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tharindu

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a heat - intercepting shield or shroud in the form of a garment , blanket or belt having on at least one surface thereof one or more pockets to receive replaceable packets of refreezable material which absorb large quantities of heat as the material melts . each pocket has two coextensive fabric layers stitched together to form opposite pocket walls . over the entire pocket area and next to the one wall are coextensive layers of non - breathable continuous reflective material and of insulating material . these materials are flexible and are stitched next to that one pocket wall in seams at the edge of the pocket so that both heat reflection and retardation of heat flow by the insulation occurs over the entire pocket area . between the layer of insulation and the other pocket wall is a space for a heat absorbing packet or packets of frozen gel . the side of the shield or shroud with the packet or packets is placed toward the object to be cooled or protected from external radiant , conductive or convective heat .

in the preferred embodiment of fig1 a vest - like garment 1 has two main panel portions located above and below the neck opening 3 , respectively . the portion shown below the neck opening 3 forms the front panel 4 of the garment when it is worn and the portion in the drawing above the neck opening 3 is the rear panel 5 of the garment . the exterior of the garment is a essentially a casing in which the exterior of the front panel is formed primarily by fabric members 6 and 7 and the exterior of the rear panel is formed primarily by the fabric members 8 and 9 . along the left side of the garment as seen in fig1 the facing fabric strips 10 and 11 form outer face portions on the front and rear panels 4 and 5 , respectively . within the garment and next to the outer panel members 6 and 8 are located flexible layers 14 and 15 , respectively , of heat - reflective material . further to the inside of the garment and next to the reflecting layers are flexible layers 18 and 19 , respectively , of heat - insulating material . the multiple layers of fabric and the heat - reflective and heat - insulating materials are stitched together to form a series of side - by - side pockets 20 , 21 and 22 in the front garment panel 4 and a series of side - by - side pockets 30 , 31 and 32 in the rear garment panel 5 . as seen in fig1 the upper sides of the pockets 20 , 21 and 22 are formed by stitched seams 25 , 26 and 27 and the lower sides of the pockets 30 , 31 and 32 are formed by stitched seams 35 , 36 and 37 . the right ends of the pockets 20 , 21 and 22 are formed by a single straight stitched seam 28 and the right ends of the pockets 30 , 31 and 32 are formed by a single straight stitched seam 38 . the outer sides of the outer pockets 22 and 32 are portions of a stitched seam 39 extending around the entire periphery of the garment . during assembly of the garment many of the layers of material are stitched together while the garment is essentially inside out and an initial seam 39a as seen in fig3 and 3a is stitched . thereafter the garment is turned right side out and the final seam 39 is stitched and the seam 39a remains concealed but adds significant strength to the periphery of the garment . extending along the entire length of the garment at the left end of each of the six pockets 20 , 21 , 22 , 30 , 31 and 32 are cooperating parts of an elongated hook and loop fastener comprising a hook strip 40 fastened together with the edges of the fabric member 6 and the reflective and insulating layers 14 and 18 by stitching . the other fastener part is a loop strip 41 which is fastened to the fabric members 7 and 9 also by stitching in a position where it covers the adjacent edge of the facing strips 10 and 11 . the left ends of the six pockets are closed by means of the cooperating portions of the strips 40 and 41 which extend therealong . the pocket closures formed by the strips 40 and 41 are each easily and independently opened by means of a small fabric pull tab 42 . each tab is fastened by stitching near the center of the pocket opening at the back of the hook strip 40 between it and the overlying fabric members 6 and 8 , preferably between the hook strip and the reflective layers 14 and 15 . at the ends of each pocket opening there are bar - tacks 43 stitched through the entire garment thickness for reinforcement . the fabric members 6 and 8 are stitched together at the shoulder seams 44 and 45 . the fabric members 7 and 9 are similarly stitched together at shoulder seams . the edges of the four fabric members at the neck opening are bound together by means of a ribbon member 48 folded over the edges and stitched thereto as seen in fig1 and 4 . the ribbon 48 is a grosgrain ribbon of 100 % nylon which is extremely wear - resistant , will not shrink , will not fray and is heat sealable at its ends when cut with a hot knife before stitching it in place . the garment is held in place when worn by a person by means of an elastic belt . the belt comprises two wide non - roll elastic strips 50 and 51 which are fastened by stitching at the scalloped areas 52 and 53 which form extensions of the casing beyond the ends of pocket 31 at opposite sides of the rear panel of the garment . these extensions cooperate with the securing belt to distribute the holding or securing forces across the entire width of the respective ends of the pocket so that the latter and the packet therein are held in good heat transfer relationship against the body . one end of the strip 50 is anchored in the peripheral seam 39 between fabric member 8 and the facing member 11 . one end of the other strip 51 is similarly anchored between the fabric members 7 and 9 . the other ends of these strips can be fastened to the front garment panel by means of identical cooperating hook strips 54 and 55 . these hook strips are carried on the inner faces of the belt end portions 54a and 55a , respectively , the strip 55 being on the hidden side of end portion 55a in fig1 . these hook strips are permanently . attached to the ends of elastic straps 50 and 51 and are detachably secured to loop strips 58 and 59 extending across the entire of the front panel 4 . the loop strip 58 is stitched on top of the facing strip 10 between seam 39 and the long loop strip 41 . the other loop strip 59 is stitched in place around its periphery to overlie the pocket 21 , extending near the center and along the length thereof and beyond the seam 28 to the edge of the fabric member 6 . to position the garment for use on a person , the neck opening is slipped over the head and the belt portions are slightly tensioned by pulling on the hook strips 54 and 55 and fastening these strips by engaging their hooks with the loops of the loop strips 58 and 59 on the front panel of the garment . the lengths of the hook and loop strips 54 , 55 , 58 and 59 together with the elasticity of the straps 50 and 51 provide a very wide range of adjustment of the belt so that one size of the garment fits most workers . the elastic straps 50 and 51 are made with raised transverse ribs to give its non - roll feature . the straps 50 and 51 can be stretched to twice their unstressed length of about five inches . although the garment 1 by itself can provide some protection to the worker from a heat source , it is intended to provide a much higher level of heat protection by receiving flexible heat - dissipating refreezable packets 60 in the pockets 20 , 21 , 22 , 30 , 31 and 32 . as seen most clearly in fig5 and 6 , the multi - segment packet 60 is formed from a heat - sealable transparent plastic tube 61 having four seams thereacross which define three equal - size generally flat sealed compartments . the flexibility of each packet 60 at the seams between the compartments allows the front and rear panels of the garment to conform to the person &# 39 ; s body to provide greater comfort and more freedom of movement when the garment is worn . the plastic tube 61 is made of polyethylene of about 4 mil thickness which is easily sealed to itself to form seams merely by the application of sufficient pressure and heat . the tube may be made of a tougher material such as polyvinyl chloride and the seams formed by electronic welding . a tougher material of this nature may be preferred for use in the embodiment of fig8 where the blanket illustrated may be used as a mat on which workers walk . the tube 61 may be aluminized to make it and the packets 60 reflective on the outer side for additional heat interception . each of the compartments of packet 60 contains a refreezable heat dissipating means in the form of a pack 63 of refreezable non - toxic chemical refrigerant gel . although the pack 63 is shown as gel in a single - compartment flexible plastic envelope , each pack can be made as a multi - compartmented envelope to provide more flexibility when frozen . however , the illustrated packs are more economical to manufacture and can contain more of the gel within each of the compartments of the packet 60 . the gel freezes at a temperature of about 0 degrees c . its heat of fusion is has a value approximately 10 % or more in excess of the heat of fusion of water . it compares very favorably with the value of water which is 80 cal ./ g ./ deg . c . at 0 degrees c . the gel is also much more viscous than water when melted and is much less likely to escape from the packet 60 in the event of accidental puncturing of the packet tube the envelope of the gel pack 63 . the size of each of the pockets 20 , 21 , 22 , 30 , 31 and 32 in the garment panels is about 6 by 13 . 25 inches . the packets are about 5 . 75 by 13 . 25 inches with a thickness of about 3 / 4 inch . the size of each refreezable pack is only very slightly less than the size of the compartments . throughout this specification the term fabric preferably refers to a woven material which has a weight of about five ounces per square yard and is made of 65 % polyester and 35 % cotton . this material can absorb moisture of condensation , retains its shape , has minimum shrinkage and is very durable and wear - resistant . however , in some applications where flammability of the garment is a consideration , the fabric may be of a fire retardant material such as that commercially available under the name &# 34 ; nomex .&# 34 ; the insulating material used in the various embodiments of the invention is preferably a polyester fleece material which has a thickness of about 3 / 16 inch and a weight of about 9 ounces per square yard . the heat - reflective material used in this invention preferably has an extremely thin shiny metallic non - breathable surface layer on the heat receiving side . this surface layer is carried by a thin layer of insulating foam material which is backed by a very thin plastic sheet layer . this structure of the material , its smooth surfaces and its resistance to any significant stretching makes it very suitable for stitching together with the other components used in the illustrated embodiments . these three layers are bonded together along spaced crossed lines . the bonded area is only a small percentage of the surface area of the reflective material . this material has a thickness of about 1 / 25 inches and an insulating factor of r2 . another embodiment of the invention is shown in fig7 wherein the fabric layer 8a extends to the left edge of the garment and the insulating and heat - reflecting layers extend to opposite sides of the garment . the peripheral seams are then like the seam in fig3 a . also , a facing strip 11a corresponding to strip 11 of fig1 is now on the underside of the insulation and stitched between it and the hook portion 400 of the fastener . the bottom fabric member 90 is reduced in width by an amount corresponding to the width of the strip 11a . the belt members are attached essentially as in fig1 to the edges and front face of the garment . another embodiment of the invention is shown in fig8 and 10 wherein a heat - intercepting or cooling shield or shroud is made in the form of a flexible blanket 70 . similar to the previously described garment 1 , the blanket 70 as seen in fig8 has a plurality of elongated flat equally - sized generally co - planar elongated pockets 71 through 76 for receiving refreezable packets 60 identical to those used with the garment 1 . these blanket pockets are about 61 / 4 by 141 / 2 inches . the blanket 70 has a rear fabric face member 77 essentially coex size with the blanket . the fabric member 77 forms the rear wall of each through 76 . a smaller fabric face member 78 is generally coextensive with and forms the front face of one group of side - by - side elongated pockets 71 , 72 and 73 . another fabric face member 79 forms the front face of another group of side - by - side elongated pockets 74 , 75 and 76 . the fabric members 77 , 78 and 79 are all rectangular and adjacent sides of the members 78 and 79 are spaced from each other about two inches across the width of the blanket near its center . the other three sides of the fabric members 78 and 79 are secured to the periphery of the fabric member 77 along a peripheral seam 80 which extends around the entire edge of the member 77 . details of this seam regarding initial stitching inside out correspond to the seam details shown in fig3 and 3a for the garment of fig1 . this seam 8 defines the outer sides of pockets 71 , 73 , 74 and 76 . the outer ends of pockets 71 , 72 and 73 are formed by the straight portion of the seam 80 at the left end of the blanket as seen in fig8 . the outer ends of the pockets 74 , 75 and 76 are formed by a seam 83 which is spaced from the seam 80 at the right edge of the blanket as seen in fig8 . seams 81 divide the left side of the blanket into the three equally sized pockets 71 , 72 and 73 . similarly , the seams 82 divide the right side of the blanket into the three equally sized pockets 74 , 75 and 76 . next to or just under each of the fabric members 78 and 79 are two successive layers of heat - reflective material 84 and heat - insulating material 85 , shown only at the cut away area of fig8 . in the preferred embodiment these layers for pockets 74 , 75 and 76 end in the seam 83 , but they may be extended beyond seam 83 to be stitched in the edge seam 80 . the ends of the pockets 71 through 76 extending across the center of the blanket have closures thereat formed by fastening means comprising cooperating two pairs of hook and loop strips like the strips 40 and 41 in the embodiment shown in fig1 and 2 . each hook strip is similarly stitched along and under the edge portions of one of the fabric members 78 and 79 with the edges of the layers of reflecting and insulating material 84 and 85 therebetween . pull tabs 86 are also stitched therein between the hook strips and the insulating material layers 85 . each of the loop strips 87 is stitched across the fabric member 77 directly beneath its cooperating hook strip . protective ribbon material 88 , like the ribbon 48 in fig1 is stitched over the edge of fabric member at both sides of the blanket between the fabric members 78 and 79 . the space between the members 78 and 79 may be covered across the center of the blanket by successive layers of insulation and reflective material and another layer of fabric stitched atop the fabric 77 with the edges of these additional layers stitched under the loop strips 87 and with their ends under the ribbon strips 88 . extending over the fabric member 77 at area on he back side of the blanket at the right end between the seam 83 and the peripheral seam 80 is a two - inch wide hook strip portion 90 of a hook and loop strip fastener means . this loop strip is at the outer ends of and extends transversely with respect to the elongated pockets 74 , 75 and 76 . this strip cooperates with three two - inch wide loop strip portions 91 of the fastener means located on the opposite or front side of these loop portions are stitched to the front of the fabric member 78 and each extend the peripheral seam 80 at the left and about two thirds of the distance down the center of the pockets 71 , 72 and 73 toward the closure ends of these pockets . the blanket 70 can be wrapped around all or a portion an object 100 ( in dotted lines ) to be cooled and held in place by pressing the hook strip 90 into engagement with the loop strips 91 as shown in fig1 . two or more blankets can be connected together by engaging the hook strip of one blanket with loop strips of another as seen in fig9 where three blankets 70 are connected together . one or multiple blankets can thus be wrapped and fastened about objects of varying size and shape for either cooling the objects or for protecting them against environment heat . one or more blankets can also be used as mats on hot walkways to protect the feet of workers . in such case the heat reflective material is on the side of the blanket toward the hot surface . each of the pockets 71 through 76 contains one of the removable heat - dissipating packets 60 shown and described in connection with fig5 and 6 . the space between the fabric members 78 and 79 is about two inches wide . the blanket can be suspended on the narrow edge of a horizontal two by four inch board ( not shown ) with the groups of side - by - side pockets hanging narrowly spaced on opposite sides of the board to facilitate inserting the packets 60 into open ends of the pockets , which , in the hanging position , all lie along one side of the blanket shield . the tabs 86 are pulled to open the hook and loop closure for each pocket to permit insertion of the packets 60 whereafter the hook and loop portions are pressed together to keep the packets in place . the two groups of pockets are loaded alternately so that the weight of the packets will not cause the blanket to fall off the support . the individual packets cover essentially the entire area of the respective pockets . in the embodiment of the invention shown in fig1 a belt structure 94 is provided with only a single pocket with the multilayer relationship and construction therefor essentially the same is previously described and with the peripheral side and end seams essentially the same as shown in fig3 and 3a . triangular extension portions of the casing are formed beyond the ends of the pockets for attachment of belt means comprising an elastic non - roll strap 95 about one inch wide and a few inches long and an adjustable length non - elastic strap member 96 which is looped through one part 97 of a side - release buckle . these extensions cooperate with the securing belt to distribute the holding or securing forces across the entire width of the respective ends of the pocket so that the latter and the packet therein are held in good heat transfer relationship against the body . the strap 95 is looped through the other cooperating part 97a of the buckle . the other ends of the straps 95 and 96 are stitched in the ends of the triangular portions of the belt . an alternative embodiment of a vest - like garment in fig1 is described below using for the most part the same reference numerals as in fig1 for similar or corresponding parts , but with 200 added thereto alternative embodiment of fig1 a vest = like garment 201 has two readily separable panel portions located above and below the neck opening 203 , respectively . the portion shown below the neck opening 203 forms the front panel 204 of the garment when it is worn and the portion in the drawing above the neck opening 203 is the rear panel 205 of the garment . the exterior of the garment is a essentially a casing in which the exterior of the front panel is formed primarily by the outer fabric member 206 terminating at the seam 225 and an inner member 207 similar to fabric members 6 and 7 of fig1 . the exterior of the rear panel is formed primarily by the outer fabric member 208 which terminates at the seam 235 and the inner fabric member 209 . both inner fabric members are of shapes corresponding to the outline of the respective front and rear panels respectively . along the left side of the garment the facing fabric strips 210 and 211 form outer face portions on the front and rear panels 204 and 205 , respectively . the shoulder portions 264 and 265 of the front and rear panels 204 and 205 , respectivley , on either side of neck opening 204 are made separable by use of a hook and loop fastener approximately 2 inches in width with a loop portion 266 secured to the outside surface of the shoulder of the front panel . the hook portion of the fastener 267 is secured to the inside surface of the shoulder portion of the rear panel . the shoulder portion 265 of the rear panel is sufficiently long to pass over the shoulder of a wearer and overlap the shoulder portion 264 of the front panel so that each two part fastener securing the front panel to the rear panel at the shoulders is located in a position to the front of and slightly below the shoulder and is readily accessible to a wearer of the garment . within the garment and next to the outer panel members 206 and 208 are located flexible layers 214 and 215 , respectively , of heat - reflective material . further to the inside of the garment and next to the reflecting layers are flexible layers 218 and 219 , respectively , of heat - insulating material . the multiple layers of fabric and the heat - reflective and heat - insulating materials are stitched together to form a series of side - by - side rectangular pockets 220 , 221 and 222 in the front garment panel 204 and a series of side - by - side rectangular pockets 230 , 231 and 232 in the rear garment panel 205 . as in fig1 all pockets are of equal size . as seen in fig1 the upper sides of the pockets 220 , 221 and 222 are formed by stitched seams 225 , 226 and 227 and the lower sides of the pockets 230 , 231 and 232 are formed by stitched seams 235 , 236 and 237 . the right ends of the pockets 220 , 221 and 222 are formed by a single straight stitched seam 228 and the right ends of the pockets 230 , 231 and 232 are formed by a single straight stitched seam 238 . the outer sides of the outer pockets 222 and 232 are formed by portions of the stitched seams 239 extending around the periphery of the garment . seams 226 , 227 , 236 and 237 are stitched using a double needle machine to provide additional seam strength and eliminate the need for the bar tacks 43 as shown in fig1 . extending along the length of the garment along a line at the left end of each of the pockets 220 , 221 , 222 , 230 , 231 and 232 are cooperating parts of elongated hook and loop fasteners , like those of fig1 and 2 , each comprising a hook strip fastened together with the edges of the outer fabric members 206 and 208 an the reflective and insulating layers 214 , 215 and 218 , 219 by stitching . the other fastener parts are loop strips which are fastened to the fabric members 207 and 209 also by stitching , each in a position where it covers the adjacent edge of the facing strip 210 or 211 . the left ends of the six pockets are closed by means of the cooperating portions of the fastener strips which extend therealong . the pocket closures formed by the fastener strips are each easily and independently opened by means of a small fabric pull tab 242 . each tab is fastened by stitching near the center of the pocket opening at the back of the hook strip between it and the overlying fabric members 206 and 208 . the sides of the garment are held in place when worn by a person by means of inelastic wing - like belt portions . the belt portions comprise two wide strips 250 and 251 which are further extensions of the scalloped extension areas 252 and 253 beyond the ends of pocket 231 at opposite sides of the rear panel of the garment . the width of the belt portions 250 and 251 are approximately the width of the pocket 231 . the outer ends of each of these belt portions 250 and 251 can be fastened to the front garment panel by means of a pair of generally parallel hook strips 254 and 255 attached along the opposite edges of belt portions 250 and 251 from their outer ends to the ends of pockets 231 and pairs of loop strips 258 and 259 extending across the entire front of the front panel 204 generally along the upper and lower edges of pockets 221 . the left end portions of loop strips 258 and 259 are stitched on top of the facing strip 210 between the seam 239 and the long loop strips 241 . the other parallel portions of loop strip 238 and 259 are stitched in place around their periphery to overlie upper and lower portions of pocket 221 and extending along the length thereof and beyond the seam 228 to the right edge of the fabric member 206 as seen in fig1 . the scalloped and wing - like extensions of the casing beyond the ends of pocket 231 cooperate with the hook and loop fasteners to form a securing belt to distribute the holding or securing forces across the entire width of the respective ends of the pockets 221 and 231 so that the latter and the packets therein are held in good heat transfer relationship against the body . to position the garment for use on a person , the neck opening is slipped over the head and the belt portions are slightly tensioned by pulling on the belt portions 250 and 251 and fastening the hook strips thereon with the loops of the loop strips 258 and 259 on the front panel of the garment . the lengths of the hook and loop strips 254 , 258 and 259 on the belt portions 250 an 251 provide a very wide range of adjustment of the belt so that one size of the garment fits most workers . during assembly the outer members 206 and 208 are stitched together with the reflective and insulating layers and the yokes along seams that will be hidden along the se 235 . during this initial stitching the ultimately exposed outer faces of the yokes the areas of the outer members 206 and 208 corresponding to pockets 220 and 230 . after the initial stitching the yokes are folded back on themselves at the initial seam to be essentially coplanar with the members 206 and 208 , but on opposite sides of the initial seam . the initial seam would be like seam 39a in fig3 a . the components of the respective panels 204 and 205 are then stitched together around their periphery and inside out with initial seams like the seams 39a of the french seams of fig3 and 3a , but leaving in each panel an unstitched area , for example at one of the shoulder seams . the panels are turned right side out through the unstitched shoulder area and the shoulder seam thereafter stitched and reinforced when the fastener strips for the shoulder connections are added by stitching . stitching secures the loop fastener strips over the edges of the fabric members 210 and 211 and to the respective inner fabric members to define the left ends of the several pockets as seen in fig1 . the edges of the outer members are folded over the edges of the reflecting and insulating layers along the hook fastener strips , covered by the latter and these several layers stitched together along with the tabs 242 along the entire length of the hook strips . double stitching is added through all the layers of the garment to define the upper and lower edges of the pockets 221 and 231 . the seams 239 are stitched around the periphery . the seam like 39a remains concealed but adds significant strength to the periphery of the garment . additional stitching along seams 225 and 235 through all layers of the panels will define the upper edges of the pockets 220 and 230 and seams 228 and 238 are added through al layers of the panels to define the right ends of the several pockets as seen in fig1 . in the embodiment of the invention in fig1 and 14 a vest structure 301 has the same general arrangement of layers of fabric casing , reflective material , insulating material and heat - dissipating packets as in the above disclosed embodiments . this vest has two horizontally extending equal sized pockets 304 and 306 which are end to end near the front center of the vest and extend to opposite sides and partially around toward the back near the waist of the wearer . at the front , the entire width of the adjacent ends of the vest pockets are interconnected by means of a zipper fastener 308 of low heat conductivity . the zipper does not add to the thickness of the vest as do the overlapping belt - like fasteners of fig1 and 12 . this is an advantage in improving comfort and reducing interference when such a vest is used with an air pack to support breathing in a hostile environment . the casing of the vest 301 is made up principally from eight fabric members which are stitched together to provide wear resistant tough strong french seams around the entire periphery of the vest . the entire inner facing of the vest casing is formed by two fabric panel members 311 and 312 which are joined together at the rear center around the inside of the vest to the front center where they terminate at opposite zipper . these panels form the inside walls of the pockets 304 and 306 . the outside of the pocket structures are formed primarily by rectangular fabric panel members 312 and 313 which extend to the pocket openings at the front . the panel 312 extends around the left side of the garment to the adjustable elasticized corset - like laced interconnection 314 between the sides of the vest at the rear center . the panel 313 extends around to the back where it joins a folded small fabric member which is stitched to provide a small pocket 315 , on the outside of and about half the height of the pocket 304 , with an opening facing the laced interconnection 314 to receive and confine excess end portions of the elastic lacing thereof . the opening is provided with a suitable hook and loop fastener to retain the excess lacing in the pocket when the vest is being used . the lacing threads through eyelets at each side of the connection 314 and is secured in an adjusted position by any well known cord tie 316 . the eyelets are in commercially available plastic strips 317 designed to be stitched into the seams of the casing defining the rear ends of the pockets . these strips 317 extend over a major portion of the vertical extent of the rear ends of the pockets 304 and 306 so that the lacing will provide a large area of support at the back of the wearer to distribute across the ends of the pockets the forces which hold the packets to the body , to support the weight of packets in the pocket of the vest and keep them snug against and in good heat transfer relationship with the wearer &# 39 ; s body as various positions are assumed during use of the vest . the zipper similarly supports the front ends of the refrigerant pockets . the relatively heavy refrigerant pockets are just like the packets of the other embodiments . the outer surfaces of the casing of the vest in the area of the shoulders is formed by the fabric yoke pieces 321 and 322 at the front and 323 and 324 at the rear . these front and rear pieces are joined at each side near the top of the shoulder and the rear pieces are joined at a vertical seam at the rear center of the vest at approximately shoulder blade height . the cut - away areas of fig1 and 14 show portions of the reflective layer 331 , the insulating layer 332 and the refrigerant packet 333 in the pocket 306 . the adjacent ends of the pockets 304 and 306 at the front of the vest have openings which face the zipper 308 and which are closely to closely retain the packets therein by hook and loop fasteners like those of the other embodiments and similar tabs are provided at the center of each opening to facilitate opening of the pocket to insert or remove the refrigerant packet . to assemble the various fabric parts of the vest of fig1 and 14 the members 311 and 312 are stitched together along the vertical rear center to form a vest - like subassembly . the outsides of the pockets 304 and 306 are stitched together with the reflective and insulating layers and the outer hook strips of the pocket closure fasteners . the yoke p together at the shoulders , armpits and the vertical rear center . after the assemb pieces are stitched to the outsides of the pockets there exist two vest - shaped subassemblies which will be stitched together inside out to provide further seams along with those stitched areas just mentioned which will be hidden stitching in the completed garment . while stitching inside out the zipper and the plastic eyelet strips are installed . the vest is later turned right side out through a pocket opening . the hidden armpit seams are stitched via access through this pocket opening and after all the hidden stitching is completed the armpits and other peripheral seams are overstitched and the inner and outer vest layers are overstitched along the tops of the pockets and the pocket opening fastener loops are stitched over the small facing strips along the sides of the zipper and to the back or inner walls of the pockets . the vest of fig1 and 14 may be loaded with frozen packets by laying it on a flat surface so that the pockets overlie one another with the openings therein facing the same direction . alternatively the vest may be hung with the zipper closed and horizontal and resting on the upper edge of a suitable narrow support whereby the upwardly opening pockets would again be at the same side of the garment and could then be filled from above . another embodiment of the invention provides a helmet garment which is similarly constructed to fit over the head and neck of a worker . it uses the same relationship of fabric members , gel packets and insulation and reflective layers to protect the head and neck from the shoulders up . it has a plurality of narrower and shorter pockets with closures on the outside to receive the gel packets . this garment must be sufficiently loosely fitting about the head and neck to permit turning and nodding movement without inconveniencing or annoying the wearer . other variations within the scope of this invention will be apparent from the described embodiments and it is intended that the present descriptions be illustrative of the inventive features encompassed by the appended claims .

US-64474991-A

an athletic glove having at least one padded insert is provided . the padded insert comprises reticulated or open cell form , or a rubber formed into a matrix that allows ventilation paths .

referring now to fig1 to 6 , the present invention will be described . the present invention will be described with specific reference to cycling gloves , but one of skill in the art would understand on reading the disclosure that other padded gloves , such as , for example , golfing gloves , batting gloves , and the like , could be substituted for cycling gloves without departing from the scope or spirit of the present invention . referring first to fig1 , pads 104 , 106 , 108 , and 110 lack ventilation , in part , because of the foam and leather , synthetic leather , or other wear resistant covering ( generally referred to hereinafter as “ covering ”). conventional foam and covering lack sufficient breathability to provide sufficient air circulation and / or venting . glove 100 therefore creates “ hot spots ” on the palm over which the padding resides . some modicum of ventilation is provided by perforations 116 , but glove 100 is typically designed to fit snuggly to the hand of the wearer causing perforations 116 to provide an unsatisfactory solution . referring now to fig2 , a glove 200 consistent with the present invention is shown . glove 200 includes a palm 202 with a wear resistant portion 204 , such as , for example , leather , synthetic leather , or the like , and finger and thumb extensions 206 . wear resistant portion 204 and extensions 206 include a number of perforations 208 for ventilation . strategically placed on palm 202 are one or more pad sections 210 . referring now to fig3 , and exploded view of pad section 210 is shown which will be explained in more detail . pad section 210 includes a base 302 ( which would be closer to the wearer &# 39 ; s skin ) having perforations 304 . base 302 could be the same as wear resistant portion 204 or a separate piece joined to wear resistant portion 204 by thermal welding , adhesives , stitching or other conventional joining devices . a layer of foam 306 is aligned with and resides external to base 302 . foam 306 would have ventilation paths 308 extending through foam 306 . foam 306 could be closed cell foam formed with ventilation paths 308 or be an open cell , reticulated , or other breathable foam that does not require especially formed paths such as , for example , polyurethane foam . ideally , a majority of ventilation paths 308 align with perforations 304 . foam 306 does not necessarily reside directly on base 302 and other material layers could reside between foam 306 and base 302 . finally , a mesh layer 310 resides external to foam 306 . mesh 310 provides some wear protection to foam 306 , but the large mesh loops 312 provide ventilation pathways from perforations 304 through ventilation paths 308 and mesh loops 312 . while shown as a large grade mesh , mesh 310 could be other types of breathable fabrics , such as , for example , polyester , nylon , and the like . substantially surrounding pad section 210 is a boarder 314 . boarder 314 is connected to mesh 310 and base 302 ( or wear resistant portion 204 ). boarder 314 is connected using a conventional coupling 316 . coupling 316 could be , for example , welding , embossing , stitching , adhesives , or the like . foam 306 may have material 316 contained therein . material 316 may be one or more or anti - microbial materials , wickable materials , absorbent materials , or temperature regulating materials for hygiene management , moisture management and / or temperature management of the wearer . optionally , wear resistant portion 204 could have surface texture 112 to assist with gripping . moreover , glove 200 could have un - vented padding portions 212 , such as the eva pad shown . un - vented padding could use foam similar to vented foam 306 or other foams / gels . referring to fig4 , an exploded view of un - vented padding portion 212 is shown . padding portion 212 comprises base 402 , foam 404 , and top layer 406 . base 402 is typically contiguous with wear resistant portion 204 , but may be a separate piece coupled to portion 204 . foam 404 may be any conventionally used foam , such as , for example , a moshi foam . top layer 406 is a durable fabric such as leather or synthetic leather . top layer 406 could be the same as wear resistant portion 204 , but does not need to be the same . padding 212 is connected to glove 200 using conventional coupling 316 . while fig3 is described with reference to foam 306 , foam 306 could be replaced with a formed rubber 500 , such as , for example , tpr rubber shown in fig5 a - d . fig5 a shows a top elevation view of formed rubber 500 . formed rubber 500 is formed into a soft webbing 502 having openings 504 . openings 504 are similar to ventilation paths 308 described above and , ideally , are aligned with perforations 304 . referring to fig5 b , a perspective view of webbing 502 and openings 504 is shown . webbing 502 includes a base 506 , a channel support 508 , and webbing walls 510 . notice the particular pattern shown in fig5 a - 5d is exemplary and should not be considered limiting . referring now to fig5 c , it is believed formed rubber 500 should have a domed shaped such that ends 512 are shorter than a central portion 514 . finally , fig5 d shows an exploded view of pad 210 with formed rubber 500 instead of foam 306 . referring now to fig6 , an alternative padding section 600 . padding section 600 could replace or be used in conjunction with padding section 210 , see fig2 . padding section 600 comprises a base 602 , an insert 604 , and a non - breathable wear resistant top layer 606 with a plurality of perforations 608 . base 602 is shown as a breathable fabric or liner , such as , for example , polyster , nylon , or the like . however , base 602 could comprise perforated non - breathable material similar to base 302 described above ( moreover , base 302 could be replaced with base 602 ). insert 604 could be a foam , such as , close cell foam with openings 308 , open cell foam or reticulated foam , such as foam 306 , or insert 604 could be a formed rubber 500 , such as tpr rubber shown in fig5 . top layer 606 is a non - breathable material , such as , for example , leather , synthetic leather , or the like . generally , when formed rubber 500 is used for the breathable padding construction , mesh 310 is used to provide increased ventilation because formed rubber 500 is , itself , relatively durable . however , when open cell or reticulated foam 306 is used for the breathable padding , top layer 606 with perforations 608 is used as the reticulated and / or open cell foam is less durable and / or wear resistant . structure 600 is similarly surrounded by boarder 314 to connect alternative padding to the glove . boarder 314 is connected to the glove using conventional coupling 316 . while the invention has been particularly shown and described with reference to embodiments thereof , it will be understood by those skilled in the art that various other changes in the form and details may be made without departing from the spirit and scope of the invention .

US-7058205-A

a surgical blade assembly comprises a scalpel blade and handle . a guard is attached to the assembly and is pivotally moveable between a sheathed and an unsheathed position . a spring resiliently biases the guard to the sheathed position . a hinge may attach the guard to the assembly and allow pivoting of the guard relative to the blade .

[ 0020 ] fig1 a illustrates an embodiment of the invention , surgical blade assembly 10 , comprising scalpel blade 14 , body 18 , and guard 22 . as shown , guard 22 is mounted to handle body 18 , through a hinge pin 26 . scalpel blade 14 is attached to body 18 as known . additionally , spring 30 , shown in relatively uncompressed state , in hole 34 of body 18 urges guard 22 to be in a closed state , or sheathed , as shown in fig1 . one end of spring 30 is fixed within guard 22 . spring is also inclined along an z axis in hole 34 relative to a top plane 35 of the body 18 . space k between guard 22 and body 18 creates room for guard 22 to pivot relative to scalpel blade 14 in the direction of arrow y to an open state or unsheathed position . in this state , spring 30 is compressed . a force in the direction of arrow g will move guard in this direction compressing spring 30 and making space k smaller as guard 22 pivots on hinge 26 . preferably , the area 28 on top of the hood 22 receives a finger or other portion of the surgeon &# 39 ; s hand . the force is passed through this area down against the spring to bias the spring to its unsheathed position . once the surgeon releases the hood , the spring will return the hood to its sheathed position . one of ordinary skill in the art would know of other techniques to resiliently bias guard 22 . as shown in fig1 b , the pivot pin 26 is spaced to one side of the hole 34 . the hole 34 is spaced at an angle a along the axis z relative to the top surface 35 of the handle body 18 . in this way , the force from the spring will cause the hood to pivot counter - clockwise , as shown in this view , about the hinge pin 26 . this will provide a sure and prompt closing of the hood once released . [ 0023 ] fig2 illustrates a bottom view of guard 22 . guard 22 has slot 42 to at least partially receive scalpel blade 14 . slot 42 is accordingly sized to accommodate scalpel blade 14 . edge 21 of guard 22 is blunt . [ 0024 ] fig2 also shows tapered portion 38 . accordingly , guard 22 comprises first end 40 having a width w 1 and second end 41 having a width w 2 . to taper guard 22 , width w 1 is less than the width of w 2 . this taper offers an improved view of the tip of surgical blade assembly 10 so that a surgeon may track and follow scalpel blade 14 in a less obstructed fashion . indeed , fig3 illustrates a view of surgical blade assembly 10 as possibly seen by a surgeon using the instrument . as shown , tapered portion 38 offers less sight obstruction to the surgeon of cutting surface 46 . also , guard 22 may be made of generally transparent plastic to permit a direct view of scalpel blade 14 on cutting surface 46 as shown . [ 0026 ] fig4 illustrates surgical instrument 10 on cutting surface 46 . as shown , scalpel blade 14 cuts into surface 46 . guard 22 pivots relative to scalpel blade 14 to permit it to cut into cutting surface 46 without interference . as mentioned above , a surgeon may place a finger 60 on the area 28 and cause the hood to pivot relative to the handle 18 . this allows the scalpel blade 14 to be exposed for cutting . once the surgeon releases the hood , the spring 30 will return the hood to its sheathed position such as shown in fig1 a . in this way , surgical blade assembly has a guard that is easily moved out of the way of scalpel blade 14 as it is used . when guard 22 is released , it is then closed by spring 30 as it decompresses . thus , without any additional thought or effort , guard 22 protects against accidental cuts . the aforementioned description is exemplary rather that limiting . many modifications and variations of the present invention are possible in light of the above teachings . the preferred embodiments of this invention have been disclosed . however , one of ordinary skill in the art would recognize that certain modifications would come within the scope of this invention . hence , within the scope of the appended claims , the invention may be practiced otherwise than as specifically described . for this reason the following claims should be studied to determine the true scope and content of this invention .

US-98103201-A

apparatus for use in measuring the density and spatial distribution of macular pigment in an eye comprises a camera for capturing a colour image of an eye , at least one filter for filtering light reaching the camera . the filter has a transmission spectrum with one peak in the region of light absorbed by the pigment and another peak in a region where no such absorption occurs . the filter increases the sensitivity of the camera to macular pigment whilst enabling the effect of other pigments to be reduced or eliminated . a method of measuring macular pigment involves obtaining a colour image of an eye , the image having two colour components each having a spectrum having a respective one of said peaks . corresponding portions of the components are mathematically combined so as to provide a measurement of macular pigment density and the results of the combination are used to provide an output representative of the contribution of macular pigment to the image .

