and minimal space requirements due to folding the beam path . whereby achromaticity is especially important if the illumination occurs simultaneously with laser light of differing wavelengths , by way of illustration in the infrared range and the visible range . divider mirror 13 separating illumination light path 3 and examination light path 4 is , in the case of the preferred embodiment , a small mirror so that the exit pupil of the reflected beam path 4 encircles the entry pupil . naturally other divider mirrors 13 may also be utilized , which , by way of illustration , result in the entry pupil and the exit pupil being superimposed . furthermore , an acousto - optical modulator 14 , which lets the light , by way of illustration , emitted from laser 1 &# 39 ; pass in one switched state and blocks it in the other switched state , may be provided in illumination light path 3 . in this event , the switching on and off of the modulator happens so fast the light path is blocked at least once during each illumination period . the acousto - optical modulator 14 may also be employed to adjust the intensity of the laser beam &# 34 ; integrally &# 34 ;, whereby switching between the two values of intensity then occurs , by way of illustration , by appropriate triggering of the laser . this imaging is preferred with the &# 34 ; speed &# 34 ; of the present commercial modulators . the illumination period of an image point , of course , depends on the number of images generated and on the number of image points per image , with the usual video norm it typically amounts to 100 ns . as the time during which the light path is blocked necessarily has to be less than 100 ns , the eye does not perceive the switching on and off procedure , but rather &# 34 ; only sees an average integrated intensity &# 34 ;. fig2 depicts this schematically for the event that the illumination light beam is switched off and respectively on again four times during the period of illumination of an image point so that a total of five illumination periods are yielded . the actual intensity perceived by the eye depends on the ratio switch - on time / switch - off time . fig3 depicts schematically the event that the intensity of the laser beam is additionally varied , by way of illustration by , acousto - optical modulator 14 or appropriate triggering by lasers 1 &# 39 ;, respectively 1 &# 34 ;. the combination of switching the light beam on and off in connection with varying the intensity permits varying the brightness perceived by the eye by at least 50 db . in the preceding section the present invention has been described using a preferred embodiment without the intention of limiting the scope of the overall inventive concept . thus , other devices than the one described herein can be utilized as &# 34 ; basic apparatuses &# 34 ;. furthermore , it is expressly pointed out that any sources of light , i . e . even light sources other than lasers , may be employed as light sources . moreover , an additional illumination light source can be provided , which generates a &# 34 ; background brightness &# 34 ; or permits making an infrared image . as the eye does not perceive the infrared light , it is , therefore , possible to check whether very dark light spots can be perceived at low background brightness . nonetheless , the invented apparatus permits visual examination of the position of the pattern projected onto the fundus oculi . in addition to this , the invented apparatus can be utilized for measuring evociated potentials or other electrophysical data . other measures can also be used instead of the acousto - optical modulator for switching the illumination light beam on or off . by way of illustration , the light source can be switched on or off . the control unit not described in the preceding , which controls the light spots and , if need be , tracks in the event of eye movements , can be realized in an as such known manner , by way of illustration with a microcomputer .

US-86574992-A

use of factor xiii for treating hemophilia b . a patient having hemophilia b is treated by administering factor xiii , generally in conjunction with factor ix .