the camera shown in fig1 is a modified version of a non mydriatric retinal camera , in this case the topcon trc - nw6sf camera . the camera comprises a housing 1 containing illumination and imaging optics and a flash lamp . at one end of the housing 1 there is an objective lens assembly 2 , and at the other end a 3ccd ( charge coupled device ) camera 4 for generating a three component colour output signal representative of a captured image obtained via the imaging optics in the housing 1 . the rear of the housing 1 is also provided with an lcd view finder screen 6 , and supports a shutter control 8 . attached to the front of the housing 1 is a head support 10 comprising a headband 12 and a chin rest 14 . the head support 10 locates the head of the subject to facilitate the correct positioning of the eye under examination relative to the objective lens assembly 2 . fig2 shows , in simplified form , the illumination and imaging optics within the housing 1 , as well as an eye under examination 16 , the camera &# 39 ; s flash lamp 18 and a focusing lamp 20 . the focusing lamp 20 is used to illuminate the eye 16 while the operator is setting up the camera to photograph that eye . the illumination provided by the lamp 20 enables the image of the retina of eye 16 to be viewed on the view finder screen 6 so that the operator can correctly position the eye and focus the camera . light from the lamp 20 passes through a focusing lens system 22 to a beam splitter 24 in the form of a half silvered mirror , from which it is reflected through a filter assembly 26 . the assembly 26 comprises a holder 28 which holds four filters , respectively referenced 30 , 32 , 34 , and 36 , and which is rotatable about an axis parallel to the beam of light from the focusing lamp 20 to bring any selected one of those filters into registry with that beam . it will be appreciated that a holder capable of carrying different numbers ( more or fewer ) filters could be used in the camera . in the present case , the filters 30 - 34 are used for standard retina photography , whilst the filter 36 is a triple bandpass filter , described below , which enables the image captured by the camera to be used to measure macular pigment density and spatial distribution on the retina of the eye 16 . light passing through the filter 36 then passes to an annular mirror 38 via a reflecting mirror 40 and focusing lenses 42 , 44 and 46 . the mirror 38 reflects that light via the objective lens assembly 2 into the eye 16 to illuminate the retina of that eye . that light is reflected from the retina and some of it passes back through the lens 2 which directs the light through the aperture ( referenced 48 ) in the mirror 38 , through a further system of lenses 50 , 52 , 54 and 56 which focus an image of the illuminated retina onto the image plane of the ccd camera 4 . the topcon trc - nw6 camera is supplied with a neutral filter for use in normal colour photography ( for example for use in diabetic screening ) and an exciter filter for use in fluorescein angiography . these filters may be interchanged with other filters , and modification to the camera necessary to convert it into apparatus according to the invention is achieved by replacing one of those filters with the triple bandpass filter 36 . in reality , the camera has a more complex arrangement of optical elements than is indicated by fig2 , but since these are , save for the filter 36 , identical to those used in the known camera , they have not been described in detail . the output of the camera 4 is connected to a computer 5 which has a video capture card for enabling the output to be recorded onto the computer &# 39 ; s hard drive for subsequent processing . the ccd camera 4 has three ccd arrays and associated red , green and blue colour filters . each ccd array is positioned behind a respective one of the three filters , and the camera includes a beam splitter for projecting the image of the retina of the eye 16 onto each of the 3 ccd arrays through its respective filter . the output of each array will therefore represent an array of grey scale pixel values which itself constitutes an intensity map of the filtered light received from the retina . the output of the ccd arrays therefore constitutes red , green and blue channels . fig8 illustrates the spectral response of the blue ( b ) green ( g ) and red ( r ) channels in the camera 4 . were white light to be used to illuminate the retina under inspection , the blue green and red channels of the camera output would not provide sufficient colour resolution to enable macular pigment density to be measured . however , the spectral responses from the three ccd arrays in the camera 4 will be shaped into narrower wave bands by the filter 36 , since the transmission spectrum of this filter has three relatively narrow bands , referenced 50 , 52 and 54 in fig3 , in its transmission spectrum . the width of each of these bands is considerably narrower than that of the three bands , b , g and r , the transmission spectrum between adjacent bands is substantially zero , as is illustrated in the optical density map of fig4 in which the vertical axis is minus one multiplied by the log ( to base ten ) of the transmittance . thus , the transmittance of the triple bandpass filter 36 between the transmission bands does not exceed 0 . 00001 ( i . e an optical density of 5 ). a filter having these spectral characteristics is available from omega optical . the interaction between the triple bandpass filter 36 and the filters in the ccd camera 4 is such that , of the light transmitted through the filter 36 , the light within the band 50 will only affect the blue output channel for the camera 4 , all light in the band 52 will affect the green channel whilst light in the band 54 only appears in the red channel . thus , light transmitted in each of the three bands of the bandpass filter 36 will only affect the output from a respective one of the 3 ccd arrays in the camera 4 . the method of operation of the apparatus , and the analysis of the retinal image captured by the apparatus , will now be described . initially , the subject places his or her head against the head support 10 , and the focusing lamp 20 and camera 4 are activated respectively to illuminate the eye 16 and to . capture a video image thereof . that image is displayed on the display 6 and the operator adjusts the controls of the camera to focus and align that image . the manner of this adjustment is the same as for the known retinal camera on which the present apparatus is based . the operator then activates the shutter switch , causing the lamp 18 to flash and a shutter ( not shown ) in the camera 4 to operate , so that the camera 4 captures the colour image of the retina of the eye 16 when the latter is being illuminated by the lamp 18 through the filter 36 , i . e . with light having a spectrum corresponding to the transmission spectrum of fig3 . the camera supplies r , g and b signals to the computer 5 , said signals representing an array of grey scale pixel values for each of the 3 ccd arrays . image analysis software ( for example imagepro plus ) which has been pre - installed on the computer 5 is then used to analyse the captured image . this is a powerful application capable of performing many operations , including those needed to generate an optical density map of the macular pigment of the retina . however , it is envisaged that other , simpler software packages could be used to achieve the same end , using an analysis technique developed from the underlying theory summarised below . we will assume a general situation of non - uniform illumination of the retina by the camera &# 39 ; s flash lamp . let the incident intensities by i f , b , i f , r , i p , b and i p , r , where the subscripts f and p refer to a foveal and peripheral retinal location ( no macular pigment ), and the additional subsripts b and r refer to the blue ( 460 nm ) and red wavelength bands , respectively of the light source ( i . e flash lamp 18 and filter 36 ). the analysis would not be affected if the green wavelength band had been chosen instead of the red . similarly let r f , b , r f , r , r p , b and r p , r be the corresponding reflectances of all retinal layers posterior to the macular pigment . finally , t is the 460 nm transmittance of the macular pigment at the foveal location , and the logarithms / log differences in this description are to base ten . for the blue illumination , the log difference in reflected intensities between the foveal and peripheral locations will be given by ld b = log ⁢ ⁢ i f , b ⁢ t 2 ⁢ r f , b - log ⁢ ⁢ i p , b ⁢ r p , b = log ⁢ i f , b ⁢ t 2 ⁢ r f , b i p , b ⁢ r p , b , ld r = log ⁢ ⁢ i f , r ⁢ r f , r - log ⁢ ⁢ i p , r ⁢ r p , r = log ⁢ i f , r ⁢ r f , r i p , r ⁢ r p , r the factor t 2 in the first equation is due to the double passage of the light through the macular pigment . ⁢ ld r - ld b = log ⁢ i f , r ⁢ r f , r ⁢ i p , b ⁢ r p , b i p , r ⁢ r p , r ⁢ i f , b ⁢ t 2 ⁢ r f , b ( 1 ) the spectral distributions of light on the fovea and periphery will be the same , it will also be assumed that the reflectance spectrum is the same in each location , ld r - ld b = log ⁢ 1 t 2 = 2 ⁢ d where d (=− log t ) is the optical density of the macular pigment at 460 nm . thus using imagepro plus , the spatial distribution of d is obtained from a single retinal image as follows : 1 . individual grayscale images are extracted from the original image , corresponding to the modified blue and red ( and green ) channels of the camera 4 . 2 . the greyscale images are transformed to floating point format to minimise loss of information in the subsequent steps . 3 . the “ red ” and “ blue ” images are logarithmically transformed . 4 . the “ log blue ” image is subtracted from the “ log red ” image . 5 . the resulting image is halved , in accordance with equation ( 2 ). the result will be a grayscale image , an example of which is shown in fig7 , in which the light area 56 is the area of macular pigment . a variety of options is available for further analysis or presentation . the image may be rendered as a surface plot as in fig6 in which the area of macular pigment is shown as a “ hill ” in the centre of the image . a density scan may be made along a line through the fovea , for example along horizontal or vertical meridians . an example is shown in fig5 . from such a plot , the peak macular pigment optical density will be obtained as the difference between the pixel values at the peak and at a peripheral location , such as 8 ° above the fovea . alternatively , a circular “ area of interest ” corresponding to , say , 1 . 5 ° may be defined . the average pixel value along the circular line , or the average pixel value within the enclosed area , may be obtained . there is evidence that flicker photometry determines the macular pigment density at the edge of the stimulus rather than the average value over the stimulus area . thus , if a comparison is to be made between flicker photometry and reflectometry , determining the average pixel value along the circular line may be more appropriate . the new method offers several advantages over traditional reflectometry , which requires the acquisition of separate blue and green images that must be precisely registered with each other . such alignment is possible with imagepro , but it would be too time - consuming for large - scale screening . with the proposed procedure , the blue and red images will be extracted from a single image and will be perfectly registered . also , when separate images are acquired , there is the problem of non - uniform illumination of the retina that may be different in the two images . as can be seen in the derivation of equation ( 2 ), any non - uniformity is the same in both images , if these are extracted from a single image , and is self - cancelling . there remains the question of whether to use a red or green image as the reference image . either fulfils the requirement of showing zero or near zero macular pigment optical density . however , the green image shows a darkening in the same region as the macular pigment due to the presence of long and medium wavelength cone photopigments . to minimise the contribution of these photopigments , they would normally have to be bleached ( approx . 5 . 6 log td for approx . 3 minutes ) prior to the acquisition of the image . however , with a method in accordance with the invention a triple bandpass filter 36 with the red transmitting band centred at approx . 600 nm is used . at this wavelength , the optical density of the cone photopigments is approximately the same as at 460 nm , the centre of the blue transmitting band . this photopigment optical density will contribute equally to the red and blue images and will be eliminated by the subtraction process . at 600 nm , rod photopigment optical density is approx . zero , but this is not the case at 460 nm and could affect the comparison between the foveal and peripheral sites in the blue image . however , the optical density at 500 nm has been estimated to be about 0 . 016 at 7 ° to 10 ° from the fovea ( brindley g . s . and willmer e . n . ( 1952 ). the reflexion of light from the macular and peripheral fundus oculi in man . j . physiol . 116 , 350 - 356 ). this would correspond to roughly 0 . 01 at 460 nm and is comparable with the estimate of “ delori f . c ., goger d . g ., hammond b . r ., snoddlerly d . m ., burns s . a . ( 2001 ) macular pigment density measured by autofluorescence spectrometry : comparison with reflectometry and heterochromatic flicker photometry . j . opt . soc . am ., a , optics , image science , & amp ; vision 18 , 1212 - 30 . assuming no rods at the foveal site , macular pigment optical density would be underestimated by only about 2 to 4 % in the average subject . apart from photopigments , melanin and oxyhaemoglobin can potentially influence macular pigment measurements obtained by reflectometry . oxyhaemoglobin can probably be ignored because its density is the same in the fovea and periphery ( 12 °). melanin may pose a problem since it has been shown to have a non - uniform distribution in the retina , peaking in the macula . also it has an absorbance spectrum that decreases with increasing wavelength . thus the blue image would be the most affected , the green image would be moderately affected , and the red image would be least affected . this would tend to cause the macular pigment optical density to be overestimated by a factor that would be larger if the red image is used as the reference rather than the green . in principle , the effects of melanin can be removed . to achieve this , theory indicated that equation ( 2 ) would need to be replaced by where r is the ratio of the melanin extinction coefficients at 460 and 600 nm ( approx . 4 ). hence the “ log red ” image would need to be multiplied by r prior to subtracting the “ log blue ” image . however , it should be noted that equation ( 3 ) assumes uniform illumination of the retina and a spectrally flat reflector . in addition , the value d given by ( 3 ) will be affected by any non - uniform distribution of photopigment across the retina . by exploiting the green image , as well as the blue and red images , we can eliminate the contributions from non - uniform distributions of both melanin and photopigments . the appropriate equation for d is then d = 1 / 2 ⁡ [ ld r ⁢ r 2 ⁢ r 4 ⁡ ( r 1 - r 3 ) r 1 ⁢ r 4 - r 2 ⁢ r 3 ) - ld b + ld g ⁢ r 1 ⁢ r 3 ⁡ ( r 4 - r 2 ) r 1 ⁢ r 4 - r 2 ⁢ r 3 ] ( 4 ) where the coefficients , r n , are the ratios of melanin or photopigment extinction coefficients at different pairs of wavelengths . more specifically the r factors are as follows : r 1 = ext . coeff . at the blue wavelength / ext . coeff . at the green wavelength for melanin r 2 = ext . coeff . at the blue wavelength / ext . coeff . at the red wavelength for melanin r 3 = ext . coeff . at the blue wavelength / ext . coeff . at the green wavelength for cone photopigment r 4 = ext . coeff . at the blue wavelength / ext . coeff . at the red wavelength for cone photopigment the ratios are obtainable from the literature . to put equation ( 4 ) into practice , the “ log red ”, “ log green ” and “ log blue ” images will be linearly combined using the appropriate multipliers shown in the equation . here , d is the optical density of the macular pigment at the wavelength of the blue filter band ( 460 nm ) and ld r , etc are the logarithmically transformed red , green and blue grayscale images . the software ( imagepro plus ) is windows - based and performs each of the following steps . 1 . individual grayscale images are extracted from the original image , corresponding to the filter - modified blue and red and green channels of the camera . 2 . the “ red ” “ green ” and “ blue ” grayscale images are transformed to floating point format to minimise loss of information in the subsequent steps . 3 . the three grayscale images are logarithmically transformed . 4 . the 3 logarithmically transformed images are combined according to equation ( 4 ). the result is an image of the retina that shows a lighter area ( higher intensity / higher pixel value ) in the region of the macula . a “ value ” of macular pigment density may be found by taking the average of a set of pixel values within a circular region ( e . g . 1 degree in diameter ) centred on the centre of the macula , and subtracting the average of a similar set centred at a reference location at , say , 8 degrees from the centre of the macula ( where macular pigment density ≈ 0 ). this would provide the average macular pigment density in the central 1 degree . it will be appreciated that in the maps / plots of fig5 - 7 , each individual pixel represents a mathematical combination of the amounts of light transmitted through each band of the triple bandpass filter , subsequently reflected from the retina , and modified in the central part of the retina by the transmitting properties of the macular pigment . thus the macular pigment optical density , d at any point within this central part of the retina is obtained by subtracting from the corresponding pixel value the pixel value at some non - central retinal location , such as at an eccentricity of 8 °, where macular pigment density is known to be negligible . for example , in fig5 , the peak optical density d is obtained by subtracting from the peak ordinate value the ordinate value at pixel number 95 , this representing a point on the retina approximately 8 ° from the centre of the fovea . notwithstanding the above comments on the distribution of rod photopigments , it is believed that the effect of such pigments on the macular pigment measurement may be eliminated by using an image of the retina illuminated by light at a fourth wavelength . in order to obtain the second image , the triple bandpass filter 36 is exchanged for a filter with peak transmittance at 680 nm and a bandwidth of 20 nm and the eye under examination is photographed a second time . the first photographs yields the ‘ red ’ green ’ and ‘ blue ’ images , one from each respective ccd array , whilst the second photograph yields a second ‘ red ’ image ( at a wavelength longer than that of the first ‘ red ’ image ). there are therefore 4 images at difference wavelengths , and these can be used to obtain the macular pigment optical density in a way which eliminates the ( small ) effect of rod photopigment . here , briefly , is how we would obtain the macular pigment optical density distribution , including this new refinement : 1 . obtain an image using the triple bandpass filter . use image analysis software to extract the grayscale images corresponding to the red , green and blue channels , as before , and concert these to logs ( ld r , ld g , ld b ). 2 . obtain a second image using a filter with peak transmittance at 680 nm and a bandwidth of 20 nm , for example . this is a longer wavelength than the red band of the triple bandpass filter . at 680 nm , the only pigment with a significant absorption is melanin . again extract the grayscale image ( from the red channel ), and convert to logs , ld r ′ 3 . use image analysis software to align the ld r ′ image with the ld r , ld g and ld b images . 4 . obtain the macular pigment optical density distribution by combining the 4 images in a linear fashion d =− 0 . 525 * ld b + 0 . 355 * ld g − 0 . 882 * ld r + 2 . 60 * ld r ′ the numerical factors are different combinations of extinction coefficients of the 4 pigments at the 4 wavelengths , similar to those shown symbolically ( 4 ) of the specification . since there are four different images and four unknown pigment distributions , the cone and rod distributions can also be determined using the following equations : d rod = 0 . 0254 * ld b =− 0 . 355 ld g + 1 . 081 ld r − 0 . 826 * ld r ′

US-83772004-A

a portable , insulated bait container for maintaining a variety of live bait types in a plurality of bait compartments . the container includes a pivotal carrying handle and a close fitting top for mounting over each of the provided compartments . at least one of the compartments being water filled and adjacent to which a life support compartment containing a battery operated aerator is included along with circuitry for automatically at selected times aerating the contained water . alternatively , switch means permit manual operation .

referring to fig1 a perspective assembly view is shown of the present insulated bait container 2 relative to its cover member 4 . pivotally mounted to the top center of two sides of the container 2 is a carrying handle 6 . with the cover 4 mounted on the container 2 , the appearance thereof resembles that of a conventional ice cooler , both in size and shape . depending , too , upon the number of bait compartments provided and the types of bait intended , the size of the container 2 may be varied accordingly . formed interiorly of the container 2 are a number of bait compartments and which for the embodiment of fig1 comprise a dry compartment 8 and a wet compartment 10 . the dry compartment 8 being intended for baits such as night crawlers , frogs or other live bait that require a dry or slightly moist environment . the wet compartment 10 , in turn , is sized so as to accommodate a sufficient volume of water for containing a quantity of minnows , leeches or other live bait requiring a supply of water . for example , for a bait container 2 of a typical size of 16 inches long by 12 inches wide by 8 inches deep , the wet compartment 10 will typically be sized to be 10 × 10 × 8 and will contain approximately 9 quarts of water . a compartment 10 of this size , in turn , will provide space for approximately 9 dozen minnows and will maintain a significant percentage of the minnows for periods of up to a week without requiring a water change . recognizing , however , that this number of minnows for the space available would use up the available oxygen in the water in a matter of hours , the present invention includes an aerator . specifically , the present invention includes a diaphram - type aerator pump that is mounted in the auxilary compartment 12 and which is used to aerate the water of the compartment 10 so as to maintain a sufficient supply of oxygen to the water to maintain the minnows therein . as can be seen from fig1 the air is supplied to the compartment 10 via the conduit 14 and an associated porous ceramic filter 17 ( reference fig2 ) mounted at the end thereof . the details of the auxilary compartment 12 and its contents will be discussed hereinafter . mounted to the side of the compartment 12 is an operator actuable switch ( not shown ) for controlling the operation of the aerator pump . from fig1 it is also to be noted that the cover 4 is fabricated such that its lower surface is formed to contain a number of raised surfaces that mount securely with a friction fit over the tops of each of the compartments 8 and 10 . in this fashion , the cover 4 will not become dislodged during transport or when not in use . directing attention now to fig2 a cross - sectioned front view is shown as taken along section lines 2 -- 2 of fig1 . from this view , a better understanding can be had as to the mounting relationship of the foam - filled cover 4 relative to the bait container 2 . also , it is to be noted that each of the compartments 8 and 10 of the bait container 2 are full depth and are insulated as at callout numeral 19 . as presently contemplated , the bait container 2 and cover 4 would be fabricated from a suitable plastic via an appropriate molding or stamping operation to have inner and outer plastic skins 15 and 16 and which would provide a weather tight , non - rusting enclosure . at present , it is also contemplated that an injected polystyrene insulation 19 would be used . from fig2 it is also to be noted that the carrying handle 6 mounts to the sides of the container 2 in a snap - fit fashion via cap - like projections 20 formed at the ends of the cover handle 6 . upon inserting the capped ends 20 into holes formed in the container 2 sides , they are permanently pivotally secured thereto . also , it is to be noted that a vent hole 22 is formed in the cover 4 over the minnow compartment 10 so as to permit the escape of carbon dioxide therefrom . the vent hole 22 typically being formed by inserting a nylon bushing 24 through a hole formed in the cover . directing attention now to fig3 a detailed cross - sectional view taken along section lines 3 -- 3 of fig1 is shown relative to the accessory compartment 12 . this compartment like the bait compartments 8 and 10 shown in fig2 is formed as a full depth compartment and is sized to contain a suitable battery power supply 25 , an aerator 26 , switch 27 and circuitry 28 for controllng the aerator 26 . a separate insulated cover member 30 is provided over this compartment 12 and which cover member 30 friction fits within the opening so as not to be readily removed therefrom , except by pulling on the cover ring 32 provided at the top of the cover 30 . mounted immediately beneath the cover 30 is a diaphragm - type air pump 29 and which is driven via an eccentric lobed member 34 that operates the linkage arm coupled to the pump diaphragm via an adjacent dc motor 36 , together they comprise the aerator 26 . mounted , in turn , beneath the pump 29 is a rechargeable nickel cadmium battery power pack 25 . as can be seen from fig3 the outlet end of the pump 29 is coupled to a nipple member 38 via a short length of conduit 46 . the nipple member 38 passes between the accessory and minnow containing compartments 12 and 10 in sealed relation so as to prevent against water from inadvertently entering the accessory compartment 12 . the conduit 14 within the minnow containing compartment conveys air to the water via the filter element 17 , where it is despersed through the pores of the filter 17 . the air itself enters the accessory compartment 12 via appropriate vent holes 40 let into the walls thereof . for the present embodiment , the pump 26 is sized to provide a sufficient amount of oxygen to the water to keep the mentioned quantity of minnows and which pump 26 is driven at 60 cycles per minute via the lobed eccentric 34 and the dc motor 36 . the power supply 25 , as mentioned , comprises a six volt nickel cadmium power source that is mounted in the bottom center of the accessory compartment 12 . it is spaced away from the sidewalls thereof via a battery and aerator carrier 42 and a number of projections 44 that extend from an inner compartment liner 45 . together , the carrier 42 and liner 45 center the contents relative to the compartment walls , while a flexible support pad 46 mounted in the bottom thereof supports the assembly . the support pad 46 and projections 44 also dampen any vibrations that otherwise occur with the operation of the motor 36 and thus deaden and prevent the transmission of sound . at this point , it should be noted , too , that in between fishing trips , the battery power supply 25 can be removed and recharged by inserting it in an appropriate recharger . alternatively , ac / dc conversion circuitry can be mounted within the accessory compartment 12 for recharging the battery supply 25 in place . however , because of the attendant cost and space requirements of such recharging circuitry , the present embodiment contemplates recharging the battery externally of the container 2 . mounted near the top of the compartment 12 , at its back wall is the off / manual / automatic switch 27 and to which appropriate electric connections are made between the battery 25 , motor 36 , control circuitry 28 and pump 29 . the externally mounted operator switch 27 permits either manual operation of the pump 25 for operator controlled amounts of time . alternatively , because of the power required and even though it is relatively small for the present motor 36 , the pump 29 and motor 36 can be run intermittently by placing the switch 27 in its automatic position . in order to achieve this end , the present invention includes conventional time control circuitry 28 and which upon switching the switch 27 to its automatic position causes a periodic operation of the aerator pump 26 for predetermined amounts of time at a predetermined frequency . at present , the pump runs 10 minutes each half hour and which is sufficient to maintain oxygen to approximately 9 dozen minnows . at this operating frequency , the present power supply is also sized to provide for approximately 96 hours of operation and the retention of approximately 90 percent of the live bait . as mentioned , the switch 27 also permits manual operation and which feature may be used intermittently to provide additional oxygen for warm days . also , it may be used in lieu of the automatic position on cold days , since less oxygen is required as the water is cooled . furthermore , because of the insulating of the various compartments , swings in temperature are minimized . still further , because of the insulation 19 and the size of the container 12 it can be used as a seat while ice fishing without the water freezing . while the invention has been described with respect to its presently preferred embodiment , it is to be recognized that various modifications may be made thereto . for example , each of the compartments might be further segmented by forming intermediate shelf projections at various levels and upon which various tray inserts might be positioned such that more than one type of bait can be stored in a single compartment . for example , night crawlers might be stored in the bottom tray and leeches in the upper tray , while minnows are stored in the minnow compartment . alternatively , three or more compartments might be provided . still further , the cover can be formed with drink holder recesses in the upper surface thereo . still further , a waterproof light might be included in one or more of the bait compartments to facilitate night fishing and which lights would turn on , upon removal of the cover . from the foregoing , it should be apparent , therefore , that various modifications can be made to the present invention without departing from the spirit and scope thereof . accordingly , it is contemplated that the following claims should be interpreted so as to include all those equivalent embodiments within the spirit and scope thereof .

US-69262785-A

a method for monitoring respiration by illuminating the body of the subject with a luminous flux , where a lens is used to form on a set of photosensitive elements , an image of at least one region of the space within which a person under surveillance is capable of moving , a light source is used for illuminating the area , fine control and readout circuits are connected to the photosensitive elements , an analog to digital converter is to the control circuit , and a microprocessor is used to compare successive signals from the photosensitive elements and which is used to determine any significant variations in the successive signals which are due to respiration of the person being monitored . an alarm is also included which is triggered in response to an absence of variations on successive signals .

reference will be made first to fig1 in which the device 10 according to the invention is arranged , for example by means of a set of legs 11 , above the bed 12 in which the infant 13 to be monitored is lying . it goes without saying that , if the nature of the bed permits , this device 10 may possibly be arranged on the side of the latter . associated with the actual device 10 are a local light or sound alarm device 14 and a remote warning device 15 positioned at another site . the connection between the device 10 and the remote warning device 15 can be provided by any suitable means , for example by interphone or by a specialized or non - specialized information transmission channel ( for example via an electrical network ). the main components of the device 10 will now be described with reference to fig2 . the device 10 comprises a lens 16 , such as a camera lens , in the observation field of which is situated the bed 12 on which the infant 13 is lying . the lens 16 is associated with a set of photosensitive elements consisting preferably of a bar or row 17 of elementary photodetectors 19 , such as chargetransfer photodetectors , of which there may be 512 or 1024 for example . the lens 16 forms on the bar 17 of photodetectors the image of a plane of the space included in its observation field , this plane corresponding to the plane of the drawing in fig2 . the positions of the lens 16 and of the bar 17 with respect to one another and with respect to the bed 12 are chosen in such a way that the plane of the observed space intercepts the plane defined by the surface of the mattress of the bed 12 in a zone of the latter in which is situated a part of the body of the infant 13 liable to exhibit movements associated with breathing , namely the thorax or abdomen . however , since the infant is liable to move in its bed during sleep , it is preferable to form images of several different zones of the bed 12 which are distributed in such a way that , in any position of the infant in its bed , an image of a part of its thorax or its abdomen is formed on the bar 17 . thus , in accordance with the embodiment in fig3 complementary optical means , such as prisms 18 , are associated with the lens 16 in order to form images along three planes p1 , p2 and p3 extending transversely with respect to the length of the bed 12 . the optics 16 , 18 are provided in such a way that the images of three bands z1 , z2 and z3 are superposed and give rise to a composite image on the bar 17 of photodetectors . of course , this is a particular exemplary embodiment which can be the object of many variants , both as regards the number of planes of the space observed and the orientations of these planes relative to one another and relative to the plane p of the mattress on which the infant is lying . these various parameters can be optimized as a function of the size of the bed 12 , that of the infant , etc ., in order to ensure that , in any position of the latter in its bed , at least one image of a part of its thorax or abdomen is formed on the bar 17 of photodetectors . however , there is no reason to multiply to excess the number of superposed images on the bar 17 , since the result of this would be the risk of an excessive decrease in the sensitivity of the device by super - position of significant images ( parts of the body of the child showing movements associated with breathing ) and non - significant images ( observation of zones of the bed in which there is no part of the body of the infant , or parts of the latter which do not show movements associated with breathing ). in fact , each photodetector of the bar 17 is sensitive to the mean of the homologous points of the superposed images formed in the different planes of observation . the photodetectors 19 of the bar 17 are associated with circuits , generally designated by reference number 20 , which comprise circuits for measuring or reading the charges of the detectors 19 , and at least one clock for determining the integration time or the reading frequency of the photodetectors 19 . the reading circuits are connected via an analog to digital converter 21 to a microprocessor 22 effecting the processing of the output signals from the photodetectors 19 and the control of the circuits 20 . this microprocessor 22 also controls , by means of the circuits 20 , a lighting system 23 which provides a substantially constant illumination of the bands z1 , z2 and z3 , the images of which are formed on the bar 17 . the lighting system 23 preferably consists of a set of photoemission diodes illuminating the abovementioned zones at a wavelength which is not within the visible range , but remains in the range of sensitivity of the photodetectors 19 . illumination by non - visible infrared has the advantage of not harming the infant at the intensities demanded by the sensitivity of the photodetectors , and of having a satisfactory degree of reflection on the numerous types of materials with which the infant 13 may be covered . if the lighting system is fed by an alternating voltage source , the reading frequency of the photodetectors must be equal to or be an integral sub - multiple of twice the frequency of the voltage source , so that the gray level of the photodetectors is independent of the source phase . by way of example , a reading frequency of 20 hz is compatible with voltage sources of 50 hz and 60 hz . the lighting system or luminous source 23 can be arranged in the immediate vicinity of the bar 17 of photodetectors , or else be at a slight distance from the latter in such a way as to illuminate obliquely the different zones observed z1 , z2 and z3 in order to contribute , by the formation of shadows in the region of these zones , to increasing the differences in brightness between the images of one and the same zone which are formed during a respiration cycle of the infant . it should be noted at this point that the infant will preferably not be covered by a blanket or clothing which is likely to render imperceptible those movements of its body which are associated with breathing . the infant may be clothed , for example , in a close - fitting garment . on the other hand , in the absence of a specific lighting system , the luminous source may consist of the natural light . in this case , means for controlling sensitivity can be provided , so that the mean gray level seen by the photodetectors is substantially constant and independent of the lighting conditions . furthermore , the microprocessor 22 is connected to the light or sound alarm device 14 associated with the device , and also to the remote warning system 15 . these local alarm or remote warning means are triggered by the microprocessor 22 when it no longer detects breathing . the main steps in the method according to the invention and the functioning of the device will now be described with reference to fig4 a and 4b . the curves a and b in fig4 a and 4b represent the video signals obtained by reading of the elementary photodetectors 19 of the bar 17 at two instants which are separated by a predetermined time interval . each curve a , b represents the gray levels ( brightness ) which are viewed by the set of photodetectors 19 . when the scene observed has not changed between the two observation instants , the curves a and b are identical ( fig4 b ), it being assumed that the lighting is substantially constant . in contrast , when there is a respiratory movement , this is reflected by a variation in the spatial distribution of the gray levels viewed by the corresponding photodetectors ( fig4 a ). the detection of the variations in the spatial distribution of the gray levels viewed by the photodetectors thus makes it possible to demonstrate those movements of the body associated with breathing and , consequently , the absence of these movements or an abnormal character thereof results in triggering of the warning system . the processing of the video signals supplied by the bar 17 of photodetectors 19 is , in the main , as follows : two successive signals , such as those represented by the curves a and b , are compared , and their difference provides the signal represented by curve c . this signal is amplified ( curve d ) and is then straightened and converted into binary signals by comparison with a determined threshold permitting elimination of the residual noise of the photodetectors 19 . the resulting signal , represented by curve e , comprises a first notch or echo 24 , of a relatively considerable width ( fig4 a ), and a second notch or echo 25 of far lesser width . this signal is then applied to a filter in order to retain only the first echo 24 ( curve f ) which corresponds to a movement associated with breathing , and in order to eliminate the second echo 25 whose length is far too small to correspond to such a movement ( case of an insect moving within the observation field ). in greater detail , the time course of the various operations in the method according to the invention may be as follows : the images formed on the bar 17 of photodetectors are read at a determined frequency and the electrical charges of the set of photodetectors 19 scanned successively produce the video signals a and b in fig4 a and 4b . these signals read by the circuit 20 and digitalized by the converter 21 are recorded by the microprocessor 22 at a frequency which is at most equal to the reading frequency and which is most often a submultiple of this reading frequency . let us assume , for example , that this time interval is 3 seconds and that the recording frequency is such that a recording is obtained every 0 . 5 second . in other words , the first signal recorded at instant 0 is compared 3 seconds later to the signal which has just been recorded and their difference is established as described with reference to fig4 ( amplification , straightening , conversion into binary signals and filtering ) to give the result signal which is recorded at instant t = 3 seconds . the signal recorded at time t = 0 . 5 second is compared to the signal recorded at time t = 3 . 5 seconds , and so on . when a result is negative ( no breathing ), the following step consists in accumulating the following results a predetermined number of times or for a predetermined period of time and in giving the alarm after a predetermined and consecutive number of negative results indicating that the apnoea does not correspond to any respiratory pause , but to a respiratory arrest . this cumulative number of static images corresponds to the duration of the acceptable respiratory pause which may either be determined empirically and stored in the microprocessor 22 , or set by means of a manually operated selector 24 provided on the device 10 ( fig1 ). it goes without saying that the embodiments described are only examples and that they could be modified , in particular by substitution of technical equivalents , without thereby departing from the scope of the invention .

US-46013390-A

an adjustable personal treatment apparatus that is usable by women of all sizes to enable them to enjoy , without harm , the full healthful benefits of proper and necessary massage and therapy . more particularly , the apparatus permits the proper pressure to be applied to a female patient during massage , or therapeutic treatment , without causing discomfort and possible damage to breast tissue or breast implants .

referring to the drawings and particularly to fig1 and 2 , one form of the treatment , or support platform of the present invention for supporting an individual in a prone position is there shown and generally designated by the numeral 22 . platform 22 here comprises a supporting frame 24 that includes an upper frame 24 a to which a pair of forward , transversely spaced , downwardly extending legs 24 b is connected and to which a pair of rearward , transversely - spaced , downwardly extending legs 24 c is connected . connected to and supported by supporting frame 24 is an elongated , resilient body cushion 26 , having opposing upper and lower surfaces 26 a and 26 b . as best seen in fig1 of the drawings , upper surface 26 a of the body , or cushion , is provided with a receiving chamber 28 for receiving the breasts of the individual being treated . forming an important aspect of the treatment platform 22 of the present invention is a control assembly 30 for controllably positioning a breast cushion 32 that is disposed within receiving chamber 28 . control assembly 30 here includes a breast cushion positioning mechanism generally designated by the numeral 34 for moving the breast cushion 32 within receiving chamber 28 from a first elevated position to a second lowered position . as indicated in the drawings , apportion of the breast cushion positioning mechanism 34 is connected to the inner sidewalls 36 and 37 of receiving chamber 28 ( fig2 ) and is disposed below the upper surface 26 a of the resilient body cushion 26 . breast cushion positioning mechanism 34 here comprises a pair of readily commercially available linear motor assemblies 38 that include elongate tracks or slides 38 a that , in the manner shown in fig2 , are interconnected with the side walls 36 and 37 , respectively , of the cushion receiving chamber 28 . each of the linear motor assemblies also comprises a combination electric motor and moving carriage 38 b that is connected to a selected one of the tracks . breast support cushion 32 is carried by a cushion support plate 40 that is positioned between and interconnected with the carriage 38 b . when the linear motors are energized through operation of a switch 44 that is mounted on the side of the cushion 26 and interconnected with the motors by a conduit 46 , the breast support cushion can be controllably moved upwardly and downwardly within the chamber 28 manner to provide optimum support to the breasts of the patient . the linear motor assemblies 38 can be obtained from a number of sources , including the parker hannifin corporation of rohnert park , calif . and the tecnotion , b . v . company of the netherlands . in using the apparatus of the invention shown in fig1 and 2 of the drawings , the linear motor assemblies 38 are operated in a manner to move the breast support cushion downwardly within chamber 28 . this done , the patient can lay prone on the support cushion 26 with the breasts located within chamber 28 . through operation of the switch 44 , the breast support cushion 32 can be raised to a position wherein the breasts of the patient are comfortably supported by the cushion 32 . with the patient thusly positioned on the support table , massage or similar therapeutic manipulation of the patient can be accomplished without undue pressure being exerted upon the breasts of the patient . turning next to fig5 through 10 , an alternate form of the treatment platform of the present invention for supporting an individual in a prone or supine position is there shown and generally designated by the numeral 52 . platform 52 here comprises a foldable supporting frame 54 that functions to support an elongated resilient body pad 56 that includes first and second sections 58 and 60 . first section 58 has a forward portion 58 a having opposing upper and lower surfaces 62 and 64 and a generally oval shaped a guide passageway 66 ( see also fig5 , 9a and 9b ). as indicated in fig5 of the drawings , the forward portion of the support frame 54 is provided with downwardly extending adjustable front leg assemblies 70 , while the rearward portion of the support frame is provided with downwardly extending adjustable rear leg assemblies 72 . connected to the forward portion 58 a of first section 58 of the resilient body pad is the important patient support cushion assembly that is generally designated in fig9 a and 9b by the numeral 74 . patient support cushion assembly 74 here comprises an airbag housing 76 having an internal chamber 76 a that is in communication with the guide passageway 66 that is formed in the forward portion of the first section 58 a of the resilient body pad 56 . also forming a part of the important patient support cushion assembly 74 is an inflatable , deflatable airbag 78 that is disposed within the internal chamber of the airbag housing 76 . air bag 78 is movable relative to housing 76 between the first partially collapsed configuration shown in fig9 a , to the second fully expanded configuration shown in fig9 b . when the airbag 78 is in its normal at - rest configuration , it is in the position shown in fig5 and 9 of the drawings . forming another important aspect of the patient support cushion assembly 74 is a resiliently deformable patient support cushion 80 that is generally oval shaped in cross - section . cushion 80 , which includes yieldably deformable side and top walls 80 a and 80 b ( fig7 ), is operably associated with airbag 78 and is movable from a first lowered position shown in fig9 a wherein the cushion is disposed within the guide passageway 66 at a location below the upper surface 58 a of the first section 58 , to a second upraised position shown in fig9 , and to a third position shown in fig9 b , wherein the cushion is positioned a substantial distance above the upper surface 58 a of the first section 58 . more particularly , cushion 80 is coupled with the airbag by means of the plurality of generally “ s ” shaped coupling members 82 that are of the configuration shown in fig9 and 10 of the drawings . connected to airbag 78 for moving the airbag between the first partially collapsed configuration shown in fig9 a and the expanded configurations shown in fig9 and 9b is a pump assembly 86 that here comprises a foot operated bellows 88 and an airline 90 that interconnects the foot operated bellows with the inflatable , deflatable airbag 78 . airline 90 has a first end 90 a that is connected to the foot operated bellows 88 and a second end that is connected to one leg of a “ t ” connector 92 ( fig8 ). another leg of the “ t ” connector is connected to the inlet 94 a of an airbag connector 94 that is disposed within an opening 96 formed in the side wall of airbag housing 76 . airbag connector 94 has an outlet 94 b that is in communication with the interior of the airbag 78 so that air under pressure generated by the foot pump will travel through the airline 90 , through the airbag connector and into the interior of the airbag in a manner to controllably inflate the airbag . also forming a part of the pump assembly 86 is a vent line assembly 98 that is connected to airline 90 for controllably deflating the airbag . in the present form of the invention , the vent line assembly comprises a vent line 100 having a first end portion 100 a that is connected to one leg of the “ t ” connector 92 and a second end portion 100 b that is affixed to the side of the resilient body pad 56 by means of a conventional line clamp 102 which can be used to control the flow of air through vent line 100 ( fig8 ). in the present form of the invention , platform 52 further includes a head support assembly 104 that is connected to the forward portion of the first section 58 a of the resilient body pad 56 ( fig5 ). when the patient is in a prone position on the resilient body pad , the head support assembly 104 functions to support the face of the patient when the patient is lying face down , or the head of the patient when the patient is lying on his or her back . in using the apparatus of the invention , the apparatus is first erected from the collapsed , folded configuration ( not shown ) into the operable configuration illustrated in fig5 of the drawings . hand straps 106 are provided on one side of the pad 56 to assist in transporting the apparatus . the height of the platform can be adjusted by appropriately manipulating the downwardly extending adjustable front leg assemblies 70 and the downwardly extending adjustable rear leg assemblies 72 . this is accomplished by moving the second portions 70 b and 72 b of the front and rear leg assemblies upwardly or downwardly , relative to the first portions 70 a and 72 of the leg assemblies ( fig5 ). as indicated in fig5 of the drawings , the first and second portions of the front and rear leg assemblies are provided with vertically spaced apart pad receiving apertures 73 that are adapted to receive locking pins 75 . upon the sequential removal of the locking pins 75 , the second portions of the leg assemblies can be moved from a first position to a second position , to controllably adjust the overall length of each of the leg assemblies and thereby adjust the height of the support platform . when the desired length of the leg assemblies is achieved , the locking pins 75 can be reinserted into the apertures 73 to hold the first and second leg portions securely in position . with the apparatus is in the starting configuration shown in fig5 , the upper surface 80 a of the resiliently deformable patient support cushion 80 is typically flush with the upper surface of the resilient body pad 56 . due to the resilient nature of the airbag 78 that supports the patient support cushion 80 , while lying prone , any portion of the patient &# 39 ; s body that protrudes outwardly , as for example the breasts of the patient , that is positioned within the guide passageway 66 will , upon operation of the line clamp 102 , uniquely cause the support cushion 80 move telescopically downwardly within the passageway 66 to a lowered position , such as the position shown in fig6 of the drawings , so as to avoid any discomfort to the patient . similarly , when the patient is in a supine position and with line clamp 102 closed , operation of the foot pump 88 by the foot of the caregiver will cause the support cushion 80 to move upwardly relative to the surface of the body support pad 56 in the manner illustrated in fig7 of the drawings . by way of example , when the patient &# 39 ; s upper back is positioned over the pad , this controlled upward movement of the resiliently deformable support cushion raises the patient &# 39 ; s chest and enables the accomplishment of a more effective and highly satisfying massage . because of the unique positioning of the airbag within the guide passageway 66 and the ability to controllably inflate the airbag , the support cushion 80 can be raised to any degree desired by the caregiver , including into the position shown in fig7 wherein the upper surface 80 a of the support cushion resides above the surface of the body support pad by distance approximately one half the thickness “ t ” of the body support pad 56 ( see fig9 b ). when the massage is complete , the forward and rearward legs can be pivoted in a direction toward the lower surface of the body support pad and the body support pad can then be folded to form a compact unit that can be easily transported and stored .

US-80704210-A

dithiocarboxylates , and in particular , dithiocarbamates , block the induced expression of the endothelial cell surface adhesion molecule vcam - 1 , and are therefor useful in the treatment of cardiovascular disease , including atherosclerosis , post - angioplasty restenosis , coronary artery diseases , and angina , as well as noncardiovascular inflammatory diseases that are mediated by vcam - 1 .