the present invention fills this need by administering to patients with hemophilia b factor xiii in conjunction with factor ix , and by administering to patients afflicted with hemophilia b factor xiii in conjunction with factor ix . the teachings of all of the references cited herein are incorporated in their entirety by reference . hemophilia b is heterogeneous in both its clinical severity and molecular pathogenesis . clinical severity roughly correlates with the level of factor ix activity . in severe hemophilia b , the patient will have less than 1 % normal factor ix in his plasma ( about 0 . 1 u / ml of plasma ). once a bleeding disorder has been determined to be present , the physician must determine what is the cause of the disorder . for diagnostic purposes , the hemostatic system is divided into two parts : the plasma coagulation factors , and platelets . with the exception of factor xiii deficiency , each of the known defects in coagulation proteins prolongs either the prothrombin time ( pt ), or partial thromboplastin time ( ptt ), or both of these laboratory - screening assays . a pt is performed by addition of a crude preparation of tissue factor ( commonly an extract of brain ) to citrate - anticoagulated plasma , recalcification of the plasma , and measurement of the clotting time . a ptt assay is performed by the addition of a surface - activating agent , such as kaolin , silica , or ellagic acid , and phospholipid to citrate - anticoagulated plasma . after incubation for a period sufficient to provide for the optimal activation of the contact factors , the plasma is recalcified and the clotting time measured . the name of the ptt assay emanates from the phospholipid reagents being originally derived from a lipid - enriched extract of complete thromboplastin , hence the term partial thromboplastin . the ptt assay is dependent on factors of both the intrinsic and common pathways . the ptt may be prolonged due to a deficiency of one or more of these factors or to the presence of inhibitors that affect their function . although its commonly stated that decreases in factor levels to approximately 300 % of normal are required to prolong the ptt , in practice the variability is considerable in sensitivity of different commercially available ptt reagents to the various factors . in fact , the levels may vary from 25 % to 40 %. see , miale j b : laboratoiy medicine - hematology . 6 . sup . th ed ., ( cv mosby , st . louis , mo ., 1982 ). if the pt and ptt are abnormal , quantitative assays of specific coagulation proteins are then carried out using the pt or ptt tests and plasma from congenitally deficient individuals as substrate . the corrective effect of varying concentration of patient plasma is measured and expressed as a percentage of normal pooled plasma standard . the interval range for most coagulation factors is from 50 to 150 percent of this average value , and the minimal level of most individual factors needed for adequate hemostasis is 25 percent . one unit of factor ix is defined as the amount of factor ix activity present in 1 ml of pooled normal human plasma and is equivalent to 100 % activity . the dose of factor ix needed to achieve a desired level of activity can be calculated based on estimation of the patient &# 39 ; s plasma volume and knowledge of factor ix kinetics . plasma volume may be estimated as 5 % of body weight or 50 ml / kg body weight . thus the plasma volume of a 70 kg patient is approximately 3 , 500 ml . by definition , for such a patient to have 100 % factor ix activity , 1 u / ml of plasma or a total of 3 , 500 u of factor ix must be present in this plasma volume . if severe hemophilia b is present , it may be assumed that the initial factor ix activity is zero . thus , to obtain 100 % activity , at least 3 , 500 u of factor ix must be administered . because of rapid redistribution into the extravascular space and adsorption onto endothelial cells of vessel walls , however , only about 50 % of the infused factor ix remains in circulation after a short period . therefore , to obtain 100 % activity , the initial dose should be about 7 , 000 u of factor ix . to generalize to any size patient with any initial factor ix level and any desired target level , infusion of 1 u / kg of body weight of factor ix will raise the factor ix level approximately 1 %. for example , a dose of 1 , 750 u would raise a 50 - kg patient from a starting factor ix level of 15 % to a target of 50 % activity . after its initial rapid redistribution , factor ix has a second phase half - life of approximately 18 - 24 hours . because the variability in this measurement is significant , it is best determined in each individual patient to allow proper dosing . based on these data , the factor ix level of a patient raised to 100 % activity would be expected to decay to 50 % by approximately 24 hours after infusion of the initial dose . a second bolus one - half the amount of the first should then raise the level from 50 % to 100 %. factor ix is commonly administered in boluses every 12 - 24 hours . for the recombinant factor ix , beneffix ™, genetics institute , cambridge , mass ., the number of factor ix international units ( iu ) to be administered should be the percentage of factor ix increase desired multiplied by 1 . 