the term alkyl , as used herein , unless otherwise specified , refers to a saturated straight , branched , or cyclic ( in the case of c 5 or greater ) hydrocarbon of c 1 to c 10 ( or lower alkyl , i . e ., c 1 to c 5 ), which specifically includes methyl , ethyl , propyl , isopropyl , butyl , isobutyl , t - butyl , pentyl , cyclopentyl , isopentyl , neopentyl , hexyl , isohexyl , cyclohexyl , cyclohexylmethyl , 3 - methylpentyl , 2 , 2 - dimethylbutyl , and 2 , 3dimethylbutyl . the alkyl group can be optionally substituted on any of the carbons with one or more moieties selected from the group consisting of hydroxyl , amino , or mono - or disubstituted amino , wherein the substituent group is independently alkyl , aryl , alkaryl or aralkyl ; aryl , alkoxy , aryloxy , nitro , cyano , sulfonic acid , sulfate , phosphonic acid , phosphate , or phosphonate , either unprotected , or protected as necessary , as known to those skilled in the art , for example , as taught in greene , et al ., &# 34 ; protective groups in organic synthesis ,&# 34 ; john wiley and sons , second edition , 1991 . the term alkenyl , as referred to herein , and unless otherwise specified , refers to a straight , branched , or cyclic hydrocarbon of c 2 to c 10 with at least one double bond . the term alkynyl , as referred to herein , and unless otherwise specified , refers to a c 2 to c 10 straight or branched hydrocarbon with at least one triple bond . the term aralkyl refers to an aryl group with at least one alkyl substituent . the term alkaryl refers to an alkyl group that has at least one aryl substituent . the term halo ( alkyl , alkenyl , or alkynyl ) refers to an alkyl , alkenyl , or alkynyl group in which at least one of the hydrogens in the group has been replaced with a halogen atom . the term aryl , as used herein , and unless otherwise specified , refers to phenyl , biphenyl , or napthyl , and preferably phenyl . the aryl group can be optionally substituted with one or more moieties selected from the group consisting of alkyl , hydroxyl , amino , alkylamino , arylamino , alkoxy , aryloxy , nitro , cyano , sulfonic acid , sulfate , phosphonic acid , phosphate , or phosphonate , co 2 h , or its pharmaceutically acceptable salt , co 2 ( alkyl , aryl , alkaryl or aralkyl ), or glucamine , either unprotected , or protected as necessary , as known to those skilled in the art , for example , as taught in greene , et al ., &# 34 ; protective groups in organic synthesis ,&# 34 ; john wiley and sons , second edition , 1991 . the term alkoxy , as used herein , and unless otherwise specified , refers to a moiety of the structure -- o - alkyl . the term acyl , as used herein , refers to a group of the formula c ( o ) r &# 39 ;, wherein r &# 39 ; is an alkyl , aryl , alkaryl or aralkyl group . the term heteroaryl or heteroaromatic , as used herein , refers to an aromatic moiety that includes at least one sulfur , oxygen , or nitrogen in the aromatic ring . nonlimiting examples are phenazine , phenothiazine , furyl , pyridyl , pyrimidyl , thienyl , isothiazolyl , imidazolyl , tetrazolyl , pyrazinyl , benzofuranyl , benzothiophenyl , quinolyl , isoquinolyl , benzothienyl , isobenzofuryl , pyrazolyl , indolyl , isoindolyl , benzimidazolyl , purinyl , morpholinyl , carbozolyl , oxazolyl , thiazolyl , isothiazolyl , 1 , 2 , 4 - thiadiazolyl , isooxazolyl , pyrrolyl , pyrazolyl , quinazolinyl , pyridazinyl , pyrazinyl , cinnolinyl , phthalazinyl , quinoxalinyl , xanthinyl , hypoxanthinyl , pteridinyl , 5 - azacytidinyl , 5 - azauracilyl , triazolopyridinyl , imidazolopyridinyl , pyrrolopyrimidinyl , pyrazolopyrimidinyl , adenine , n 6 - alkylpurines , n 6 - benzylpurine , n 6 - halopurine , n 6 - vinylpurine , n 6 - acetylenic purine , n 6 - acyl purine , n 6 - hydroxyalkyl purine , n 6 - thioalkyl purine , thymine , cytosine , 6 - azapyrimidine , 2 - mercaptopyrmidine , uracil , n 5 - alkylpyrimidines , n 5 - benzylpyrimidines , n 5 - halopyrimidines , n 5 - vinylpyrimidine , n 5 - acetylenic pyrimidine , n 5 - acyl pyrimidine , n 5 - hydroxyalkyl purine , and n 6 - thioalkyl purine , and isoxazolyl . the heteroaromatic group can be optionally substituted as described above for aryl . the heteroaromatic can be partially or totally hydrogenated as desired . as a nonlimiting example , dihydropyridine can be used in place of pyridine . functional oxygen and nitrogen groups on the heterocyclic base can be protected as necessary or desired during the reaction sequence . suitable protecting groups are well known to those skilled in the art , and include trimethylsilyl , dimethylhexylsilyl , t - butyldimethylsilyl , and t - butyldiphenylsilyl , tritylmethyl , alkyl groups , acyl groups such as acetyl and propionyl , methylsulfonyl , and p - toluylsulfonyl . the term hydroxyalkyl , as used herein , refers to a c 1 to c 6 alkyl group in which at least one of the hydrogens attached to any of the carbon atoms is replaced with a hydroxy group . the term thiol antioxidant refers to a sulfur containing compound that retards oxidation . the term pharmaceutically acceptable derivative refers to a derivative of the active compound that upon administration to the recipient , is capable of providing directly or indirectly , the parent compound , or that exhibits activity itself . the term &# 34 ; pharmaceutically acceptable cation &# 34 ; refers to an organic or inorganic moiety that carries a positive charge and that can be administered in association with a pharmaceutical agent , for example , as a countercation in a salt . pharmaceutically acceptable cations are known to those of skill in the art , and include but are not limited to sodium , potassium , and quaternary amine . the term &# 34 ; physiologically cleavable leaving group &# 34 ; refers to a moiety that can be cleaved in vivo from the molecule to which it is attached , and includes but is not limited to an organic or inorganic anion , a pharmaceutically acceptable cation , acyl ( including but not limited to ( alkyl ) c ( o ), including acetyl , propionyl , and butyryl ), alkyl , phosphate , sulfate and sulfonate . the term &# 34 ; enantiomerically enriched composition or compound &# 34 ; refers to a composition or compound that includes at least 95 %, and preferably at least 97 , 98 , 99 , or 100 % by weight of a single enantiomer of the compound . the term amino acid includes synthetic and naturally occurring amino acids , including but not limited to , for example , alanyl , valinyl , leucinyl , isoleucinyl , prolinyl , phenylalaninyl , tryptophanyl , methioninyl , glycinyl , serinyl , threoninyl , cysteinyl , tyrosinyl , asparaginyl , glutaminyl , aspartoyl , glutaoyl , lysinyl , argininyl , and histidinyl . a &# 34 ; linking moiety &# 34 ; as used herein , is any divalent group that links two chemical residues , including but not limited to alkyl , alkenyl , alkynyl , aryl , polyalkyleneoxy ( for example -- ( ch 2 ) n o --! n --), -- c 1 - 6 alkoxy - c 1 - 10 alkyl -, n -- c 1 - 6 alkylthio - c 1 - 10 alkyl -, -- nr 3 --, and --( choh ) n ch 2 oh , wherein n is independently 0 , 1 , 2 , 3 , 4 , 5 , or 6 . it has been discovered that dithiocarboxylates are useful in the treatment of atherosclerosis and other cardiovascular and inflammatory diseases . dithiocarboxylates , including dithiocarbamates , can be used to block the ability of cells , including endothelial cells , to express vcam - 1 , which is a gene product known to be responsible for the adherence of leukocytes to cells . the fact that dithiocarboxylates , including dithiocarbamates , inhibit vcam - 1 gene expression strongly supports the importance of oxidation as an initiating signal in altered vascular - inflammatory cell interactions . the specific molecular mechanisms by which the dithiocarboxylates function in inhibiting vcam - 1 gene expression is not known . at least one of the compounds , sodium pyrrolidine dithiocarbamate ( pdtc ), inhibits vcam - 1 gene expression at a concentration of less than 1 . 0 micromolar . this compounds also exhibits preferential toxicity to proliferating or abnormally dividing vascular smooth muscle cells . it has been discovered that sodium pyrrolidine dithiocarbamate does not significantly block elam - 1 or icam - 1 expression , and therefore treatment with this compound does not adversely affect aspects of the inflammatory response mediated by elam - 1 or icam - 1 . thus , a generalized immunosuppression is avoided . this may avoid systemic complications from generalized inhibition of adhesion molecules in the many other cell types known to express them . other pharmaceutically acceptable salts of pdtc are also effective agents for the treatment of cardiovascular and inflammatory disorders . dithiocarbamates are transition metal chelators clinically used for heavy metal intoxication . baselt , r . c ., f . w . j . sunderman , et al . ( 1977 ), &# 34 ; comparisons of antidotal efficacy of sodium diethyldithiocarbamate , d - penicillamine and triethylenetetramine upon acute toxicity of nickel carbonyl in rats .&# 34 ; res commun chem pathol pharmacol 18 ( 4 ): 677 - 88 ; menne , t . and k . kaaber ( 1978 ), &# 34 ; treatment of pompholyx due to nickel allergy with chelating agents .&# 34 ; contact dermatitis 4 ( 5 ): 289 - 90 ; sunderman , f . w . ( 1978 ), &# 34 ; clinical response to therapeutic agents in poisoning from mercury vapor &# 34 ; ann clin lab sci 8 ( 4 ): 259 - 69 ; sunderman , f . w . ( 1979 ), &# 34 ; efficacy of sodium diethyldithiocarbamate ( dithiocarb ) in acute nickel carbonyl poisoning .&# 34 ; ann clin lab sci 9 ( 1 ): 1 - 10 ; gale , g . r ., a . b . smith , et al . ( 1981 ), &# 34 ; diethyldithiocarbamate in treatment of acute cadmium poisoning .&# 34 ; ann clin lab sci 11 ( 6 ): 476 - 83 ; jones , m . m . and m . g . cherian ( 1990 ), &# 34 ; the search for chelate antagonists for chronic cadmium intoxication .&# 34 ; toxicology 62 ( 1 ): 1 - 25 ; jones , s . g ., m . a . basinger , et al . ( 1982 ), &# 34 ; a comparison of diethyldithiocarbamate and edta as antidotes for acute cadmium intoxication .&# 34 ; res commun chem pathol pharmacol 38 ( 2 ): 271 - 8 ; pages , a ., j . s . casas , et al . ( 1985 ), &# 34 ; dithiocarbamates in heavy metal poisoning : complexes of n , n - di ( 1 - hydroxyethyl ) dithiocarbamate with zn ( ii ), cd ( ii ), hg ( ii ), ch3hg ( ii ), and c6h5hg ( ii ). : j . inorg biochem 25 ( 1 ): 35 - 42 ; tandon , s . k ., n . s . hashmi , et al . ( 1990 ), &# 34 ; the lead - chelating effects of substituted dithiocarbamates .&# 34 ; biomed environ sci 3 ( 3 ): 299 - 305 . dithiocarbamates have also been used adjunctively in cis - platinum chemotherapy to prevent renal toxicity . hacker , m . p ., w . b . ershler , et al . ( 1982 ). &# 34 ; effect of disulfiram ( tetraethylthiuram disulfide ) and diethyldithiocarbamate on the bladder toxicity and antitumor activity of cyclophosphamide in mice .&# 34 ; cancer res 42 ( 11 ): 4490 - 4 . bodenner , 1986 # 733 ; saran , m . and bors , w . ( 1990 ). &# 34 ; radical reactions in vivo -- an overview .&# 34 ; radiat . environ . biophys . 29 ( 4 ): 249 - 62 . a dithiocarbamate currently used in the treatment of alcohol abuse is disulfiram , a dimer of diethyldithiocarbamate . disulfuram inhibits hepatic aldehyde dehydrogenase . inoue , k ., and fukunaga , et al ., ( 1982 ). &# 34 ; effect of disulfiram and its reduced metabolite , diethyldithiocarbamate on aldehyde dehydrogenase of human erythrocytes .&# 34 ; life sci 30 ( 5 ): 419 - 24 . it has been reported that dithiocarbamates inhibit hiv virus replication , and also enhance the maturation of specific t cell subpopulations . this has led to clinical trials of diethyldithiocarbamate in aids patient populations . reisinger , e ., et al ., ( 1990 ). &# 34 ; inhibition of hiv progression by dithiocarb .&# 34 ; lancet 335 : 679 . dithiocarboxylates are compounds of the structure a -- sc ( s )-- b , which are members of the general class of compounds known as thiol antioxidants , and are alternatively referred to as carbodithiols or carbodithiolates . it appears that the -- sc ( s )- moiety is essential for therapeutic activity , and that a and b can be any group that does not adversely affect the efficacy or toxicity of the compound . in an alternative embodiment , one or both of the sulfur atoms in the dithiocarbamate is replaced with a selenium atom . the substitution of sulfur for selenium may decrease the toxicity of the molecule in certain cases , and may thus be better tolerated by the patient . a and b can be selected by one of ordinary skill in the art to impart desired characteristics to the compound , including size , charge , toxicity , and degree of stability , ( including stability in an acidic environment such as the stomach , or basic environment such as the intestinal tract ). the selection of a and b will also have an important effect on the tissue - distribution and pharmacokinetics of the compound . in general , for treatment of cardiovascular disease , it is desirable that the compound accumulate , or localize , in the arterial intimal layer containing the vascular endothelial cells . the compounds are preferably eliminated by renal excretion . an advantage in administering a dithiocarboxylate pharmaceutically is that it does not appear to be cleaved enzymatically in vivo by thioesterases , and thus may exhibit a prolonged halflife in vivo . in a preferred embodiment , a is hydrogen or a pharmaceutically acceptable cation , including but not limited to sodium , potassium , calcium , magnesium , aluminum , zinc , bismuth , barium , copper , cobalt , nickel , or cadmium ; a salt - forming organic acid , typically a carboxylic acid , including but not limited to acetic acid , oxalic acid , tartaric acid , succinic acid , malic acid , ascorbic acid , benzoic acid , tannic acid , pamoic acid , alginic acid , polyglutamic acid , naphthalenesulfonic acid , naphthalenedisulfonic acid , or polygalacturonic acid ; or a cation formed from ammonia or other nitrogenous base , including but not limited to a nitrogenous heterocycle , or a moiety of the formula nr 4 r 5 r 6 r 7 , wherein r 4 , r 5 , r 6 , and r 7 are independently hydrogen , c 1 - 6 linear , branched , or ( in the case of c 4 - 6 ) cyclic alkyl , hydroxy ( c 1 - 6 ) alkyl ( wherein one or more hydroxyl groups are located on any of the carbon atoms ), or aryl , n , n - dibenzylethylene - diamine , d - glucosamine , choline , tetraethylammonium , or ethylenediamine . in another embodiment , a can be a physiologically cleavable leaving group that can be cleaved in vivo from the molecule to which it is attached , and includes but is not limited acyl ( including acetyl , propionyl , and butyryl ), alkyl , phosphate , sulfate or sulfonate . in one embodiment , b is alkyl , alkenyl , alkynyl , alkaryl , aralkyl , haloalkyl , haloalkenyl , haloalkynyl , aryl , alkaryl , hydrogen , c 1 - 6 alkoxy - c 1 - 10 alkyl , c 1 - 6 alkylthio - c 1 - 10 alkyl , nr 2 r 3 , --( choh ) n ch 2 oh , wherein n is 0 , 1 , 2 , 3 , 4 , 5 , or 6 , --( ch 2 ) n co 2 r 1 , including alkylacetyl , alkylpropionyl , and alkylbutyryl , or hydroxy ( c 1 - 6 ) alkyl - ( wherein one or more hydroxyl groups are located on any of the carbon atoms ). in another embodiment , b is nr 2 r 3 , wherein r 2 and r 3 are independently alkyl ; --( choh ) n ( ch 2 ) n oh , wherein n is 0 , 1 , 2 , 3 , 4 , 5 , or 6 ; --( ch 2 ) n co 2 r 1 , --( ch 2 ) n co 2 r 4 ; hydroxy ( c 1 - 6 ) alkyl -; alkenyl ( including but not limited to vinyl , allyl , and ch 3 ch ═ ch -- ch 2 ch 2 ); alkyl ( co 2 h ), alkenyl ( co 2 h ), alkynyl ( co 2 h ), or aryl , wherein the aryl group can be substituted as described above , notably , for example , with a no 2 , ch 3 , t - butyl , co 2 h , halo , or p - oh group ; or r 2 and r 3 can together constitute a bridge such as --( ch 2 ) m --, wherein m is 3 , 4 , 5 , or 6 , and wherein r 4 is alkyl , aryl , alkaryl , or aralkyl , including acetyl , propionyl , and butyryl . in yet another embodiment , b can be a heterocyclic or alkylheterocyclic group . the heterocycle can be optionally partially or totally hydrogenated . nonlimiting examples are those listed above , including phenazine , phenothiazine , pyridine and dihydropyridine . in still another embodiment , b is the residue of a pharmaceutically - active compound or drug . the term drug , as used herein , refers to any substance used internally or externally as a medicine for the treatment , cure , or prevention of a disease or disorder . nonlimiting examples are drugs for the treatment or prevention of cardiovascular disease , including antioxidants such as probucol ; nicotinic acid ; agents that prevent platelets from sticking , such as aspirin ; antithrombotic agents such as coumadin ; calcium channel blockers such as varapamil , diltiazem , and nifedipine ; angiotensin converting enzyme ( ace ) inhibitors such as captopril and enalopril , β - blockers such as propanalol , terbutalol , and labetalol , nonsteroidal antiinflammatories such as ibuprofen , indomethacin , fenoprofen , mefenamic acid , flufenamic acid , sulindac , or corticosteriods . the -- c ( s ) sa group can be directly attached to the drug , or attached through any suitable linking moiety . in another embodiment , the dithiocarbamate is an amino acid derivative of the structure ao 2 c -- r 9 -- nr 10 -- c ( s ) sa , wherein r 9 is a divalent b moiety , a linking moiety , or the internal residue of any of the naturally occurring amino acids ( for example , ch 3 ch for alanine , ch 2 for glycine , ch ( ch 2 ) 4 nh 2 for lysine , etc . ), and r 10 is hydrogen or lower alkyl . b can also be a polymer to which one or more dithiocarbamate groups are attached , either directly , or through any suitable linking moiety . the dithiocarbamate is preferably released from the polymer under in vivo conditions over a suitable time period to provide a therapeutic benefit . in a preferred embodiment , the polymer itself is also degradable in vivo . the term biodegradable or bioerodible , as used herein , refers to a polymer that dissolves or degrades within a period that is acceptable in the desired application ( usually in vivo therapy ), usually less than five years , and preferably less than one year , on exposure to a physiological solution of ph 6 - 8 having a temperature of between 25 ° and 37 ° c . in a preferred embodiment , the polymer degrades in a period of between 1 hour and several weeks , according to the application . a number of degradable polymers are known . nonlimiting examples are peptides , proteins , nucleoproteins , lipoproteins , glycoproteins , synthetic and natural polypeptides and polyamino acids , including but not limited to polymers and copolymers of lysine , arginine , asparagine , aspartic acid , cysteine , cystine , glutamic acid , glutamine , hydroxylysine , serine , threonine , and tyrosine ; polyorthoesters , including poly ( α - hydroxy acids ), for example , polylactic acid , polyglycolic acid , poly ( lactide - co - glycolide ), polyanhydrides , albumin or collagen , a polysaccharide containing sugar units such as lactose , and polycaprolactone . the polymer can be a random or block copolymer . b can also be a group that enhances the water solubility of the dithiocarbamate , for example , - lower alkyl - o - r 8 , wherein r 8 is -- po 2 ( oh ) m + or po 3 ( m + ) 2 wherein m + is a pharmaceutically acceptable cation ; -- c ( o )( ch 2 ) 2 co 2 m + , or -- so 3 m + ; - lower alkylcarbonyl - lower alkyl ; - carboxy lower alkyl ; - lower alkylamino - lower alkyl ; n , n - di - substituted amino lower alkyl -, wherein the substituents each independently represent lower alkyl ; pyridyl - lower alkyl -; imidazolyl - lower alkyl -; imidazolyl - y - lower alkyl wherein y is thio or amino ; morpholinyl - lower alkyl ; pyrrolidinyl - lower alkyl ; thiazolinyl - lower alkyl -; piperidinyl - lower alkyl ; morpholinyl - lower hydroxyalkyl ; n - pyrryl ; piperazinyl - lower alkyl ; n - substituted piperazinyl - lower alkyl , wherein the substituent is lower alkyl ; triazolyl - lower alkyl ; tetrazolyl - lower alkyl ; tetrazolylamino - lower alkyl ; or thiazolyl - lower alkyl . in an alternative embodiment , a dimer such as b -- c ( s ) s -- sc ( s )-- b can be administered . dithiocarboxylates should be chosen for use in treating atherosclerosis and other cardiovascular and inflammatory diseases that have the proper lipophilicity to locate at the affected cite . the compound should not compartmentalize in low turnover regions such as fat deposits . in a preferred embodiment for treatment of cardiovascular disease , the pharmacokinetics of the compound should not be dramatically affected by congestive heart failure or renal insufficiency . for topical applications for the treatment of inflammatory skin disorders , the selected compound should be formulated to be absorbed by the skin in a sufficient amount to render a therapeutic effect to the afflicted site . the dithiocarboxylate must be physiologically acceptable . in general , compounds with a therapeutic index of at least 2 , and preferably at least 5 or 10 , are acceptable . the therapeutic index is defined as the ec 50 / ic 50 , wherein ec 50 is the concentration of compound that inhibits the expression of vcam - 1 by 50 % and ic 50 is the concentration of compound that is toxic to 50 % of the target cells . cellular toxicity can be measured by direct cell counts , trypan blue exclusion , or various metabolic activity studies such as 3h - thymidine incorporation , as known to those skilled in the art . the therapeutic index of pdtc in tissue culture is over 100 as measured by cell toxicity divided by ability to inhibit vcam - 1 expression activated by tnfa , in huve cells . initial studies on the rapidly dividing cell type ht - 18 human glioma demonstrate no toxicity at concentrations 100 - fold greater than the therapeutic concentration . disulfiram , an orally administered form of diethyldithiocarbamate , used in the treatment of alcohol abuse , generally elicits no major clinical toxicities when administered appropriately . there are a few dithiocarbamates that are known to be genotoxic . these compounds do not fall within the scope of the present invention , which is limited to the administration of physiologically acceptable materials . an example of a genotoxic dithiocarbamate is the fungicide zinc dimethyldithiocarbamate . further , the anticholinesterase properties of certain dithiocarbamates can lead to neurotoxic effects . miller , d . ( 1982 ). neurotoxicity of the pesticidal carbamates . neurobehav . toxicol . teratol . 4 ( 6 ): 779 - 87 . the term dithiocarboxylate as used herein specifically includes , but is not limited to , dithiocarbamates of the formulas : wherein r 1 is h or a pharmaceutically acceptable cation , including but not limited to sodium , potassium , or nr 4 r 5 r 6 r 7 , wherein r 4 , r 5 , r 6 , and r 7 are independently hydrogen , c 1 - 6 linear , branched , or cyclic alkyl , hydroxy ( c 1 - 6 ) alkyl ( wherein one or more hydroxyl groups are located on any of the carbon atoms ), or aryl , and r 2 and r 3 are independently c 1 - 10 linear , branched or cyclic alkyl ; --( choh ) n ( ch 2 ) n oh , wherein n is 0 , 1 , 2 , 3 , 4 , 5 , or 6 ; --( ch 2 ) n co 2 r 1 , --( ch 2 ) n co 2 r 4 ; hydroxy ( c 1 - 6 ) alkyl -, or r 2 and r 3 together constitute a bridge such as --( ch 2 ) m --, wherein m is 3 - 6 , and wherein r 4 is alkyl , aryl , alkaryl , or aralkyl , including acetyl , propionyl , and butyryl . specific examples of useful dithiocarbamates , illustrated in fig8 include sodium pyrrolidine - n - carbodithioate , sodium n - methyl - n - carboxymethyl - n - carbodithioate , trisodium n , n - di ( carboxymethyl )- n - carbodithioate , sodium n - methyl - d - glucamine - n - carbodithioate , sodium n , n - diethyl - n - carbodithioate ( sodium diethyldithiocarbamate ), and sodium n , n - diisopropyl - n - carbodithioate . the active dithiocarboxylates and in particular , dithiocarbamates are either commercially available or can be prepared using known methods . at the molecular level , pdtc has been shown to inhibit the activation of the transcriptional regulatory factor nf - kb in response to certain cytokine and non - cytokine stimuli ( schreck , rieber et al . 1991 ; schreck , meier et al . 1992 ). however , by gel mobility shift assay of huvec nuclear extracts with various kb - like enhancer motifs , it has been discovered that endothelial cells activate vcam - 1 gene expression through an apparently novel transcriptional regulatory factor that is not nf - kb . this suggests that pdtc may regulate endothelial cell gene expression through its effect on a new transcriptional regulatory protein . it has also been demonstrated that vcam - 1 expression is induced by multiple factors in cultured kaposi &# 39 ; s sarcoma cells , which may be important in its pathogenesis . pdtc blocks vcam - 1 expression in kaposi &# 39 ; s sarcoma cells that have been activated by tnf , il - 1 , and poly ( i : c ). the ability of dithiocarboxylates to inhibit the expression of vcam - 1 can be measured in a variety of ways , including by the methods set out in detail below in examples 1 to 7 . for convenience , examples 1 - 3 and 6 - 7 describe the evaluation of the biological activity of sodium pyrrolidine - n - carbodithioate ( also referred to as pdtc ). these examples are not intended to limit the scope of the invention , which specifically includes the use of any of the above - described compounds to treat atherosclerosis , and other types of inflammation and cardiovascular disease mediated by vcam - 1 . any of the compounds described above can be easily substituted for pdtc and evaluated in similar fashion . examples 4 and 5 provide comparative data on the ability of a number of dithiocarbamates to inhibit the gene expression of vcam - 1 . the examples below establish that the claimed dithiocarbamates specifically block the ability of vcam - 1 to be expressed by vascular endothelial cells in response to many signals known to be active in atherosclerosis and the inflammatory response . cell cultures huve cells were isolated from human umbilical veins that were cannulated , perfused with hanks solution to remove blood , and then incubated with 1 % collagenase for 15 minutes at 37 ° c . after removal of collagenase , cells were cultured in m199 medium supplemented with 20 % fetal bovine serum ( hyclone ), 16 μg / ml heparin ( esi pharmaceuticals , cherry hill , n . j . ), 50 μg / ml endothelial cell growth supplement ( collaborative research incorporated , bedford mass . ), 25 mm hepes buffer , 2 mm l - glutamin , 100 μg / ml penicillin and 100 μg / ml streptomycin and grown at 37 ° c . on tissue culture plates coated 0 . 1 % gelatin . cells were passaged at confluency by splitting 1 : 4 . cells were used within the first 8 passages . incubation with cytokines and other reagents confluent huve cells were washed with phosphate buffered saline and then received fresh media . the indicated concentrations of pdtc were added as pretreatment 30 minutes before adding cytokines . cytokines and other inducers were directly added to medium for the times and at the concentrations indicated in each experiment . human recombinant il - lb was the generous gift of upjohn company ( kalamazoo , mich .). tnfa was obtained from bohringer engelheim . bacterial lipopolysaccharide ( lps ), polyinosinic acid : polycitidilic acid ( poly i : c ), and pyrrolidine dithiocarbamate ( pdtc ) were obtained from sigma chemical ( st . louis , mo .). all other reagents were of reagent grade . rna isolation total cellular rna was isolated by a single extraction using an acid guanidium thiocyanate - phenol - chloroform mixture . cells were rinsed with phosphate buffered saline and then lysed with 2 ml of guanidium isothiocyanate . the solution was acidified with 0 . 2 ml of sodium acetate ( ph 4 . 0 ) and then extracted with 2 ml phenol and 0 . 4 ml chloroform : isoamyl alcohol ( 24 : 1 ). the rna underwent two ethanol precipitations prior to being used for northern blot analysis . northern blot analysis total cellular rna ( 20 μg ) was size fractionated using 1 % agarose formaldehyde gels in the presence of 1 ug / ml ethidium bromide . the rna was transferred to a nitrocellulose filter and covalently linked by ultraviolet irradiation using a stratlinker uv crosslinker ( stratagene , la jolla , calif .). hybridizations were performed at 42 ° c . for 18 hours in 5 × ssc ( 1 ×= 150 mm nacl , 15 mm na citrate ), 1 % sodium dodecyl sulfate , 5 × denhardt solution , 50 % formamide , 10 % dextran sulfate and 100 ug / ml of sheared denatured salmon sperm dna . approximately 1 - 2 × 10 6 cpm / ml of labeled probe ( specific activity & gt ; 108 cpm / ug dna ) were used per hybridization . following hybridization , filters were washed with a final stringency of 0 . 2 × ssc at 55 ° c . the nitrocellulose was stripped using boiled water prior to rehybridization with other probes . autoradiography was performed with an intensifying screen at - 70 ° c . 32 probes 32 p labeled dna probes were made using the random primer oligonucleotide method . the icam - 1 probe was an eco r1 fragment of human cdna . the elam - 1 probe was a 1 . 85 kb hind iii fragment of human cdna . the vcam - 1 probe was a hind iii - xho i fragment of the human cdna consisting of nucleotide 132 to 1814 . enzyme linked immunosorbent assay ( elisa ) huve cells were plated on 96 - well tissue culture plates 48 to 72 hours before the assay . primary antibodies in m199 with 5 % fbs were added to each well and incubated one hour at 37 ° c . the cells were then washed and incubated for one hour with peroxidase conjugated goat anti - mouse igg ( bio rad ) diluted 1 / 500 in m199 with 5 % fbs . the wells were then washed and binding of antibody was detected by the addition of 100 μl of 10 mg / ml 3 , 3 , 5 , 5 &# 39 ;- tetramethyl - benzidine ( sigma ) with 0 . 003 % h 2 o 2 . the reaction was stopped by the addition of 25 μl of 8n sulfuric acid . plates were read on an elisa reader ( bio rad ) at od 450 nm after blanking on rows stained only with second step antibody . data represent the means of triplicate . antibodies monoclonal antibody ( mab ) 4b9 recognizing vascular cell adhesion molecule - 1 ( vcam - 1 ) was the generous gift of dr . john harlan ( university of washington ). mab e9a1f1 recognizing endothelial cell adhesion molecule ( elam - 1 ) was the generous gift of dr . swerlick ( emory university ). hybridomas producing mab 84h10 recognizing intercellular adhesion molecule 1 ( icam - 1 ) are routinely grown in our laboratory and antibody was used as tissue culture supernatant . pdtc blocks il - lb mediated induction of huvec vcam - 1 , but not icam - 1 or elam - 1 , mrna accumulation to determine whether the oxidative state of the endothelial cell can alter the basal or induced expression of cell adhesion molecule genes , cultured human vascular endothelial cells were exposed to the inducing cytokine , il - lb ( 10 u / ml ) in the presence or absence of the thiolated metal chelating antioxidant , pyrrolidine dithiocarbamate ( pdtc , 50 μm ) for up to 24 hours . as shown in fig1 il - lb alone ( lanes 2 , 4 , 6 , 8 ) induces the expected rapid and transient induction of vcam - 1 ( panel a ), e - selectin ( elam - 1 , panel b ) and icam - 1 ( panel c ) mrna accumulation , all of which peak at four hours . however , in the presence of pdtc , il - lb induction of vcam - 1 mrna accumulation is dramatically inhibited by over 90 % ( panel a , lanes 3 , 5 , 7 , 9 ). in contrast , although il - lb mediated induction of elam - 1 is slightly inhibited at 2 and 24 hours ( compare lane 2 and 3 , 8 and 9 , panel b ), pdtc does not inhibit the induction at 4 and 8 hours ( lane 5 and 7 , panel b ). il - lb mediated induction of icam - 1 mrna accumulation is not affected ( panel b , lanes 3 , 5 , 7 , 9 ). indeed , a mild augmentation of il - lb induction of icam - 1 mrna accumulation (˜ 30 %) is observed ( compare lanes 4 and 5 , panel b ). equivalent amounts of nitrocellulose transferred rna per lane was confirmed by ethidium bromide staining and visualization . a dose - response analysis was performed to determine whether pdtc inhibits the induction of vcam - 1 gene expression by il - lb in a dose dependent manner . as shown in fig2 pdtc inhibits il - lb mediated induction of vcam - 1 gene expression with a steep dose - response curve ( fig2 panel a ) with a calculated ec 50 of approximately 10 μm , while pdtc does not inhibit il - lb mediated induction of elam - 1 expression with these concentrations ( fig2 panel b ). the il - lb mediated induction of icam - 1 mrna accumulation is enhanced by pdtc with the concentration higher than 0 . 5 μm ( fig2 compare lane 2 and lane 4 - 7 , panel c ). these data demonstrate that il - lb utilizes a dithiocarboxylate , and in particular , a dithiocarbamate sensitive step as part of its signaling mechanism in the induction of vcam - 1 gene expression . the data also appear to indicate that this dithiocarbamate sensitive step does not play a significant role in the il - lb mediated induction of elam - 1 or icam - 1 gene expression . pdtc blocks induction of huvec vcam - 1 mrna accumulation by multiple stimuli to determine whether other well - described activators of vcam - 1 gene expression also utilize a pdtc sensitive step , three distinct classes of activators were tested : another classic receptor mediated inducing agent ( tnfa ), a non - receptor mediated inducer ( lipopolysaccharide ( lps )) and a recently described novel inducer ( double stranded rna , poly ( i : c )). in all three cases , pdtc dramatically inhibited the induction of vcam - 1 mrna accumulation in huvecs after four hours ( fig3 panel a ). although the tnfa mediated elam - 1 gene expression is suppressed to some extent ( fig3 lane 1 and 2 , panel b ), lps and poly ( i : c ) mediated elam - 1 mrna accumulation was unaffected ( fig3 lane 3 - 6 , panel b ). the induction of icam - 1 mrna accumulation was unaffected ( fig3 panel c ). this data indicates that structurally distinct inducing agents , acting through distinct pathways , share a common regulatory step specific for the induction of vcam - 1 gene expression . pdtc blocks huve cell surface expression of vcam - 1 induced by multiple stimuli to determine whether , like its mrna , the induction of endothelial cell surface protein expression of vcam - 1 could also be inhibited by pdtc , monoclonal antibodies were used in an elisa assay to quantitate the induction of cell surface vcam - 1 and icam - 1 in cultured huve cells . as shown in fig4 multiple classes of activating agents , in the absence of pdtc (- pdtc ), induce the rapid and transient accumulation of vcam - 1 ( top left panel ) at the cell surface peaking at six hours . in the presence of pdtc (+ pdtc , top right panel ), the induction of cell surface expression of vcam - 1 by all agents tested is dramatically inhibited ( 80 - 90 %). in contrast , the induced expression of cell surface icam - 1 is unaffected under identical conditions ( bottom left and right panels ). these data demonstrate that , like its mrna accumulation , cell surface vcam - 1 expression are selectively inhibited by dithiocarbamates and that multiple classes of activating agents utilize a similar , dithiocarbamate sensitive mechanism to induce vcam - 1 gene expression . to determine whether structurally similar or dissimilar antioxidants could also inhibit vcam - 1 gene expression , and with what potency , huve cells were exposed to tnfa for six hours in the presence or absence of different concentrations of four different antioxidants . as shown in fig5 both diethyldithiocarbamate ( detc ) and n - acetyl cysteine ( nac ) inhibited vcam - 1 expression at concentrations of 5 μm and 30 μm , respectively . in contrast , pdtc ( pdtc ) was effective between 5 and 50 μm . the iron metal chelator , desferroximine , had no effect at the concentrations tested . the ability of a variety of antioxidants to inhibit tnfa induction of vcam - 1 in huve cells was evaluated by the method set out in example 4 . fig6 is a graph of the relative vcam - 1 cell surface expression ( o . d . 595 nm ) in tnfa activated huve cells versus concentrations of ptdc ( sodium n - pyrrolidine dithiocarbamate ), didtc ( sodium n , n - diethyl - n - carbodithioate ), sardtc ( sodium n - methyl - n - carboxymethyl - n - carbodithioate ), idadtc ( trisodium n , n - di ( carboxymethyl )- n - carbodithioate ), mgdtc ( sodium n - methyl - d - glucamine - n - carbodithioate ), meobgdtc ( sodium n -( 4 - methoxybenzyl )- d - glucamine - n - carbodithioate ), dedtc ( sodium n , n - diethyl - n - carbodithioate ), di - pdtc ( sodium n , n - diisopropyl - n - carbodithioate ), and nac is ( n - acetyl cysteine ). in order to define whether pdtc inhibition of vcam - 1 regulation is associated with functional consequences , we examined the binding of molt - 4 cells to huvec cells either unstimulated or stimulated with tnfa ( 100u / ml ) for six hours in the presence or absence of pdtc . molt - 4 cells have been previously shown to bind to activated huvec via a vcam - 1 dependent mechanism . as shown in fig6 the percentage of molt - 4 binding to huvec cells decreased when pdtc was present in the media . pdtc inhibits monocyte binding to the thoracic aorta of cholesterol fed rabbits an experiment was performed to determine whether the thiol antioxidant pdtc would be efficacious in blocking the first monocyte binding component of atherosclerosis in an experimental animal model . one mature new zealand white rabbit ( 3 . 5 kg ) received an intravenous injection of pdtc ( 20 mg / kg , as a concentration of 20 mg / ml in pbs ) once daily for 5 days . injections were given via an indwelling cannula in the marginal ear vein , which as kept patent by flushing with heparinized saline solution . the pdtc solution was mixed fresh daily or on alternate days ( stored light - protected at 4 ° c . ), and filtered ( 0 . 45 mm pore filter ) just prior to use . after the first injection , when the cannula was placed , the drug was administered with the rabbit in the conscious state without apparent discomfort or other ill effect . on the second day of injections , the rabbit was given chow containing 1 % cholesterol by weight , which was continued throughout the remainder of the experiment . on the fifth day , the animal was euthanized and the thoracic aorta was excised and fixed . after appropriate preparation , the sample was imaged on the lower stage of an isi ds - 130 scanning electron microscope equipped with a lab emitter . using dual - screen imaging and a transparent grid on the crt screen , 64 adjacent fields at a 620 × magnification were assessed , to cover an area of ˜ 1 . 3 mm 2 . within each field , the number of adherent leukocytes ( wbc ) and erythrocytes ( rbc ) were counted and recorded . the data from the arch sample are as follows : 5 wbc and ˜ 25 rbc per 1 . 3 mm 2 field . this level of wbc adhesion is similar to control animals fed regular chow ( about 7 per field have been seen in arch and thoracic samples from 2 ` negative control ` experiments ). ` positive control ` rabbits fed 1 % cholesterol for 4 days but not given antioxidant show about a 5 - fold increase in adhesion , to 38 wbc / 1 . 3 mm 2 . a considerable amount of mostly cell - sized debris was observed adherent to each arch sample . it is unclear whether this material is an artifact of preparation , or was present in vivo , and if so , whether it is related to pdtc administration . these studies suggest that pdtc infusions can effectively block initial monocyte adhesion to the aortic endothelium . humans , equine , canine , bovine and other animals , and in particular , mammals , suffering from cardiovascular disorders , and other inflammatory conditions mediated by vcam - 1 can be treated by administering to the patient an effective amount of one or more of the above - identified compounds or a pharmaceutically acceptable derivative or salt thereof in a pharmaceutically acceptable carrier or diluent . the active materials can be administered by any appropriate route , for example , orally , parenterally , intravenously , intradermally , subcutaneously , or topically . as used herein , the term pharmaceutically acceptable salts or complexes refers to salts or complexes that retain the desired biological activity of the above - identified compounds and exhibit minimal undesired toxicological effects . nonlimiting examples of such salts are ( a ) acid addition salts formed with inorganic acids ( for example , hydrochloric acid , hydrobromic acid , sulfuric acid , phosphoric acid , nitric acid , and the like ), and salts formed with organic acids such as acetic acid , oxalic acid , tartaric acid , succinic acid , malic acid , ascorbic acid , benzoic acid , tannic acid , pamoic acid , alginic acid , polyglutamic acid , naphthalenesulfonic acid , naphthalenedisulfonic acid , and polygalacturonic acid ; ( b ) base addition salts formed with polyvalent metal cations such as zinc , calcium , bismuth , barium , magnesium , aluminum , copper , cobalt , nickel , cadmium , sodium , potassium , and the like , or with an organic cation formed from n , n - dibenzylethylene - diamine , d - glucosamine , ammonium , tetraethylammonium , or ethylenediamine ; or ( c ) combinations of ( a ) and ( b ); e . g ., a zinc tannate salt or the like . the active compound is included in the pharmaceutically acceptable carrier or diluent in an amount sufficient to deliver to a patient a therapeutically effective amount without causing serious toxic effects in the patient treated . a preferred dose of the active compound for all of the above - mentioned conditions is in the range from about 0 . 1 to 500 mg / kg , preferably 1 to 100 mg / kg per day . the effective dosage range of the pharmaceutically acceptable derivatives can be calculated based on the weight of the parent compound to be delivered . if the derivative exhibits activity in itself , the effective dosage can be estimated as above using the weight of the derivative , or by other means known to those skilled in the art . for systemic administration , the compound is conveniently administered in any suitable unit dosage form , including but not limited to one containing 1 to 3000 mg , preferably 5 to 500 mg of active ingredient per unit dosage form . a oral dosage of 25 - 250 mg is usually convenient . the active ingredient should be administered to achieve peak plasma concentrations of the active compound of about 0 . 1 to 100 μm , preferably about 1 - 10 μm . this may be achieved , for example , by the intravenous injection of a solution or formulation of the active ingredient , optionally in saline , or an aqueous medium or administered as a bolus of the active ingredient . the concentration of active compound in the drug composition will depend on absorption , distribution , inactivation , and excretion rates of the drug as well as other factors known to those of skill in the art . it is to be noted that dosage values will also vary with the severity of the condition to be alleviated . it is to be further understood that for any particular subject , specific dosage regimens should be adjusted over time according to the individual need and the professional judgment of the person administering or supervising the administration of the compositions , and that the concentration ranges set forth herein are exemplary only and are not intended to limit the scope or practice of the claimed composition . the active ingredient may be administered at once , or may be divided into a number of smaller doses to be administered at varying intervals of time . oral compositions will generally include an inert diluent or an edible carrier . they may be enclosed in gelatin capsules or compressed into tablets . for the purpose of oral therapeutic administration , the active compound can be incorporated with excipients and used in the form of tablets , troches , or capsules . pharmaceutically compatible binding agents , and / or adjuvant materials can be included as part of the composition . the tablets , pills , capsules , troches and the like can contain any of the following ingredients , or compounds of a similar nature : a binder such as microcrystalline cellulose , gum tragacanth or gelatin ; an excipient such as starch or lactose , a disintegrating agent such as alginic acid , primogel , or corn starch ; a lubricant such as magnesium stearate or sterotes ; a glidant such as colloidal silicon dioxide ; a sweetening agent such as sucrose or saccharin ; or a flavoring agent such as peppermint , methyl salicylate , or orange flavoring . when the dosage unit form is a capsule , it can contain , in addition to material of the above type , a liquid carrier such as a fatty oil . in addition , dosage unit forms can contain various other materials which modify the physical form of the dosage unit , for example , coatings of sugar , shellac , or other enteric agents . the active compound or pharmaceutically acceptable salt or derivative thereof can be administered as a component of an elixir , suspension , syrup , wafer , chewing gum or the like . a syrup may contain , in addition to the active compounds , sucrose as a sweetening agent and certain preservatives , dyes and colorings and flavors . the active compound or pharmaceutically acceptable derivatives or salts thereof can also be administered with other active materials that do not impair the desired action , or with materials that supplement the desired action , such as antibiotics , antifungals , antiinflammatories , or antiviral compounds . the active compounds can be administered with lipid lowering agents such as probucol and nicotinic acid ; platelet aggregation inhibitors such as aspirin ; antithrombotic agents such as coumadin ; calcium channel blockers such as varapamil , diltiazem , and nifedipine ; angiotensin converting enzyme ( ace ) inhibitors such as captopril and enalopril , and β - blockers such as propanalol , terbutalol , and labetalol . the compounds can also be administered in combination with nonsteroidal antiinflammatories such as ibuprofen , indomethacin , aspirin , fenoprofen , mefenamic acid , flufenamic acid , sulindac . the compound can also be administered with corticosteriods . solutions or suspensions used for parenteral , intradermal , subcutaneous , or topical application can include the following components : a sterile diluent such as water for injection , saline solution , fixed oils , polyethylene glycols , glycerine , propylene glycol or other synthetic solvents ; antibacterial agents such as benzyl alcohol or methyl parabens ; antioxidants such as ascorbic acid or sodium bisulfite ; chelating agents such as ethylenediaminetetraacetic acid ; buffers such as acetates , citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose . the parental preparation can be enclosed in ampoules , disposable syringes or multiple dose vials made of glass or plastic . suitable vehicles or carriers for topical application are known , and include lotions , suspensions , ointments , creams , gels , tinctures , sprays , powders , pastes , slow - release transdermal patches , aerosols for asthma , and suppositories for application to rectal , vaginal , nasal or oral mucosa . thickening agents , emollients , and stabilizers can be used to prepare topical compositions . examples of thickening agents include petrolatum , beeswax , xanthan gum , or polyethylene glycol , humectants such as sorbitol , emollients such as mineral oil , lanolin and its derivatives , or squalene . a number of solutions and ointments are commercially available . natural or artificial flavorings or sweeteners can be added to enhance the taste of topical preparations applied for local effect to mucosal surfaces . inert dyes or colors can be added , particularly in the case of preparations designed for application to oral mucosal surfaces . the active compounds can be prepared with carriers that protect the compound against rapid release , such as a controlled release formulation , including implants and microencapsulated delivery systems . biodegradable , biocompatible polymers can be used , such as ethylene vinyl acetate , polyanhydrides , polyglycolic acid , collagen , polyorthoesters , and polylactic acid . many methods for the preparation of such formulations are patented or generally known to those skilled in the art . if administered intravenously , preferred carriers are physiological saline or phosphate buffered saline ( pbs ). the active compound can also be administered through a transdermal patch . methods for preparing transdermal patches are known to those skilled in the art . for example , see brown , l ., and langer , r ., transdermal delivery of drugs , annual review of medicine , 39 : 221 - 229 ( 1988 ), incorporated herein by reference . in another embodiment , the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body , such as a controlled release formulation , including implants and microencapsulated delivery systems . biodegradable , biocompatible polymers can be used , such as ethylene vinyl acetate , polyanhydrides , polyglycolic acid , collagen , polyorthoesters , and polylactic acid . methods for preparation of such formulations will be apparent to those skilled in the art . the materials can also be obtained commercially from alza corporation and nova pharmaceuticals , inc . liposomal suspensions may also be pharmaceutically acceptable carriers . these may be prepared according to methods known to those skilled in the art , for example , as described in u . s . pat . no . 4 , 522 , 811 ( which is incorporated herein by reference in its entirety ). for example , liposome formulations may be prepared by dissolving appropriate lipid ( s ) ( such as stearoyl phosphatidyl ethanolamine , stearoyl phosphatidyl choline , arachadoyl phosphatidyl choline , and cholesterol ) in an inorganic solvent that is then evaporated , leaving behind a thin film of dried lipid on the surface of the container . an aqueous solution of the active compound or its monophosphate , diphosphate , and / or triphosphate derivatives are then introduced into the container . the container is then swirled by hand to free lipid material from the sides of the container and to disperse lipid aggregates , thereby forming the liposomal suspension . modifications and variations of the present invention will be obvious to those skilled in the art from the foregoing detailed description of the invention . such modifications and variations are intended to come within the scope of the appended claims .

US-48530795-A

the innovative strategy of treatment described here utilizes configurable microscopic medical payload delivery devices to act as a transport mechanism to deliver medically therapeutic payloads to specific cell types in the body . utilizing probes on the exterior of the configurable microscopic medical payload delivery devices , these transport devices locate specific types of target cells in the body . once a specific target cell is encountered and engaged , the configurable microscopic medical payload delivery device inserts its payload into the target cell . these medically therapeutic payloads are intended to improve cell function or the longevity of the cell or eliminate cells that pose a hazard to the general health of the body . by utilizing configurable microscopic medical payload delivery devices as a delivery system , the efficacy of medications and biologic tools are dramatically improved and there is a resultant significant reduction in the occurrence of unwanted side effects .

the future of medical treatment is the widespread utilization of configurable microscopic medical payload delivery devices ( cmmpdd ) to deliver medications or biologic tools directly to targeted cell types in the body . for purposes of this text a medication includes chemical molecule , elements such as oxygen , sugars such as glucose , and other nutrients , which when purposely delivered to cells in the body produces a beneficial medical effect . for purposes of this text a ‘ biologic tool ’ is a segment of dna , a segment of rna molecule , or a protein molecule such as an enzyme . for purposes of this text an ‘ external envelope ’ refers to the outermost covering of a virus or a virus - like transport device or a configurable microscopic medical payload delivery device . the external envelope may be comprised of a lipid layer , a lipid bilayer , the combination of a lipid layer affixed to a protein matrix or the combination of a lipid bilayer affixed to a protein matrix . for purposes of this text an ‘ internal shell ’ refers to a protein matrix shell nested inside the external envelope . the inner most protein matrix shell is termed the nucleocapsid . the proteins that comprise the nucleocapsid are termed capsid proteins . in the center or core of the nucleocapsid is where the payload is carried . for purposes of this text ‘ external probes ’ are molecular structures that are utilized to locate and engage cell - surface receptors on biologically active cells . external probes are generally comprised of a portion which is anchored or fixed in the external envelope and a second portion that extends out and away from the external envelope . external probes may be comprised solely of a protein structure or an external probe may be a glycoprotein molecule . for purposes of this text ‘ glycoprotein molecule ’ refers to a molecule comprised of a carbohydrate region and a protein region . glycoprotein molecules that act as probes are generally anchored or fixed to a lipid layer utilizing the carbohydrate portion of the molecule as an anchor . the protein portion of the glycoprotein molecule which extends outward and away from the exterior envelope the glycoprotein has been affixed such that the protein region may function as a probe to locate and attach to the cell - surface receptor it was created to engage . the concept of configurable microscopic medical payload delivery devices is modeled after naturally existing viruses . configurable microscopic medical payload delivery devices in general are spherical in shape ; though other shapes may be used as function might warrant the use of a particular shape . the spherical configurable microscopic medical payload delivery devices are comprised of an exterior envelope and one or more inner nested protein shells . a quantity of exterior protein structure probes and / or glycoprotein probes are anchored in the exterior lipid envelope and extend out and away from the exterior lipid envelope . nesting of protein shells refers to progressively smaller diameter shells fitting snugly inside protein shells of a larger diameter . inside the inner most protein shell , referred to as the nucleocapsid , is a cavity referred to as the core of the device . the core of the device is the space where the medically therapeutic payload the device carries is located . configurable microscopic medical payload delivery devices are generated to target certain specific cell types in the body . configurable microscopic medical payload delivery devices target specific cell types by the configuration of probes affixed to the exterior envelope of the cmmpdd . by affixing specific probes to the exterior envelope of the cmmpdd , these probes intended to engage and attach only to specific cell - surface receptors located on certain cell types in the body , the cmmpdd will deliver its payload only to those cell types that express compatible and engagable specific cell - surface receptors . in a similar fashion where the exterior probes of a naturally occurring virus engage specific cell - surface receptors present on the surface of the virus &# 39 ; s host cell and only the designated host cell , the cmmpdd &# 39 ; s exterior probes are configured to engage cell - surface receptors on a specific type of target cell . in this manner , the payload of medication or biologic tools carried by cmmpdd will be delivered only to specific types of cells in the body . the exterior probes on the surface of a cmmpdd will vary as needed so as to effect the cmmpdd delivery of payloads to cell types as needed to effect a medical treatment . the size of configurable microscopic medical payload delivery devices is to depend upon the volume size of the payload the cmmpdd is required to carry and deliver to a target cell . the size of a cmmpdd is dependent upon the diameter of the inner protein matrix shells . the diameter of each inner protein matrix shell is governed by the number of protein molecules utilized to construct the protein matrix shell at the time the protein matrix shell is generated . increasing the number of proteins that comprise a protein matrix shell , increases the diameter of the protein matrix shell . the external lipid envelope wraps around and covers the outermost protein matrix shell . the larger the volume of the core of the cmmpdd , the greater the physical size payload the cmmpdd is able to carry . the size of the configurable microscopic medical payload delivery device is to be the size of cell ( approximately 10 − 4 m in diameter ) or less , generally detectable by a light microscope or , as needed , an electron microscope . the size of the cmmpdd is not to be too large such that it would generate a burden to the body by damaging organ tissues through clogging blood vessels , and the maintaining a small enough size that the cmmpdd can be properly disposed of by the body once the cmmpdd has delivered its payload to its target cell . the dimensions of each type of cmmpdd are to be tailored to the mission of the cmmpdd , which takes into account the type of target cell , the size of the payload that is to be delivered to the target cells and the length of time the cmmpdd may engage the target cell . being enveloped in an external lipid layer , configurable microscopic medical payload delivery devices possess the advantage of having their exterior appear similar to the plasma membrane that acts as an outside covering for the cells that comprise the body . by appearing similar to existing plasma membranes , the cmmpdds appear similar to naturally occurring structures found in the body , affording the cmmpdd the capability to avoid detection by a body &# 39 ; s immune system because the exterior of the cmmpdd mimics the cells comprising the body and the surveillance cells of the immune system find it difficult to discern between the cmmpdd and naturally occurring cells comprising the body . to carry out the process of manufacturing a configurable microscopic medical payload delivery device , a primitive cell such as a stem cell is selected . the reason for utilizing primitive cells such as stems cells as the host cell , is that the cmmpdd acquires its outer envelope from the host cell and the more primitive the host cell , the fewer in number the identifying protein markers are present on the surface of the cmmpdd . the fewer the identifying surface proteins present on the outer envelope of the cmmpdd , the less likely a body &# 39 ; s immune system will identify the cmmpdd as an invader and therefore less likely the body &# 39 ; s immune system will react to the presence of the cmmpdd and reject the cmmpdd by attacking and neutralizing the cmmpdd . stem cells used as host cells to manufacture quantities of cmmpdd product are selected per histocompatibility markers present on their surface . certain histocompatibility markers present on the surface of the final cmmpdd product will be less likely to cause a reaction in a specific patient based on the genetic profile of the patient &# 39 ; s histocompatibility markers . a similar histocompatibility match is done when donor organs are selected to be given to recipients to avoid rejection of the donor organ by the recipient &# 39 ; s immune system . the selected stem cell used to manufacture configurable microscopic medical payload delivery devices goes through several steps of maturation before it is capable of generating therapeutic cmmpdd product . messenger rna would be inserted into the host stem cell that would code for the general physical outer structures of the cmmpdd . messenger rna would be inserted into the host that would generate surface probes that would target the surface receptors on specifically target cells . messenger rna would be inserted into the host that would be used to generate the therapeutic payload . similar to how copies of a naturally occurring virus are produced , assembled and released from a host cell , copies of the cmmpdd would be produced , assembled and released from a host cell . once released from the host cell , the copies of the cmmpdd would be collected , then pooled together to produce a therapeutic dose that would result in a medically beneficial effect . the construction of the configurable microscopic medical payload delivery devices is performed by taking stem cells and inserting modified viral genetic programming into the stem cells . stem cells are chosen as the host cell due to the low number of surface markers , which leads to less antigenicity in configurable microscopic medical payload delivery devices when the configurable microscopic medical payload delivery devices are released by the host cells and wrapped in an outer envelope comprised of the host cells &# 39 ; plasma membrane . the stem cells used as host cells are suspended in a broth of nutrients and are kept at an optimum temperature to govern the rate of production of the cmmpdd product . similar to the natural production of the hepatitis c virus , the configurable microscopic medical payload delivery devices ‘ production genome ’ is introduced into the host stem cells . the configurable microscopic medical payload delivery devices production genome carries genetic instructions to cause the host cells to manufacture the configurable microscopic medical payload delivery devices &# 39 ; outer protein wall , the inner protein matrixes , the surface probes the configurable microscopic medical payload delivery device is to have affixed to its outer envelope and the payload the configurable microscopic medical payload delivery devices are to carry ; and the instructions to assemble the various pieces into the final form of the configurable microscopic medical payload delivery devices and the instructions to activate the budding process . the resultant configurable microscopic medical payload delivery devices are collected from the nutrient broth surrounding the host cells and placed together into doses to be used as a treatment for a medical disease . the ‘ production genome ’ are an array of messenger rnas that are directly translated by the host cell &# 39 ; s internal enzymes . the production genome dictates the characteristics of the final version of the cmmpdd that buds from the host stem cell and is released and is to be utilized as a medical treatment . the production genome is specifically tailored to code for the surface probes that will seek and engage a specific type of target cell . the production genome also carries the instructions to code for the production of the type of payload to be delivered to the specific type of target cell . in the case of a nutrient , the production genome carries the instructions to place a proper amount of nutrient into the cmmpdd . the ‘ production genome ’ varies depending upon the configuration of the cmmpdd to effect a specific medical treatment . the configurable microscopic medical payload delivery device represents a very versatile delivery device . there are an estimated 100 , 000 genes located in the human genome . cmmpdd could be used to deliver any of the 100 , 000 genes to any specific cell type in the body . regarding rnas , cmmpdd could be utilized to deliver to specific cell types messenger rnas , ribosomal rnas , transport rnas , small nuclear rnas . with regards to messenger rnas , there are at least 210 different cell types in the human body and there are at least 30 , 000 different proteins that the human body produces . each of the 30 , 000 proteins are generated by a cell translating one or more mrnas responsible for production of a particular protein . the number of different medical treatment options that are possible as a result of delivering messenger rnas to specific cell types is approximately 6 , 000 , 000 . a wide variety of proteins could be transported to specific cell types by means of cmmpdd . there are numerous presently existing medications and numerous emerging medications that could be delivered directly to specific cell types per the transport capability of cmmpdd . there are a wide variety of nutrients that could be delivered to specific cells by means of cmmpdd . as an example of this method , to treat diabetes mellitus utilizing configurable microscopic medical payload delivery devices to deliver to beta cells messenger rna coded to produce insulin , the following production process is followed in the lab : ( 1 ) human stem cells are selected . ( 2 ) into the selected stem cells is placed the production genome constructed , in this case , specifically as a means to treat diabetes mellitus . the rna production genome contains genetic instructions to cause the host stem cells to manufacture the configurable microscopic medical payload delivery devices &# 39 ; outer protein wall , the inner protein matrix , surface probes to include glycoprotein probes that engage the gpr40 cell - surface receptor present on the surface of beta cells located in the islets of langerhans in the pancreas , and the payload , in this case messenger rna constructed to effect the production of the insulin molecule ; and the biologic instructions to assemble the components into the final form of the configurable microscopic medical payload delivery devices ; and the biologic instructions to activate the budding process . ( 3 ) upon insertion of the rna production genome dedicated to producing a messenger rna coded to produce insulin , into the host stem cells , host stem cells respond by ( i ) simultaneously translating the different segments of the rna production genome to produce the proteins that comprise the exterior protein wall , the inner protein matrix molecules , the surface probes to seek out and engage beta cells , the mrna payload to produce insulin , and ( ii ) decoding the rna instructions to assemble the components into the configurable microscopic medical payload delivery devices . ( 4 ) upon assembly , the configurable microscopic medical payload delivery devices bud through the cell membrane of the host stem cell . ( 5 ) at the time of the budding process , the configurable microscopic medical payload delivery devices acquire an outside envelope wrapped over the outer protein shell , this outer envelope comprised of a portion of the plasma membrane from the host stem cell as the configurable microscopic medical payload delivery devices exit the host cell . ( 6 ) the resultant configurable microscopic medical payload delivery devices are collected from the nutrient broth surrounding the host stem cells . ( 7 ) the configurable microscopic medical payload delivery devices are washed in sterile solvent to remove contaminants . ( 8 ) the configurable microscopic medical payload delivery devices are removed from the sterile solvent and suspended in a hypoallergenic liquid medium . ( 9 ) the configurable microscopic medical payload delivery devices are separated into individual quantities to facilitate storage and delivery to physicians and patients . ( 10 ) the configurable microscopic medical payload delivery devices transported in the hypoallergenic liquid medium is administered to a diabetic patient per injection in a dose that is tailored to receiving patient &# 39 ; s requirement to produce sufficient amount of insulin to control the blood sugar . ( 11 ) upon being injected into the body , the configurable microscopic medical payload delivery devices migrate to the beta cells located in the islets of langerhans by means of the patient &# 39 ; s blood stream . ( 12 ) upon the configurable microscopic medical payload delivery devices reaching the beta cells , the configurable microscopic medical payload delivery devices engage the cell - surface receptors located on the beta cells and insert the payload they carry into the beta cells . the payload , in this case being messenger rna coded to produce insulin , is translated by the cell &# 39 ; s ribosomes to produce insulin molecules . the increase in insulin production by beta cells successfully manages diabetes mellitus . accordingly , the reader will see that the configurable microscopic medical payload delivery device to deliver medically therapeutic payloads to specifically targeted cell types provides advantages over existing art by being a delivery device that ( 1 ) is constructed to seek out and engage specific types of cells by design based on medical need , ( 2 ) is versatile enough in its construction to deliver a wide variety of possible payloads to specific cell types , and ( 3 ) is constructed with a surface envelope that will avoid detection by the innate immune system so as not to activate the immune system to its presence ; for these reasons this represents a new and unique medical delivery device that has never before been recognized nor appreciated by those skilled in the art . although the description above contains specificities , these should not be construed as limiting the scope of the invention but as merely providing illustrations of some of the presently preferred embodiments of the invention . thus the scope of the invention should be determined by the appended claims and their legal equivalents , rather than by the examples given .

US-71536210-A

a method for preventing and / or treating ischaemic and / or iron - related retinal or brain disorders comprising administering an effective amount of ferulic acid , tetramethylpyrazine or their pharmaceutically acceptable salt , ester , solvate , hydrate , analogs , metabolite , enantiomer , isomer , tautomer , amide , derivative or prodrug to a subject . the former diseases comprise retinal ischemia , glaucoma as well as brain ischaemia . the latter ones comprise age - related macular degeneration , intraocular hemorrhage , siderosis oculi , oxidative stress of the retina as well as brain hemorrhage or alzheimer disease . clinically , fa alone or in combination of tmp can be administered systemically , orally , intravitreously , topically , as well as other routes such as periocular , subconjunctival , and intracamera .

acutely raising the intraocular pressure ( iop ) of a rat eye , followed by reperfusion , is known to cause physiological dysfunction , the formation of oxygen free radicals and the death to rgcs and cholinergic amacrine cells as described . the present salicylate trapping assay has indicated that retinal ischemia induced by high iop ( hiop ) for 45 , 60 , and 75 minutes respectively resulted in mild , moderate and severe oxidative stress . the 60 - minute hiop - induced retinal ischemia was presently selected to evaluate the . oh scavenging activity of fa and tmp against moderate oxidative stress . in the present invention , whether fa and tmp are able to protect against retinal ischaemia / experimental glaucoma induced by raising iop for 60 minutes were investigated . overall , this would provide evidence to support the view that therapies unrelated to lowering the iop might be useful and help to improve physiological function , as well as reverse the pathological and molecular changes . the former is assessed in this invention by measuring the attenuation in the reduced erg b - wave amplitude and indexation of the retinal ischaemia ( block , f ., et al . gen pharmacol . 30 ( 3 ): 281 - 7 , 1998 ). the latter is estimated by analyzing alleviation of inner retina damage to , for example , amacrine cells and rgcs ( osborne , n . n ., et al . neurochem int . 29 ( 3 ): 263 - 70 , 1996 ). quantification of changes in the levels of chat / thy - 1 by immunoreactivity and in the mrna levels of thy - 1 was also carried out . in this context , the aim of this invention was to confirm whether fa or tmp can protect retinal neurons against the ischaemic insult and whether the action is elicited via inhibition of . oh formation . as mentioned , the present invention provides an approach for preventing against and managing with retinal ischemia or glaucoma comprising administering to a subject an effective amount of ferulic acid or its pharmaceutically acceptable salt , ester , solvate , hydrate , analogs , metabolite , enantiomer , isomer , tautomer , amide , derivative or prodrug . the ferulic acid or its prodrug reduces the b - wave of electroretinogram ( erg ), inhibits the drastic reduction in the levels of thy - 1 mrna and protein , and inhibits the formation of . oh . another oxidative stress experiments were carried out intraocularly in vivo . an iron particle ( 2 mm , 7 . 5 mg )/ 3 μl feso4 ( 24 mm , 8 mm , and 0 . 8 mm ), or an acrylate chip ( 2 mm )/ saline ( 3 μl ) was intravitreously administered into one eye of a wistar rat , the first two being the experimental treatments and the latter two being the respective controls . the final sham operation control was a needle inserted intra - jocularly and then removed . the aim of the 2nd invention was to evaluate the oxidative stress effect of iron implant ( chronic ) or feso4 ( acute ) and the protective effect against iron - induced oxidative stress of putative neuroprotectants . the latter consisted of , as defined , two active compounds present in the chinese herbal medicine chuan xiong , namely ferulic acid ( fa ) and tetramethylpyrazine ( tmp ). the prevent invention provides a method for preventing or treating retinal or brain disease comprising administering an effective amount of ferulic acid , tetramethylpyrazine or their pharmaceutically acceptable salt , ester , solvate , hydrate , analogs , metabolite , enantiomer , isomer , tautomer , amide , derivative or prodrug to a subject . the said retinal disease comprises retinal ischemia , oxidative stress of the retina , glaucoma , age - related macular degeneration , or ocular hemorrhage , as well as brain ischaemia ( i . e . stroke , infarction typed ). the effective amount of ferulic acid or tetramethylpyrazine is 0 . 1 - 25 nmole / kg . in a preferred embodiment of this invention , the effective amount is 0 . 5 - 5 nmole / kg . in a more preferred embodiment of this invention , the effective amount is 1 - 2 nmole / kg . the said subject is mammalian . in a preferred embodiment of this invention , the subject is human being . the effective amount of ferulic acid or tetramethylpyrazine can be in form of an eye drops , a solution , a syrup , a tonic , dry matter , powder , granules , or a tablet or capsule containing dry matter , powder , or granules . in a preferred embodiment of this invention , the effective amount of ferulic acid or tetramethylpyrazine is in form of an eye drops . the ferulic acid , tetramethylpyrazine or their prodrug inhibits the formation of retinal / barin free radical . the said free radical is hydroxyl radical induced by raising intraocular pressure or cerebral ischaemia . the ferulic acid , tetramethylpyrazine or their prodrug not only inhibits the drastic reduction in the levels of thy - 1 mrna and the thy - 1 immunoreactivity , indexing retinal ganglion cells but also inhibits the drastic reduction in the chat immunoreactivity , an index of amacrine cells . also , it reduces the b - wave of electroretinogram ( erg ). the present invention further provides a method for preventing or treating iron - related disorder comprising administering an effective amount of ferulic acid , tetramethylpyrazine or its pharmaceutically acceptable salt , ester , solvate , hydrate , analogs , metabolite , enantiomer , isomer , tautomer , amide , derivative or prodrug to a subject . the said iron - related disorder is retained intraocular iron , brain hemorrhage ( stroke , hemorrhagic type ) or alzheimer disease . the effective amount of ferulic acid or tetramethylpyrazine is 0 . 1 - 25 nmole / kg . in a preferred embodiment of this invention , the effective amount is 0 . 5 - 5 nmole / kg . in a more preferred embodiment of this invention , the effective amount is 1 - 2 nmole / kg . the said subject is mammalian . in a preferred embodiment of this invention , the subject is human being . the way for administering an effective amount of ferulic acid , tetramethylpyrazine or its prodrug comprises administering an eye drops , a solution , a syrup , a tonic , dry matter , powder , granules , or a tablet or capsule containing dry matter , powder , or granules . in a more embodiment of this invention , the way for administering to a subject is administering an eye drops . the ferulic acid , tetramethylpyrazine or its prodrug inhibits the formation of retinal / barin free radical . the said free radical is hydroxyl radical induced by ferrous iron . also , the ferulic acid or its prodrug inhibits the drastic reduction in the chat immunoreactivity , an index of amacrine cells and reduces the b / a - wave of electroretinogram ( erg ). the methods were utilized to evaluate whether the defined agents could firstly ameliorate the detrimental physiological , biochemical , molecular biological and histopathological ischaemic / siderotic oxidative stress effects and , secondly , to identify the mechanism by which the damaged cells in the ischaemic / siderotic retina were protected . all investigations involving the use of animals conformed to the association for research in vision and opthalmology ( arvo ) statement for the use of animals in opthalmology and vision research and were approved by institutional review committee in taipei veterans general hospital . the wistar rats were bred at the animal house in taipei veterans general hospital where the humidity was 40 %- 60 % and the temperature 19 ° c .- 23 ° c . they were kept on a 12 hour light / dark cycle with 12 to 15 air changes / hour . the animals were provided with food and water ad libitum . wistar rats were anaesthetized with an intramuscular injection of ketamine ( 100 mg / kg ) and xylazine ( 5 mg / kg ). this combination provided sufficient analgesia / anesthesia to allow at least 60 minutes of surgery on the animals and then a rapid recovery . a half dose of both anesthetics was needed for the flash erg recording in rats . the animals &# 39 ; perception of pain / discomfort and vital sign changes were closely monitored during the experimental procedure and recovery period with the body temperature being 36 ° c .- 40 ° c ., the heart rate being 250 - 450 / minute and the respiration rate being 70 - 115 / minute . a humane method listed in schedule 1 of the animals ( scientific procedures acts 1986 ) was used to kill the animals . wistar rats were killed with an overdose ( at least 140 mg / kg ) of sodium pentobarbitone injected into the intraperitoneal cavity . six - week old wistar rats ( body weight : 250 ˜ 500 g ) were anaesthetized with an intramuscular injection of ketamine and xylazine as described above and placed in a stereotaxic frame . the anterior chamber of one eye , with the other serving as control , was cannulated with a 30 - gauge needle connected to a 0 . 9 % saline reservoir ; this caused an increase in iop to 120 mmhg . a whitening of the iris and the fundus of the retina confirmed induction of an ischaemic insult ( block , f ., et al . gen pharmacol . 30 ( 3 ): 281 - 7 , 1997 ). animals were kept normothermic with a heated water jacket after the initial anaesthesia and were placed on a heating pad during recovery ( both at 37 ° c .). effect of 120 - minute retinal ischaemia on 2 , 3 - dihydroxybenzoic acid ( dhba ) formation : in vivo microdialysis rats were anesthetized and placed in a stereotaxic frame . this approach was adapted from louzada - junior et al with further modification . the microdilaysis tube was inserted into the vitreous cavity through the nonvascular pars plana of the sclera ( 0 . 5 mm from the corneal limbus ) after it had been pre - punctured with a 25 - gauge needle . this avoided the problem of bleeding into the vitreous cavity with consequent contamination of vitreous . with the microdialysis probe in position , the whole retina was subjected to hiop - induced ischaemia for 120 minutes . trapping of . oh ( liu , d ., et al . free radic . biol . med . 34 : 64 - 71 , 2003 ; chang , a . y ., et al . exp . neuro . 195 : 40 - 48 , 2005 ) was accomplished by perfusing physiological saline containing 5 mm salicylic acid through a microdialysis probe ( cma / 12 , pc 14 / 01 , cma / microdialysis , stockholm , sweden ) inserted into the vitreous cavity of each rat &# 39 ; s eye before and after the ischaemia . salicylate was infused at the rate of 1 . 1 μl / min using a 1 - ml exmire microsyringe attached to a microdialysis pump ( cma - 100 , cma / microdialysis , stockholm , sweden ). after an equilibration period of 45 min , a stable baseline was obtained . hiop - induced retinal ischaemia was then performed . samples were collected every 15 minutes starting 45 minutes before ischaemia and continuing for the subsequent 120 - minute ischaemia . the microdialysates collected from the microdialysis probe were deposited into polyethylene vials ( microbiotech , stockholm , sweden ) containing 15 μl of 0 . 1 m perchloric acid and were stored at − 70 ° c . until analysis . the formation of . oh was quantified as the increase in 2 , 3 - dhba , which is the hydroxylative product of salicylic acid . since 2 , 5 - dhba can also be produced via enzymatic pathways by virtue of p - 450 , 2 , 3 - dhba is considered to be a specific marker of . oh . eluted microdialysates were directly injected into and 2 , 3 - dhba was analyzed by a high performance liquid chromatograph coupled with an electrochemical detector ( hplc - ec ; model lc - 4c , bioanalytical system inc ., west lafayette , in , usa ). the detector output voltage ( signal ) was monitored using one data system ( csw 32 , dataapex , cosmobio , czech ). samples were eluted at a flow rate of 0 . 8 ml / min . the hplc - ec system was consisted of a cma / 200 refrigerated micro - sampler ( 20 μl loop ), a solvent delivery system ( bas , pm - 80 ) and an alltima c18 column ( 5 - μm particle size ; 250 mm × 4 . 6 mm i . d . ; alltech , ill ., usa ). isocratic separation was achieved at 4 ° c . a high - efficiency pulse damper was incorporated into the system to reduce background noise . the dhba compound was oxidized using a glassy carbon working electrode ( oxidation potential : + 750 mv ; model mf 1000 , bioanalytical system inc ., west lafayette , in , usa ) and an ag / agcl reference electrode ( model mw 2021 , bioanalytical system inc ., west lafayette , in , usa ) with a special thin - layer gasket for the microbore lc - ec . in order to minimize dead volume , the column was connected directly between the micro - sampler and the working electrode . the mobile phase included 1 - heptane sulfonic acid sodium salt ( mw : 202 . 25 ) 3 . 15 g , edta 0 . 15 g , phosphoric acid 4 . 5 ml , triethylamine 5 . 25 ml , acetonitrile 255 ml , distilled water ( added to 1 . 5 liters ), ph 2 . 7 . before use , the mobile phase was filtered through a 0 . 22 μm filter ( millipore , billerica , mass ., usa ) using vacuum assistance . the . oh were quantified using a standard curve , namely 12 , 24 , 36 , 48 and 60 pmoles of 2 , 3 - dhba ( which is photosensitive and can be dissolved in ethanol ). this is the first invention utilizing the defined modified microdialysis system for the measurement of . oh in the rat eye in vivo . the production of . h was measured by establishing a standard curve utilizing different amounts of pure 2 , 3 - dhba ( 12 - 60 pmoles ), for example 12 pmoles in fig1 a . generally , the relevant peak representing 2 , 3 - dhba ( hydroxylative products of salicylic acid ) appeared at 18 ˜ 21 minutes in the hplc chromatogram ( arrows in fig1 left and right ). as shown in fig2 , the basal levels of 2 , 3 - dhba content in the vitreous dialysate samples following the intravitreous perfusion of salicylic acid in the sham operation rats were not different from those in ischaemic rats . as compared with the sham operation group , during the 120 minutes of retinal ischaemia , the levels of 2 , 3 - dhba and therefore . oh gradually increased , reaching a peak at 75 minutes ( fig2 ). as shown in fig1 right , 13 . 1 pmoles of 2 , 3 - dhba was formed from 15 μl of a vitreous dialysate sample at 75 minutes of ischaemia . furthermore , in comparison with the levels of 2 , 3 - dhba ( pmole / 15 μl perfusate ) in the sham operation rats ( n = 4 ; 1 . 6296 ± 0 . 9668 , 1 . 5510 ± 1 . 0459 , 1 . 4728 ± 1 . 1732 , and 1 . 2845 ± 0 . 5806 at 45 , 60 , 75 , and 105 minutes of sham operation , respectively ), the increases were statistically significant at defined 4 time - points of hiop - induced retinal ischaemia ( n = 5 ; 4 . 6155 ± 0 . 6169 , 5 . 4964 ± 0 . 6771 , 13 . 1950 ± 1 . 9699 , and 4 . 0222 ± 0 . 4819 , respectively ). however , in comparison with the levels of 2 , 3 - dhba ( pmole / 15 μl perfusate ) in the sham operation rats ( n = 4 ; 1 . 2881 ± 0 . 9183 ), an increase with no significance was found at 90 minutes of ischaemia ( n = 5 ; 4 . 2770 ± 1 . 3837 ). for electro - physiological , immuohistochemical , and molecular biological studies , drug administration was carried out with pre - administration ( 60 minutes before hiop ) of vehicle ( saline for fa / tmp ), fa ( 0 . 5 or 0 . 1 nmole ), or tmp ( 0 . 5 nmole ). the 60 - minute hiop procedure to induce ischaemic damage was carried out as defined . intra - vitreous injection ( i . v . i .) of 5 μl of each compound was given to the ‘ ischaemic ’ eye of each test rat using a 30 - gauge needle attached to a 20 μl hamilton syringe . as a control , the same volume of vehicle was intravitreously injected into the “ ischaemic ” eye of each control rat . in both cases , the fellow untreated eye acted as a normal control eye . in this case , fa , tmp , or vehicle was applied only to the eye ( ipsilateral ) which received ischaemia . dose - response experiments for fa will also be performed . the animals were first dark adapted for at least 8 hours , anaesthetized as already described and the pupils dilated with 1 % tropicamide and 2 . 5 % phenylephrine . the animal was then placed in a stereotaxic frame and the body temperature maintained at 37 ° c . with an electrical blanket . a platinum wire loop was placed on the corneal surface to act as the recording electrode . a ground electrode was connected to the scruff of the back together with a reference electrode to the tongue of the animal . a strobe was placed 5 cm in front of the animal to provide a stimulus of 0 . 5 hz . fifteen consecutive responses were recorded at two - second intervals and at 10 khz ; the responses were amplified and averaged using an amplifier p511 / regulated power supply rps107 / stimulator ps22 ( grass - telefactor , astro - med . inc ., r1 , usa ). the a - wave amplitude was measured from the baseline to the trough of the a - wave and the b - wave amplitude was measured from the trough of the a - wave to the peak of the b - wave . however , variations were found to exist between the normal b - wave amplitudes in the various animals and therefore , for comparative purposes , the b - wave ratio [ the b - wave amplitude of the ischaemic / sham operation eye compared with that of the contralateral normal ( control ) eye ] was calculated and used in this invention . as shown in the fig3 , in comparison with the pre - ischaemia b - wave ratio baseline ( 0 day ; n = 16 ; 104 . 8553 ± 2 . 6866 ), after i / r ( induced by 60 minutes hiop ), there was a significant reduction in the erg b - wave amplitude in the ischaemic retina pre - treated with vehicle . moreover , the ischaemia - reduced b - wave amplitude was irreversible on 3 rd ( 16 . 4438 ± 4 . 4678 ), 5 th ( 16 . 0258 ± 4 . 7506 ), or 7 th day ( 14 . 8545 ± 4 . 5586 ) after i / r . what is more , as compared with the vehicle - pre - treated rats , the pre - treatment of fa [ 0 . 5 nmoles ( n = 12 ); 0 . 1 nmoles ( n = 12 )] significantly and dose - dependently attenuated the ischaemia - reduced b - wave amplitude ( ratio ) at 3 ( 48 . 3576 ± 3 . 1633 ; 32 . 2402 ± 6 . 3012 ), 5 ( 56 . 4287 ± 6 . 9891 ; 35 . 0948 ± 4 . 6412 ), or 7 days ( 65 . 8600 ± 6 . 0998 ; 47 . 0775 ± 5 . 5396 ) after ischaemia / reperfusion . in contrast , at defined time - points ( 17 . 9250 ± 11 . 7135 at 3 rd day i / r ; 17 . 1500 ± 6 . 8996 at 5 th day i / r ; 20 . 1750 ± 8 . 5027 at 7 th day i / r ), the pre - treatment of tmp ( n = 4 ) only showed a slight and insignificant attenuating effect on the retinal physiological dysfunction caused by retinal ischaemia . on day 7 after retinal ischaemia pre - treated with vehicle or tested compounds , the wistar rats were killed by an overdose of sodium pentobarbitone injected into the peritoneal cavity as mentioned earlier . rat retinas were carefully and rapidly dissected from the eyecups with the aim of completely detaching the sensory retina from the rpes . they were incubated in mg 2 + - free locke &# 39 ; s buffer containing : 154 mm nacl , 5 . 6 mm kcl , 2 . 3 mm cacl 2 , 3 . 6 mm nahco 3 , 5 mm n -[ 2 - hydroxyethyl ] piperazine - n ′-[ 2 - ethanesulfonic acid ] ( hepes ) and 5 . 6 mm d - glucose . the locke &# 39 ; s solution was briefly equilibrated before use with a gas mixture of 95 % o2 and 5 % co 2 at 37 ° c ., ph 7 . 4 . retinal pieces were fixed for a further 45 minutes in 4 % ( w / v ) paraformaldehyde in sodium phosphate buffer ( 0 . 2 m nah 2 po 4 . 2h 2 o ; 0 . 2m na 2 hpo 4 ; ph 7 . 4 ) and then transferred to 30 % sucrose in sodium phosphate buffer for cryosectioning . retinas were orientated and similarly mounted on a metal stand using o . c . t . compound ( merck ltd ) and then promptly frozen with dry ice . in this way , sections from similar areas were produced and thus the retinal sections ( 10 μm ) had approximately the same eccentricity , which allowed direct comparison . the frozen retinal sections created on a microtome ( leica cm1900 , leica instrument ltd , usa ) were placed on gelatin - coated slides and stored at − 20 ° c . until use . further retinal pieces were used for immunohistochemical study and the reverse transcriptase polymerase chain reaction ( rt - pcr ) assay . rats were intracardially perfused first with 0 . 9 % saline and then with 4 % ( w / v ) paraformaldehyde . seven days after sham operation alone or retinal ischaemia pre - treated with vehicle or defined agents , retinal pieces were processed as described . retinal sections were incubated with primary antibody , rabbit anti - chat polyclonal : antibody ( 1 : 500 ; ab143 ; chemicon , temecula , calif ., usa ). after washing with phosphate buffer saline ( pbs ), retinal sections were then incubated with secondary antibody , rhodamine - conjugated affinity purified antibody ( 1 : 50 ; chemicon , temecula , calif ., usa ). the nuclei of the cells were labeled by 4 , 6 - diamidine - 2 - phenylindole dihydrochloride ( dapi ; 30 nm ; molecular probes , eugene , oreg ., usa ). as revealed in fig4 , in the sham operation ( normal ) retina ( a ), chat immunoreactivity is associated with amacrine cell bodies ( short arrows ) found in the inl and rgc layer and with their processes in the ipl , which are seen as a two - band pattern ( long arrows ). retina ischaemia plus reperfusion for 7 days caused an almost complete disappearance of chat immunoreactivity in the ipl and the number of chat immunopositive amacrine cell bodies was drastically decreased ; the immunoreactive changes were not influenced by the pre - treatment of vehicle ( c ). the effect of ischaemia / reperfusion was obviously or partially counteracted by pre - administration of 0 . 5 nmole or 0 . 1 nmole fa , respectively ( e : 2 - band distribution of neuronal processes in the ipl and numerous chat - labeled amacrine cell bodies on either side ; g : a single cell body in the rgc layer and strata pattern in the ipl ); however , 0 . 5 nmole tmp had no effect ( i : loss of neuronal process in the ipl and amacrine cell body on either side ). the retinal cellular nuclei in different groups were counterstained with dapi . the merged images for chat and dapi labeling are shown in pictures b , d , f , h , and j . as indicated by the short arrows , dapi - counterstained cellular nuclei ( blue ) in the normal ( sham ) or fa - treated ischaemic retina were confined within the range of chat - labeled amcrine cells ( red ; b , f and h ). moreover , as shown by the long arrow indicators , chat - labeled 2 - band ( red ; b and f ) or 1 - band neuronal process distribution ( h ) was present in the ipl . this was repeated with another primary antibody , anti - thy - 1 monoclonal antibody ( clone ox - 7 ; santa cruz biotechnology , santa cruz , calif ., usa ; 1 : 100 ), a marker of rgcs , and in this case the secondary antibody was fitc - conjugated anti - mouse immunoglobulin ( igg ) ( jackson immunoresearch , west grove , pa ., usa ; 1 : 100 ). after rinsing several times with pbs , the retinal sections were mounted using glycerol - pbs ( 1 : 1 ). coverslips were placed on the slides , sealed and air dried . the retinal sections were examined using a confocal microscope . an independent scientist within the laboratory was asked to observe the change in the ischaemic retina pre - treated with vehicle or the test compounds in terms of immunolabeling compared to the sham operation ( normal ) retina . as shown in the fig6 , thy - 1 is primarily associated with the rgc dendrites , bodies , and axons . this is illustrated in picture a where thy - 1 immunoreactivity is located over the ipl ( dendrites ) and rgc layer ( axons / cell bodies ). thy - 1 immunolabeling in the normal retinas subjected to sham operation is associated with a broad band in the ganglion cell layer ( gcl ) and ipl ( a ). a thinning of thy - 1 immunoreactivity can be observed 7 days after ischemia / reperfusion in the ischaemic retinas pre - administered with vehicle ( b ). in contrast , in the ischaemic retinas pre - treated with 0 . 5 nmole fa ( c ), the ischaemia - induced reduction in the thickness of thy - 1 immunoreactivity was less pronounced . as revealed in the bar chart ( d ), the vehicle - pre - treated ischaemic retinas ( n = 4 ; ipl + gcl thickness = 34 . 3125 ± 1 . 4156 μm ) showed a significant reduction in the thickness of thy - 1 immunolabeling of the rgc layer plus the ipl by around 29 %, in comparison to the control normal retinas ( sham operation ; n = 4 ; ipl + gcl thickness = 48 . 3750 ± 4 . 1590 m ). this ischaemia - induced reduction was significantly attenuated by around 15 % with the treatment of 0 . 5 nmole fa ( n = 4 ; ipl + gcl thickness = 41 . 62501 . 1250 μm ). the effect of ferulic acid on retinal ischaemia revealed by rt - pcr levels of thy - 1 mrnas present in the retinas were determined using a semi - quantitative rt - pcr technique . these were compared with the mrna levels measured for the house - keeping gene β - actin as an internal standard ( nucci , c ., et al . invest opthalmol v is sci . 48 ( 7 ): 2997 - 3004 , 2007 ). seven days after sham operation alone or retinal ischaemia pre - treated with vehicle or defined chemicals , the rats were killed and the retinas removed and sonicated in trireagent ( as per manufacturer &# 39 ; s instructions ). total retinal rna was isolated and first strand cdna synthesis was performed on 4 μg dnase - treated rna ( nash , m . s ., et al . invest . opthalmol . vis . sci . 40 : 1293 - 8 , 1999 ). the pcr reaction was then initiated by an incubation at 94 ° c . for 10 min and this was followed by the required number of pcr cycles that ensured saturation had not been reached , but were suitable for comparison of cdna levels in each sample ( for β - actin : 24 cycles of 94 ° c ., 40 s ; 55 ° c ., 40 s ; 62 ° c ., 60 s ; for thy - 1 : 34 cycles of 94 ° c ., 40 s ; 48 ° c ., 40 s ; 72 ° c ., 40 s ). cycling was performed using a machine geneamp ® pcr system 9700 ( ab applied biosystems , ca , usa ). after the final cycle was completed , there followed a final incubation of samples at 72 ° c . for 3 min . the pcr oligonucleotide primers were obtained from gibco life technologies ( paisley , scotland , uk ) and were listed at seq id nos : 1 , 2 , 3 , and 4 . the pcr reaction products were separated on 1 . 5 % agarose gels using ethidium bromide for visualization . the relative abundance of each pcr product was determined by analyzing photographs of the gels by sigmascan ( jandel scientific , corte madera , calif .). one - way analysis of variance ( anova ) was performed followed by the tukey multiple - comparison test and a p value less than 0 . 05 was considered significant . in fig5 , the minigel result ( upper picture ) suggests that expression of thy - 1 mrna in the ischaemic retina pre - treated with vehicle ( lane 2 ) was down - regulated as compared with that in the normal retina ( sham operation ; lane 1 ). this down - regulation was inhibited by pre - administration with 0 . 5 ( lane 3 )/ 0 . 1 nmole ferulic acid ( lane 4 ) and 0 . 5 nmole tmp ( lane 5 ). moreover , the inhibitory effect of 0 . 5 nmole fa was the greatest , followed by 0 . 1 nmole fa and then by 0 . 5 nmole tmp . consistent with this , quantitative analysis ( n = 4 ; lower picture ) showed that when the ratio of thy - 1 mrna to β - actin mrna was compared between the normal retina ( sham operation ; 100 . 0000 ± 9 . 1287 ) and the vehicle - pre - treated ischaemic retina ( 33 . 7102 ± 12 . 0285 ) there was a significant reduction by 66 % ( lower panel ). furthermore , the inhibitory effect of 0 . 5 nmole and 0 . 1 nmole fa as well as 0 . 5 nmole tmp on this ischaemia - induced reduction as measured by the thy - 1 mrna / β - actin mrna ratio was consistent with the minigel results and the order of effect by the different chemicals described above ( 85 . 1745 ± 10 . 3177 , 65 . 8968 ± 11 . 9579 , and 46 . 5876 ± 14 . 4476 , respectively ). furthermore , the inhibitory effect of 0 . 5 nmole fa was significant . as shown in the fig7 , at 60 minutes of sham operation or hiop - induced retinal ischaemia , as compared with those from the sham group ( n = 4 ; 1 . 5510 ± 1 . 0459 ), the measurements of the vitreous dialysates from the vehicle - pre - treated ischaemic eyes showed a significant ( around 3 . 5 folds ) increase in the levels of 2 , 3 - dhba (. oh ; n = 4 ; 5 . 4964 ± 0 . 6771 ). importantly , the pre - treatment of 0 . 5 nmole fa revealed a significant ( around 2 folds ) attenuation in the ischameia - evoked increased 2 , 3 - dhba levels ( n = 4 ; 2 . 8574 ± 0 . 7186 ). in contrast , the pre - administration of 0 . 1 nmole fa ( n = 4 ; 3 . 4807 + 0 . 7707 ) or 0 . 5 nmole tmp ( n = 4 ; 4 . 6865 ± 1 . 2661 ) only had a trend with no significance to attenuate ischameia - stimulated increase of . oh production . the wistar rats were anesthetized with an intramuscular injection of ketamine ( 100 mg / kg ) and xylazine ( 5 mg / kg ), and placed in a stereotaxic frame . the chronic model of experimental siderosis was established as follows . through a port punctured by a 20 - gauge intravenous catheter ( 0 . 5 mm from the corneal limbus ), an autoclaved defined iron particle was slowly and carefully implanted into the vitreous cavity of one eye of each experimental rat through the catheter sheath by the catheter inner shaft ( a needle ). the punctured wound was then sutured with sterilized 10 - 0 nylon to keep a close system . similarly ( 0 . 5 mm from the corneal limbus ) and guided by the 20 - gauge intravenous catheter , an autoclaved acrylate chip was implanted into the vitreous cavity of one eye of each control rat . similarly , the acute model of experimental siderosis was set up utilizing various concentrations of iron sulfate with the control group being injected with saline . the animals were kept normothermic with a heated water jacket after anesthesia and were placed on an electrical blanket during recovery ( both set at 37 ° c .). iron toxicity and the formation of . oh were stimulated by an intravitreous application of feso 4 with or without the presence of the test compounds fa and / or tmp . for the dose - response iron toxicity experiments , 24 mm ( 72 nmoles ), 8 mm ( 24 nmoles ) and 0 . 8 mm ( 2 . 4 nmoles ) of feso4 were utilized . to test drug biochemical effects on the oxidative stress caused by the experimental siderosis , an intravitreous injection of fa ( 100 mm ) was carried out 60 minutes before siderosis . in further electro - physiological and immuohistochemical studies , with or without pre - administration of 0 . 5 or 0 . 1 nmoles of fa / tmp , a medium amount of feso 4 ( 25 nmole ) was chosen to induce damage due to such as an oxidative stress so as not to reach the maximal pharmacological effect . the steps of recording of flash erg were described in example 4 . the iron particle , after four weeks intraocular insertion into the rat &# 39 ; s vitreous cavity , was obviously oxidized on retrieval ( fig8 a ). notably , when the defined iron particle was retained intraocularly for 1 day , both a - and the b - wave amplitudes in the siderotic eye were drastically reduced compared to the normal untreated eye ( fig8 b ). specifically , measuring every two hours ( 4 ˜ 24 / 2 ˜ 12 hours ; fig8 c and 8d ) after intravitreous administration of an iron particle ( n = 5 ) or feso4 [ 8 mm ( n = 4 ); 24 mm ( n = 4 )], respectively , the introduction was associated with a significant reduction in the erg b - wave amplitudes compared to either the sham ( n = 3 , data not shown ) or control groups [ acrylate ( n = 4 ), saline treatment ( n = 3 )]. the reduction was greatest with 24 mm feso4 , then with 8 mm , and least with 0 . 8 mm ( fig8 d ). furthermore , when the iron and acrylate chips were compared in terms of b - wave ratio , the signal was reduced to about 65 % at 2 hours ( fig8 c ). similarly , with 8 mm feso4 , the ration was , to a greater extent , reduced to about 45 % at 2 hours ( fig8 d ). compared with the pre - siderotic a - or b - wave amplitude ratio ( 0 day ), the 25 nmole feso4 significantly ( p & lt ; 0 . 05 ) induced a reduction in the a - ( fig1 d and 12e ; n = 5 ) or b - wave ratio ( fig1 d and 14a ; n = 5 ) at 3 and 5 days after iron injection . in a dose - responsive manner , tmp tended to alleviate , and fa significantly alleviated feso 4 induced reduction in the b - wave amplitudes at 3 and 5 days after siderosis compared to the saline - treated animals ( fig1 a ). fa was more effective that tmp . trapping of hydroxyl radicals was accomplished by perfusing physiological saline containing 5 mm salicylic acid through a microdialysis probe ( cma / 12 , pc 14 / 01 , cma / microdialysis , stockholm , sweden ) inserted into the vitreous cavity of a rat eye after intra - vitreous implantation of either an iron or acrylate chip for the defined chronic model and its control . a similar approach was used for the acute model and its control where , iron sulphate or distilled water was intra - vitreously injected with / without the drug to be tested . salicylate was infused at the rate of 1 . 1 μl / min using a 1 - ml exmire microsyringe attached to a microdialysis pump ( cma - 100 , cma / microdialysis , stockholm , sweden ). this was carried out every 15 or 20 minutes starting either 60 or 20 minutes before the implantation / injection and continued for 6 hours or 120 minutes following treatment , respectively . the formation of hydroxyl radicals was quantified as the increase in dhba as the steps described in example 2 . the hydroxyl radicals were quantified by using 8 , 16 , 24 , 32 and 40 pmoles of 2 , 3 - dhba ( which is photosensitive and can be dissolved in ethanol ) as an internal standard . a standard curve was established for 2 , 3 - dhba ( fig9 a and 9d ; for example 16 pmoles of 2 , 3 - dhba at fig9 a , or 40 pmoles at fig9 d ). when the various intravitreous introductions were carried out , 36 pmoles and 91 . 23 pmoles of 2 , 3 - dhba ( fig9 b and 9e ), were formed at 135 or 20 minutes after iron implant or injection ( 8 mm feso4 ), respectively . generally , the peak appeared at 18 ˜ 21 minutes in the hplc chromatogram ( fig9 a , 9 b , 9 d , and 9 e ) representing 2 , 3 - dhba , the hydroxylative products of salicylic acid as defined . furthermore , as compared with the control groups , the intravitreous iron [ particle ( n = 4 ); 8 mm feso4 ( n = 4 ); 24 mm feso4 ( n = 3 )] all significantly enhanced the production of toxic . oh , at many time - points . the level of 2 , 3 - dhba stimulated by iron reached a peak around 300 minutes in the chronic model after a slow rise ( fig9 c ) but peaked at 20 minutes in the acute model after a rapid rise ( fig9 f ). overall , compared to the saline treatment group , the iron - induced 2 , 3 - dhba levels rose dose - dependently and significantly in the acute model from 20 to 120 minutes after siderosis ( fig9 f ). as indicated by fig9 f , fa ( 100 and 20 mm ; the latter not shown ) dose - dependently and significantly decreased the formation of . oh compared with the controls ( receiving 8 mm feso4 alone ). using the same microdialysis system as the ros assay in vivo , each microdialysate was assayed for the presence of derivatized glutamate product by hplc with a fluorescence detector ( fl ; model cma / 280 , cma / microdialysis , stockholm , sweden ). the derivatization reaction was carried out at room temperature . o - phthalaldehyde ( opa ; 27 mg ; fisher scientific , loughborough , uk ) was dissolved in 1 ml methanol , 9 ml 0 . 4 m potassium tetraborate ( mw : 303 . 53 ; borate buffer : 1 . 5 g borate plus pure water adjusted to ph 9 . 5 with 6 m naoh and then added with water to 100 ml ) and 5 μl β - mercaptoethanol ( fisher scientific , loughborough , uk ). the opa stock reagent was covered in foil and stored at − 20 ° c . for 1 month . the opa working solution was prepared each day by diluting 1 ml of the opa stock reagent with 3 ml of potassium tetraborate ( 0 . 4 m ). the derivatized agent ( 20 μl ) was reacted with 20 μl of dialysate or glutamate standard for 2 min before injection onto the analytical column ( yang , c . h . et al ., j chromatogr b biomed sci appl 734 ( 1 ): 1 - 6 , 1999 ). for the hplc separation , the detector output voltage ( signal ) was monitored using one data system ( scientific information service corporation , taiwan ). samples were injected onto the column and eluted at a flow rate of 0 . 8 ml / min . the hplc - fl system consisted of a cma / 200 refrigerated micro - sampler ( 20 μl loop ), a solvent delivery system ( bas , pm - 80 ) and a hypersil ods column ( 5 μm particle size ; 100 × 2 . 1 mm i . d ., thermo fisher scientific , inc ., waltham , mass ., usa ). gradient separation was achieved at 4 ° c . a high - efficiency pulse damper was incorporated into the system to reduce background noise . before use , the mobile phase was filtered through a 0 . 22 μm filter ( millipore ) using vacuum assistance . the linear gradient started with 100 % mobile phase a [ 5 % ( v / v ) acetonitrile , 0 . 55 % acetic acid , 95 % ( v / v ) sodium acetate buffer ( 11 . 5 ml glacial acetate added with 1800 ml deionised h 2 o and titrated with 6 m naoh to reach ph 6 . 0 and then mixed with deionised h 2 o to 2 liter )] for 4 minutes , 100 % mobile phase b [ 90 % ( v / v ) acetonitrile , 0 . 058 % acetic acid , 10 % ( v / v ) sodium acetate buffer ] was reached at time 5 minute and for 5 minute . at time 11 minute , mobile phase a was 100 %. using this protocol , glutamate was successfully separated . external standard solutions , containing 0 , 5 × 10 − 8 , 10 − 7 , 10 − 6 , 2 × 10 − 6 , 10 − 5 , 10 − 4 m standard glutamate ( sigma , st . louis , mo ., usa ), were run before and after each sample group . the glutamate stock solution ( 10 − 2 m ) was prepared in double deionised water and kept at 4 ° c . the detection sensitivity was 10 m . all standard samples and test samples were analyzed in duplicate . this is also the first invention utilizing this method for the rat eye in vivo . a standard curve for glutamate was created ( fig1 a and 10b ). compared to the saline control group ( n = 4 ), in the retina , the presence of feso 4 resulted in a dose - dependent release of glutamate , which was significant at peaks occurring 20 minutes and 40 minutes after siderosis with 24 mm ( n = 6 ) and / or 8 mm feso 4 ( n = 4 ; fig1 c ). the cortical cells to be tested were placed on a cover slip and loaded with calcium ion sensitive dye by incubation with a final concentration of 5 μm of the acetoxymethyl ester form of fura - 2 for 30 min at 37 ° c . in the 1 ml loading buffer . the cover slip was washed three times with buffer containing 150 mm nacl , 5 mm kcl , 2 . 2 mm cacl 2 , 1 mm mgcl 2 , 5 mm glucose , 10 mm hepes , ph 7 . 4 . a micropipette was pulled from a glass capillary by a micropipette puller ( p - 97 , sutter instrument co .) and the tip was polished in a microforge ( o . d . 2 μm , mf - 83 , narishige ). the micropipette was backfilled with the test compound ( 40 μm feso 4 or saline ) using a fine tip syringe . the cover slip was mounted on an inverted microscope to measure single - cell fluorescence . the ejection mircropipette was positioned at a distance of 10 μm from a cell . a short pulse ( 0 . 5s ) of the test compound was then applied to a single cell through the micropipette by a microinjection system ( picospritzer ii , general valve ) with a pressure of 15 psi . the intracellular calcium concentration , [ ca 2 + ] i , was calculated using the ratio between the fluorescence at 340 nm and at 380 nm ( f340 / f380 ). changes in the fluorescence ratio represent the changes in the [ ca 2 + ] i ( yang , d . m ., et al . j microsc 209 : 223 - 227 , 2003 ). a digital calcium imaging assay using the fura - 2 fluorescence system was used to compare the saline treatment group ( n = 5 ) with the 40 μm feso 4 ( n = 5 ) group and there was a significant increase in the [ ca 2 + ] i in the cortical cells ( fig1 b ). fig1 a shows the fura - 2 fluorescence ratios ( f340 / f380 ) for various time points after treatment ; a representative cortical cell was shown after stimulation with feso 4 : saline was found to have no affect on the cell &# 39 ; s [ ca 2 + ] i . the steps of isolation and cryosection of rat retina were described in example 5 . the time course of the experiments involved enucleation of the rat eyes and retrieval of the retinal pieces on day 1 ( western blot ), day 5 ( immunohistochemistry ) and day 28 ( histopathology ) after experimental siderosis with / without each test compound . equivalent amounts of protein were separated on a 12 % sodium dodecyl sulfate - polyacrylamide gel electrophoresis after denaturation and then transferred to nitrocellulose membrane ( nc ; amersham pharmacia biotech ., england ). the membranes were blocked for 2 h at room temperature with blocking buffer ( 150 mm nacl , 25 mm tris - hcl , ph 7 . 6 and 0 . 005 % tween ) containing 5 % skimmed milk . the blots were then incubated overnight , at 4 ° c ., with mouse monoclonal anti - beta - actin antibody , ( 1 : 4000 , zymed laboratories , inc ., san francisco , calif ., usa ), rabbit anti - catalase antibody ( 1 : 8000 , calbiochem , darmstadt , germany ) or rabbit polyclonal anti - magnanese superoxide dismutase ( sod ) antibody ( 1 : 100 ; upstate , lake placid , n . y ., usa ). the primary antibodies were diluted in blocking buffer containing 1 % skimmed milk . after three washes , the membranes were incubated for 2 h at room temperature with horseradish peroxidase conjugated goat anti - mouse igg or anti - rabbit igg ( amersham ; 1 : 25000 dilution in blocking buffer containing 1 % skimmed milk ) and then developed using the enhanced chemiluminescent ( ecl ) analysis system ( supersignal west pico chemiluminescent substrate , pirece , rockford , ill .). an x - ray film was exposed to the ecl treated membrane for 30 - 60 seconds and then developed . for immunohistochemical analysis , rats were intracardially perfused first with 0 . 9 % saline and then with 4 % ( w / v ) paraformaldehyde . a defined period after the experimental siderosis , retinal pieces were processed as described previously ( chao , h . m ., et al ., brain res 904 ( 1 ): 126 - 136 , 2001 ; wood , j . p . m ., et al ., exp eye res 72 : 79 - 86 , 2001 ). in order to observe the expression of ‘ ros - related enzymes ’, retinal sections were incubated with primary antibody : rabbit polyclonal anti - rat manganese sod ( 1 : 100 ; upstate , ny ) or rabbit anti - catalase ( 1 : 1000 ; calbiochem , ca ). after washing with pbs , retinal sections were then incubated with secondary antibody , cy ™ 3 - conjugated donkey anti - rabbit igg ( 1 : 100 ; jackson immunoresearch laboratories , inc , pa , usa ). this was repeated with another primary antibody , rabbit polyclonal anti - rat chat ( 1 : 500 ; ab143 ; chemicon , temecula , calif ., usa ) and in this case the secondary antibody was rhodamine - conjugated affinity purified secondary antibody ( 1 : 50 ; chemicon , temecula , calif ., usa ). the nuclei of the whole number of cells were labeled by dapi ( 30 nm ). after rinsing several times with pbs , retinal sections were mounted using glycerol - pbs ( 1 : 1 ). coverslips were put on the slides , sealed and air dried . the retinal sections were examined using a confocal microscope . an independent scientist within the laboratory was asked to observe the change in the siderotic retina with / without the test compound in terms of labeling compared to the normal retina . based on the western blot results and the immunohistochemical results , it is clear that the intravitreous implanted iron particle activated sod ( fig1 b and 12c ) but not catalase ( data not shown ) as part of the retinal cell &# 39 ; s self - defense anti - oxidative enzyme system . this occurred at 24 hours after siderosis . interestingly , the enhanced sod immunoreactivity was mainly confined to the outer retina , particularly the retinal pigment epithelial ( rpe ) and the outer nuclear layers ( onls ). on the other aspect , the retinal cellular nuclei were co - stained with dapi for the analysis ( fig1 b 1 , b 2 and b 3 ). in the normal retina ( fig1 c 1 ), chat immunoreactivity is specific to cholinergic amacrine neurones in the inner nuclear layer ( inl ) and ganglion cell layer ( gcl ; as indicated by short arrows ) and to their neuronal processes in the inner plexiform layer ( ipl ); these appear as two well - defined bands ( as indicated by long arrows ). iron ( 25 nmole feso 4 for 5 days ) was able to cause loss of 2 - band chat immunoreactivity in the ipl . this was accompanied by a drastic reduction in the number of total dapi - stained retinal nuclei and , in particular , chat positive amacrine neurons in the inl and gcl . these results were similar to the immunopathological findings for retinas subjected to feso 4 with treatment of saline ( fig1 c 2 ). furthermore , similar to the normal retina ( fig1 c 1 ), these iron - induced changes were counteracted by 0 . 5 nmole fa given 60 minutes before the siderosis ( fig1 c 3 ). retinal pieces were prepared as described previously ( chao , h . m ., et al ., brain res 904 ( 1 ): 126 - 136 , 2001 ; wood , j . p . m ., et al ., exp eye res 72 : 79 - 86 , 2001 ). each retinal section was incubated with 200 μl of mixed solution ( 7 . 4 % hcl : 2 % potassium ferrocyanide = 1 : 1 ) for 20 minutes and washed with pbs . it was then incubated with 200 μl of nuclear fast red for 20 minutes and washed with pbs . after rinsing with pbs , the slides of the retinal sections were prepared as described ( chao , h . m ., et al ., brain res 904 ( 1 ): 126 - 136 , 2001 ; wood , j . p . m ., et al ., exp eye res 72 : 79 - 86 , 2001 ) and examined under a light microscope . again , an independent scientist was assigned to assess the alterations in the siderotic retina compared to the normal retina . analysis of the histopathological results shows that 28 days after chronic siderosis by an intravitreous iron particle , obvious retinal disorganization with massive loss of the photoreceptor outer segment was visible ( os ; fig1 a ); this did not occur with the acrylate chip control . these changes would seem to be associated with a wide - spread distribution of ferric irons throughout all retinal layers ( fig1 a ). the unpaired student &# 39 ; s t - test was used when comparing two independent groups and paired student &# 39 ; s t - test when comparing paired groups . one - way analysis of variance ( anova ) was performed to compare three or more independent groups . following the one - way anova , the tukey multiple - comparison test was carried out in order to compare the control column ( e . g . vehicle - treated ischaemic / siderotic rats ) with all other columns ( e . g . fa / tmp - treated ischaemic / siderotic rats ).