2 iu / kg of body weight . factor ix is produced by a number of companies in both a recombinant and plasma - derived formulations . among these are the following : benefix ® ( recombinant product produced by genetics institute , cambridge , mass . ), monoine ™ concentrate ( centeon , king of prussia , pa . ), alphanine ™ sd ( alpha therapeutic corp . los angeles , calif . ), bebulne vh immuno ™ ( immuno , rochester , minn . ), konyne 80 ™ ( bayer corporation , biological , west haven , conn . ), proplex t ™ ( baxter healthcare , glendale , calif .) and profilnine sd ™ ( alpha corporation ). the method of the present invention improves upon the above - described treatment of hemophilia b by administering factor xiii in conjunction with factor ix . the factor xiii can be administered at any time alone or at the same time as factor ix either to stop a hemorrhage or for prophylaxis . factor xiii , also known as fibrin - stabilizing factor , circulates in the plasma at a concentration of 10 - 20 mg / ml . the protein exists in plasma as a tetramer comprised of two a subunits and two b subunits . each subunit has a molecular weight of 85 , 000 da , and the complete protein has a molecular weight of approximately 330 , 000 da . factor xiii catalyzes the cross - linkage between the γ - glutamyl and ε - lysyl groups of different fibrin strands . the catalytic activity of factor xiii resides in the a subunits . the b subunits act as carriers for the a subunits in plasma factor xiii . recombinant factor xiii can be produced according to the process described in european patent no . 0 268 772 b1 . see also u . s . pat . no . 6 , 084 , 074 . the level of factor xiii in the plasma can also be increased by administering a factor xiii concentrate derived from human placenta called fibrogammin ™ ( aventis corp .) or by administration of recombinant factor xiii . a pharmaceutical composition comprising factor xiii can be formulated according to known methods to prepare pharmaceutically useful compositions , whereby the therapeutic proteins are combined in a mixture with a pharmaceutically acceptable carrier . a composition is said to be a “ pharmaceutically acceptable carrier ” if its administration can be tolerated by a recipient patient . a suitable pharmaceutical composition of factor xiii will contain 1 mm edta , 10 mm glycine , 20 % sucrose in water . an alternative formulation will be a factor xiii composition containing 20 mm histidine , 30 % wt / volume sucrose , 2 mm glycine and 0 . 010 % wt / vol . polysorbate , ph 8 . the concentration of factor xiii should preferably be 1 - 10 mg / ml , more preferably about 5 mg / ml . other suitable carriers are well known to those in the art . see , for example , gennaro ( ed . ), remington &# 39 ; s pharmaceutical sciences , 19th edition ( mack publishing company 1995 ). factor xiii can be administered intravenously , intramuscularly or subcutaneously to treat hemophilia b . when administering therapeutic proteins by injection , the administration may be by continuous infusion or by single or multiple boluses . the levels of factor xiii in an individual can be determined by assays well known in the art such as the berichrom ™ 0 f xiii assay ( dade behring marburgh gmbh , marburg , germany ). the normal adult has an average of about 45 ml of plasma per kg of body weight . each liter of blood has 1000 units ( u ) of factor xiii . the amount of factor xiii administered should be enough to bring an individual &# 39 ; s level of factor xiii in the plasma to 100 % of normal plasma or slightly above to 1 - 5 % above normal , a dose of 0 . 45 u / kg would raise the level of factor xiii by about 1 % compared to normal . one unit of factor xiii is about 10 μg of recombinant factor xiii , which contains only the dimerized a subunit . thus , to raise the level of factor xiii by 1 %, one would administer about 4 . 5 μg of the a2 subunit per kilogram weight of the individual . so to raise the level 30 % of normal , one would administer 13 . 5 u / kg . for a 75 kg individual this would be about 1 , 012 . 5 u . some patients may have consumptive coagulopathies that involve factor xiii losses . in such cases , a higher dosing ( e . g ., 1 - 2 u / kg -%) or multiple dosing of factor xiii ( e . g ., 1 - 2 u / kg -%- day ) may be required .

US-52190206-A

a fishhook has a tapered conical sinker mounted on the upper end of the shank . the eyelet is offset at a 90 ° angle to the shank . when this fishhook is mounted in an artificial lure , the entire fishhook , except the eyelet , is hidden by the body of the lure . the fishhook is sized to fit the lure so that there is no significant distortion of the lure . the position of the eyelet and the sinker prevent the lure from rotating during retrieval and the lure rides naturally in the water .