US-5342508-A

a vascular access monitoring device for monitoring characteristics of a skin piercing vascular access device comprising : an acoustic sensor operable to detect an acoustic emission created by flow through said vascular access device and produce an electrical signal indicative of said emission ; electronics processing means for processing and monitoring said electrical signal , and to determine , by identifying a change of characteristic of said signal , the possibility that the vascular access device has become dislodged from its normal working position .

referring to fig1 and 2 the device 1 is shown attached to a patient &# 39 ; s arm 2 by means of an attachment strap 3 . the device 1 is located adjacent the entry point of a needle 4 which is connected to a medical apparatus 5 by means of a conduit 6 . the medical apparatus 5 can be used to either add fluid to or remove fluid from the patient via the needle 4 . referring to fig2 a cross section through the device in use is shown . the device 1 is positioned adjacent a patients arm . in use an acoustic sensor 8 picks up acoustic signals generated by the flow of fluid through the needle 4 and also background noise generated , at least in part , by the flow of blood through he veins of the patient . the acoustic sensor 8 can be any type of sensor commonly used in electronic stethoscopes and functions in a similar manner . the sensor 8 generates an electrical signal indicative of the sensed sound and transmits the signal to control electronics 7 . the control electronics 7 contain filters to filter the received signal to remove the majority of unwanted background noise . this may be done with passive low pass electronic filters or a more complex active filtering may be used . where active filtering is required the sensor monitors the background noise and identifies , within the background noise , noise created by the beat of the heart . this noise can then be subtracted from the signal to give a signal representative of flow through the needle . where the needle 4 is being used to remove or to return blood from or to the patient the flow through the needle 4 will be cyclic dependant on the pump being used . the sensor 8 measures the background noise between cycles of the blood pump and the control electronics 7 subtract the background noise from the signal created during the pump cycle . optionally the control electronics 7 can constantly monitor the signal . within the signal they can identify the timing of the sound pulse created by the beat of the heart and the sound pulse created by the cyclic flow driven by the blood pump . in this configuration the control electronics 7 receive a signal from the blood pump identifying when it is cycling enabling the electronics to identify the signal coinciding with the pumping . as the pump cycle and be heartbeat will not be synchronised , and as the sound pulse associated with the pump cycle can easily be identified the remaining sound pulse will be indicative of the heart beat . in the simplest monitoring device 1 these signals are monitored and , as the sensor 8 is adjacent the patients skin above the needle 4 , if the needle 4 becomes dislodged then the pulse identified as coming from flow induced by the blood pump will be lost and an alarm can be raised . the alarm can be raised by any one of a number of known techniques , for example an audible alarm or visual alarm may be incorporated into the device 1 , or alternatively where a wireless or wired communication is included as described below the alarm may be raised on a separate medical apparatus or a dedicated alarm unit . in a more complex device , once the signal representative of the flow through the needle 4 has been identified , it can be monitored for changes in amplitude or frequency which may indicate an occlusion or partial occlusion , the occlusion or partial occlusion resulting in a reduced flow through the needle 4 and a corresponding change in signal . in this configuration the device 1 is powered by a battery 11 which is encapsulated within the device 1 . the battery may be recharged by an inductive recharger . in this way the battery can be recharged without needing to open the device to remove the battery . furthermore , as the device is totally encapsulated it is easy to clean and / or sanitise between uses . the device 1 further comprises a wireless communications module 10 by which the device can wirelessly communication with the control system of a medical apparatus . in this manner it can receive the signals from the blood pump such that it can perform the identification and separation of noise associated with flow through the needle 4 and background noise described above . furthermore , in this way , if the needle 4 becomes dislodged from the patient , the device 1 senses it and sends a signal to the medical apparatus 5 to which the needle 4 is connected . the apparatus 5 can then take appropriate action , for example it may sound a warning and / or may stop the medical process using the needle 4 . for example , if the needle 4 is being used to remove blood from the patient then if the needle 4 becomes dislodged then the medical apparatus can sound a warning to alert a nurse and can also stop the medical process . referring to fig3 an alternative arrangement of a device according to the invention is shown . in this arrangement two devices 1 a , 1 b are used . device 1 a is positioned on the patients arm adjacent the vascular access point 12 and sensor 1 b is positioned adjacent the patients arm at a position discreet from the vascular access point . both devices are substantially as described with reference to fig2 , except in so far as they communicate wirelessly with one another so that the signals can be processed together . in addition wireless communication between the sensors can be used periodically or constantly to ensure that the system is functioning correctly . in this arrangement the signal generated by device 1 a will contain two signals superimposed on top of one another , the signal representative of sound caused by the flow of fluid through the needle , and the signal representative of background noise including that associated with heartbeat . the signal generated by device 1 b will contain the signal representative of background noise . the signal from device 1 b is communicated to the control electronics of device 1 a by wireless communication means . by subtracting one signal from the other a clean signal representative of the noise created by flow through the needle 4 can be achieved . this signal can then be monitored for any changes in amplitude , frequency or frequency distribution that may indicate that the needle 4 has become dislodged from its position , or that the flow path from the needle 4 has become at least partially occluded . in this arrangement as a cleaned signal is being monitored for changes it is not necessary for the control electronics of the sensor to receive data from the pump . depending on the characteristic of the signal being monitored , the control electronics 7 may perform functions commonly used in the field of signal processing , for example fourier transforms , to the signal to best isolate and identify changes . such signal processing is common to those skilled in the art of signal electronics . referring to fig4 an arrangement of the apparatus is shown providing the arrangement described in relation to fig1 and 2 in combination with an ultrasonic needle monitoring system . by this method having two independent needle monitoring methods the two systems can be verified against one another to confirm the presence or displacement of the needle . in addition to the details described above , the device further includes a thin gel pack 13 which comprises an ultrasonic coupling gel in a thin flexible plastic pouch . the gel pack 13 conforms to the surface of the patient &# 39 ; s arm 2 and to the device 1 such that the space between the patients arm 2 and the device 1 is substantially filled with ultrasonic coupling gel . in use an ultrasonic transceiver 14 transmits an ultrasonic pulse through the gel pack and into the patient &# 39 ; s arm 2 . the gel pack 13 has walls made of a flexible membrane that has a thickness less than one third of the wavelength of the ultrasound transmitted from the device and the composition of the gel is such that it has an optimum transmission frequency substantially that of the transmission frequency of the device . the patient &# 39 ; s arm will absorb some of the ultrasonic signal and reflect some of the signal . the transceiver also receives the reflected signal . the transceiver is connected to control electronics 7 a which control the transmitter to transmit ultrasound and receive signals indicative of the received reflected signal from the transceiver 14 . the control electronics then compare the received signal , either to the transmitted signal or to a model signal stores in storage means 15 connected to the control electronics 7 a to detect if it shows characteristics relating to absorption and reflection by the patient &# 39 ; s arm 2 , or if it also shows characteristics relating to reflection by a needle 4 . signals relating to a needle 4 will be clearly distinguishable from signals relating to just the patients body as a needle 4 , in particular a metal needle as is commonly used , will reflect a much greater amount of ultrasound . the acoustic sensor 8 , is designed not to receive sound frequencies in the ultrasound spectrum such that the ultrasonic transducer does not interfere with the acoustic needle monitoring . referring to fig5 and 6 , signal comparisons typical of those use in the device are shown . fig5 shows a typical ultrasonic pulse emitted by the device and fig6 shows two signals , one relating to the reflection of ultrasound by the patients body and the other showing how this changes when a metal needle is present . the control electronics can compare the shape of the received signals and easily identify whether there is a needle present or not . other embodiments will be obvious to the person skilled in the art and are included in this invention , for example , the wireless connection could be replaced with a wires connection and the battery could be replaced with a connection to a remote power source .

US-201013393438-A

a model racing toy including a convertible model transport vehicle , a model vehicle and model vehicle accessories . the model transport vehicle may be converted by means of a push button or other such device into a model racing pit stop . the convertible transport includes a storable deployment ramp which is ejected when the conversion button is pressed , allowing the model vehicle to move from an exemplary position atop the model transport vehicle . the vehicle is equipped with activation points , motors and a speaker . the activation points compose a variety of different switches , designed to resemble vehicle parts . when a specific activation point is activated , it triggers a series of actions by the motors and speaker , prompting the user to make certain repairs . the successful making of repairs activates other activation points , which provide affirming messages and vehicle motion to simulate the continuance of a race after repair has been made .

a model toy racing set 20 constructed in accordance with the invention is shown in fig1 . model vehicle 24 is positioned atop model transport vehicle 28 , in an exemplary transport position , held in place by transport wing 36 and wheel barrier 32 , which is best shown in fig2 . racing pit door 40 is shown in its closed position in fig1 . as shown in fig2 activation of functionalities and conversion of the model transport vehicle 28 can be accomplished by pressing push button 44 , which causes the downward opening of racing pit door 32 by rotation around pit door hinge 48 . deployment ramp 52 is also deployed by the activation of the push button 44 , sliding out from the interior of the transport vehicle 28 . the deployment ramp 52 serves to allow the model vehicle 24 to move from the surrounding ground 56 to its exemplary transport position atop model transport 28 in a smooth rolling motion , that is , as a real vehicle might move . fig2 also shows a number of various model vehicle accessories 60 located behind racing pit door 40 that appear upon pressing push button 44 , which may be used with this embodiment . the model vehicle accessories 60 shown in fig2 can include , for example , model spare tires 64 , model replacement engine 88 , model gas can 72 , model headlights 93 and 95 and model hex - wrench 76 . in the present embodiment , the model vehicle accessories 60 are coupled to various attachment points ( not shown ). in this preferred embodiment , attachment is accomplished by a plastic peg attachment point that fits into a corresponding hole in each model vehicle accessory . numerous such attachment schemes , however , are possible and will be ascertainable to those of skill in the art . fig3 further illustrates the model vehicle 24 and the various model vehicle accessories 60 . model vehicle wing 80 can be removed by loosening hex bolt 84 , which can be accomplished with hex - wrench 76 ( shown in fig2 ). the model replacement engine 88 can be removed by lifting model vehicle hood 92 by means of hood catch 96 , and pulling the replacement engine 88 from within the engine compartment ( not shown ). the replacement engine 88 can be attached through the above described attachment scheme used with the model vehicle accessories 60 . in this embodiment , model vehicle front tires 100 can be removed by loosening the hex bolt 104 , by means of the hex wrench 76 ( shown in fig2 ). fig3 also shows model activation points 108 , 112 , 116 , 120 , 124 and 125 of the model vehicle 24 of the present embodiment . these various activation points , which also may be referred to as part of overall activation systems , can be activated by the user to invoke functions of the model vehicle 24 . for example , the model vehicle activation points 108 , 112 and 116 are buttons , which can be depressed . the activation points 120 and 124 are hex bolt sensors which are activated by the loosening of the hex bolts 84 and 104 , respectively . the model vehicle 24 can also have activation points 125 for the headlights 93 and 95 , respectively . another activation point 126 present in the interior of the model vehicle hood space is activated by the removal of the replacement engine 88 . in one embodiment of the invention , activation points 120 and 124 resemble actual vehicle components , but it is also possible to have such points resemble other items or to resemble words that describe the component that is supposed to be manipulated by the user . numerous types of such activation points are possible and will be readily ascertainable to those of skill in the art . fig4 shows an interior vertical cross section of the transport vehicle 28 , along the 4 — 4 axis as shown in fig1 . the push button 44 serves as a means to initiate the conversion from a transport vehicle to a racing pit environment ( see fig1 and 2 for reference ). the function of push button 44 could be accomplished by any of a variety of means ascertainable to those of skill in the art , including levers , retractable buttons , dials , slideable blocks , pins , wheels , rods , pulleys . electronic or motor means are also possible . in this embodiment , depressing the push button 44 forces pin 132 downward , in turn deforming member 136 . deformation of member 136 causes catch 140 to disengage , thus allowing the release of spring 144 . the spring 144 is an example of an actuating device , which may be used in conjunction with the embodiments to facilitate conversion to a model racing pit . other actuating devices can include , for example , a deformed rod or member with good elastic memory , a motor or a chemical or electrochemically expansive material . the spring 144 thus releases and expands against interior horizontal edge 148 of the deployment ramp 52 , shown in its fully closed position . when in the fully closed position , the deployment ramp 52 is completely within the model transport vehicle 28 , such that only the exterior angled edge 152 of the deployment ramp 52 is visible . the deployment ramp 52 is slideably attached to deployment ramp exit cuff 156 of the model transport vehicle 28 , and through the release of the spring 144 , is forcibly ejected through the exit cuff 156 . stop 160 serves to prevent the deployment ramp 52 from becoming detached from the transport vehicle 28 upon conversion , by breaking against another stop 164 . as the deployment ramp 52 exits the transport vehicle 28 , gravity pulls the leading edge downward , causing the deployment ramp 52 to rotate outward and into the fully open position shown in fig2 . when the deployment ramp 52 is in its fully open position ( as shown in fig2 ), it may be reset to its fully closed position ( as shown in fig1 and 4 ) by pressing on the exterior angled edge 152 until the interior horizontal edge 148 recompresses the spring 144 and the catch 140 re - engages . the catch 168 is a minimal friction catch , serving to hold the deployment ramp 52 in place against the force of gravity should the transport vehicle 28 be lifted and rotated . fig5 shows a vertical cross section of the transport vehicle 28 , taken along the 5 — 5 axis shown in fig4 . when the push button 44 is pressed , the deforming member 136 presses on hinged bar member 172 , which rotates in the direction of the arrows , working against spring 176 . this action serves to release catch 180 . hinge 184 is placed slightly to the interior of the racing pit door 40 , allowing weight on the interior side of the racing pit door 40 to produce an opening torque around hinge 184 . fig6 is a horizontal cross section taken along the 6 — 6 axis as shown in fig3 of the model vehicle 24 . switch 188 is an on - off - demo switch , serving as the primary power connection switch . the activation points 108 and 112 are “ race begin ” and “ repair begin ” switches , respectively . these activation points 108 and 112 are shown as button devices in the preferred embodiment . the activation point 116 is a refuel switch , also shown as a button . the activation point 120 is the stabilizing wing switch , shown as a hex - bolt release detector . this wing switch closes when the stabilizing wing hex bolt 84 has been loosened to a sufficient degree . the activation points 124 are wheel bolt switches , shown as a hex bolt release detectors , which close when wheel hex bolts 104 are loosened to a sufficient degree directly over the activation point 124 . an activation point 126 for the engine switch is closed when the engine is sufficiently loosened from its attachment points . the activation points of the present embodiment have been designated to simulate vehicle components . for example , the activation points 120 and 124 appear from the outside to be actual bolts . the activation point 116 appears in the position where a vehicle &# 39 ; s fuel tank opening would normally appear . the activation point for the engine is not visible , being located underneath the model vehicle replacement engine 88 . also shown in fig6 are a number of mechanisms for the physical operation of the model vehicle 24 of the present embodiment . actuating motor 188 serves to provide drive to rear wheels 191 ( see fig3 ) when activated . actuator 192 as shown in fig6 serves to provide vibrations to the model vehicle 24 , simulating the vibration of a gasoline engine . speaker 196 is used to generate race car sounds , such as engine idling , engine revving , gear shifting , engine malfunction , tire skidding and driver instructions . circuit board 200 controls the logical flow of these operations and regulates voltage to mechanisms 188 , 192 and 196 . further details will be provided hereinafter . the mechanisms 188 , 192 and 196 are employed when the user activates , for example , one of the activation points 108 , 112 , 116 , 120 and 124 . when activation occurs , for example , pressing the button 108 , the present embodiment performs a series of functions : the race begin switch causes the speaker mechanism 196 to emit engine revving sounds , the mechanism 192 emits vibrations , and after a short delay , the actuating motor mechanism 188 provides drive to the rear wheels 191 . pressing the activation point 112 ( the repair begins switch ) causes speaker mechanism 196 to emit high rpm engine noises , followed by one of four malfunction noises corresponding to engine failure , empty fuel tank , loose stabilizing wing or flat front tires . the driver &# 39 ; s voice then instructs the user to return to the pit to make suitable repairs . it will be understood that other malfunction noises and responses can be implemented in other embodiments . in the case of engine failure , the user must remove the replacement engine 88 to a sufficient extent to activate an engine activation point ( the engine switch ). in case of an empty fuel tank , the user must actuate the activation button 116 , preferably using the model gas can 72 . if the tires are flat , the user must loosen the hex bolt 104 , preferably using the hex wrench 76 , to such an extent that the activation points 124 and 131 ( the tire switches ) are activated . if the vehicle wing 80 is loose , the user must loosen stabilizing the wing hex bolt 84 to such an extent that the activation point 120 ( the stabilizing wing switch ) is activated . if the user performs the correct operation successfully , the driver speaks an encouraging message , and motor mechanism 188 is activated , causing the model vehicle 24 to move , according to engine acceleration sounds provided through speaker device 196 . if the user fails to make the correct repair within a certain time period , the driver speaks a warm but failure message , and the sequence is reset of course , any imaginable variety of activation switches and accompanying functionalities can be used , according to the functions desired to be simulated by the manufacturer . fig7 is a logical diagram of an exemplary circuit board 200 of the preferred embodiment . this is in addition to connections to the various devices 108 , 112 , 116 , 120 , 124 , 188 , 192 , 196 , and the like which are to be found in the logical presentation of circuit board 200 , but are not entirely physically located on circuit board 200 . the diagram of fig7 can be roughly divided into four subcircuits . subcircuit 204 consists of an integrated circuit , which provides memory and processing for pre - programmed functions via execution of one or more programs stored in memory . the subcircuit 204 includes a microcontroller 230 for processing the various signals in the system . in one embodiment of the invention , the microcontroller 230 is a w562s0 microcontroller , produced by winbond electronics corp . it is possible , however , for other brands and varieties of microcontrollers to be used . such chips are readily available , and can also be manufactured by those of ordinary skill in the art to a manufacturer &# 39 ; s specification . subcircuit 204 provides episodic voltage control through various transistors to the three other subcircuits , depending on the state of inputs 208 , 212 , 216 , 220 , 224 , and 231 ( corresponding to the actuation of the activation points 108 , 112 , 116 , 120 , 124 , and 131 , respectively ). subcircuit 214 supplies current and provides cycle control for the speaker device 196 . subcircuit 218 periodically supplies current to the actuating motor device 188 depending on the output of the subcircuit 204 . subcircuit 222 provides current to actuator 192 to induce vibration . while exemplary embodiments have been described and illustrated , numerous departures therefrom can be contemplated by persons skilled in the art . for example , the model vehicle might include a pre - programmed race course or a variety of different repair features . therefore , the present invention is not limited to the foregoing description but only by the scope and spirit of the appended claims .

US-62826800-A

an inhibitor of wnt / β - catenin signaling for use in the treatment and / or prevention of a pathology having vascular malformation is provided . the inhibitor may be a small molecule , a protein , a peptide or an antisense nucleic acid . the invention also relates to pharmaceutical compositions and to method of treatment .