the fishhook of the present invention is shown generally at 1 . the shank 11 is shaped into a hook 10 at one end and the hook ends in a barb 12 which is laterally radially offset from the shank 11 . at the end of shank 11 opposite from the hook 10 , an eyelet 13 is joined to the shank 11 by an eyelet connecting means or shank extension 14 . the eyelet connecting means or shank extension 14 is preferably formed by simply bending the end of the shank 11 during the fabrication of the fishhook 1 . similarly , the eyelet 13 is also formed during the fabrication of the fishhook 1 by simply bending the end of the eyelet connecting means or shank extension 14 back upon itself to form a generally circular loop or torus . the eyelet 13 , eyelet connecting means 14 , hook 10 and barb 12 are arranged generally coplanar . after the fishhook 1 has been fabricated , an oblique knife cut is made into the surface of the shank 11 which produces a prong 15 . a sinker 16 is then formed around the shank 11 so that the sinker 16 encompasses the prong 15 . the sinker 16 can be formed out of any suitable material , such as lead , and attached to the shank 11 in any suitable manner , such as lead molding . the prong 15 provides additional support to hold the sinker 16 on the shank 11 . this prevents the sinker 16 from either sliding longitudinally along the shank 11 or from rotating around the axis of the shank 11 . the particular shape of the sinker 16 is an important aspect of the present invention . the portion of the sinker closest to the eyelet connecting means or shank extension 14 should have a flat end or base 17 to inhibit the sinker from being pulled through the end of an artificial lure mounted on the fishhook 1 as will be more fully explained herein . the preferred shape for the sinker 16 is generally conical with the tapering portion of the cone lying coaxially with the shank 11 . the flat end or base 17 of the sinker 16 faces toward the end of the shank that carries the eyelet connecting means 14 and the eyelet 13 . the maximum diameter or width of the sinker 16 occurs at the flat end 17 and the diameter is selected so that the entire sinker 16 fits within an artificial lure as will be explained more fully herein . it is important to the objects of the invention that , in use , the entire sinker 16 is covered by an artificial lure so that a fish will not sense or feel any part of the fishhook 1 , including the barb 12 or the sinker 16 , when the fish approaches or closes its mouth on the lure . alternatively , the sinker 16 may be formed in a variety of shapes as long as the base 17 is flat . for example , the sinker 16 may be formed in the shape of a prism , a cylinder or a pyramid as well as the cone shown in fig1 and 2 . the location of the sinker 16 along the length of the shank 11 is also important to the objects of the invention . as an artificial lure is retrieved through the water , it is desirable for the lure to simulate , as nearly as possible , the actions of natural bait so that the artificial lure will attract fish . in the present invention , the sinker 16 is located on the shank 11 adjacent to the bend 18 where the shank 11 joins the eyelet connecting means 14 . the angle of the bend 18 is selected such that the eyelet 13 is offset from the axis of the shank 11 and this angle is preferably about 90 °. this configuration allows the fishhook 1 , and an artificial lure 20 carried by the fishhook 1 , to ride through the water with the eyelet 13 in a relatively upward orientation is depicted in fig2 . having the eyelet 13 offset from the axis of shank 11 also mitigates the tendency of either the fishhook 1 or the artificial lure 20 to rotate around the axis of the shank 11 as the lure is retrieved through the water . any axial rotation detracts from the desire to have the artificial lure behave like live bait . it is often desirable to have differently weighted fishhooks so that the speed in which the fishhook sinks through the water can be varied . the weight of the fishhook of the present invention can be varied by changing the size of the sinker . during the molding process , the sinker 16 can be made longer by extending it along the length of the shank 11 to make the sinker 16 heavier without changing the diameter of flat end 17 . a longer sinker 16 yields a heavier fishhook 1 . fig2 shows the fishhook 10 of the present invention mounted inside a typical one - piece artificial lure 20 . the fishhook 1 can be used with known artificial lures such as the fat gitzit or the jumbo gitzit , which are available from bass &# 39 ; n man lure co ., dept . 