the ccm3 - flox / flox mice were generated at taconicartemis ( koeln , germany ). two p - lox sequences were inserted that flank exons 4 and 5 of the murine ccm3 gene , to produce a loss - of - function mutation after excision by ore recombinase . these ccm3 - flox / flox mice were bred with cdh5 ( pac )- creert2 mice ( wang et al , 2010 ) for tamoxifen - inducible endothelial - cell - specific expression of ore - recombinase and ccm3 gene recombination . the ccm3 - flox / flox - cdh5 ( pac )- creert2 mice were further bred with bat - gal mice ( maretto et al , 2003 ) to monitor the activation of b - catenin transcription signaling , and with rosa 26 - enhanced green fluorescent protein ( eyfp ) ( rosa26eyfp ) mice ( srinivas et al , 2001 ) to monitor the expression of ore - recombinase through the expression of eyfp . tamoxifen ( sigma ) was dissolved in corn oil and 10 % ethanol ( at 10 mg / ml ), and then diluted 1 : 5 in corn oil before single intragastric administration to dpn 1 - 2 pups ( 35 mg / kg body weight ), as described in 14 . the control ( wild - type ) mice included ccm3 - flox / flox - cdh5 ( pac )- creert2 - bat - gal mice treated with the vehicle used to dissolve the tamoxifen ( corn oil plus 2 % ethanol ), and ccm3 +/+ - cdh5 ( pac )- creert2 - bat - gal mice treated with tamoxifen . ccm1 - ecko and ccm2 - ecko have been obtained from ccm1 - flox / flox and ccm2 - flox / flox mice as described in details above for ccm3 - ecko mice , see also maddaluno et al , 2013 and boulday et al , 2011 . the following probes were used for the mouse genotyping : wild - type ccm3 allele : 5 ′ gat agg aat tat tao tgc cct tcc 3 ′ ( seq id no . 1 ), 5 ′ gao aag aaa gca ctg ttg acc 3 ′ ( seq id no . 2 ); deleted ccm3 gene after recombination induced by cre recombinase : 5 ′ gat agg aat tat tao tgc cct tcc 3 ′ ( seq id no . 3 ), 5 ′ gct acc aat cag ctt ctt agc cc 3 ′ ( seq id no . 4 ), cdh5 ( pac )- creert2 gene : 5 ′ cca aaa ttt gcc tgc att acc ggt cga tgc 3 ′ ( seq id no . 5 ), 5 ′ atc cag gtt acg gat ata gt 3 ′ ( seq id no . 6 ); bat - gal gene : 5 ′ cgg tga tgg tgc tgc gtt gga 3 ′ ( seq id no . 7 ), 5 ′ acc acc gca cga tag aga ttc 3 ′ ( seq id no . 8 ); rosa 26 eyfp gene : 5 ′ gcg aag agt ttg tcc tca acc 3 ′ ( seq id no . 9 ), 5 ′ gga gcg gga gaa atg gat atg 3 ′ ( seq id no . 10 ), 5 ′ aaa gtc gct ctg agt tgt tat 3 ′ ( seq id no . 11 ). sulindac sulfide ( sigma ) and sulindac sulfone ( sigma ) were both dissolved in dmso and further diluted 1 : 50 in corn oil . they were administered intragastrically , daily ( 30 mg / kg body weight ), starting one day after the induction of recombination . the control mice were treated in parallel with vehicle only ( corn oil plus 2 % dmso ). the inventors did not observe either increased bleeding from vascular lesions or mortality in drug - treated ccm3 - ecko mice in comparison to vehicle - treated ones . drugs were added to confluent cells for 48 h before the indicated assays . final concentrations for iwp2 and iwp12 , both from sigma - aldrich , were : 0 . 5 , 2 , 5 dm . drugs were dissolved in dmso , control treatment ( vehicle ) was 0 . 1 % dmso final concentration , as for drug treatment . murine recombinant dkk1 ( r & amp ; d ) was 0 . 5 dm on cells . murine recombinant wnt3a ( r & amp ; d ) was 5 ng / ml for the time indicated in the figure legends . in vitro isolation , culture and recombination of endothelial cells from the ccm3 - flox / flox mice endothelial cells from the ccm3 - flox / flox mice ( 8 - 10 weeks old ) were isolated from the brain as previously described 13 . recombination of the floxed ccm3 gene was induced by treating the cells at culture day 1 with the adenocre viral vector , as previously described 59 . the control endothelial cells were an aliquot of the same endothelial cell preparation treated with adenogfp , instead of adenocre . the cells were then maintained in culture for up to a further 7 days before analysis , as described in the main text . drug treatments were for 48 h before the processing of the cells . in some experiments , endothelial cell lines from the lungs of ccm3 - flox / flox mice ( 8 - 10 weeks old ) were immortalized in culture through retroviral expression of polyoma middle t gene 60 . ablation of the ccm3 gene was achieved with the adenocre viral vector ( with adenogfp in the control cells ). these cells were then maintained in culture for up to 25 passages without detectable changes in the effects of this ccm3 ablation . these endothelial cell lines responded to the absence of ccm3 in a comparable way to both primary cultures of brain endothelial cells in vitro and brain endothelial cells in vivo . drugs were added to confluent cells for 48 h before the indicated assays . the final concentrations used were : 135 mm sulindac sulfide , 125 mm sulindac sulfone , 200 mm silibinin , 40 mm curcumin , 40 mm resveratrol , and 250 mm salinomycin ( all from sigma - aldrich ). as all of these were dissolved in dmso , control treatment ( vehicle ) was 0 . 1 % dmso final concentration , as for drug treatment . immuno - staining for fluorescence microscopy of brain sections , retinas and cells in culture brains and eyes from mice pups were fixed in 3 % paraformaldehyde immediately after dissection , and this fixing was continued overnight at 4 ° c . the retinas were dissected from the eyes just before staining as the whole mount . fixed brains were embedded in 4 % low - melting - point agarose and sectioned along the sagittal axis ( 150 mm ) using a vibratome ( 1000 plus , the vibratome company , st . louis , mo ., us ). brain sections and retinas were stained as floating samples in 12 - well and 96 - well plates , respectively . they were blocked overnight at 4 ° c . in 1 % fish - skin gelatin with 0 . 5 % triton x100 and 5 % donkey serum in phosphate - buffered saline ( pbs ) containing 0 . 01 % thimerosal . the samples were incubated overnight at 4 ° c . with the primary antibodies diluted in 1 % fish - skin gelatin with 0 . 25 % triton x100 in pbs containing 0 . 01 % thimerosal . following washing with 0 . 1 % triton x100 in pbs , the secondary antibodies were added for 4 h at room temperature in 1 % fish - skin gelatin with 0 . 25 % triton x100 in pbs containing 0 . 01 % thimerosal . the incubation with dapi was in pbs for 4 h , which was followed by several washes in pbs , post - fixating with 3 % paraformaldehyde for 5 min at room temperature , and further washes in pbs . the brain sections were mounted in vectashield with dapi , and the coverslips fixed with nail varnish ; the retinas were mounted in prolong gold with dapi . cells cultured in vitro were fixed and stained as described previously 46 . the following antibodies were used : anti - pecam ( hamster ; mab1398z , millipore ); anti - b - galactosidase ( chicken ; ab9361 , abcam ); anti - ve - cadherin ( rat monoclonal ; 550548 , bd biosciences ); anti - ve - cadherin ( goat ; sc - 6458 , santa cruz ); anti - active - b - catenin ( mouse monoclonal clone 8e7 ) dephosphorylated on ser37 and thr41 , millipore ); anti - total - b - catenin ( mouse monoclonal ; cell signaling ); anti - s100a4 ( rabbit ; 07 - 2274 , millipore ); anti - klf4 ( goat ; af3158 , r & amp ; d ); anti - cd44 ( rat ; 553131 , bd biosciences ); anti - id1 ( rabbit ; sc - 488 , santa cruz ); anti - asma ( mouse monoclonal ; f3777 , sigma ); anti - gfp ( rabbit ; a - 6455 , invitrogen ); anti - podocalyxin ( goat ; af1556 , r & amp ; d ); anti - phospho - histone h3 ( rabbit ; ab51776 , millipore ); anti - ccm3 ( rabbit ; eurogentec ); anti - p - smad1 ( rabbit ; 9516 , cell signaling ); anti - endomucin ( rabbit ; sc - 65495 , santa cruz ); anti - α - tubulin ( mouse monoclonal ; t9026 , sigma ). biotin - conjugated isolectin b4 ( vector lab ), revealed with alexa555 - conjugated streptavidin ( molecular probes ), was also used to identify endothelial cells in retina and brain sections . the secondary antibodies for immunofluorescence were anti - alexa448 and anti - alexa555 , and cy3 - conjugated antibodies raised in the donkey against immunoglobulin of the appropriate animal species ( molecular probes or jackson laboratories ). the secondary antibodies for western blotting were hrp - linked anti - mouse , anti - rat and anti - rabbit antibodies ( cell signaling ), and hrp - linked anti - goat antibodies ( promega ) rna extraction was performed with rneasy kits ( 74106 ; promega ). the rna ( 1 μg ) was reverse transcribed with random hexamers ( high capacity cdna archive kits ; applied biosystems ). the cdna was amplified with taqman gene expression assays ( applied biosystems ) using a 7900 ht thermocycler ( abi / prism ). for each sample , the expression levels were determined with the comparative threshold cycle ( ct ) method , and normalized to the housekeeping genes encoding 18s and glyceraldehyde - 3 - phosphate dehydrogenase ( gapdh ). for amplification , the following probes ( applied biosystems ) that have been validated to recognize the mouse transcripts in rtpcr were used : axin2 , nkd1 , lef1 , ccnd1 , cmyc - klf4 , ly6a , s100a4 , id1 , cdh2 , acta2 , cd44 . the probes to identify the ccm3 mrna transcript were custom designed , as : forward , cgagtccctccttcgtatgg ( seq id no . 12 ); reverse , gctctggccgctcaatca ( seq id no . 13 ); reporter sequence , ctgatgacgtagaagagtaca ( seq id no . 14 ). for the detection of b - catenin - dependent transcription of a reporter target , the top - flash plasmid was used ( 0 . 3 mg / cm 2 cell culture area ), which contains seven tcf / lef binding sites that control the transcription of firefly luciferase ( lluis et al , 2008 ). this was transfected into the endothelial cells from lung using lipofectamine 2000 , according to the manufacturer instructions ( invitrogen ). the pcmv plasmid for constitutive expression of b - gal was co - transfected ( 0 . 1 mg / cm 2 ), for normalization of luciferase expression over transfection efficiency . as the negative control , a fop - flash plasmid was used that contained six mutated ( i . e ., inactive ) tcf / lef sites upstream of a minimal promoter and the firefly luciferase gene ( 0 . 3 mg / cm 2 ). this was co - transfected with the b - gal plasmid , for normalization , as above . the dual - light reporter gene assay system ( applied biosystems ) for the combined detection of firefly luciferase and b - gal was used . the cell extraction and detection of chemiluminescence ( glomax 96 microplate luminometer ; promega ) was carried out according to the manufacture instructions . standard procedures were used to extract and analyze the protein content by western blotting and immunoprecipitation 46 . nuclear fractionation was as described previously 62 . for the classification and counting of lesions , entire brains from dpn 9 littermate pups were sectioned and immunostained for pecam as described above and in the methods . sections were then examined under wide - field fluorescence microscopy ( 10 × and 20 ×). lesions were classified as described in 63 as mulberry ( multiple cavernae , group of more than two contiguous cavernae ), single caverna ( single dilated vessel with maximal diameter accommodating more than 25 red blood cells ), or telangiectases , tortuous small vessels with abnormally dilated lumen ). the total numbers of lesions were calculated by summing all of the types of lesions . as the sections were 150 - mm thick , a correction was applied to the number of mulberry lesions , which can span two sections . therefore , the number of mulberry lesions was divided by 2 . 5 . the lesions were counted and classified independently by two observers who were blinded to the treatments . the maximal diameter of the mulberry lesions and single cavernae was used for statistical comparison . ve - cadherin expression was silenced using sirna oligos to murine ve - cadherin ( smart pool , thermo scientific ; target sequences : agacagaccccaaacguaa ( seq id no . 15 ), gaaaauggcuugucgaauu ( seq id no . 16 ); agggaaacaucuauaacga ( seq id no . 17 ); ccgccaacaucacggucaa ( seq id no . 18 )), respectively , and lipofectamine 2000 for transduction as described in lampugnani et al , 2010 . non - parametric wilcoxon signed - rank tests were used to determine the statistical significance of the lesion burdens after the pharmacological treatments in vivo . student &# 39 ; s two - tailed non - paired t - tests were used to determine the statistical significance in the other in vitro and in - vivo analyses . the significance level was set at p & lt ; 0 . 05 . transcription activity of b - catenin is enhanced in vivo in endothelial cells of endothelial - cell - specific ccm3 - knockout mice the in vivo mouse system presented here was initially generated through the cross of ccm3 - floxed / floxed mice with cdh5 ( pac )- creert2 mice 14 , for tamoxifen - inducible endothelial - cell - specific expression of cre - recombinase and ccm3 gene recombination . these mice were then further crossed with bat - gal mice 15 , which show b - catenin - activated expression of the nuclear b - galactosidase ( b - gal ) reporter gene . as previously reported for ccm2 6 , these mice with endothelial - specific - inactivation of ccm3 gene induced postnatally ( ccm3 - ecko ) presented marked malformations and hemorrhages in the brain and retina vasculature comparable to ccm vascular lesions in patients . this was previously reported for ccm2 in an identical murine model 6 and for ccm2 and ccm3 in a distinct murine system 7 . as ccm3 ecko mice develop vascular malformations in the central nervous system this model provides a tool for testing pharmacological treatments as described below . for details of this experimental model , see methods and fig1 . here , b - catenin - dependent transcription of the nuclear b - gal reporter gene is increased in vivo in endothelial cells of brain vessels of the newborn ccm3 - ecko , in comparison to matched control animals . as illustrated in the immunostaining in fig1 a and 1 b , the quantification by random - field counting using pecam labeling of endothelial cells saw the b - gal - positive nuclei ( 0 . 86 ± 0 . 15 positive nuclei per field ; 7 . 2 % positive nuclei of total 600 endothelial nuclei scored ) of the control brain endothelial cells from the wild - type bat - gal mice significantly increased by 4 - fold in the ccm3 - ecko brain endothelial cells ( 5 . 0 ± 1 . 7 positive nuclei per field ; 36 % positive nuclei of total 700 endothelial nuclei scored , p & lt ; 0 . 05 ; t - test ) ( dpn 9 littermate pups ). in these ccm3 - ecko brain endothelial cells , the b - gal - positive nuclei were distributed both in established caverns and in telangiectases ( 67 % b - gal - positive endothelial nuclei in vascular lesions ) and in pseudo - normal vessels ( 15 % b - gal - positive endothelial nuclei in pseudo - normal vessels ). expression of b - gal was also observed in endothelial cells of the retina of the ccm3 - ecko mice , in comparison with those from the control wild - type bat - gal mice ( fig1 c ). endothelial cells isolated from the brain of the ccm3 - floxed / floxed mice ( fig2 a , wt , primary culture ) were compared with those after recombination of the ccm3 gene in vitro ( ccm3 - knockout brain endothelial cells ; see methods ) ( fig2 a , ko , primary culture ), which showed active b - catenin in the nucleus ( i . e ., dephosphorylated on ser37 and thr41 16 ). this effect paralleled strong alterations to the adherens junction organization that was seen as delocalization from the junctions of both active b - catenin ( fig2 a ) and ve - cadherin ( fig3 c , vehicle ). for the similar disorganization of ve - cadherin from endothelial junctions in vivo , see fig4 b , vehicle . due to limitations in both the supply of freshly isolated endothelial cells from the brain and their extremely limited mitotic index after the first in vitro passage detailed analyses of their b - catenin nuclear distribution and signaling were not possible . the inventors therefore established cultured endothelial cell lines where ccm3 was recombined in vitro as above 17 ( ccm3 - knockout endothelial cell line ) ( see methods ). in these ccm3 - knockout endothelial cell line , the inventors confirmed enhanced nuclear localization of b - catenin both by immunofluorescence ( fig2 b ) and cell fractionation ( fig2 c ). in addition , beta - catenin and tcf / lef - dependent transcription of the exogenous luciferase gene was measured in top / fop flash reporter assays . in these ccm3 - knockout endothelial line , the transcription activity of b - catenin was significantly increased by 2 . 7 - fold , compared to control wild - type cells (± 0 . 2 sd ; p & lt ; 0 . 01 ) ( fig1 d ). furthermore , the expression of some typical endogenous targets of b - catenin transcription activity was increased in these ccm3 - knockout endothelial line ( i . e ., axin2 , lef1 , ccnd1 18 ) and inhibited by in vitro infection with the adeno viral vector coding for a dominant - negative tcf4 17 ( fig2 d ). the inventors also analyzed the expression of genes related both to acquisition / maintenance of endothelial progenitor phenotype and endothelial - to - mesenchymal transition , ( endmt ) 20 , 21 , as b - catenin transcription signaling has been shown to regulate the processes of differentiation and epithelial - to - mesenchymal transition ( emt ) in other cell types 22 , 23 , 24 . in addition , endmt was found to play a critical role in the development of the vascular lesions in a murine model of endothelial - specific ccm1 knockout ( maddaluno , l . et al ., nature 498 ( 7455 ): 492 , 2013 ). transcription of klf4 25 , 26 , ly6a 27 , 28 and s100a4 29 , 20 , id1 30 , 31 , cdh2 20 , acta2 20 were found to be significantly enhanced in ccm3 - knockout endothelial cells as compared to control cells ( fig2 e , endothelial line and fig3 b , primary culture ). in addition , these increases were dependent on b - catenin transcriptional activity , as they were inhibited by dominant - negative tcf4 17 , as above , ( fig2 e ). the enhanced transcription of these genes also corresponded to their increased protein expression ( see vehicle - treated ccm3 - knockout in fig1 and 19 , endothelial line , and fig3 c , primary endothelial cells , and their up - regulation in vivo in vehicle - treated ccm3 - ecko brain endothelial cells in fig5 and fig2 ). thus , abrogation of ccm3 expression in endothelial cells leads to increase in b - catenin transcriptional activity and target gene expression both in vivo and in vitro . in the light of these data , the inventors investigated the effects of anti - b - catenin agents in vivo , on the brain vascular lesions of these ccm3 - ecko mice . sulindac sulfide reduces b - catenin transcription activity and expression of endothelial progenitor and endmt markers in endothelial cells from the ccm3 - ecko mice the inventors then initially tested a range of agents in their experimental model in vitro that have been described as affecting b - catenin signaling 32 and , most importantly , are already in clinical use : sulindac sulfide , sulindac sulfone 33 , 34 , silibinin 35 , curcumin 36 and resveratrol 37 , 38 . salinomycin 39 , a reported inhibitor of wnt receptor signaling , was also included , although its use to date has been limited to experimental models . sulindac sulfide and sulindac sulfone were the most effective of these for inhibition of expression of endogenous targets of b - catenin transcription activity ( see above ) in the ccm3 - knockout endothelial cell line ( fig1 a ). in addition , sulindac sulfide reduced b - catenin transcriptional activity as measured by the top / fop flash reporter assays ( fig1 d ). the inventors therefore further analyzed the effects of sulindac sulfide on the ccm3 null phenotype . in primary cultures of ccm3 - knockout brain endothelial cells , the inventors found that sulindac sulfide effectively inhibited the expression of endogenous b - catenin target genes ( fig3 a and see inhibition by dominant - negative tcf4 , as above , fig3 b ). in parallel , sulindac sulfide strongly inhibited the nuclear localization of active b - catenin while increasing its concentration at cell - cell junctions ( fig3 c ). in parallel , ve - cadherin was also more localized to cell - cell contacts in these cells ( fig3 c ) and in ccm3 - knockout endothelial cell line ( fig1 b ). consistently , by co - immunoprecipitation and western blotting analysis sulindac sulfide restored the reduced association between b - catenin and ve - cadherin ( minus 35 %± 0 . 32 sd , p & lt ; 0 . 05 ) in ccm3 - knockout endothelial line ( fig1 c ). in parallel with inhibition of transcription of b - catenin target genes , sulindac sulfide also inhibited the overexpression of respective proteins in ccm3 - knockout endothelial cells ( fig3 c , primary culture , and fig1 , endothelial cell line ). sulindac sulfide was then investigated in vivo in newborn mice after induction of ccm3 - ecko . the inventors found that treatment with sulindac sulfide inhibited the expression of nuclear reporter gene b - gal ( fig4 a ) and of b - catenin target genes ( fig5 ) in the endothelial cell of brain vasculature too . ve - cadherin also appeared to be better localized at endothelial cell - cell junctions in vivo in the brain vessels of newborn ccm3 - ecko mice treated with sulindac sulfide ( fig4 b ). sulindac sulfide reduces development of vascular lesions in the brain and retina of the ccm3 - ecko mice a crucial aspect of the present study is whether inhibition of b - catenin signaling by sulindac sulfide may also reduce the vascular lesions in ccm3 - ecko pups . the inventors found that , indeed , the mean number and dimension of vascular lesions were reduced by sulindac sulfide treatment . as illustrated in the immunostaining in fig6 a and quantified in fig6 b , the mean number (± sd ) of vascular lesions per brain in the vehicle - treated ccm3 - ecko pups was 166 . 8 ± 22 , with 72 . 6 ± 9 vascular lesions with sulindac sulfide treatment ( p & lt ; 0 . 005 ; non - parametric wilcoxon signed - rank test ) and the mean maximal diameter of mulberry lesions (± sd ) in the vehicle - treated ccm3 - ecko pups was 386 ± 56 mm and 244 ± 38 mm with sulindac sulfide treatment ( p & lt ; 0 . 05 , t - test ). sulindac sulfide treatment did not significantly reduce the maximal diameter of single cavernae . sulindac sulfide treatment also inhibited the vascular malformations in the retina of ccm3 - ecko mice . in these mice the retinas show multiple - lumen vascular lesions that are particularly concentrated at the periphery of the vascular network . such lesions develop from veins , which are enlarged , although straight ( compare vehicle for wt and ccm3 - ecko in fig6 c and 6 e and fig1 for the venous marker endomucin ). sulindac sulfide partially normalized this aberrant vascular network in ccm3 - ecko mice ( fig6 c and 6 d ). in addition , the enlargement of the most internal tract of the veins that characterizes the retinas of these ccm3 - ecko mice was inhibited after sulindac sulfide ( 89 . 5 ± 7 . 1 mm in vehicle - ecko versus 35 ± 7 . 8 mm in sulindac sulfide - ecko , mean ± sd of 30 measurements in 14 retinas each for wt and ko ) ( fig6 e and fig1 a and 18 b , for the effects of sulindac sulfide on vessel diameter and veins in the brain of ccm3 - ecko pups ). at variance , arteries do not show this aberrant phenotype ( fig6 c and 6 e ). the data reported above strongly suggest that sulindac sulfide may have a therapeutic activity in ccm patients . however , it has been reported that this drug inhibits cycloxygenease in platelets possibly increasing the risk of hemorrhage . the inventors therefore tested sulindac sulfone , which is devoid of anti - cyclooxygenase activity 33 and does not have an impact on coagulation response . as observed after sulindac sulfide treatment , sulindac sulfone also reduced the nuclear accumulation of active b - catenin and restored cell - cell junctions in cultured ccm3 - knockout endothelial cell line ( fig1 ). in addition , sulindac sulfone inhibited the expression of b - catenin target genes , ( see for instance klf4 and s100a4 in fig1 ), as did sulindac sulfide ( see above ). when tested in vivo , sulindac sulfone reduced the number of lesions in the brain of the ccm3 - ecko mice to a level comparable to sulindac sulfide ( the mean number of lesions per mouse brain (± sd ) in the untreated control was 153 . 5 ± 28 and was reduced to 68 . 6 ± 10 with sulindac sulfone treatment , p & lt ; 0 . 01 ; non - parametric wilcoxon signed - rank test ; fig2 a and 20 b ). in addition , in vivo , in the endothelium of brain vessels of the ccm3 - ecko mice , sulindac sulfone inhibited the expression of klf4 and s100a4 ( fig2 c ). similar results indicating that sulindac sulfone ( exisulind ) inhibits the formation of cavernoma lesions in the brain of ccm1 - ecko mice have also been obtained . kinetics of activation of βeta - catenin signaling in endothelial cells in brain cavernomas of ccm3 - ecko mice ccm3 ecko murine model is first choice in proof of principle experiments , in particular testing the inhibitory activity of a drug as it develops the most serious phenotype as also observed in patients . as reported in fig7 βeta - catenin signaling is early enhanced in the lesion and such activation precedes the activation of tgf - β / bmp pathway that the inventors have reported to contribute to the maintenance of the ccm phenotype ( maddaluno et al , 2013 ). the in - vivo mouse system used was generated through the cross of ccm3 - flox / flox mice with cdh5 ( pac )- creert2 mice , to obtain tamoxifen - inducible endothelial - cell - specific expression of cre - recombinase and ccm3 gene recombination ( ccm3 - ecko mice ). these mice were then crossed with bat - gal reporter mice ( 16 ), which show βeta - catenin - activated expression of nuclear β - galactosidase ( β - gal ). as reported in fig7 a ( upper panels ) the inventors could observe a significantly higher β - catenin transcription signal in the nuclei of endothelial cells in ccm3 - ecko mice in comparison to matched controls . this difference was detectable since early stages ( 3dpn ) after induction of ccm3 recombination ( at 1dpn ). in brain sections of ccm3 - ecko mice endothelial cells with j3 - gal - positive nuclei could be found both in pseudo - normal vessels and in cavernae of any size ( fig8 ). in contrast , phospho - smad1 ( p - smad1 ) staining , in separate sections ( fig7 a lower panels ) and in co - staining for β - gal ( fig7 b ) was not enhanced after ccm3 ablation in 3dpn pups , but it was increased in 9dpn pups ( fig7 c ). similar results were obtained for p - smad3 ( not shown ). p - smad1 was significantly high in middle - large size lesions only ( maximal diameter 50 μm in 9dpn pups ) ( fig8 ). this result strongly support the pharmacological targeting of β - catenin signaling for the inhibition of initiation of new lesions . the appearance of de - novo lesions is a specific feature of the familiar form of ccm in patients . in vitro data on regression of mutated phenotype using sulindac sulfide and sulindac sulfone to inhibit β - catenin signaling are shown in fig4 and fig1 . correlation between β - catenin signaling and expression of endmt markers analyzing in vivo the kinetics of the two processes in endothelial cells of brain cavernomas of ccm3 - ecko mice expression of stem - cell / endmt markers ( klf4 , ly6a , s100a4 and id1 ) was high in 3dpn ccm3 - ecko pups ( fig9 a - d , and e , single positive ) and was concentrated in endothelial cells with β - gal positive nuclei ( fig9 e , co - localization ). at 9dpn β - gal expression in endothelial cells of ccm3 - ecko pups decreased while stem - cell / endmt markers remained high ( fig9 e ). the role of β - catenin signaling in established lesions is under scrutiny , at the present as discussed in the previous paragraph a canonical target of activated β - catenin - driven transcription , axin2 , is indeed enhanced in endothelial cells in culture after ablation of ccm1 and ccm2 genes besides ccm3 ( fig1 ), as well as endmt markers . analyzing in details ccm1 ko endothelial cells in culture , the inventors observed nuclear localization of active β - catenin ( dephosphorylated on ser37 and thr41 and escaping proteosomal degradation fig1 a ), as already reported in ccm3 - ko endothelial cells ( fig2 ). in addition , such nuclear β - catenin is transcriptionally active as indicated by the two fold - increase expression of the exogenous luciferase gene as measured in top / fop flash reporter assays ( a measure of activation of β - catenin / tcf / lef - dependent transcription ; fig1 b ). most importantly , inhibition of β - catenin signaling using sulindac sulfone ( exisulind ) inhibits the expression of endmt markers in ccm1 ko endothelial cells in culture ( fig1 c ). these data supports the concept that mutation of any ccm gene induces β - catenin signaling in association to acquisition of de - differentiated phenotype ( expression of endmt markers , fig1 ). in addition , sulindac sulfone ( exisulind ) induces re - organization of endothelial cell - to - cell contacts in ccm1 ko endothelial cells in culture , as reported for ccm3 ko endothelial cells in fig3 . similar results were also obtained in ccm2 ko models . mechanism through which β - catenin signaling is activated in response to ccm ablation in endothelial cells activation of β - catenin - mediated transcription in ccm3 - knockout endothelial cells was cell - autonomous since : a ) it was observed in absence of exogenous wnt ; b ) the porcupine inhibitors iwp2 and iwp12 ( 26 , 27 ) that inhibit ligand production , as well as dkk1 , an inhibitor of ligand - receptor interaction that is a competitor of wnt co - receptor lrp5 / 6 ( 26 , 27 ), did not inhibit transcription of typical β - catenin ( fig1 a - d ); c ) lrp6 phosphorylation was not increased ( fig1 e and f ); d ) stimulation by exogenous wnt3a did not induce expression of stem - cell / endmt markers , while the constitutively active form of β - catenin , lef - δ13cta ( 28 ), did ( fig1 g and h ). taken together these data indicate that in ccm3 - knockout endothelial cells enhanced nuclear localization and transcription activity of β - catenin do not depend on a classical ligand - receptor interaction . the inventors reported previously that silencing or dismantling of ve - cadherin from endothelial junctions can up - regulate β - catenin signaling ( 18 ). consistently , the inventors observed here that silencing ve - cadherin by sirna activated the expression of endmt markers ( s100a4 and id1 ) besides typical β - catenin targets ( axin2 , ccnd1 and nkd1 , fig1 i ) and promoted nuclear localization of active β - catenin ( fig1 a ). on the contrary , ve - cadherin knockdown did not enhance the phosphorylation of smad1 ( fig1 b ). these data suggest that in ccm the first trigger of β - catenin signaling is the dismantling of ve - cadherin junctions that , in turn , causes the release of β - catenin in the cytoplasm and nuclear translocation . this process precedes and possibly contributes to the activation of tgf - β / bmp signaling for lesion progression . interestingly , dismantling of cell - to - cell junction in endothelial cells represents a common feature of the brain cavernomas induced by ablation of any ccm gene , as reported for ccm1 - ecko , ccm2 - ecko and ccm3 - ecko ( fig1 ). the inventors have previously reported disorganization of ve - cadherin in brain cavernomas of ccm1 patients ( lampugnani et al , 2010 ). therefore , disorganization of junctional ve - cadherin appears a general feature of endothelial cells lining vascular cavernous malformations both in murine models and in patients . this may be accompanied by dissociation of β - catenin from ve - cadherin with enhanced nuclear translocation and increased β - catenin driven transcription also in patients , as reported above in experimental murine models . at the present , a direct proof of the activation of β - catenin signaling in brain cavernomas in patients is very difficult due to technical limitations in detecting markers of such activation in human samples . in summary , these results support the use of anti - β - catenin compounds for treatment of pathologies characterized by vascular malformation , in particular ccm patients . here , the inventors report that endothelial - cell - selective deletion of the ccm3 gene activates b - catenin transcription signaling in vivo in brain endothelial cells . pharmacological inhibition of b - catenin transcriptional activity with the nsaids sulindac sulfide and sulindac sulfone reduces the number and dimension of cerebral and retinal vascular malformations in this murine model suggesting that b - catenin transcription signaling in endothelial cells contributes to the pathogenesis of ccm3 - mediated vascular lesions . ccm malformations develop largely , although not exclusively , in the central nervous systems in patients and in mouse models 6 , 8 . consistent with a critical role for deregulated b - catenin signaling in the endothelium in ccm pathology , the canonical wnt pathway is a well - established determinant for the specification of the phenotype of endothelial cells at the blood - brain barrier 11 - 13 . however , wnt signaling must be abrogated postnatally to avoid abnormal vascular proliferation and morphogenesis in the central nervous system 11 - 13 . in a murine model of endothelial specific b - catenin - gain - of - function the inventors observed vascular lesions in the retina comparable to those observed here in ccm3 - ecko 40 . in tumor cells , the sustained induction of canonic wnt signaling is associated to increased growth and invasion 18 , 24 . in particular , upon b - catenin - mediated transcriptional activation , carcinoma cells switch from an epithelial to a mesenchymal phenotype ( emt ) 18 , 24 . the inventors report here that ccm3 - knockout endothelial cells undergo a similar change in phenotype and upregulate a series of genes typical of emt / endmt 20 . thus , a reasonable hypothesis is that ccm lesions originate from uncontrolled kinetics and location of b - catenin signaling in endothelial cells of brain vessels . it has recently been reported in retina and brain endothelial cells that activation of the canonical wnt pathway by norrin / frizzled4 induces development and maintenance programs through both cell - autonomous and cell - nonautonomous signaling 41 . this can explain local vascular phenotypes in different regions of the central nervous system 41 . deregulated b - catenin signaling in ccm could be supported by either endothelial - autonomous activation of the wnt / b - catenin pathway or by abnormal responses of mutated endothelial cells to environmental wnt , or by a combination of the two . the inventors &# 39 ; data indicate that at least the first of these mechanisms appears to operate in endothelial cells in culture after ablation of the ccm3 gene . indeed , some b - catenin targets and progenitor / endmt markers are activated through b - catenin transcription signaling under basal conditions in the ccm3 - knockout endothelial cells , as their expression is inhibited by a dominant - negative tcf4 . glading and ginsberg 10 reported similar activation of b - catenin transcription activity in bovine aorta endothelial cells and primary human arterial endothelial cells in culture after depletion of ccm1 using rna interference . they also reported inhibition of b - catenin signaling by ccm1 in epithelial cells , both in vitro and in vivo . in addition , they reported that the phenotype of b - catenin - driven intestinal adenomas in apc min /+ mice is exacerbated in a ccm1 +/− background . this implies a more general regulatory role for ccm1 , and possibly ccm3 , in b - catenin signaling in other cells as well as in endothelial cells . as the occurrence of intestinal and other neoplasias in familial ccm patients does not appear to be increased , the specificity of vascular and organ localization for the ccm pathology suggests that endothelial differentiation and / or local factors in the organ cooperate with wnt / b - catenin signaling for the expression of the mutated phenotype 42 . in particular , as far as is known for ccm3 , mutation of this gene in neuronal cells activates astrocytes and produces vascular lesions that resemble this pathology 9 . this thus reinforces the importance of cellular crosstalk within the neurovascular unit . although nuclear accumulation of active b - catenin appears to be a significant characteristic of the mutated genotype , the inventors do not have direct indications of the processes that drive the b - catenin concentration into the nucleus of the ccm3 - knockout endothelial cells . in general , the issue of the molecular mechanisms that regulate nuclear accumulation of b - catenin remain virtually unknown ( for review , see 18 ). however , concomitant with the increase in concentration into the nucleus , the inventors observed that b - catenin dissociates from cell - cell junctions in both the inventors &# 39 ; in vitro and in vivo models of endothelial - cell - specific deletion of ccm3 . junctional b - catenin is mostly associated with ve - cadherin , the transmembrane constituent of the adherens junctions 43 , as well as with the b - catenin destruction complex 44 . in the ccm3 - knockout endothelial cells , the adherens junctions are disorganized , as also observed after ablation of both ccm1 45 , 46 and ccm2 6 . in addition , the b - catenin associated with ve - cadherin is reduced here , as has also been observed after ablation of ccm1 10 . speculate that this decreased association of b - catenin with ve - cadherin is accompanied by accumulation of active b - catenin in the nucleus . this concentration of active b - catenin into the nucleus characterizes conditions of decreased junction stability in endothelial cells , as observed in sparse endothelial cells and in ve - cadherin - knockout endothelial cells 17 . in both of these cases , the total amount of b - catenin is reduced , even to very low levels , although the residual active b - catenin accumulates in the nucleus . inhibition of proteosomal degradation with ‘ passive ’ redistribution of active b - catenin into the nucleus appears not to be likely , as the total amount of active b - catenin actually decreases . of particular interest , the inventors have identified two inhibitors of b - catenin transcription signaling , sulindac sulfide and sulindac sulfone , that also inhibit the development of vascular lesions in ccm3 - ecko mice . these agents are both nsaids that have significant chemopreventive efficacies against colon cancer in human patients , and they are under evaluation in experimental models of other types of cancer 47 - 52 . sulindac sulfone is potentially more interesting than the sulindac sulfide for therapy of pathologies characterized by vascular malformation such as ccm since it lacks anti - platelet activity . the relative efficacy of sulindac sulfide versus sulindac sulfone varies depending on the type of cancer 33 , 53 - 56 . in conclusion , the targeting of b - catenin signaling in endothelial cells with specific pharmacological tools represents an effective strategy for the reduction of vascular malformations and the prevention of the appearance of new vascular lesions , in particular in ccm patients . 1 . clatterbuck , r . e ., et al . journal of neurology , neurosurgery , and psychiatry 71 , 188 - 192 ( 2001 ). 2 . wong , j . h ., et al ., neurosurgery 46 , 1454 - 1459 ( 2000 ). 3 . rigamonti , d ., et al . the new england journal of medicine 319 , 343 - 347 ( 1988 ). 4 . li , d . y . & amp ; whitehead , k . j . stroke 41 , s92 - 94 ( 2010 ). 5 . plummer , n . w ., et al ., current neurology and neuroscience reports 5 , 391 - 396 ( 2005 ). 6 . boulday , g ., et al . the journal of experimental medicine 208 , 1835 - 1847 ( 2011 ). 7 . chan , a . g ., et al . j clin invest 121 , 1871 - 1881 ( 2011 ). 8 . he , y ., et al . science signaling 3 , ra26 ( 2010 ). 9 . louvi , a ., et al . proc natl acad sci usa 108 , 3737 - 3742 ( 2011 ). 10 . glading , a . j . & amp ; ginsberg , m . h . disease models & amp ; mechanisms 3 , 73 - 83 ( 2010 ). 11 . stenman , j . m ., et al . science 322 , 1247 - 1250 ( 2008 ). 12 . daneman , r ., et al . proc natl acad sci usa 106 , 641 - 646 ( 2009 ). 13 . liebner , s ., et al . the journal of cell biology 183 , 409 - 417 ( 2008 ). 15 . maretto , s ., et al . proc natl acad sci usa 100 , 3299 - 3304 ( 2003 ). 16 . van noort , m ., meeldijk , j ., van der zee , r ., destree , o . & amp ; clevers , h . j biol chem 277 , 17901 - 17905 ( 2002 ). 17 . taddei , a ., et al . nature cell biology 10 , 923 - 934 ( 2008 ). 18 . clevers , h . & amp ; nusse , r . cell 149 , 1192 - 1205 ( 2012 ). 19 . fadini , g . p ., losordo , d . & amp ; dimmeler , s . circ res 110 , 624 - 637 ( 2012 ). 20 . medici , d . & amp ; kalluri , semin cancer biol 22 , 379 - 384 ( 2012 ). 21 . kovacic , j . c ., et al ., circulation 125 , 1795 - 1808 ( 2012 ). 22 . sanchez - tillo , e ., et al . proc natl acad sci usa 108 , 19204 - 19209 ( 2011 ). 23 . li , j . & amp ; zhou , b . p . bmc cancer 11 , 49 ( 2011 ). 24 . holland , j . d ., et al ., curr opin cell biol ( 2013 ). 25 . li , x ., et al . microvasc res 84 , 270 - 277 ( 2012 ). 26 . margariti , a ., et al . proc natl acad sci usa 109 , 13793 - 13798 ( 2012 ). 27 . van solingen , c ., et al . cardiovasc res 92 , 449 - 455 ( 2011 ). 28 . liang , s . x ., et al . j thromb haemost 9 , 1628 - 1637 ( 2011 ). 30 . james , d ., et al . nat biotechnol 28 , 161 - 166 ( 2010 ). 31 . tobin , n . p ., et al ., bmc cancer 11 , 417 ( 2011 ). 32 . kundu , j . k ., et al ., biochimica et biophysica acta 1765 , 14 - 24 ( 2006 ). 33 . thompson , h . j ., et al . cancer research 57 , 267 - 271 ( 1997 ). 34 . boon , e . m ., et al . british journal of cancer 90 , 224 - 229 ( 2004 ). 35 . rajamanickam , s ., et al ., pharmaceutical research 26 , 2558 - 2567 ( 2009 ). 36 . prasad , c . p ., et al ., chemico - biological interactions 181 , 263 - 271 ( 2009 ). 37 . hope , c ., et al . molecular nutrition & amp ; food research 52 suppl 1 , s52 - 61 ( 2008 ). 38 . teiten , m . h ., et al ., current pharmaceutical biotechnology 13 , 245 - 254 ( 2012 ). 39 . lu , d ., et al . proc natl acad sci usa 108 , 13253 - 13257 ( 2011 ). 40 . corada , m ., et al . dev cell 18 , 938 - 949 ( 2010 ). 42 . wray , j . & amp ; hartmann , c . trends cell biol 22 , 159 - 168 ( 2012 ). 43 . lampugnani , m . g ., et al . the journal of cell biology 118 , 1511 - 1522 ( 1992 ). 44 . maher , m . t ., et al ., the journal of cell biology 186 , 219 - 228 ( 2009 ). 45 . glading , a ., et al ., the journal of cell biology 179 , 247 - 254 ( 2007 ). 46 . lampugnani , m . g ., et al . journal of cell science 123 , 1073 - 1080 ( 2010 ). 47 . meyskens , f . l ., jr ., et al . cancer prevention research 1 , 32 - 38 ( 2008 ). 48 . huang , l ., et al . cancer research 71 , 7617 - 7627 ( 2011 ). 49 . takayama , t ., et al . clinical cancer research : an official journal of the american association for cancer research 17 , 3803 - 3811 ( 2011 ). 50 . steinert , g ., et al . plos one 6 , e22540 ( 2011 ). 51 . giardiello , f . m ., et al . the new england journal of medicine 328 , 1313 - 1316 ( 1993 ). 52 . smalley , w ., et al ., archives of internal medicine 159 , 161 - 166 ( 1999 ). 53 . chang , w . c ., et al . annals of the new york academy of sciences 1059 , 41 - 55 ( 2005 ). 54 . piazza , g . a ., et al . cancer research 57 , 2909 - 2915 ( 1997 ). 55 . mahmoud , n . n ., et al . carcinogenesis 19 , 87 - 91 ( 1998 ). 57 . mackenzie , g . g ., et al . cancer prevention research 4 , 1052 - 1060 ( 2011 ). 58 . srinivas , s ., et al . bmc developmental biology 1 , 4 ( 2001 ). 59 . cattelino , a ., et al . the journal of cell biology 162 , 1111 - 1122 ( 2003 ). 60 . balconi , g ., spagnuolo , r . & amp ; dejana , e . arteriosclerosis , thrombosis , and vascular biology 20 , 1443 - 1451 ( 2000 ). 61 . lluis , f ., et al . cell stem cell 3 , 493 - 507 ( 2008 ). 62 . zhang , n ., et al . cancer cell 20 , 427 - 442 ( 2011 ). 63 . mcdonald , d . a ., et al . stroke 43 , 571 - 574 ( 2012 ). kundu j k et al . biochimica et biophysica acta 1765 ( 2006 ): 14 - 24 . park et al biochem biophys res commun 2005 mar . 4 ; 328 ( 1 ): 227 - 34 . gurney et al , proc natl acad sci usa . 2012 jul . 17 ; 109 ( 29 ): 11717 - 22 liang et al , 2011 journal of thrombosis and haemostasis : jth 9 , 1628 - 1637 medici d & amp ; kalluri r , 2012 seminars in cancer biology 22 , 379 - 384

US-201515302288-A

a device for the repair of tissue and methods of use and manufacturing thereof are described herein . applications for the use of the device include , e . g ., repair of atrial septal defects , patent foramen ovale , left atrial appendage closure and stent graft fixation among other applications throughout the anatomy . the implant portion of the device is available in a variety of sizes and configurations to accommodate the vast complexity of the target anatomy .

fig1 is an illustration of two surgical micro implants or fasteners 100 and 200 . the surgical implants 100 and 200 , which may be absorbable or non - absorbable , are designed to penetrate and join two adjacent viscera or tissue planes . the implants 100 and 200 are designed to pass through the first tissue and the second tissue under controlled rapid deployment . the implant is shaped similarly to a needle with a predetermined geometry . each implant 100 , 200 has an elongated body 105 , 205 that tapers in a distal region to a needle - like tip 110 , 210 . each implant 100 , 200 may be deployed , as described in greater detail below , by being pushed from a precisely placed hollow needle or tube containing the implant 100 , 200 . the implants disclosed herein may be formed using e . g ., micromachining techniques . the micro implants 100 and 200 , as well as any other implants disclosed herein may have a diameter of one millimeter , or approximately one millimeter , and a length that is in a range from 5 millimeters to 10 millimeters . according to some example embodiments , the diameter is less than one millimeter . according to some example embodiments , the diameter is in a range from 0 . 8 millimeters to 1 . 2 millimeters . it should be understood , however , that other dimensions may be provided . the body 105 , 205 of each implant 100 , 200 has specifically designed micro anchoring filaments 115 , 215 which arise from a core 120 , 220 of the implant 100 , 200 to extend outwardly from the core 120 , 220 . the anchoring filaments 115 , 215 are located around the circumference and along at least a portion of the length of the body 105 , 205 of the implant 100 , 200 . this allows the implant to resist removal once it has penetrated the tissue . the filaments 115 , 215 , or any other filaments described herein may have any suitable dimensions . for example , it may be advantageous to provide a filament tip ( i . e ., free end ) diameter of 0 . 1 millimeters and tapering toward a diameter of 0 . 25 millimeters at the body . the core 120 , 220 has a constant diameter along a substantial length of the body 105 , 205 of the implant 100 , 200 . for example , the core 120 of the implant 100 has a constant cross - section , and constant diameter , from a head portion 125 to a substantially conically shaped tapered portion toward the tip 110 . it should be understood however , that the implants 100 and 200 may have a more continuous taper and / or have a constant or non - constant rate of taper . the anchoring filaments 115 , 215 extend outwardly at an angle with respect to the longitudinal axis of the implant 100 , 200 . in this regard , the filaments , in addition to extending outwardly away from the longitudinal axis , also extend in a proximal direction , away from the tip 110 , 210 . this allows for the filaments 115 , 215 to slide along the pierced tissue during distal driving or insertion . however , proximal movement of the implants 100 , 200 from the inserted position is prevented or resisted by engagement of the outer , free ends of the filaments 115 , 215 with the relatively soft tissue . the filaments 115 , 215 may be flexible or substantially rigid . the filaments 115 , 215 should , however , have sufficient stiffness or strength to resist proximal withdrawal of the implant 100 , 200 from the inserted position . further , although the filaments 115 , 215 are illustrated as being straight , it should be understood that some or all of the filaments 115 , 215 may be at least partially curved , and / or have one or more bends between straight portions and / or curved portions . moreover , the filaments 115 , 215 of a given implant 100 , 200 may have constant or differing lengths , radial extensions , and / or angles with respect to the longitudinal axis of the implant 100 , 200 . the filaments 115 , 215 , or any other anchoring filaments described herein may be provided with any appropriate density and relative spacing , depending on the particular application . for a given application , a greater density ( i . e ., a greater number of filaments per unit of surface area ) of smaller filaments may be provided , or a lesser density of larger filaments ( optionally reinforced with a shape memory alloy , e . g ., nitinol and / or spring - loaded steel ), while presenting the same or comparable suture retention or “ pull through strength .” the optional reinforcement could be a “ v ” shaped portion formed of shape memory alloy , e . g , nitinol and / or spring - loaded steel . the filaments 115 , 215 may be absorbable or non - absorbable in whole or in part . each implant 100 , 200 includes a proximal head 125 , 225 . the head 125 , 225 extends radially beyond the core 120 , 220 and has a larger axial cross section than the core 120 , 220 . the head 125 , 225 may prevent the implant 100 from being driven too deeply into , or entirely through , the tissue . as the implant 100 , 200 is driven distally along its longitudinal axis , the core 120 , 220 pierces into and progresses through the tissue . the head 125 , 225 , having a larger diameter or cross section , prevents or resists the proximal portion of the implant 100 , 200 from extending into the tissue . thus , where two layers of tissue are pierced and joined , the distal layer of tissue is constrained against distal movement away from the proximal layer of tissue by engagement of the distal layer with the filaments 115 , 215 , and the proximal layer is constrained against proximal movement away from the distal layer by engagement of the proximal layer ( e . g ., the outer proximal surface of the proximal layer ) with the head 125 , 225 . the implant 100 differs from the implant 200 in that the implant 100 has anchoring filaments 115 provided from the tip region to an axially fixed , proximal head 125 , whereas the implant 200 has a predetermined length that is externally threaded with micro threads 230 to allow the head 225 , which has corresponding internal threads , to rotate about the implant , thus bringing the two adjacent tissues into approximation . in this regard , the implant 200 may be initially driven into the tissue , the distance to which is driven being limited by , e . g ., friction between the implant 200 and the tissue . after the initial driving , the head 225 may be rotated , e . g ., in a clockwise direction , to move the head or nut 225 distally along the longitudinal axis of the implant 200 . the rotation may be performed by a rotatable driver having projections configured to engage driving recesses 227 of the head 225 , as described in greater detail below . although the head 225 has four evenly spaced recesses 227 , it should be understood that any appropriate number of recesses 227 may be provided . further , the micro tightening nut or head 225 may have projections as an alternative or in addition to the recesses , the projections engageable by the driver to rotate the head 225 . moreover , any other appropriate driving mechanism may be provided . for example , the driver may grip the outer surface of the head 225 to impart rotation via friction , or the radially outwardly facing surface of the head 225 may have one or more flat surfaces engageable by the driver . contact between the distal face of the head 225 and the proximal surface of the proximal layer of tissue would in turn cause the proximal layer of tissue to move toward the distal layer of tissue , which is axially constrained by the filaments 215 . the head 225 may be prevented from rotating in the opposition direction by friction between the threads or any appropriate locking or securing mechanism , e . g ., detents . during the tightening rotation of the head 225 , the body 205 may be prevented from rotating by the engagement of the filaments 215 with the tissue or any other appropriate mechanism . each implant 100 , 200 has a proximal surface 135 , 235 via which a driving force may be applied . the proximal surface 135 of the implant 100 corresponds to the proximal surface of the proximal head 125 , while the proximal surface 235 of the implant 200 has a smaller diameter , which is the same or substantially the same as the diameter of the core 220 . although the implants 100 , 200 have cores 120 , 220 and heads 125 , 225 with circular cross sections , it should be understood that other cross - sections may be provided , e . g ., rectangular , triangular , oval , polygonal , and / or any other regular or irregular shape . further , it should be understood that the anchoring filaments 115 , 215 may be evenly spaced apart or may have non - uniform spacing . moreover , the filament density , i . e ., the number of the filaments 115 , 215 per unit of surface area of the core 120 , 220 may be constant , or may vary . modern manufacturing processes allow for near nano technology applications . this allows the implants 100 , 200 to be manufactured in a size and complexity that may not have been possible in years past . the implant 100 , 200 may be injection molded of either absorbable or non absorbable polymers and then processed to add the features of the protruding filaments 115 , 215 and the threaded features 227 . the head 225 of the implant 200 is manufactured separately and to the same or similar tolerances so that the interface between the implant threads 230 and the head 225 of the implant 200 will thread precisely upon one another . although the implants 100 and 200 are formed of polymer , it should be appreciated that any appropriate material may used , e . g ., metal or a composite material . the materials and methods of manufacturing the implants 100 and 200 are applicable to any of the implants described herein . in order to accurately penetrate adjacent tissues that are not held or secured on a distal side , a rapid penetration of each layer of tissue may be required in order to affect penetration of both tissue layers . if an implant 100 , 200 is applied slowly , the tissue may be pushed distally away by the implant and / or needle without adequate penetration . thus , some example delivery mechanisms eject the implant a relatively high velocity . in some preferred examples , saline is used to pressurize the channel within the catheter or needle at such a rate that the plunger will eject the implant at the precise velocity . other example embodiments utilize a spring - loaded mechanical mechanism to eject the implant . further example embodiments push the implant using long push rods which run the length of the catheter . the ejection modality is computer - controlled . however , it should be understood that the ejection may be , e . g ., operator - controlled . for example , the ejection force may be predetermined and repeatable by a mechanical system , e . g ., a spring - loaded system , which is triggered by an operator , e . g ., a surgeon . fig2 a and 2b are schematic illustrations of surgical implants 300 and 500 with driving mechanisms including catheters or needles 400 and 600 . referring to fig2 a , implant 300 shares many features in common with implants 100 and 200 . implant 300 differs , however , in that it includes reverse threads 330 and a proximal head 325 having a driving recess 327 . the driving recess has a geometry that corresponds to a rotatable driver 405 of the catheter 400 , such that the driver 405 is insertable into the recess 327 to impart axial rotation to the implant 300 . in this regard , rotation of the driver in a first direction 410 causes the driver to rotate in the direction 410 . although the direction 410 is clockwise ( when view from a proximal location ), it should be appreciated that the driver may be configured to rotate the implant 300 in the counter - clockwise direction , e . g ., where the threading is reversed . the driver is configured to progressively move distally along its axis during driving to correspond to a distance which the implant is driven . the corresponding geometry of the driver 405 and the recess 327 may be selected to have any appropriate cross section , e . g ., rectangular or hexagonal . the catheter has , at a distal end portion , a pair of retention tabs 415 . the retention tabs 415 have inner diameters that are less than the diameter of the proximal head 325 but greater than the diameter of the other , more distal portions of the implant 300 . thus , the retention tabs allow the distal portions of the implant 300 to be driven beyond the distal end of the catheter and into tissue , but retains the head 325 within the catheter . after the driving of the implant 300 , the retention tabs may be actuated radially outwardly away from each other to allow the release of the head of the implant 300 and withdrawal of the catheter 400 away from the implant site . referring to fig2 b , the catheter 600 shares many features in common with the catheter 400 , including , e . g ., retention tabs 615 , but differs in that it includes a spring driver 605 . the spring driver 605 imparts a spring force onto the proximal head 525 of the implant 500 to impart a rapid movement from an initial proximal position to an extended distal position . the spring driver 605 may have an initial preloaded position that is not in contact with the implant 500 . thus , the spring and / or a driver portion driven by the spring may build momentum prior to engaging the implant 500 . this may be suitable for imparting a more aggressive acceleration to the implant 500 . when the implant is able to achieve a high speed quickly , it is able to pierce a proximal face 551 of the tissue and penetrate across the thickness of the tissue to the distal face 552 , rather than simply compressing the outer proximal surface 551 of the tissue . this may be particularly suitable in allowing a system that does not require any initial structure on the back side of the tissue during the driving process . fig3 is a schematic illustration of a surgical implant 700 with a driving mechanism . the driving mechanism is a catheter 800 sharing features with the catheters 400 and 600 described above , including , e . g ., retention tabs 815 , which are shown in their opened , or radially extended position , thereby allowing distal axial passage therethrough of the head 725 of the implant 700 . the implant 700 includes many features in common with the implants 100 , 200 , 300 , and 500 described above , but differs in that it includes a plurality of spring loaded tabs 702 , which may be formed , e . g ., of a shape memory alloy , e . g ., nitinol or spring - loaded steel . the spring - loaded tabs are maintained in their closed , or radially inward , position when the proximal free ends of the tabs 702 are axially disposed in the catheter 800 ( in its closed position ) and in the tissue through which the tabs are driven after piercing of the tissue , including a proximal face 751 , by the needle - like tip 710 . however , when the proximal ends of the spring loaded tabs 702 clear the distal side 752 of the tissue , the tabs are no longer radially constrained by the tissue and are able to spring radially outwardly into their open position . in the open position , the implant 700 is prevented or constrained from being proximally withdrawn through the tissue via contact between the extended tabs 702 and the distal surface 752 of the tissue . the nut or head 725 of the implant 700 may then be rotated and distally advanced as described above with regard to the head 225 of the implant 200 in order to bring the layers of tissue together . the driver may be configured to drive the any of the fasteners described herein to a predetermined depth . the precision of the depth may be accomplished by any appropriate mechanism , e . g ., a precise hydraulic driving force , engagement with flanges or other similary stops , or a filament / suture that tautens to limit the depth . further the depth may be monitored using fluoroscopy or any other appropriate imaging mechanism . the driving mechanism may include pressurized saline or other hydraulic fluid that is pressurized through the endoscopic catheter shaft . thus , very precise control may be accomplished . fig4 shows a fastener or implant 250 . the fastener 250 includes features in common with the other fasteners disclosed herein and may be used in conjunction with any of the other fastening applications described herein . however , the fastener 250 includes a corrugated body 251 . the body 251 includes grooves 253 that extend axially along the length of the body 251 . thus , extending circumferentially around the body 251 , a plurality of grooves 253 alternate with a plurality of ridges 255 . further , the fastener body 251 includes a pair of split portions or clevises 257 and 258 . the split portions are formed by respective splits or cuts 259 into the body 251 . in this regard , the splits 259 may be formed by making a cut radially into the body 251 and extending in an axial direction . thus , the two split portions 257 and 258 are attached to the remainder of the body 251 at a distal position and extend proximally to free ends . the free ends include a plurality of sharp protrusions along a curved surface . these points are formed due to the corrugations . in particular , the ridges 255 form the sharp protrusions , as illustrated in the inset partial side view in fig4 , which are advantageous for gripping tissue and preventing distal sliding of the fastener 250 . although each split portion 257 and 258 includes three such protrusions as illustrated , it should be understood that the fastener 250 may be designed such that one or more of the split portions has any other number of protrusions , including a single sharp protrusion . for example , if a larger number of sharp protrusions are desired , the body 251 could be more densely corrugated ( i . e ., a greater number of alternating grooves 253 and ridges 255 could be provided ) and / or the angle of the cut or slice could be adjusted . further , the length of proximal extension of the projections may be adjusted by varying the depth of the grooves 253 with respect to the ridges 255 . the split portions 257 and 258 do not substantially impede distal insertion into tissue but resist proximal movement from an insertion location by engaging the tissue . it has been discovered that the combination of the pointed and / or sharp - edged proximal ends of the split portions 257 and 258 with the alternating ridges on the proximal end of the split portions creates improved performance . further , the split portions or wings 257 and 258 are axially offset from each other . for example , split 257 is axially located at position a along axis x and split 258 is axially located at position b along axis x . this allows for greater structural strength of the other portions of the body 251 as compared to a non - offset configuration . in particular , since the cuts progress continually radially inward as they progress distally , a non - offset portion would have a substantially smaller amount of material in cross - section in the distal end of the cut . this would lead to a mechanically weak point or region along the axis of the body and could lead to mechanical failure , especially in fasteners of small dimensions . the distal tip of the fastener 250 is pyramidal , with a sharp point , and a plurality of surfaces separated by edges that converge at the sharp point . although four planar surfaces are provided , it should be appreciated that any appropriate suitable number of surfaces may be provided and that one or more or all of the surfaces may be non - planar . the fastener 250 also includes a hooked end portion 260 . the hooked portion may be suitable for coupling any other temporary and / or permanent implant . the fastener 250 may be produced by first forming the body 251 with the corrugations , e . g ., by injection molding or extrusion , and subsequently forming clevises 257 and 258 , e . g ., by cutting radially into the side of the body 251 . as illustrated , the cut is curved , with an angle ( at the proximal entry point ), relative to the longitudinal axis of the body 251 , that gradually decreases from the proximal initial cutting location toward the distal end of the fastener 250 and eventually becoming linear . although the split or cut of the illustrated example is made with a curved or varying angle with respect to the longitudinal axis of the body 251 , it should be understood that any appropriate cut , including a linear cut , may be made . although the fastener 250 includes two wings or split portions spaced equally around the radial periphery of the body 251 , it should be appreciated that any number of clevises , including a single clevis may be provided and at any appropriate spacing around the radial periphery . furthermore , it should be understood that the corrugated split - bodied configuration may be employed in combination with any of the other fastener features disclosed herein . for example , the fastener 250 may have a split corrugated distal portion and a threaded proximal portion configured to receive a proximal head as disclosed in greater detail above , and / or include filaments in addition to the split portions . fig5 a and 5b illustrate a surgical micro implant or fastener 900 . fig5 b is a cross - sectional view of the surgical implant 900 with a cross - sectional plane extending along and including the longitudinal axis of the fastener 900 of fig5 a . the fastener 900 includes many feature of the other example fasteners described herein . further , the fastener includes a filament / suture 950 extending proximally from a proximal end of the fastener body 905 . in this regard , when a driver fires the fastener 900 , e . g ., by application a saline or other precise hydraulic force or any other appropriate mechanism , the depth to which the fastener 900 is driven is limited by the amount of slack in the suture 950 . this may be accomplished by fixing a proximal end and / or other proximal portion of the suture 950 to a structure , e . g ., a fixed position within the driver device , with a predetermined length and / or slack between the fixing location and the fastener body 905 . referring to the cross - sectional view of fig5 b , the suture 950 may extend longitudinally into an interior location of the fastener head 905 . an example manufacturing method may include molding , coextruding , or otherwise forming the fastener head 905 over the suture 950 . coextrusion may be particularly advantageous . it should be appreciated however , that any appropriate manufacturing method may be employed . further , although a suture 950 of non - stretchable material is provided , it should be understood that other materials , e . g ., stretchable materials , may be provided . however , it may be preferable that , even if stretchable , the material have a predeterminable extension limit for particular driving momentums and / or applications . further , a braided , non - braided , mono - filament , and / or multi - filament material may be provided . although the fastener 900 includes micro filaments to anchor into a tissue and resist proximal dislocation after implantation , it should be understood that any other anchoring mechanism , e . g ., wings or split portions as described above , may be provided . moreover , any of the features disclosed with regard to the other example fasteners disclosed herein may be provided in conjunction with the fastener 900 . fig6 a to 6c schematically and sequentially illustrate the bringing into apposition of two tissues using a surgical implant 1300 , which shares many features in common with the other implants described herein . implant 1300 has a distal anchoring portion with micro filaments and a proximal threaded portion configured to mate with an internally threaded head 1325 , analogous to the implant 200 described above . implant 1300 also includes a proximally extending filament / suture 1350 , analogous to the implant 900 described above . referring to fig6 a and 6b , a surgical system 1200 includes a handpiece 1202 configured to drive the fastener 1300 to a predetermined depth . the depth is limited , e . g ., by a predetermined amount of slack in the suture 1350 . the proximal end of the suture 1350 is attached to a capstan 1205 configured to adjust the length of the suture 1350 extending from capstan 1205 . in this regard , the capstan 1205 , which may be actuated by a motor system or any other appropriate mechanism , may set the slack by reeling off a predetermined length of suture 1350 prior to driving the fastener 1300 and / or the capstan 1205 may have a predetermined amount of allowed rotation such that driving of the fastener 1300 causes the capstan 1205 to rotate only the predetermined amount , thereby setting the driving depth of the fastener 1300 . the determination of the depth and / or the driving velocity of the fastener 1300 may be determined in a processor 1210 of the handpiece 1202 . although the processing takes place in a processor 1210 located in the handpiece 1202 , it should be understood that the processor may be disposed in other parts of the device , e . g ., in the shaft 1215 and / or the processing may take place at a location separate from the handpiece 1202 and shaft 1215 , e . g ., at a remote computing unit that communications , e . g ., wirelessly , with the surgical device . further , it should be understood that the capstan 1210 may be disposed in the shaft 1215 . using any appropriate location determining mechanism , e . g ., an imaging mechanism such as a fluoroscopy or ultrasound imaging unit , which may be located in the handpiece 1202 , shaft 1215 and / or an external device , the system 1200 determines the location of the first layer of tissue 980 and the second layer of tissue 990 . depending on the application , it may be sufficient for the system 1200 to determine just the respective locations of the tissues 980 and 990 . the location may be an approximate location of the center of the tissue or a face , e . g ., a proximal face , of each tissue . in the illustrated example , the system determines , e . g ., via the imaging device and / or the processor 1210 , the respective positions of a first or proximal face 981 of the first tissue 980 , a second or distal face 982 of the first tissue 980 , a first or proximal face 991 of the second tissue 990 , and a second or distal face 992 of the second tissue 990 taken along the line or approximately along the line that the fastener 1300 is to be driven . based on these positional values , the processor 1210 may determine the thickness of each tissue 980 , 990 and the space between the distal face 982 of the first tissue 980 and the proximal face 991 of the second tissue , in addition to the location of each of the distal and proximal faces . based on the these values , or a portion thereof , the system 1200 , e . g ., via processor 1210 , calculates a precise distance and velocity to drive the fastener . the system 1200 may also take into account the features of the particular fastener being driven ( e . g ., dimensions , mass , and / or coefficient of friction ) and / or the hardness and / or density of the tissue , which may be approximated , e . g ., where the tissue is of a known or expected density and / or hardness , or determined based on the imaging data , e . g ., fluoroscopy data . the velocity and / or distance may optionally be facilitated by incorporating empirical data into the algorithm or purely based . the depth is controlled , e . g ., by precisely controlling the length of suture 1350 via the capstan 1215 . the velocity is precisely controlled , e . g ., by a hydraulic driver , e . g ., a saline driver . where the shaft 1215 abuts the first or proximal face 981 of the tissue 980 , position of the first or proximal face 981 of the tissue 980 may be determined without using imaging . as illustrated in fig6 a , after the shaft 1215 is placed adjacent the proximal face 981 of the first tissue 980 and the precise driving velocity and depth / position are determined , e . g ., by processor 1210 in the handpiece 1205 , the system 1200 drives the fastener 1300 in the proximal direction indicated by arrow 1250 through the first tissue 980 across any gap between the first and second tissues 980 and 990 , and into the second tissue 990 , where the fastener 1300 anchors against distal retraction from the second tissue 990 . referring to fig6 b , the capstan 1210 is then actuated , e . g ., by a motor system controlled by , e . g ., processor 1210 , to proximally reel the suture 1350 , thereby drawing the fastener 1300 , along with the tissue 990 to which it is anchored , proximally toward the shaft 1215 and the first tissue 980 adjacent the shaft 1215 . the proximal direction of movement is indicated by arrow 1260 in fig6 b . the first tissue 980 is restrained from proximal movement by , e . g ., contact with the distal end of the shaft 1215 . as also illustrated in fig6 b the proximal head , or threaded nut , 1325 is moved distally , e . g ., by a rotatable driver . the distal direction of movement is illustrated by arrow 1250 in fig6 b . the proximal head 1325 may be moved distally at any point after the anchoring fastener 1300 is driven from the shaft 1215 . once the fastener is pulled a sufficient proximal distance , the threaded proximal portion of the body of the fastener 1300 protrudes through the proximal face 981 of the first tissue 980 . the proximal head 1325 is then coupled to the threaded portion to form a threaded connection . a rotatable driver then rotates the head 1325 to distally drive the head 1325 to its implanted position , illustrated in fig6 c . it should be understood than any final portion of the gap between the distal face 982 of the first tissue and the proximal face 991 of the second tissue 990 may be taken up by continuing to reel in the suture 1350 and / or driving the proximal head 1325 in the distal direction along the threads of the body of the fastener 1300 . after the proximal head 1325 has been fully driven on the threaded shaft of the fastener 1300 , the suture 1350 , or a portion thereof , may be separated from the fastener 1300 , e . g ., by cutting . in this regard , the system 1200 may include a cutter or other trimming device , e . g ., at the distal end of the shaft 1215 , in order to cut the suture 1350 . in applications where there is an undesired excess length of externally threaded shaft of the fastener 1300 extending proximally from the fully driven proximal head 1325 , the system 1200 may provide for trimming some or all of the excess . in this regard , the system may include a cutter or other trimming device , e . g ., at the distal end of the shaft 1215 , which may be the same or different than the cutter for the suture 1350 , in order to remove some or all of the excess . further although two tissues 980 and 990 are illustrated in fig6 a to 6c , it should be understood that the fastener may be driven through any desired number of tissue layers before reaching its anchored position . moreover , any other example fasteners described herein may be formed with a suture and used in analogous manner to the fastener 1300 . during the procedure illustrated in fig6 a to 6c , the system 1200 may hydraulically drive the implant 1300 or use any other appropriate driving mechanism . regarding hydraulic delivery , it is noted that a very precise force may be delivered at the distal end portion of the shaft 1215 to drive the fastener 1300 . this force may be controlled by the processor 1210 in connection with hydraulics , e . g ., in the handpiece . for example , the hydraulic fluid , e . g ., saline , may be disposed in a tube extending along the shaft 1215 . hydraulics and controls in the handpiece 1202 may then transmit a very precise force , via the hydraulic fluid extending along the shaft 1215 , to the distal end portion of the shaft 1215 to precisely drive the fastener 1300 . fig7 is an illustration of a surgical implant 1000 . the fastener 1000 includes many feature of the other example fasteners described herein . further , the fastener 1000 includes a proximal portion having a ratcheting mechanism including a micro ratcheting head 1025 and ratchet teeth 1030 . the ratcheting mechanism of the implant 1000 performs a function analogous to that of the micro threaded arrangement of the fastener 200 described above . however , as opposed to rotation of the head 225 about the threads 230 of the fastener 200 , the ratcheting head 1025 slides , e . g ., linearly , along the fastener body 1005 . as each ratchet tooth 1030 or circumferential set of ratchet teeth 1030 is distally traversed , the proximal retraction of the head 1025 is resisted or prevented by the ratcheting engagement of a proximal surface of the head 1025 with a distal surface of the ratcheting tooth or teeth 1030 . in this regard , for each axial ratcheting position of the head 1025 , the fastener body 1005 may have any appropriate number of ratcheting teeth 1030 , including a single ratcheting tooth 1030 , arranged to engage the ratcheting head 1025 . further , a single tooth 1030 may extend continuously around the entire radial periphery of the fastener body 1005 . although the fastener 1000 includes micro filaments to anchor into a tissue and resist proximal dislocation after implantation , it should be understood that any other anchoring mechanism , e . g ., wings or split portions as described above , may be provided . moreover , any of the features disclosed with regard to the other example fasteners disclosed herein may be provided in conjunction with the fastener 1000 . fig8 is an illustration of a distal end portion of a surgical implant 1100 . this distal arrangement may be provided on the distal end of any example fastener disclosed herein . the distal arrangement includes three concave surfaces 1105 that distally converge to form a sharp point 1110 . separating the three concave surfaces 1105 are three tapered cutting edges 1115 . these tapered cutting edges 1115 may facilitate penetration of tissue , e . g ., soft tissue . although the end portion illustrated in fig8 includes three concave surfaces 1105 and separated by three corresponding tapered cutting edges 1115 , it should be understood that any appropriated number of concave surfaces 1105 and corresponding cutting edges 1115 may be provided . the various mechanisms described herein provide for a tissue repair system that allows great flexibility . for example , smaller defects may be repairable with a single fastener ( e . g ., fastener 100 or any other fastener described herein ), and larger defects may be repairable with a plurality of fasteners , with or without a washer or plate 2200 , as described above . larger defects , e . g ., hernias or large holes , may be more suited for a mesh 1300 application , as described above . the various implants described herein , e . g ., fasteners or anchors 100 , 200 , 300 , 500 , and 700 and / or nuts 225 , may be formed by molding , e . g ., injection molding . further , any of the implantable elements described herein , e . g ., fasteners 100 , 200 , 300 , 500 , and 700 and / or nuts 225 , and / or sutures , may be formed wholly or partly of a material absorbable into the patient &# 39 ; s body , or of a non - absorbable material , depending on , e . g ., the specific application . for example , these elements may be formed of polyglycolic acid ( pga ), or a pga copolymer . these elements may also , or alternatively , be formed of copolymers of polyester and / or nylon and / or other polymer ( s ). moreover , these elements may contain one or more shape - memory alloys , e . g ., nitinol and / or spring - loaded steel . absorbable materials may be advantageous where there is a potential for misfiring or improper locating of the various implants . for example , in a situation where a fastening arm 1100 drives a fastener at an unintended location , or where the tissue does not properly receive the implant , the fastener , e . g ., fastener 100 , even where not needed , would relatively harmless , as it would eventually absorb into the patient &# 39 ; s body . although the present invention has been described with reference to particular examples and exemplary embodiments , it should be understood that the foregoing description is in no manner limiting . moreover , the features described herein may be used in any combination .

US-201313828256-A

a jaw - thrust device includes a base with an extension arm disposed on each side of a patient &# 39 ; s head mounted on the base . a mandible rest is mounted on each extension arm such that the mandible rest may be deployed proximate to a patient &# 39 ; s mandible . a chin pad and at least one connector connects the chin strap to at least one of the base or extension arm ; whereby jaw thrusting pressure on the mandible rests causes rotational force on the chin straps such that the patient &# 39 ; s mouth opens without substantially tilting the patient &# 39 ; s head . the device maintains an open airway unattended .

the following description of the preferred embodiment ( s ) is merely exemplary in nature and is in no way intended to limit the invention , its application , or uses . fig3 is a perspective view of the present invention . the components are mounted on a base , which in the depicted embodiment is a backboard 10 or a panel that may be fixedly attached to a pre - existing backboard , serves as a platform for mounting the various features of the present invention . a pair of telescoping extension arms 12 are mounted on either side of the backboard 10 , on an upper surface facing a patient . these extensions 12 may slide medially and laterally , in order that they may be moved closer or farther away from the patient &# 39 ; s mandible , thus allowing a firm engagement of the mandible rests 14 , which are mounted on top of the telescoping extensions 12 . in the depicted embodiment , medial and lateral translation of the extending arms 12 is achieved by mounting the extending arms 12 within a groove 16 . the extending arms telescope vertically in order that the mandible rests 14 may again be put in engagement with a dorsal aspect of a patient &# 39 ; s mandible , bilaterally . attached to an upper portion 18 and a lower portion 20 of the extending arms 12 are straps or bands . the straps are joined in a center portion 22 which comprises a chin strap . in the depicted embodiment the chin strap includes a pad . an upper strap 24 is attached to an upper portion 18 of each extending arm 12 , bilaterally . a lower portion 28 of the strap is attached to a fixed lower portion 20 of the extendible arms 12 , bilaterally . the lower straps 28 are not extendable . they may be adjusted to the patient &# 39 ; s size initially , but during the jaw thrust maneuver and thereafter they do not flex or extend . in the depicted embodiment , straps 28 are non - elastic fabric straps . they have a series of holes for initial adjustment . the fixation of the straps to separate portions of the telescoping extension arm assure that the ends of straps 28 will be separated from the ends of straps 24 when the mandible rests are elevated and the thrust maneuver is executed . supplemental features of the present invention in the depicted embodiment include side bars 40 for stabilizing the patient &# 39 ; s head . the side bars 40 may be moved in and out of position by rotation or translation towards and away from the sides of the patient &# 39 ; s head . also shown in the depicted embodiment are pillows 50 and 52 . these pillows are designed to be extended and retracted vertically in any manner , as for example by inflation , as in the depicted embodiment . the first pillow 50 is for use with adult patients , who typically have bulkier shoulders and optimally have a straight spine and airway maintained by elevating the head relative to the body . conversely , children have larger heads proportional to their body size . accordingly , the best technique for maintaining a straight spine and airway in children is by elevating their shoulders . for this purpose a second pillow 52 is placed below the chin strap assembly . optionally , the pillows may be adjustable towards the patient &# 39 ; s head or feet in order to best position the patient &# 39 ; s head . in use , a patient is placed on the backboard 10 , the side bars 40 and one of the pillows 50 or 52 are adjusted to the patient &# 39 ; s head and shoulders . thereafter , the extending arms 12 are translated medially or laterally in order to approximate the mandible rests 14 to a dorsal aspect of the patient &# 39 ; s mandible . the chin strap 22 is put on and slightly above the patient &# 39 ; s chin , below the lower lip . thereafter the extendible arms 12 are telescopically extended so that the mandible rests exert pressure on the patient &# 39 ; s mandible , forcing it upwards such that the mandible advances outwards relative to the patient &# 39 ; s maxilla . the chin strap 22 , being non - extendibly anchored to the lower extension member 20 , will be restrained relative to the upward pressure on the mandible rests 14 , and accordingly be forced by the upwards pressure to move in the only available direction , which is to rotate downwards and away from the patient &# 39 ; s maxilla , thereby achieving the desired opening of the jaw and airway beneath it . once the desired degree of extension and opening of the patient &# 39 ; s jaw has been achieved , it may be maintained in that position by upward pressure of the mandible rests 14 and rotational pressure of the chin strap 22 in turn being maintained by locking the extending arms 12 in their telescoped , extended position . this may be achieved by any known means . as for example , selective insertion of a locking pin , tightening of a set screw or a ratchet . once set , the user may let go of the jaw thrust device of the present invention and proceed to other medical care and the patient &# 39 ; s airway will be advantageously maintained in the open jaw thrust position by the device without further support from any medical practitioner . fig4 - 7 refer to an alternate embodiment of the present invention . this embodiment is comprised generally of a platform 110 which may be a portion of a backboard or a plate attachable to a backboard . mounted on the plate 110 , generally , are a first side bar assembly 140 a and a second side bar assembly 140 b , corresponding respectively to the patient &# 39 ; s left and right side . these side bar assemblies may be used as head stabilizers , head positioners and / or head rest . the second embodiment also is comprised of a first mandible rest assembly 108 a and a second mandible rest assembly 108 b corresponding to a patient &# 39 ; s left side and a patient &# 39 ; s right side , respectively . finally , a chin strap 122 is non - elastically attached to the plate 110 at attachment 120 , which may be a buckle , such as a cam buckle , although other adjustment members may be used . in the illustrated embodiment , attachment 120 is located below the vertical adjustment member 112 . alternatively , chin straps may be mounted with four anchors , with extra substantially symmetrical anchors 121 being positioned higher than the first anchors 120 , for example between the side bar and mandible rest assemblies . each of the head stabilization assemblies 140 is mounted on a transverse slot 142 . the head stabilization / immobilization assemblies each include a base block 144 and a vertical adjustment element 146 which may , as depicted , be a vertical rod . the head stabilization assemblies 140 may be adjusted medially and laterally by sliding them in and out along the slots 142 . they may be fixed in a user selected position by application of a fixating device ( not shown ) as for example a set screw . these assemblies may be used to immobilize the head , for example in the midline of the overall plate and back board . each head stabilization assembly 140 has a vertical riser block 148 . vertical riser blocks have mounted to them head rest blocks 150 . the vertical riser blocks 148 and head rest 150 may be raised and lowered by sliding along the vertical rods 146 . when raised or lowered to a user selected position they may be locked in placed by application of a locking device which may be , as depicted a tensioning lever 152 . the head rests 150 are located at a user selected position on the patient &# 39 ; s head , for example , at the temple , so that the patient &# 39 ; s head may be advantageously stabilized both in keeping with the general medical principal that some patients &# 39 ; injuries should be treated with head stabilization and also so that the head may be stabilized for application of the mandible engagement assemblies 108 . fig4 depicts the head stabilization assemblies 140 in a first position that is a beginning position . the beginning position is laterally spaced away from the patient and the head rests 150 are lowered . fig5 depicts both head stabilization assemblies 140 in a position to stabilize the patient &# 39 ; s head ; that is , each has been moved medially to a position where the patient &# 39 ; s head may be engaged and each head rest 150 has been raised to a position selected by the user to best stabilize the patient &# 39 ; s head , for example at the temple . mandible rest assemblies are similar to the head stabilization assemblies in their adjustment mechanisms . the mandible rest assemblies also include a base block 160 and a riser 162 . the mandible rest themselves 114 are mounted on the risers 162 and extend medially inwards towards the patient and the patient &# 39 ; s mandible . the mandible rest assemblies 108 also each slide medially and laterally along a slot 164 and may be locked in a user selected position by means of a fixating element ( not shown ) such as for example a set screw . the mandible rests ( and head rests 150 ) may include cushions or pads for patient comfort . the pads may be removable for cleaning . the riser 162 may be raised and lowered along the vertical adjustment member 112 , which may be , as depicted , a vertical rod . when a user selected position of the mandible rest 114 has been reached , the mandible rest may be locked into position by a locking device , as for example in a depicted embodiment a torsion lever 166 . in this manner , the mandible rest 114 may be placed approximate to the dorsal aspect of the patient &# 39 ; s mandible , that is the back of the jaw closest to the back plate 110 , and thereafter raised by raising the risers 162 along the vertical element 112 . the consequent lifting pressure on the patient &# 39 ; s mandible will execute the advantageous maneuver of a jaw thrust . the force applied for a therapeutic jaw thrust may be in the range of from 2 to 18 pounds , and preferably about 8 pounds . accordingly , components should be of sufficient strength to support and maintain such amounts of force . the vertical rods may be of sufficient height to maintain component positions exerting these force ranges on the patient , for example up to about 10 inches high for pediatric use . materials for components may be any material capable of maintaining these forces , including for example plastics , fiberglass or metal such as stainless steel . in operation , a patient is placed on a backboard ( not shown ) which has the plate 110 either incorporated integrally into it or attached to it . as seen in fig8 , the patient &# 39 ; s head is placed between the head support assemblies 140 and the mandible rest assemblies 108 . the head support assemblies 140 are moved medially and the head rest 150 are raised until stabilizing contact is made with the patient &# 39 ; s head . then adjustment locks such as for example set screws and the torsion levers 152 are set so that the head stabilization assemblies 140 are locked into position in engagement with the patient &# 39 ; s head , immobilizing it . thereby , the patient &# 39 ; s head is stabilized in a manner advantageous for both general medical purposes , as for example in stabilizing the head of a suspected neck injury victim or multiple trauma victim , and for purposes of executing a jaw thrust to maintain a patent airway . thereafter the chin strap 122 , which is non - elastic , is placed over the patient &# 39 ; s chin and the length of the strap 122 is appropriately adjusted for the healthcare provider with adjustment means such as for example a buckle 120 . in the illustrated embodiment 122 is advantageously anchored below the patient &# 39 ; s glenoid fossa . next , the mandible adjustment assemblies 108 are each slid medially towards the patient &# 39 ; s neck and mandible until the mandible rest 114 are engaged with the mandibular ramus , i . e ., the back or dorsal aspect of the patient &# 39 ; s mandible . thereafter the risers 162 are elevated and slid along the vertical adjustment element 112 away from the back plate 110 . in so doing , the healthcare provider using the apparatus will execute the advantageous jaw thrust maneuver . simultaneously with elevation away from the back plate 110 of the patient &# 39 ; s mandible , the chin strap will prevent the ventral aspect of the patient &# 39 ; s mandible , i . e ., his chin , from rising with the rest of the mandible . the chin will accordingly move in the only direction available for it to move , which is to rotate away from the patient &# 39 ; s maxilla towards the patient &# 39 ; s chest . thus , the upward movement of the mandible rest 114 and the consequent rotation affected by the restraint of the chin strap 122 , will automatically and advantageously execute the jaw thrust maneuver for maintaining a patient &# 39 ; s airway . in order to aide in symmetrical application of all risers , the vertical members may include hash marks and / or calibrations 170 . after use removable cushions or pads 180 and 182 may be removed and either cleaned or disposed of and replaced . other components may be cleaned after the pads are removed . as various modifications could be made to the exemplary embodiments , as described above with reference to the corresponding illustrations , without departing from the scope of the invention , it is intended that all matter contained in the foregoing description and shown in the accompanying drawings shall be interpreted as illustrative rather than limiting . thus , the breadth and scope of the present invention should not be limited by any of the above - described exemplary embodiments , but should be defined only in accordance with the following claims appended hereto and their equivalents .

US-57758409-A

an automatic baking machine includes a loading unit having a plurality of carriers on a first conveyor configured for receipt of individual goods to be baked . a downstream oven unit has a transportation device to transport the goods received from the loading unit through the oven unit . a delivery unit is arranged downstream from the oven unit and includes a second conveyor with a plurality of carriers for receipt of baked goods from the transportation device . a vertically stationary linear conveyor is arranged between the first conveyor and the transportation device , wherein the goods to be baked are transferred from the first conveyor to the linear conveyor , conveyed by the linear conveyor in a vertically fixed plane , and transferred from the linear conveyor to the transportation device .

reference will now be made to embodiments of the invention , one or more examples of which are shown in the drawings . each embodiment is provided by way of explanation of the invention , and not as a limitation of the invention . for example features illustrated or described as part of one embodiment can be combined with another embodiment to yield still another embodiment . it is intended that the present invention include these and other modifications and variations to the embodiments described herein . fig1 - 3 show schematic views of an embodiment of an automatic baking machine according to the invention , in which some parts are not shown in all figures for better clarity . the main components of the automatic baking machine are a loading unit 1 for loading baked goods b ( rolls , loaves of bread , baguettes , pretzels , etc .) that need to be baked or fully baked , an oven unit 20 and a delivery unit 30 for delivering the baking goods ready to be eaten at the request of the customers . in this case , loaves of bread have been chosen as baked goods b . the loading unit 1 has a housing 2 that stands on feet 3 in which a first conveyor device 6 in the form of a paternoster elevator 6 has been arranged on the loading side . to this end , numerous oblong carriers 8 are attached to their respective front sides with motor - driven conveying chains 9 . the waiting staff p preferably puts the baked goods b manually side by side on the carriers 8 . for this purpose , an opening 4 has been provided in the housing 2 that can be closed with a door 7 ( see fig3 ). in the embodiment shown , a loading table 5 has been provided before the opening so a container ( such as a cardboard box , for example ) with baked goods can be placed on it . using an input panel equipped with a display 10 , the staff can request a free carrier 8 ( i . e . one not yet loaded with baked goods b ). in addition , staff instructions can be issued on the display — for example , which type of baked good should be baked at the moment owing to consumer demand . the first conveyor device 6 runs peripherally in arrow direction f 1 ( fig1 ), but its direction can also be reversed . especially when a free carrier 8 is requested for loading with baked goods b , this feature is welcome for shortening the running time of the corresponding carrier 8 if need be . the baked goods b that are not yet baked or pre - baked are stored in the conveyor device 6 until a control unit ( not shown ) well known to those skilled in the art moves them . for this purpose , on the side facing the waiting staff p , a stationary linear conveyor 15 executed as a conveyor device belt , for example , has been provided for running sideways in the direction of the longitudinal extension of the carriers 8 . as can be especially seen in fig1 & amp ; 2 , baked goods b are pushed from a carrier 8 moved correspondingly in position by sliders 16 on the linear conveyor device 15 . other transfer mechanisms — in other places of the automatic baking machine as well , see farther below — are certainly possible , for example by having the carriers 8 tilt the baked goods b on the linear conveyor device 15 . the running direction of the stationary linear conveyor 15 is reversible , see double arrow f 3 . when it runs forward , the linear conveyor device 15 transports the baked goods b to the inlet opening of the housing 21 of the oven unit 20 . through the oven unit 20 runs a transportation device 22 that can be executed as a peripheral chain link or network conveyor device . for transferring the baked goods b from the linear conveyor device 15 to the transportation device 22 , a wide , motorized slider 19 has been provided here . instead of a single slider 19 , it is possible to use several sliders for one or a portion of the baked goods b . conversely , this also applies to the sliders 16 . heating elements 23 that can be executed as conventional heating spirals have been arranged in the oven unit 20 . the throughput speed and / or baking temperature can be preset or also electronically controlled . an adjustment to the respective type of baked good presents itself . the oven unit 20 is accessible from below , because the connection in series of the stationary linear conveyor 15 diverts the baked goods twice by 90 °. thus , very easy accessibility to the oven unit 20 is created for the waiting and service staff . the delivery unit 30 , in turn surrounded by a housing 31 , is connected to the oven unit 20 . the delivery unit 30 is provided for display in a supermarket &# 39 ; s sales room or something similar , in which case — to minimize the standing area of the automatic baking machine in the sales room — the loading unit 1 and the oven unit 20 are set up outside of the sales room and separated from it by a wall 28 . after baking or full baking , the slider 24 ( shown only in fig1 ) pushes the baked goods from the transportation device 22 on peripheral carriers 34 of a second peripheral conveyor device 32 shaped like a paternoster elevator , which is driven by front - sided conveyor device chains 35 located in the delivery unit 30 that stores the baked goods b that have just been baked until they are delivered to the customer k . a corresponding service display for the customer k is not shown here , but readily known to the expert . a temporary storage compartment 38 has been provided between carrier 34 and a dispensing compartment 41 accessible to the customer k on which in the embodiment shown here , the baked goods b are tilted by a carrier 34 . to accomplish this , the corresponding carrier 34 runs from above against electronically - controlled pins 36 movable from a resting to a working position and this swivels the carrier 34 . the baked goods b then slide on a first slide 37 on the temporary storage compartment 38 mentioned above , from which one or several baked goods b are pushed — if requested by a customer k — with the help of the slider 39 into a funnel slide 40 on which the requested baked goods b slide to the dispensing compartment 41 . since the baked goods lie only loose on all transportation elements , the transfer to the next one cannot always be ensured . for this purpose , a collection device 11 located on the frontal side facing away from the oven unit 20 has been especially provided for the linear conveyor device 15 . in the present case , the collection device 11 consists of one chute 12 running perpendicularly and a collecting container 13 placed underneath that can be manually emptied . when the linear conveyor device 15 cannot successfully push the baked goods b to the transportation device 22 , the conveying direction of the linear conveyor device 15 is reversed and it runs as long as all baked goods b that are still on it are dropped off into the chute 12 . the reverse movement of the linear conveyor device 15 can be initiated , for example , every time the slider 19 is activated , so that the linear conveyor device 15 runs nonetheless backwards too when the baked goods b are successfully delivered to the transportation device 22 . according to an alternative , the reverse movement can be triggered when a sensor ( not shown ) registers the presence of at least one baked good b on the linear conveyor device after the slider 19 has been activated . in any case , the reverse path of the linear conveyor device 15 is always longer than the transportation path from the carriers 8 to the transfer position before the oven unit 20 . fig4 shows a schematic top view of an automatic baking machine in which the loading unit 1 has two conveyor devices 6 , the oven unit 20 has two continuous baking ovens , and the delivery unit 30 likewise has two conveyor devices 32 with two dispensing compartments 41 as well , in which case each stationary linear conveyor 15 supplies the two continuous baking ovens . various baked goods b ( on the one hand , loaves of bread , on the other hand , pretzels ) are stored in the carriers 8 of the two conveyor devices 6 . three loaves can be placed on one carrier 8 ; in the case of the pretzels , four . needless to say , it is also possible for various baked goods b to be placed on different carriers 8 of an individual conveyor device 6 and held in various correspondingly provided temporary storage compartments in the delivery unit 30 until they are requested . such variability makes it possible to adjust the different spatial circumstances to the number of visiting customers and taste preferences in the respective regions and supermarkets . the modular construction shown exemplarily in fig4 not only allows larger quantities of different baked goods to be offered , but the total throughput quantity is also naturally larger compared to the design shown in accordance with the fig1 - 3 . the automatic baking machine according to fig4 has only one collection device 11 . so that pretzels transported to the oven unit 20 cannot be removed either from this stationary linear conveyor 15 ( in fig4 top ), it is kept operating in forward motion so the pretzels ( in this case , two ) can be transferred to the other stationary linear conveyor 15 ( in fig4 , bottom ), which will then transport these pretzels to the collection device 11 for disposal . the waiting staff must therefore empty merely one single collection container 13 . in addition , the material for another collection device 11 — which would require more space — is saved . all the operations taking place in the automatic baking machine according to the invention are preferably controlled by a centralized electrical control system ( not shown ) that controls especially the transportation of the baked goods , determines the demand for goods to be baked and indicates this on the input panel with the display 10 . this invention is not restricted to the embodiments shown . variations within the claims are certainly possible .

US-201013322681-A

the present invention relates to a method for producing patient cancerous disease modifying antibodies using a novel paradigm of screening . by segregating the anti - cancer antibodies using cancer cell cytotoxicity as an end point , the process makes possible the production of anti - cancer antibodies for therapeutic and diagnostic purposes . the antibodies can be used in aid of staging and diagnosis of a cancer , and can be used to treat primary tumors and tumor metastases . the anti - cancer antibodies can be conjugated to toxins , enzymes , radioactive compounds , and hematogenous cells .

the hybridoma cell line 11bd - 2e11 - 2 was deposited , in accordance with the budapest treaty , with the american type culture collection , 10801 university blvd ., manassas , va . 20110 - 2209 on nov . 11 , 2003 , under accession number pta - 5643 . in accordance with 37 cfr 1 . 808 , the depositors assure that all restrictions imposed on the availability to the public of the deposited materials will be irrevocably removed upon the granting of a patent . 11bd - 2e11 - 2 monoclonal antibody was produced by culturing the hybridomas in cl - 1000 flasks ( bd biosciences , oakville , on ) with collections and reseeding occurring twice / week and with purification according to standard antibody purification procedures with protein g sepharose 4 fast flow ( amersham biosciences , baie d &# 39 ; urfé , qc ). with reference to fig1 and 2 , 4 to 8 week old female scid mice were implanted with 5 million mcf - 7 human breast cancer cells in 100 microlitres saline injected subcutaneously in the scruff of the neck . the mice were randomly divided into 2 treatment groups of 11 - 13 mice . on the day after implantation , 20 mg / kg of either 11bd - 2e11 - 2 test antibody or isotype control antibody ( known not to bind mcf - 7 or ovcar - 3 cells ) was administered intraperitoneally at a volume of 300 microliters after dilution from the stock concentration with a diluent that contained 2 . 7 mm kcl , 1 mm kh 2 po 4 , 137 mm nacl and 20 mm na 2 hpo 4 . the antibodies were then administered once per week for a period of 7 weeks in the same fashion . tumor growth was measured about every seventh day with calipers for up to 8 weeks or until individual animals reached the canadian council for animal care ( ccac ) end - points . body weights of the animals were recorded for the duration of the study . at the end of the study all animals were euthanised according to ccac guidelines . 11bd - 2e11 - 2 significantly reduced the tumor burden in treated mice in comparison to controls ( fig1 ). after treatment ( day 51 ), 11bd - 2e11 - 2 prevented tumor growth by 80 percent ( p = 0 . 0098 ) in comparison to isotype control antibody treated mice . there was also a post - treatment survival benefit ( fig2 ) associated with 11bd - 2e11 - 2 administration . the isotype control antibody treated group reached 100 percent mortality by day 197 post - treatment while 40 percent of the 11bd - 2e11 - 2 treated group were still alive at day 233 . in summary , 11bd - 2e11 - 2 increased survival and decreased tumor burden in a well - established model of human breast cancer ( blakey et al . clinical cancer research 8 : 1974 - 1983 2002 ; klement et al . clinical cancer research 8 : 221 - 232 2002 ; waud et al . relevance of tumor models for anticancer drug development , fiebig and burger , eds . 54 : 305 - 315 1999 ; karpanen et al . cancer research 61 : 1786 - 1790 2001 ). with reference to the data shown in fig3 and 4 , 4 to 8 week old , female scid mice were implanted with 5 million ovcar - 3 human ovarian cancer cells in 1000 microliters saline injected intraperitoneally . the mice were randomly divided into 2 treatment groups of 10 . on the day after implantation , 20 mg / kg of 11bd - 2e11 - 2 test antibody or buffer control antibody was administered intraperitoneally at a volume of 300 microliters after dilution from the stock concentration with a diluent that contained 2 . 7 mm kcl , 1 mm kh 2 po 4 , 137 mm nacl and 20 mm na 2 hpo 4 . the antibodies were then administered once per week for a period of 9 weeks in the same fashion . body weights of the animals were recorded for the duration of the study . at the end of the study all animals were euthanised according to ccac guidelines . in the ovcar - 3 ovarian cancer xenograft model , increasing body weight can be used as a surrogate indicator of disease progression since this reflects the accumulation of ascites from increased tumor burden ( fig3 ). at day 80 post - implantation ( 16 days after the end of treatment ), 11bd - 2e11 - 2 administration prevented body weight gain by 12 . 4 percent ( p = 0 . 015 ) compared to the buffer control group . mice were monitored post - treatment for survival ( fig4 ). by day 87 , the buffer control group had reached 90 percent mortality while the 11bd - 2e11 - 2 treated group still had 80 percent survival . the 11bd - 2e11 - 2 treated group did not reach 90 percent mortality until day 125 . in summary , 11bd - 2e11 - 2 antibody treatment reduced tumor burden , delayed disease progression and enhanced survival in comparison to a buffer control antibody in a well - recognized model of human ovarian cancer . therefore treatment with 11bd - 2e11 - 2 significantly decreased the tumor burden of established tumors in two well - recognized models of human cancer disease ( breast and ovarian cancers ) suggesting pharmacologic and pharmaceutical benefits of this antibody for therapy in other mammals , including man ( smith et al . the prostate 48 : 47 - 53 2001 ; olson et al . international journal of cancer 98 : 923 - 929 2002 ; guilbaud et al . clinical cancer research 7 : 2573 - 2580 2001 ; von gruenigen et al . international journal of gynecologic cancer 9 : 365 - 372 1999 ; guichard et al . clinical cancer research 7 : 3222 - 3228 2001 ; xiao et al . protein expression and purification 19 : 12 - 21 2000 ). all patents and publications mentioned in this specification are indicative of the levels of those skilled in the art to which the invention pertains . all patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference . it is to be understood that while a certain form of the invention is illustrated , it is not to be limited to the specific form or arrangement of parts herein described and shown . it will be apparent to those skilled in the art that various changes may be made without departing from the scope of the invention and the invention is not to be considered limited to what is shown and described in the specification . one skilled in the art will readily appreciate that the present invention is well adapted to carry out the objects and obtain the ends and advantages mentioned , as well as those inherent therein . any oligonucleotides , peptides , polypeptides , biologically related compounds , methods , procedures and techniques described herein are presently representative of the preferred embodiments , are intended to be exemplary and are not intended as limitations on the scope . changes therein and other uses will occur to those skilled in the art which are encompassed within the spirit of the invention and are defined by the scope of the appended claims . although the invention has been described in connection with specific preferred embodiments , it should be understood that the invention as claimed should not be unduly limited to such specific embodiments . indeed , various modifications of the described modes for carrying out the invention which are obvious to those skilled in the art are intended to be within the scope of the following claims .

US-10266208-A

the dry steamer apparatus delivers steam and heated air to produce dry steam to treat a surface as a method of eradicating bed bugs or other insect pests , and / or for cleaning purposes . the apparatus provides a vacuum to immediately remove the dry steam , and dead pests and other debris . a treatment substance dispensing assembly may also be provided , to dispense treatment substances onto the surface after steaming and vacuuming . the apparatus may incorporate the vacuum , or may attach to an external vacuum , for example the central vacuum unit of a home . where the vacuum is part of the apparatus , the vacuum fan may have its exhaust connected to supply air to an assembly to produce the heated air , and if applicable , to the treatment substance dispensing assembly to dispense the treatment substance .

in the following detailed description , reference will be made primarily to the apparatus as configured for eradication of bed bugs or other insect pests . however , it should be understood that the apparatus can be used strictly for dry steam cleaning if desired , with no intention to treat for bed bugs or other insect pests . in such embodiments , obviously the treatment substance dispensing assembly described below is not required . however , if the apparatus does have a treatment substance dispensing assembly , obviously it can still be used for purely steam cleaning , with the treatment substance dispensing assembly simply not being used , or possibly being used to dispense some other cleaning product or disinfectant or the like . fig1 and 2 illustrate a first example of the invention . the apparatus includes : a steam generating assembly 1 for generating and delivering steam ; a vacuum assembly 2 for drawing the exterminated bugs and other debris away from a treated surface ; an air heating assembly 3 for heating air exhausted from the vacuum assembly 2 , and delivering the heated air to the treated surface ; a treatment substance dispensing assembly 4 for dispensing chemical treatment substances onto the treated surface ; a mixing chamber 5 for mixing steam from the steam generating assembly 1 and hot air from the air heating assembly 3 ; and an operating nozzle assembly 6 , for spraying the steam / heat mixture from the mixing chamber 5 and at the same time applying suction from the vacuum assembly 1 . the steam generating assembly 1 preferably includes a water reservoir 11 , a heating element 12 by which the water is turned into steam , and an insulated steam hose 13 to transfer steam to the mixing chamber 5 . the heating element 12 is submerged in the water reservoir 11 . distilled water is preferred , to minimize mineral accumulation . optionally , the heating element 12 can be separate from the reservoir 11 . in such an embodiment , the steam generating assembly 1 preferably would employ a pump ( not shown ) to draw water from the water reservoir 11 to supply the heating element 12 with water . alternatively , the water could be supplied from the water reservoir 11 to the heating element 12 by the force of gravity if the water reservoir 11 is mounted above the heating element 12 . the apparatus could also employ a valve ( not shown ) located between the water reservoir 11 and the heating element 12 to supply only desired amounts or flow rates of water to the heating element 12 . preferably , the water reservoir 11 can be removed for filling . otherwise , it can have an inlet or connector that can be used to fill it . the vacuum assembly 2 preferably includes a vacuum fan 21 driven by an electric motor , a waste reservoir 23 , a vacuum hose 22 connected to an opening of the operating nozzle assembly 6 through which matter is drawn by the vacuum fan 21 to the waste reservoir 23 . a filter 24 is positioned upstream of the fan 21 . the fan has three outlets , namely one connected to an exhaust valve 26 for venting air , one connected to an air supply pipe 25 leading to an air heating assembly 3 , and one connected to an air supply pipe 45 of a treatment substance supply assembly 4 . it is preferred that the vacuum hose 22 has a smooth bore which prevents the bed bugs from clinging to and remaining in the vacuum . preferably , the waste reservoir 23 can be removed . it may be desirable to establish fluid - tight connections between the waste reservoir 23 and the vacuum fan 21 and the vacuum hose 22 . preferably , the waste reservoir 23 can be provided with a door ( not shown ) which is removable , hinged , slidable , or otherwise openable with respect to adjacent walls of the waste reservoir 23 . the air heating assembly 3 preferably includes an air supply pipe 33 , which is connected to the exhaust from the fan 21 of the vacuum assembly 2 for supplying exhaust from the vacuum assembly 2 to the air heating assembly 3 . the heating element 31 heats the exhaust from the vacuum fan 21 and a blower hose 32 channels the heated air to the mixing chamber 5 , in which the heated air and steam mix and exit through an opening to the operating nozzle 6 . the heating element 31 can be sheathed and located within the air heating assembly 3 to be directly contacted by the exhaust from the vacuum assembly 2 to the air heating assembly 3 . any suitable heating element of the prior art can be used for heating the air . the air heating assembly 3 heats the air , and the hot air mixes with the steam from the steam generating assembly 1 , so the steam used in the apparatus is essentially dry steam ( i . e . with little or no fluid water ). therefore , the surface that is treated can be kept essentially dry , by immediately removing the steam before there is any opportunity to condense to any significant degree . the air heating assembly also uses the vacuum fan 21 , instead of a separate fan , thus reducing the amperage needed to run all functions , and thus saving energy and simplifying the operation and structure of the apparatus . referring to fig2 , the insulated steam hose 13 runs inside the blower hose 32 , preferably concentrically . the air gap created by the differences in tube diameters protects the exterior tube from getting too hot and potentially dangerous to handle . it can also prevent steam in the steam hose 13 from condensing and turning into water . the insulated steam hose can be held concentrically periodically along the length of the blower hose 32 with small clips ( not shown ). alternatively , the steam hose 13 and blower hose 32 can be separated . optionally , the steam hose 13 and the blower hose 32 can run and mix in one hose , eliminating the need for the mixing chamber 5 . the treatment substance dispensing assembly 4 preferably includes a treatment substance reservoir 41 to contain a treatment substance that can be used to kill bed bugs or other pests , a treatment substance hose 42 and a treatment substance dispensing nozzle 43 for spraying the treatment substance upon the surfaces to be treated . the treatment substance that can be used in the apparatus may vary depending upon the type of pest to be eradicated . the treatment substance could be a chemical treatment substance or a natural treatment substance ; it could be a powder , small solid particles , or a liquid . for example , the treatment substance could be a powder such as diatomaceous earth for killing bed bugs . preferably but not necessarily , the force for spraying the treatment substance is supplied by the vacuum fan 21 . the treatment substance reservoir 41 is connected to the fan exhaust by air supply pipe 45 . the flow of the treatment substance to treatment substance dispensing nozzle 43 can be controlled by controlling the flow of air from the fan exhaust by a valve 47 on the pipe 45 . alternatively , a separate pump could be used to supply the force needed to dispense the treatment substance . optionally , the treatment substance dispensing assembly 4 can be a manually - operated sprayer for dispensing a chemical . preferably , the flow of treatment substance in the treatment substance reservoir 41 to the treatment substance dispensing nozzle 43 can be controlled by the operator using a hand manipulated valve 44 in the treatment substance hose 42 . the treatment substance dispensing nozzle 43 preferably is attached to the outside of the operating nozzle 6 . however , it should be slightly away or offset from the operating nozzle , so that the powder or other treatment substance is not simply vacuumed up by the operating nozzle . preferably , the treatment substance dispensing nozzle 43 therefore is offset and directed at an angle away from the outlet of the operating nozzle 6 , so the treatment substance is dispensed on the treated area without being affected by the suctioning of the vacuum . the operating nozzle 6 is used to spray the steam / heated air mixture on the surface to be treated , and to then immediately suction it away from the surface . the nozzle 6 needs to be designed in a way that each element does not interfere with the other , i . e . the steam / heated air or “ steam nozzle ” 62 needs to be slightly separated from the vacuum inlet or “ vacuum nozzle ” 61 . referring to fig2 , in one example , the operating nozzle 6 includes two separate nozzles , namely a vacuum nozzle 61 and a steam nozzle 62 . ribs or the like , or a bracket arrangement , keep the two nozzles somewhat separated so that the functions do not interfere with each other unduly . with the vacuum nozzle , steam nozzle and treatment substance dispensing nozzle suitably secured in proximity to each other as a nozzle unit , an operator can move the nozzle unit appropriately across the surface so as to apply the dry steam , then apply the vacuum , and then apply the treatment substance . in another embodiment , as shown in fig5 , the operating nozzle 6 features two concentric ports . the center port emits the steam and heat mixture whereas the outermost ring is used for the vacuum . the concentric design is preferred as it allows for the operator to move the nozzle in any direction . as another alternative , as shown in fig6 , the operating nozzle 6 features three concentric ports for heat / steam 62 , vacuum 61 and treatment substance 43 . in such an embodiment , it is preferable that the three elements can be switched on and off independently , to avoid for example the treatment substance being vacuumed up as soon as it is applied . however , a consequence of this design is that live bugs may be vacuumed into the waste reservoir 23 prior to being exterminated . three solutions to this problem are considered . a first option is to superheat the vacuum hose such that as the bugs travel through the hose the exposure to the hot air would exterminate them prior to arriving in the waste reservoir 23 . a second option would be to heat the waste reservoir 23 to a sufficient temperature such that any bugs still alive are guaranteed to be exterminated . a third and preferred option is to have a sealable vacuum bag which contains an amount of the treatment substance used in the treatment substance dispensing assembly 4 ( such as diatomaceous earth ), ensuring the bugs are eventually exterminated and sealed in the sealable vacuum bag . the operating nozzle 6 , connected to the body assembly ( including the steam generating assembly 1 , the vacuum assembly 2 , the air heating assembly 3 and the treatment substance dispensing assembly 4 ) via hoses and tubing , preferably is a hand - held unit which when manipulated makes it very easy to direct and apply the heated steam , vacuum and treatment substance . the operating nozzle 6 preferably includes various mounts to receive and connect the various hoses from the body assembly as well as mounts to attach other nozzle attachments ( extension tubes , flexible crevice tools , upholstery tool , and surface agitators such as a brush 80 ), a switch for the heating elements , a selectively controllable switch for each function , and suitable gripping areas for maximum control and manipulation . preferably the apparatus incorporates a failsafe switch on the operating nozzle 6 which specifically controls the heating elements . the switch when engaged turns the heating apparatus on and when disengaged turns the heating apparatus off . another embodiment incorporates a temperature sensor and automatic shut off near or preferably attached to the body assembly which provides additional safety measures to ensure the heating apparatus doesn &# 39 ; t overheat . referring to fig1 , for improved ability to manipulate and control the apparatus , the body assembly , comprising the steam generating assembly 1 , the vacuum assembly 2 , the air heating assembly 3 and the treatment substance dispensing assembly 4 , are preferably mounted on a base assembly 7 which preferably is provided with wheels for ease of movement . in some embodiments , as shown in fig7 , the body assembly may be connected to a lightweight chassis assembly with flexible ergonomic straps to be worn by the operator and used as a portable backpack unit . if desired , the base or chassis assembly may also include tools such as brushes or the like to agitate the surface or access narrow spaces . during operation of the apparatus , the user removes the water reservoir 11 for filling at least partially with water , or otherwise fills the water reservoir 11 while on the steam generating assembly 1 . the user then turns on the heating element 12 to heat water , and steam is thereafter generated within the water reservoir 11 and is transferred through insulated steam hose 13 . at the same time , the user can turn on the power to drive the vacuum fan 21 and to generate suction through the vacuum nozzle 61 , to draw dirt , soil , dust and other debris through the vacuum nozzle 61 and into the waste reservoir 23 , where the air is then separated from the solids , with the solids settling to the bottom of the waste reservoir 23 . the air then exits the waste reservoir 23 through the filter 24 and then exits the waste reservoir 23 through the vacuum exhaust 25 . part of the air is drawn to the air heating assembly 3 through air supply pipe 33 . the heating element 31 heats the air and sends it to the blower hose 32 . the steam and the heated air meet in the mixing chamber 5 and the steam is further heated by the hot air . as a result of the additional heat , the steam turns into dry steam and is sprayed from steam nozzle 62 of the operating nozzle 6 . the high temperature steam cleans the surface and kills bed bugs or other pests . the vacuum nozzle 61 sucks the dead bed bugs or other pests to the waste reservoir . at the same time , the user can also spray treatment substance onto the surface . the bed bugs can also be killed by the treatment substance and be sucked to the waste reservoir . when the cleaning is completed , the user can move to another spot . when all the cleaning is completed , the user can turn off all power and preferably empty the waste reservoir 23 . other embodiments of the invention permit a user to switch between full treatment mode which has all features functioning ( steam , heat , vacuum and treatment substance ), vacuum cleaning mode , heated steam treating mode , and treatment substance application mode by manipulating a switch connected to the operating nozzle . furthermore , a preferred embodiment would have the temperature and steam intensity adjustable via a user manipulated control ( such as dial or knob ) near the body assembly and connected either to the air heating assembly or steam apparatus . referring to fig3 and 4 , another example of the dry steamer pest control apparatus is shown , configured to attach to and use the pre - existing central vacuum units in a house or other edifice . the body assembly in this embodiment does not need to accommodate the vacuum assembly 2 , but does require an additional fan 8 for the air heating assembly 3 and the treatment substance dispensing assembly 4 . specifically , the dry steamer pest control apparatus of this embodiment includes : a steam generating assembly 1 for generating and delivering steam ; an additional fan 8 ; a heating element 3 for heating and delivering the air from the additional fan 8 ; a treatment substance dispensing assembly 4 for dispensing treatment substances onto a surface to be treated ; a mixing chamber 5 for mixing steam from the steam generating assembly 1 and hot air from the heating element assembly 3 ; and an operating nozzle assembly 6 , for spraying the steam / heat mixture from the mixing chamber 5 and drawing air for the central vacuum 9 . referring to fig4 , in this example the vacuum nozzle 61 is connected to the central vacuum by a hose . the air heated in the air heating assembly 3 is from the additional fan 8 , and therefore the air supply pipe 33 is connected to one of the outlets of the additional fan 8 . also , the power for spraying the treatment substance is supplied by the additional fan 8 , and therefore the air supply pipe 45 is connected to one outlet of the additional fan 8 . the flow of the treatment substance in the treatment substance dispensing nozzle 43 can be controlled by controlling the flow of the air from the additional fan 8 . other parts are essentially as described in relation to the embodiment of fig1 and 2 . during operation of the apparatus of the fig3 and 4 embodiment , the user removes the water reservoir 11 for filling at least partially with water , or otherwise fills the water reservoir 11 . the user turns on the heating element 12 to heat water , and steam is thereafter generated within the water reservoir 11 and is transferred through the insulated steam hose 13 . at the same time , the user can connect the vacuum nozzle 61 to the central vacuum with a hose , to generate a vacuum through the nozzle 61 . dirt , soil , dust and other debris are thereby drawn up into the operating nozzle 61 and into the central vacuum system . at the same time , turning on the additional fan 8 sends air to the air heating assembly 3 through air supply pipe 33 . the heating element 31 heats the air and sends it to the blower hose 32 . the steam and the heated air meet in the mixing chamber 5 and the steam is further heated by the hot air . the steam turns into dry steam and is sprayed from the steam nozzle 62 of the operating nozzle 6 . the high temperature steam cleans the surface and kills bed bugs or other pests . the vacuum nozzle 61 sucks the dead bed bugs or other pests to the central vacuum system . at the same time , the user can also spray treatment substance onto the surface . bed bugs or other pests can also be killed by the treatment substance and be sucked to the central vacuum system . when the cleaning is completed , the user can move to another spot . when all the cleaning is completed , the user can turn the power switch to its off position . preferably , the apparatus is powered by connecting to any standard electrical outlet and drawing power from one 15 or 20 amp circuit . in some preferred embodiments , the body assembly could be powered by other means such as generators , battery packs or liquid fuel . it will be evident to those knowledgeable in the field of the invention that many variations on the example described above are conceivable within the scope of the invention . it should therefore be understood that the claims which define the invention are not restricted to the specific examples described above .