5a , p . 0 . box 340 , washington , utah . these artificial lures are typically formed of extremely soft , almost jelly - like plastic . the plastic is semitransparent and may be colored as desired to resemble natural baits . the artificial lures are externally shaped to resemble insects or other natural bait . the objects of the present invention are further achieved through specific design relationships between the lure 20 and the fishhook 1 . the lateral radial offset distance from the tip of the barb 12 to the shank 11 is selected to approximately coincide with the inside diameter of the body 21 of the lure . if this lateral radial offset distance is much smaller than the inside diameter of the body 21 , then the fishhook 1 may flop around inside the lure and the fish may be able to bite on the lure without contacting the barb 12 . if this lateral radial offset distance is larger than the inside diameter of the body 21 of the lure , then the fishhook 1 will significantly distort the body of the lure detracting from the intended natural appearance of the lure as live bait . in this situation , the barb 12 will also tend to puncture through the surface of the body 21 during the movement of the lure during casting and retrieving . when a fish approaches the lure , the fish may sense or feel a hook that has punctured through a lure as the mouth of the fish closes about the lure . the fish may then realize that the lure is not natural bait and withdraw from the lure . an exposed barb 12 is also susceptible to snagging on weeds or other foreign objects in the water . the diameter of the flat end or base 17 of the sinker 16 must also be smaller than the inside diameter of the body 21 of the lure 20 . this likewise prevents the sinker 16 from distorting the appearance of the lure . the flat end 17 of the sinker 16 also functions as an abutment surface to prevent the fishhook 1 from being pulled through the closed end 22 of the body 21 of the lure as the lure is being retrieved through the water . a small aperture 23 approximately the diameter of shank 11 is provided in the otherwise closed end 22 of the body 21 of the lure . due to the exceptional pliability of the lure 20 , the fishhook 1 can be inserted into the lure eyelet - end first with the eyelet 13 and the eyelet connecting means or shank extension 14 passing through the aperture 23 in the otherwise closed end 22 of the lure 20 . the flat end or base 17 of the sinker 16 then abuts against the closed end 22 of the lure 20 . the fishhook 1 is fully inserted into the body 21 of the lure 20 when only the eyelet 13 and the eyelet connecting means 14 remain on the outside of the body 21 of the lure 20 as shown in fig1 . since the diameter of flat end 17 of the sinker 16 is relatively larger than the diameter of the aperture 23 , the flat end 17 serves as an abutment surface and prevents the fishhook 1 from being pulled out of the body 21 of the lure 20 when force is applied to the eyelet 13 by the fishing line 25 during the act of casting and retrieving the lure . another important feature of the present invention is the position of the eyelet 13 in relation to both the closed end 22 and the diameter of the body 21 of the lure 20 . the radial offset distance of the eyelet 13 should not extend beyond the lateral surface of the body 21 when the fishhook 1 is mounted in the lure 20 as shown in fig1 and 2 . because of the pliability of the lure 20 , the eyelet 13 and the eyelet connecting means or shank extension 14 will closely abut the closed end 22 of the lure 20 . if the eyelet 13 extends beyond the lateral surface of the body 21 , the eyelet will be susceptible to snagging on weeds or other foreign objects in the water . also , the eyelet 13 would then present an unnatural object that a fish may sense or feel as the fish bites on the lure . if the eyelet 13 is located directly in line with the axis of shank 11 , the pulling force from fishing line 25 on eyelet 13 would promote spinning or rotation of the lure 20 along the axis of shank 11 which detracts from the intended natural appearance of the lure . both snagging and rotation of the lure 20 are discouraged by having the eyelet 13 offset radially from the axis of the shank 11 with the length of the offset limited to being no more than the radial distance from the aperture 23 to the lateral surface of the body 21 . another important feature of the invention is the distance from the flat end 17 of the sinker 16 to the eyelet connecting means or shank extension 14 and the eyelet 13 . the sinker 16 is mounted on the shank 11 at a point along the shank that is remote from the point at which the eyelet connecting means or shank extension 14 joins the shank 11 . this distance is selected so that the thickness of the wall of the lure 20 fits snugly between the flat end 17 of the sinker 16 and the eyelet connecting means 14 and the eyelet 13 as shown in fig1 . this arrangement minimizes the amount of hook material that is outside of the body of the lure 20 during use . another advantage of the present invention is realized by having the eyelet connecting means or shank extension 14 joined to the shank 11 at the location of and on the outside of the aperture 23 in the closed end 22 of the lure 20 . as casting and retrieving of the lure proceeds during the act of fishing , the barb 12 will begin to dig into the surface of the body 21 . this will also occur as fish nibble at the lure but are not caught . eventually barb 12 will wear through the surface of the body 21 and begin to stick out of the lure . this exposed barb 12 will then cause the lure 20 to be susceptible to snagging . also , fish will be able to sense or feel the exposed barb which detracts from the intended natural bait effect of the artificial lure . if the barb 12 wears through the surface of body 21 , this condition can be easily corrected . the fisherman merely manually rotates the body 21 of the lure 20 around the axis of the shank 11 until the barb 12 abuts a &# 34 ; fresh meat &# 34 ; area on the body 21 . this manual rotation of body 21 can be accomplished because the fishhook 1 is only press fit into the lure 20 , aperture 23 is coaxial with shank 11 and the eyelet connecting means 14 joins the shank 11 at the location of and on the outside of the aperture 23 . during professional sport fishing , and particularly during professional bass fishing tournaments , speed is critical because of the time limits imposed on the participants . the present invention allows a participant in a tournament to change the type of artificial lure 20 being used without the necessity of disconnecting the fishhook 1 from the fishing line 25 . it is merely a matter of sliding one lure off and substituting a different lure in its place . thus a tournament participant can utilize many different types of artificial lures until he discovers which lure is the most effective that particular day . while the fishhook of the present invention can be made in a variety of sizes , the preferred embodiments contemplate a size 1 / 0 fishhook and a size 2 fishhook . the size 1 / 0 fishhook is made from 0 . 052 &# 34 ; diameter steel wire . the eyelet 13 is formed in the shape of a generally circular loop or torus having an inside diameter of approximately 0 . 055 inches . the eyelet 13 extends at an angle of approximately 90 ° to the shank 11 and the distance from the farthest tip of the eyelet 13 to shank 11 is about 7 . 0 mm . the prong 15 is cut into the shank 11 at a location about 8 . 7 mm from the eyelet end of the shank . the flat end 17 of the sinker 16 lies along the shank 11 about 1 / 8 &# 34 ; from the eyelet 13 . the lateral radial offset distance from the barb 12 to the shank 11 is about 13 . 0 mm and the overall length of the size 1 / 0 fishhook is about 52 . 5 mm . the size 2 fishhook is made from 0 . 044 &# 34 ; diameter steel wire . the eyelet 13 has an inside diameter of about 0 . 047 &# 34 ; and the distance from the farthest tip of the eyelet 13 to the shank 11 is about 7 . 0 mm . the prong 15 is cut into the shank 11 at a location about 8 . 7 mm from the eyelet end of the shank . the flat end 17 of the sinker 16 lies along the shank 11 about 1 / 8 &# 34 ; from the eyelet 13 . the lateral radial offset distance from the barb 12 to the shank 11 is about 11 . 0 mm and the overall length of the size 2 fishhook is about 42 . 5 mm . the size 2 fishhook has generally the same configuration as the size 1 / 0 fishhook . while the invention has been illustrated with respect to several specific embodiments thereof , these embodiments should be considered as illustrative rather than limiting . various modifications and additions may be made and will be apparent to those skilled in the art . accordingly , the invention should not be limited by the foregoing description , but rather should be defined only by the following claims .

US-17366988-A