US-201313973095-A

the invention relates to anticarious delivery vehicles , specifically chewing gums , candies , confectioneries , toothpastes , dentifrices and gels . the invention specifically provides chewing gums , candies , confectioneries , toothpastes , dentifrices and gels containing non - toxic sparingly soluble calcium and phosphate compounds as additives , causing the release of calcium and phosphate ions into the oral cavity gradually and persistently for a period no less than 5 minutes . the invention provides released calcium phosphate ions that diffuse into partially demineralized tooth enamel or dentin , leading to remineralization and repair of caries lesions , dental plaque , open dentinal tubules and exposed dentin . the invention thus provides agents and methods for remineralization of teeth and for reducing or eradicating cariogenic challenge in plaque following sucrose intake . the formulations of the invention can thereby produce effective anticaries actions without the use of fluoride . in addition , the formulations of the invention can be used to desensitize hypersensitive teeth .

it has been known for some time that hydroxyapatite materials have the basic properties of human bones and teeth . a considerable amount of research has been directed to the remineralization of incipient dental lesions , including plaque deposits , by deposition of hydroxyapatite , ca 5 ( po 4 ) 3 oh , on such lesions , so that the hydroxyapatite is incorporated into the dental structure at the point of lesion . remineralization of tooth enamel has been carried out experimentally both in vivo and in vitro . these studies have concentrated on the remineralizing properties of saliva and synthetic solutions supersaturated with respect to hydroxyapatite . chewing gums , candies and confectioneries , toothpastes , dentifrices and gels as provided herein are useful as vehicles for delivering hydroxyapatite - depositing calcium phosphate compositions to teeth in vivo . an advantage of these delivery vehicles is that calcium phosphates and compounds that release calcium and phosphate ions into the mouth are provided as simple mixtures in the chewing gum , candy , confectionery , toothpaste , dentifrice or gel , because delivery to teeth is effectively achieved simply by having a human use the delivery vehicle of the invention ( e . g ., by chewing the calcium phosphate - containing gums , candies and confectioneries and using the calcium phosphate - containing toothpastes , dentifrices and gels ). compounds that release calcium and phosphate ion are selected from a number of commercially - available and other compounds that are recognized as food additives in other contexts . all such additives encompassed by the present invention are intended to be non - toxic . for the purpose of this invention , the term &# 34 ; non - toxic &# 34 ; is intended to conform with accepted and established definitions of safety , such as are described by the designation &# 34 ; generally accepted as safe &# 34 ; by the food and drug administration . also encompassed in this definition are those compounds that have been added to food for some time and which are recognized as safe under conditions of their intended use . the additives of the invention , including calcium and phosphate salts should be non - toxic enough for oral use at the intended levels on a regular basis , and stable for the desired shelf life . preferred calcium ion - releasing compounds are sparingly soluble calcium - containing salts of biologically - compatible acids and other basic calcium compounds , i . e ., calcium compounds having a solubility greater than about 0 . 1 % and less than about 10 % under conditions of neutral ph . sparingly soluble calcium compounds include but are not limited to the calcium salts of gluconate , glycerophosphate , lactate , and fumarate , ca ( oh ) 2 , cao , monocalcium phosphate , dicalcium phosphate anhydrous , dicalcium phosphate dihydrate , α - tricalcium phosphate , octacalcium phosphate , tetracalcium phosphate , and combinations and mixtures thereof . there are two major categories of gums useful as components of the instant invention : neutral ph gums and acidic ph gums . acidic ph gums include most fruit flavored chewing gums and bubble gums . neutral ph gums include all mint flavored gums and some other non - fruit flavored gums . it has been found that none of the calcium phosphate compounds tested ( with the exception of monocalcium phosphate monohydrate ) was capable of releasing calcium or phosphate ions unless the gum had an acidic ph and produced an acid ph in saliva ( i . e ., ph less than 7 . 0 ), as shown herein in table iii below . this new finding may explain why dicalcium phosphate dihydrate - containing mint - flavored ( neutral ph ) gums were previously reported to show only marginal anti - caries effects ( see finn and jamison , 1967 , ibid . and richardson et al ., 1972 , ibid .). in contrast , monocalcium phosphate monohydrate ( mcpm ) was found to be capable of releasing calcium and phosphate ions into saliva from non - acidic gums ( table iii ). however , the acidity of mcpm produces a tart taste which may be incompatible with some gum flavors . in addition , mcpm produces an unpleasant after - taste if the gum contain more than 2 or 3 % mcpm . thus , the most useful calcium phosphate - containing gums are acidic ph gums , which represent only a minor portion of the gums being consumed . however , neutral gums have surprising been found to be capable of releasing anticarious calcium phosphate agents under certain conditions , specifically , by adding separate calcium - containing and phosphate - containing compounds to the gum . several non - toxic calcium compounds are sparingly soluble , and when used as chewing gum additives , allowed calcium ions to be released into saliva gradually and continuously ( see table iv ). these compounds include the calcium salts of gluconic acid , lactic acid , fumaric acid , and glycerophosphoric acid . unlike calcium phosphates , the solubilities of these calcium - containing compounds are essentially independent of ph , resulting in these additives being capable of performing well in both acid and neutral ph gums . in order to obtain significant calcium ion release , the calcium source should have a solubility that is greater than 0 . 5 % at neutral ph ; solubilities of 2 % and above are preferred . preferred calcium salts are sparingly soluble , that is , having a solubility of less than 10 % at neutral ph . calcium carbonate , and calcium citrate and calcium tartrate ( the calcium salts of two commonly - used food acids ) are too insoluble to produce effective release ( see table iv ). on the other hand , highly soluble calcium - continuing compounds such as calcium acetate and calcium chloride are of limited usefulness because these compounds are incapable of sustained release of calcium ions from the chewing gums . ( however , soluble calcium compounds may be useful with other delivery vehicles of this invention such as candies and confectioneries which take 5 minutes or longer to dissolve .) the anticaries effects of calcium ion - releasing compounds of the invention are significantly augmented by adding a non - toxic phosphate salt as a second additive . preferred phosphate salts include sodium phosphate ( most preferably comprising an equimolar mixture of na 2 hpo 4 and nah 2 po 4 , to maintain ph at 7 ). addition of sodium phosphate to the calcium ion - releasing additives of the invention results in the desired release of both calcium and phosphate ions in quantities capable of depositing calcium phosphate mineral ( including hydroxyapatite ) on the surface of teeth in vivo ( see table iv ). in alternative embodiments , a sparingly - soluble calcium source can be admixed with a calcium phosphate salt , such as mcpm , which serves as a source for both calcium and phosphate ions . candies and confectioneries of the invention comprise preferably sweeteners such as sorbitol , mannitol , aspartame and saccharine . sugar ( specifically sucrose , fructose , glucose , and combinations thereof ) containing candies and confectioneries are also provided by the invention . flavorings , such as citrus and other flavorings , that are naturally acidic are used to provide an advantageous acidic environment as discussed above . in addition , calcium compounds having substantially higher solubility than those calcium compounds useful in the gums and dentifrices of the invention can be used in the candies and confectioneries as provided herein ; non - limiting examples of such calcium compounds are calcium chloride and calcium acetate . preferred candies of the invention are non - chewable hard candies . preferably , particles of the calcium and phosphate compounds comprising the candies and confectioneries of the invention are uniformly distributed throughout the candy or confectionery . in preferred embodiments , the candies and confectioneries of the invention are formulated wherein calcium and phosphate ions are released from the candies and confectioneries as they dissolve . it will be understood that the release rate of the calcium and phosphate ions depends on the concentration and distribution of these ions in the candies and confectioneries and on the rate of dissolution of the candies and confectioneries , which in turn is dependent on the surface area of the candy or confectionery and its composition . in these formulations , the solubilities of the calcium and phosphate - containing compounds contribute relatively less to the release rates of calcium and phosphate ions than does the candy or confectionary dissolution rate . calcium and phosphate ion release kinetics can be formulated accordingly by those of skill in the art based on these parameters . remineralizing gels of the invention comprise a non - toxic gelling compound as are conventionally used in foods , including but not limited to agar , geletine , carboxymethyl cellulose , chitin , gum acacia , gum arabic , gum xanthum , hydroxyethyl cellulose and hydroxypropyl methylcellulose . the gels of the invention are formulated to have a neutral ph to avoid irritation of oral tissues upon prolonged exposure . each gel also comprises sufficient water or other aqueous solution to produce the desired consistency , as well as high molecular weight crystal growth inhibitors , and flavoring and coloring agents . high molecular weight crystal growth inhibiting agents include the gelling agents themselves , as described above , and also phosphoproteins ( such as are disclosed in ternine & amp ; conn , 1976 , calcif . tiss . res . 22 : 149 - 157 ), polycarboxylates ( such as are disclosed in howie - meyers et al ., 1995 , in mineral scale formation and inhibition , amjad , ed ., plenum press : new york , ch . 15 , pp . 169 - 182 ), and polyphosphorylated polyvinyl alcohol ( as are described in shimabayashi et al ., 1995 , in mineral scale formation and inhibition , amjad , ed ., plenum press : new york , ch . 14 , pp . 157 - 168 ). such gels also comprises a sparingly - soluble calcium salt or a phosphate salt as described above for the gums of the invention . calcium phosphate - containing gels of the invention are preferably provided as a dry powder comprising the calcium phosphate compound and , optionally , dry flavorings , sweeteners , gelling agents , and other components are described above . in these embodiments , the gel is reconstituted by adding water or other liquid comprising advantageous additives ( such as colorings , flavorings , sweeteners , gelling agents , and the like ). dentifrices and toothpastes of the invention comprise conventional components of dentifrices and toothpastes , including but not limited to sweeteners such as sorbitol or saccharine , abrasives such as hydrated silica , foaming agents such as sodium lauryl sulfate , binders such as various forms of cellulose or gums , lubricants such as glycerin , pigment whiteners such as titanium oxide , food coloring and water . as with the gels of the invention , the dentifrices and toothpastes of the invention are advantageously provided as a dry powder comprising the calcium phosphate compound and , optionally , dry flavorings , sweeteners , gelling agents , and other components are described above . in these embodiments , the gel is reconstituted by adding water or other liquid comprising advantageous additives ( such as colorings , flavorings , sweeteners , gelling agents , and the like ). an additive of particular significance in dental applications is fluoride containing compounds . in toothpaste and gel embodiments of this invention , fluoride salts such as naf , caf 2 , snf 2 , na 2 po 3 f or na 2 sif 6 are added in sufficient quantity they increase the rate of formation of ha and fluorapatite . preferably , embodiments of the invention will have a fluoride content of about 200 to 2200 ppm . the total amount of fluoride released during use of the toothpastes gels of this invention is 0 . 05 to 10 mg . using the chewing gums of the invention , sustained release of calcium and phosphate ions from the gums , candies and other delivery vehicles of the invention should be maintained for at least about 3 - 5 minutes and preferably , at least about 3 - 10 minutes and most preferably , at least about 3 - 15 minutes . the following examples are intended to further illustrate certain preferred embodiments of the invention and are not limiting in nature . calcium phosphate - containing gums were prepared as follows . calcium lactate , calcium gluconate , calcium glycerophosphate , monocalcium phosphate monobasic , disodium hydrogen phosphate , and sodium dihydrogen phosphate were all obtained commercially as food grade chemicals . α - tricalcium phosphate ( α - tcp ) was prepared by heating a mixture containing 2 moles of commercially - available dcpa and 1 mole of commercially available calcium carbonate ( caco 3 ) to 1200 ° c . for 6 h . gums used were lifesaver ® peppermint gum ( as a neutral ph gum ) or lifesavers ® grape flavored bubble gum ( as an acidic ph gum ). experimental gums were prepared by uniformly dispersing the calcium phosphate additive into the control gums . release of calcium and phosphate ions from the gum into saliva the ability of calcium phosphate - containing chewing gums of the invention to release calcium and phosphate ions into the mouth upon chewing by a subject was determined as follows . three human subjects with normal salivary flow (≧ 0 . 2 ml saliva per minute ) chewed gums with or without various formulations of calcium phosphate for between 0 - 16 minutes . saliva samples were collected at intervals of either 0 - 2 minutes or 14 - 16 minutes . calcium ion concentration in the saliva samples were determined using a calcium electrode ( orion ; see vogel et al ., 1987 , j . dent . res . 66 : 1691 - 1697 ). phosphate ion concentration in saliva were determined by spectrophotometry ( vogel et al ., ibid .). the results of these studies are shown in table i below . the data in table i show the effect on salivary calcium ion concentration in saliva released after chewing an acidic ph gum containing 1 to 5 wt % α - tcp was chewed . calcium ion release from the 5 % α - tcp gum was statistically equivalent to that of the 5 % ( dcpa / ttcp ) gum . table i______________________________________release of ca into saliva from acid ph gums containingvarious calcium phosphate additives calcium concentration . sup .#, mmol / ladditive 0 - 2 min . 14 - 16 min______________________________________control 0 . 41 ± 0 . 27 0 . 80 ± 0 . 305 % ( ttcp / dcpa ) 10 . 08 ± 1 . 72 1 . 29 ± 0 . 105 % α - tcp 9 . 04 ± 2 . 03 1 . 82 ± 0 . 592 . 5 % α - tcp 4 . 27 ± 0 . 72 1 . 81 ± 0 . 861 % α - tcp 2 . 71 ± 0 . 01 1 . 02 ± 0 . 05______________________________________ . sup .# mean ± s . d ( n = 3 ) the ability of calcium phosphate - containing chewing gums of the invention to remineralize plaque upon chewing by a subject was determined as follows . twelve human subjects with normal salivary flow chewed gums with or without various formulations of calcium phosphate . in these experiments , plaque was allowed to accumulate for 48 h prior to each experiment . baseline samples of plaque were collected prior to the beginning of each experiment , and then subjects rinsed the oral cavity with a 10 % sucrose solution for about 1 min . subjects then chewed control or experimental gums for between 0 - 15 minutes . two pooled plaque samples from upper and lower molars of each subject were collected 7 and 15 min after gum chewing began , with 1 min saliva samples collected just before each plaque sample . for each sample , plaque ph was determined using microelectrodes ( glass ph electrode ; vogel et al ., 1990 , j . dent . res . 69 : 1316 - 1323 ). in addition , plaque fluid was separated from plaque solids by centrifugation and acidified with 0 . 1m perchloric acid to prevent precipitation of calcium phosphate ( as the result of increased calcium phosphate levels in saliva and removal of dissolved carbonate anion as carbon dioxide from saliva after sample collection ). free calcium ion concentration in the saliva samples were determined using a calcium electrode as described above . total calcium and phosphate ion concentration in saliva were determined by spectrophotometry ( as described in vogel et al ., ibid .). data on salivary and plaque ph , and calcium and phosphate ion concentrations were used to calculate the degree of saturation with respect to tooth mineral in plaque . the results from these experiments are shown in table ii . the data in table ii show that chewing gum containing 2 . 5 % α - tcp produced significant increases in the calcium and phosphate ion concentrations in plaque . these increases prevented a decrease in mineral saturation in plaque after sucrose intake and completely eradicated the acidic challenge produced by sucrose . in contrast , the subject group that used the control gum experienced a decreased plaque mineral saturation level after the sucrose rinse that was indicative of increased caries risk . table ii__________________________________________________________________________plaque composition after a sucrose rinse and chewing acidic ph gums ph ca !. sub . f ca !. sub . t p !. sub . t piaptime ( min ) ctrl . sup . 1 exp . sup . 2 ctrl exp ctrl exp ctrl exp ctrl exp__________________________________________________________________________ - 1 7 . 08 . sup . 3 7 . 07 0 . 77 0 . 83 1 . 87 1 . 89 13 . 1 12 . 5 48 . 5 49 . 2 (. 45 ). sup . 3 (. 33 ) (. 27 ) (. 48 ) (. 50 ) (. 78 ) ( 2 . 6 ) ( 1 . 3 ) ( 1 . 4 ) ( 1 . 6 )- 1 to 0 sucrose challenge 0 to 15 gum chewing 7 6 . 15 6 . 50 1 . 42 & lt ; 3 . 58 . sup . 4 2 . 69 & lt ; 5 . 82 8 . 88 & lt ; 11 . 1 52 . 7 & gt ; 48 . 8 (. 42 ) (. 48 ) (. 50 ) ( 1 . 9 ) (. 78 ) ( 2 . 0 ) ( 1 . 2 ) ( 3 . 0 ) ( 2 . 3 ) ( 1 . 9 ) 15 6 . 58 6 . 31 1 . 33 & lt ; 2 . 51 2 . 23 & lt ; 3 . 96 8 . 69 9 . 70 50 . 4 & gt ; 47 . 8 (. 50 ) ( 1 . 9 ) (. 34 ) ( 1 . 37 ) (. 70 ) ( 1 . 53 ) ( 1 . 64 ) ( 1 . 84 ) ( 2 . 5 ) ( 1 . 0 ) __________________________________________________________________________ . sup . 1 control gum was lifesavers grape flavored bubble gum . . sup . 2 experimental gum was the 2 . 5 % tcp added to the control gum . . sup . 3 mean ( std dev ); n = 12 to 14 . sup . 4 means of the control and experimental groups are significantly different ( p & lt ; 0 . 05 ). ca !. sub . f = free ca concentration ( mmol / l ) measured by ca electrode ; ca . sub . t ! and p . sub . t ! = total ca and p concentrations measured by spectrophotometric methods ; piap = log ( iap ) where iap is ion activity product of hydroxyapatite . two types of gums were tested as components of the invention : neutral ph and acidic ph gums . an example of an acidic ph gum tested was lifesavers ® grape bubble gum , as disclosed above in table i . a neutral ph gum tested was lifesavers ® peppermint gum , in experiments performed as described above to produce the data comprising table i . the results of experiments with neutral ph gums are shown in table iii . the data in table iii show that calcium and phosphate ions are not efficiently released from a neutral ph gum ( lifesavers ® peppermint gum ). in fact , none of the calcium phosphate compounds tested ( with the exception of mcpm ) was capable of releasing calcium or phosphate ions unless the gum has an acidic ph and produces an acid ph in saliva ( i . e ., ph less than 7 . 0 ; compare the data in table i with the data in table iii ). table iii______________________________________release of ca . sup .++ ions into saliva from ph neutralgums containing calcium phosphate additives calcium concentration . sup . 1 , mmol / ladditive 0 - 2 min . 14 - 16 min______________________________________control 1 . 11 ± 0 . 11 0 . 90 ± 0 . 075 % ( ttcp / dcpa ) 0 . 82 ± 0 . 03 0 . 82 ± 0 . 025 % α - tcp 0 . 72 ± 0 . 03 0 . 77 ± 0 . 035 % ttcp 1 . 03 ± 0 . 14 1 . 05 ± 0 . 222 % mcpm 3 . 74 ± 0 . 68 1 . 15 ± 0 . 205 % mcpm 6 . 56 ± 0 . 84 0 . 92 ± 0 . 23______________________________________ . sup . 1 mean ± s . d . ( n = 3 ) in other experiments , neutral gums were used to release anticarious calcium phosphate agents under certain conditions . this was achieved by adding separate calcium - containing and phosphate - containing compounds to the gum . calcium - containing compounds used as separate calcium - containing additives were the calcium salts of gluconic acid , lactic acid , fumaric acid , and glycerophosphoric acid . results using these compounds are shown in table iv . in these experiments it was found that the solubilities of these calcium - containing compounds are essentially independent of ph ( in contrast to calcium phosphate compounds , which require acidic ph ). calcium carbonate and the calcium salts of two commonly used food acids , citric acid and tartaric acid , were too insoluble to produce effective release ( table iv ). the anticaries effects derived from the calcium compounds were significantly augmented by adding an equimolar mixture of na 2 hpo 4 and nah 2 po 4 ( to maintain ph at 7 ). this caused a significant release of phosphate ions into saliva . the data further showed that the combination of a calcium source ( e . g ., calcium glycerophosphate ) and a phosphate source ( e . g ., sodium phosphate ) in a gum resulted in the desired release of both calcium and phosphate ions . it was also found that a sparingly - soluble calcium source ( such as calcium glycerophosphate ) could be used with mcpm ( which served as a source for both calcium and phosphate ions ). table iv______________________________________release of calcium and phosphate ions into saliva from phneutral gums containing separate calcium and phosphate additives concentration . sup . 1 , mmol / ladditive 0 - 2 min 14 - 16 min______________________________________control ca ! 1 . 11 ± 0 . 11 0 . 90 ± 0 . 075 % ca lactate ca ! 10 . 3 ± 2 . 20 2 . 48 ± 0 . 205 % ca gluconate ca ! 4 . 85 ± 1 . 32 1 . 87 ± 0 . 275 % ca citrate ca ! 1 . 20 ± 0 . 12 1 . 30 ± 0 . 135 % ca glycerophosphate ca ! 8 . 84 ± 1 . 45 2 . 14 ± 0 . 71 p ! 3 . 59 ± 1 . 33 3 . 51 ± 0 . 733 % ca glycerophosphate + ca ! 5 . 80 ± 0 . 54 1 . 21 ± 0 . 092 % mcpm p ! 12 . 8 ± 1 . 70 6 . 63 ± 1 . 702 % na phosphate ca ! 0 . 55 ± 0 . 07 0 . 76 ± 0 . 14 p ! 20 . 3 ± 0 . 26 4 . 15 ± 0 . 705 % ca carbonate ca ! 0 . 80 ± 0 . 00 0 . 93 ± 0 . 07______________________________________ . sup . 1 mean ± s . d . ( n = 3 ) one embodiment of the remineralizing toothpastes of the invention comprise a calcium - containing component and a phosphate - containing component , stored in separate containers to prevent premature development of hydroxyapatite in the presence of the wet components of the toothpaste . in a first example , a calcium phosphate - containing toothpaste is prepared as described in table v . in this example , the calcium source is calcium glycerophosphate and the phosphate cource is monohydrogenphosphate heptahydrate and sodium dihydrogen phosphate . the phosphate - containing component also advantageously contains sodium fluoride as a fluoride source . a second example of a calcium phosphate - containing toothpaste is shown in table vi . in this example , the calcium source is calcium gluconate and the phosphate source is monocalcium phosphate monohydrate . the phosphate - containing component also advantageously contains sodium monofluorophosphate as a fluoride source instead of sodium fluoride , since the latter fluoride source will react with monocalcium phosphate monohydrate to form calcium fluoride and fluoroapatite ( thus preventing the release of either phosphate or fluoride in the toothpaste during application ). in both examples , the toothpastes are forumulated so that the calcium source component and the phosphate source component are used in equal amounts ( by weight ) during application , using established packaging means and other methods known in the dental arts . table v______________________________________remineralzing toothpaste example 1component paste a paste b______________________________________calcium glycerophosphate 4 . 2 g 0sodium monohydrogen phosphate 0 2 . 68 gheptahydratesodium dihydrogen phosphate dihydrate 0 1 . 56 gsodium fluoride 0 0 . 48 gsorbitol ( 70 % solution ) 15 g 15 gsilica 35 g 35 gglycerine 15 g 15 gsodium carboxymethyl cellulose 1 g 1 gsodium η - lauryl sarcosinate 1 g 1 gwater , coloring , flavoring q . s . to 100 g q . s . to 100 g______________________________________ table vi______________________________________remineralzing toothpaste example 2component paste a paste b______________________________________calcium gluconate 8 . 96 g 0monocalcium phosphate monohydrate 0 2 . 52 gsodium monofluorophosphate 0 1 . 67 gsorbitol ( 70 % solution ) 15 g 15 gsilica 35 g 35 gglycerine 15 g 15 gsodium carboxymethyl cellulose 1 g 1 gsodium η - lauryl sarcosinate 1 g 1 gwater , coloring , flavoring q . s . to 100 g q . s . to 100 g______________________________________ another embodiment of the remineralizing toothpastes of the present invention comprises a dry powder containing a calcium phosphate source . preferred calcium phosphate compositions are tetracalcium phosphate , α - tricalcium phosphate and monocalcium phosphate . upon use the powder can be mixed with a liquid , i . e ., water , to form a paste . the paste is then applied to the teeth . all remineralizing gels comprise a calcium - containing component and a phosphate - containing component , stored in separate containers to prevent premature development of hydroxyapatite in the presence of the wet components of the gel . in a first example , the formulation of which is shown in table vii , these components comprise a liquid component and a dry ( powder ) component . in this embodiment , the liquid is combined with the powder immediately prior to use to obtain a smooth gel , which is then applied to the areas in which reminieralization is desired ( including , for example , sensitive root surfaces and caries lesions on the chewing surfaces of teeth ). in the practice of this aspect of the invention , it is anticipated that an amount of about 10 g of the gel described herein will be advantageously applied for remineralizing purposes , and the example set out in table vii is formulated therefore . table vii______________________________________remineralizing gel example 1components dry powder liquid______________________________________α - tricalcium phosphate 0 . 8 g 0sodium carboxymethyl cellulose 0 . 35 g 0sodium fluoride 0 . 024 g 0sorbitol ( 70 % solution ) 0 1 . 5 gwater 0 7 . 326 g______________________________________ in a second example , the formulation of which is shown in table viii , the formulation comprises an equal amount of two gels , one comprising a calcium source and the other comprising a phosphate source , which are mixed immediately prior to use to produce a homogeneous gel . table viii______________________________________remineralizing gel example 2component gel 1 gel 2______________________________________calcium glycerophosphate 8 . 4 g 0sodium monohydrogen phosphate 0 5 . 36 gheptahydratesodium dihydrogen phosphate dihydrate 0 3 . 12 gsodium fluoride 0 0 . 95 gsorbitol ( 70 % solution ) 15 g 15 gsodium carboxymethyl cellulose 6 g 6 gwater , flavoring , coloring q . s . to 100 g q . s . to 100 g______________________________________ both sugar - free candies ( table ix ) and sugar - containing candies ( table x ) are described . in this aspect of the invention , calcium and phosphate sources can be combined in the same phase without concern of premature hydroxyapatite - producing reactions between the two compounds , since there is essentially no free water in such candies . table ix______________________________________remineralizing sugar - free candy examplecomponent amount______________________________________calcium glycerophosphate 8 . 4 gsodium monohydrogen phosphate heptahydrate 5 . 36 gsodium dihydrogen phosphate dihydrate 3 . 12 gsorbitol , flavoring , coloring q . s . to 100 g______________________________________ table x______________________________________remineralizing candy examplecomponent amount______________________________________α - tricalcium phosphate 8 gsugar , corn syrup , flavoring , coloring q . s . to 100 g______________________________________ it should be understood that the foregoing disclosure emphasizes certain specific embodiments of the invention and that all modifications or alternatives equivalent thereto are within the spirit and scope of the invention as set forth herein .

US-70442096-A

a height adjustment mechanism for a dish rack of a dishwasher is provided , having an attachment channel for attaching the dish rack to the dishwasher . a wheel assembly slideably engages the attachment channel at first and second spaced apart locations . the wheel assembly includes engagement features corresponding to a plurality of dish rack heights . a rack mounting assembly is attached to the dish rack and slideably attached to the wheel assembly . a lever is pivotably engaged relative to the rack mounting assembly and is configured to selectively engage one of the engagement features . a biasing element is configured to urge the lever into selective engagement with the engagement features , and the rack mounting assembly may be moved from a first to a second dish rack height position by applying a force to the rack mounting assembly generally perpendicular to the attachment channel . an associated method and system are also provided .

the present invention now will be described more fully hereinafter with reference to the accompanying drawings , in which some , but not all embodiments of the inventions are shown . indeed , these inventions may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein ; rather , these embodiments are provided so that this disclosure will satisfy applicable legal requirements . like numbers refer to like elements throughout . fig1 and 2 illustrate a height adjustment mechanism for a dish rack of a dishwasher according to an embodiment of the present invention , the height adjustment mechanism being generally indicated as numeral 100 . generally described , this embodiment of the present invention is intended to provide a height adjustment for a dish rack 105 of a dishwasher , wherein the rack may be an upper rack 105 or lower rack , as appropriate . as will be understood by those of skill in the art , an upper dish rack may be slideably mounted relative to the inner side - walls of a dishwasher such that the upper dish rack can move in a substantially horizontal plane from a position inside the dishwasher to a position at least partially outside the dishwasher . in one embodiment , attachment of the dish rack to the dishwasher is facilitated by a pair of c - shaped channels ( see e . g ., fig2 a ). each channel may be secured to an inner side - wall of the dishwasher by two pair of rollers , which maintain the c - shaped channel in a substantially horizontal plane while allowing the c - shaped channel to slide at least partially outside of the dishwasher . referring to fig1 , the height adjustment mechanism 100 includes a wheel assembly 110 , a rack mounting assembly 130 and a lever assembly 140 . generally described , the wheel assembly 110 facilitates attachment of the height adjustment mechanism 100 to the dishwasher , and the rack mounting assembly 130 facilitates attachment of the height adjustment mechanism 100 to the dish rack 105 . the lever 140 cooperates with the wheel assembly 110 and the rack mounting assembly 130 to selectively position the dish rack 105 at a desired height . the rack 105 generally includes a height adjustment mechanism 100 engaged on each lateral side thereof . the wheel assembly 110 includes a wheel mounting plate 112 and a pair of wheels 120 a - b . the wheel mounting plate 112 has a substantially planar base portion 113 and two substantially planar flange portions 114 a - b positioned at opposite ends of the base portion 113 . the flange portions 114 a - b are within substantially the same plane , which is also substantially parallel to the planar base portion 113 . attached to each flange portion is a wheel 120 a - b , which is sized to engage a mounting track ( not shown ) in a dishwasher . in one embodiment , the mounting track is a c - shaped channel and the wheels engage the channel as generally shown in fig2 a . the wheels 120 a - b are aligned such that the rack will be positioned in a substantially horizontal plane . in addition , the wheels 120 a - b are preferably spaced apart so as to support the rack 105 relative to the mounting track . although the wheels shown in the figures are generally round , one of skill in the art will appreciate that other shapes may be used to engage a dishwasher mounting track . the base portion 113 of the wheel mounting plate 112 defines two substantially parallel vertical slots 115 a - b . these slots are sized to cooperate with pins 122 a - b and bushings 124 a - b , which provide a slideable attachment between the wheel assembly 110 and the rack mounting assembly 130 . generally described , the movement of the rack mounting assembly 130 , and therefore the dish rack 105 in relation to the wheel assembly 110 , is restricted by the movement of the pins 122 a - b and bushings 124 a - b within the slots 115 a - b . in other words , movement of the rack mounting assembly 130 in relation to the wheel assembly 110 is in a direction substantially parallel with the longitudinal axis of the slots 115 a - b . the base portion 113 also defines two slots 118 a - b that are spaced apart and oriented such that the longitudinal axes of the two slots 118 a - b are substantially aligned . these slots 118 a - b are positioned to accept a portion of the lever 140 as will be discussed in greater detail below , and are oriented generally perpendicular to slots 115 a - b . the base portion 113 further defines an upper locating edge 116 and a lower locating edge 117 . in one embodiment , the lower locating edge 117 as well as the upper edges of the slots 118 a - b of the base portion 113 are configured with a substantially inclined or arcuate flange . as will be discussed later , these locating edges and slots may be selectively engaged by the lever to selectively position the upper dish rack at a desired height . the locating edges and slots may be referred to herein as engagement features . fig2 illustrates the rack attachment assembly 130 , which includes an outside rack mounting plate 132 and an inside rack mounting plate 136 . the outside rack mounting plate 132 is positioned on the outside of the dish rack 105 , while the inside rack mounting plate 136 is positioned inside the dish rack 105 . these two mounting plates are secured together using fasteners ( not shown ) with the dish rack 105 therebetween . in the embodiment shown in fig2 , the outside rack mounting plate 132 includes multiple rack attachment mechanisms 134 , which are u - shaped and sized to engage a wire of the upper dish rack 105 . as will be understood by those of skill in the art , the parallel walls of the u - shaped mechanisms 134 may have complementary scalloped portions such that a wire of the upper dish rack can be retained by snapping it into the scalloped portion between the parallel walls . it should be understood that other types of attachment mechanisms for connecting the outside rack mounting plate 132 to the dish rack may be used in connection with the present invention such as other snap - fit designs or fasteners . as shown in fig1 and 2 , the wheel assembly 110 and the rack mounting assembly 130 are slideably attached using pins 122 a - b and bushing 124 a - b . specifically , a portion of pins 122 a - b pass through bushings 124 a - b and slots 115 a - b in the wheel mounting plate 112 before engaging the outside rack mounting plate 132 . in use , the rack mounting assembly 130 can move relative to the wheel assembly 110 in a direction substantially parallel with the longitudinal axis of the slots 115 a - b . referring now to fig1 - 4 , the lever 140 selectively engages engagement features of the wheel mounting plate 112 to allow a user to position the dish rack 105 at a desired height . the lever 140 includes a handle portion 142 , a biasing element interface portion 143 and two engagement arm portions 144 a - b . the handle portion 142 extends above the biasing element interface portion 143 with the two engagement arm portions 144 a - b extending downwardly from the biasing element interface portion 143 . in use , the two engagement arm portions 144 a - b are positioned between the outside rack mounting plate 132 and the inside rack mounting plate 136 . fig3 provides a side view of an engagement arm portion 144 a of the lever 140 . engagement arm portion 144 a extends downwardly with a generally arcuate shape and terminates at free end 145 a . the free end 145 a includes a wedge portion 146 a extending substantially horizontally and sized to engage the slot 118 a in the wheel mounting plate 112 , with the upper end of each wedge portion 146 a being inclined and the lower end being substantially horizontally disposed . the free end 145 a also includes a horizontal stop member 148 a that discourages engagement of the wedge portion 146 a with the wheel mounting plate 112 beyond a predetermined distance whether engaging the slots 118 a - b or the locating edges 116 , 117 . the engagement arm portion 144 b also extends downwardly with a generally arcuate shape terminating at free end 145 b . free end 145 b also includes a wedge portion 146 b , which is shaped to engage slot 118 b as generally described with respect to wedge portion 146 a . the engagement arm portions 144 a - b are spaced laterally apart with respect to the interaction thereof with the wheel mounting plate 112 so as to provide longitudinal stability for the rack 105 relative to the wheel mounting plate 112 , alone or in combination with the pin 122 a - b , bushing 124 a - b and slot 1 i 5 a - b arrangement previously discussed . fig4 illustrates the interaction between the biasing assembly 150 and the lever 140 . as illustrated , the biasing assembly 150 includes a housing 152 connected to the dish rack 105 and a biasing element 154 . in the illustrated embodiment , the biasing element is a coil spring with cantilevered diverging tag ends ( i . e ., such as the spring used by a clothespin ). the biasing element 154 biases the free ends 145 a - b of the lever 140 toward the wheel mounting plate 112 . a force may be applied to the handle portion of the lever causing the lever to pivot about pivot point “ p ” thereby counteracting the biasing force of the biasing element 154 . this pivoting may disengage the free ends 145 a - b from the locating edges 116 , 117 or the slots 118 a - b as will be discussed in greater detail below . fig5 and 6 illustrate an alternative embodiment of the height adjustment mechanism . this alternative embodiment is generally indicated as numeral 200 . similar to the embodiments described above , the height adjustment mechanism 200 includes a wheel assembly 210 , a rack mount assembly comprising an outside rack mounting plate 232 and an inside rack mounting plate 236 , and a lever assembly 240 . referring to fig6 , the wheel assembly 210 includes a wheel mounting plate 212 and a pair of wheels 220 a - b configured substantially the same as the wheel assembly 110 described above . the wheel mounting plate 212 includes a base portion 213 that defines two substantially parallel vertical slots 215 a - b . these slots are sized to cooperate with pins 222 a - b and bushings 224 a - b to provide a slideable attachment between the wheel assembly 210 and the outside rack mounting plate 232 . the wheel mounting plate 212 also includes two substantially planar flange portions 214 a - b . one distinction between the wheel mounting plate 212 and the wheel assembly 112 is that the wheel mounting plate 212 includes c - shaped features 219 a - b extending from the planar flange portions 214 a - b that open toward the center of the wheel mounting plate 212 . these c - shaped features are configured to slideably engage the outside mounting plate 232 when in use . this feature provides additional stability to the dish rack by discouraging movement of the outside rack mounting plate 232 relative to the wheel mounting plate 212 in a direction other than parallel with the vertical slots 215 a - b . as with the height adjustment mechanism 100 , the wheel mounting plate 212 of the height adjustment mechanism 200 includes features configured to be selectively engaged by the lever assembly 240 . specifically , the wheel mounting plate 212 defines two slots 218 a - b that are spaced apart and oriented such that the longitudinal axes of the slots 218 a - b are substantially aligned . the wheel mounting plate 212 further defines an upper locating edge 216 and a lower locating edge 217 . turning to fig5 , the outside rack mounting plate 232 is positioned on the outside of the dish rack 105 , while the inside rack mounting plate 236 is positioned inside the dish rack 105 . these two mounting plates are secured together using fasteners 238 a - b with the dish rack 105 therebetween . the embodiment illustrated in fig5 does not include a rack engagement mechanism ( e . g ., 135 ) as describe above with reference to the height adjustment mechanism 100 ; however , one of ordinary skill in the art will recognize that a rack engagement mechanism 135 could be utilized in the height adjustment mechanism 200 if desired . the lever 240 is similar to the previously described lever 140 , in that it includes a handle portion 242 , a biasing element interface portion 243 and two engagement arm portions 244 a - b . the biasing element interface portion defines a recess 247 , which is sized and shaped to receive a wire of the dish rack 105 . in use , attachment bracket 255 and fastener 256 secure the wire of the dish rack 105 into the recess such that the lever 240 can pivot about the wire . one distinction between the lever 240 and the lever 140 is that the engagement arm portions 244 a - b of lever 240 are substantially planar as opposed to having an arcuate shape like the engagement arm portions 144 a - b described above with reference to lever 140 . the engagement arm portions 244 a - b include free ends 245 a - b . these free ends include wedge portions 246 a - b , which are generally the same shape as wedge portions 146 a - b described with reference to the earlier embodiments . the biasing assembly 250 includes a housing 252 and a biasing element 254 . in the illustrated embodiment , the biasing element is a flat spring with one free end engaging the housing 252 , which is attached to the dish rack 105 . as one of ordinary skill in the art will recognize , the housing 252 may be attached to the dish rack through the use of c - shaped recesses formed in the housing that create a “ snap ” fit with portions of the wire rack or it could be attached using other known or developed fastening mechanisms . the other free end of the flat spring engages the biasing element interface portion 243 of the lever 240 such that the engagement arms 244 a - b of the lever 240 are biased ( or pivoted ) toward the wheel mounting plate 212 . in one embodiment of the present invention , an upper dish rack is attached to dishwasher using two adjustable height mechanisms 100 — one on each side . the adjustable height mechanisms allow a user to select one of a plurality of possible upper rack heights . in one embodiment , a user can raise the height of upper rack from one of the lower positions by simply applying an upwardly directed force to the dish rack . the inclined upper end of the wedge portions 146 a - b of the free ends 145 a - b cooperate with the inclined or accurate flanges of the lower locating edge 117 or the upper edges of the slots 118 a - b such that the free ends 145 a - b disengage the engagement features of the wheel mounting plate 112 without having to apply a force to handle portion 142 of the lever 140 . to lower the rack , a user applies a force to the handle portion 142 of the lever 140 on the two adjustable height mechanisms , which disengages the horizontal lower ends of the wedge portions 146 from the engagement features , and then lowers the rack to the desired height . the embodiments illustrated in fig1 - 6 include three possible heights , but one of ordinary skill in the art will recognize that the wheel mounting plate 112 may include additional slots similar to slots 118 a - b to facilitate additional height options . in one embodiment , the locating edges 116 , 117 may be spaced apart by a distance , for example of about 3 inches , with the slots 118 a - b being disposed about half way therebetween . in such instances , the rack 105 may have about a 3 inch height adjustability range in increments of about 1 . 5 inches . however , one skilled in the art will appreciate that the actual height adjustability may vary considerably depending on the desired configuration of the dishwasher . for instance , the actual height adjustability may be greater than zero inches , up to about 6 inches or greater , as necessary or desirable . fig7 illustrates a height adjustment mechanism 100 at its lowest height position . at this position , the pins 122 a - b engage the lower end of the slots 115 a - b such that the rack mounting assembly and therefore the dish rack itself are supported by the pins 122 a - b and the wheel mounting plate 112 . the upper surfaces of the wedge portions 146 a - b of the lever 140 engage the lower locating edge 117 of the wheel mounting plate 112 . to raise the dish rack from the lowest position as shown in fig7 , a user may apply an upwardly directed force to the rack 105 and / or the rack mounting assembly 130 . as the rack mounting assembly 130 is raised , the geometry of the wedge portions 146 a - b will create a force that counteracts the pivoting force created by the biasing element , thereby allowing the wedge portion to slide away from the lower locating edge 117 . once free of the lower locating edge 117 , the wedge portions 146 a - b will continue to be biased against the surface of the wheel mounting plate 112 by the biasing element 154 and will slide against this surface as the rack mounting assembly 130 rises . upon reaching the intermediate height position as determined by the height of slots 118 a - b , the wedge portions 146 a - b engage the slots 118 a - b with the horizontal stop members 148 engaging the inner surface of the wheel mounting plate 112 . fig8 illustrates the height adjustment mechanism 100 in an intermediate position . in this position , the rack mounting assembly and therefore the dish rack is supported by the engagement of the free ends 145 a - b of the lever 140 with the wheel assembly 110 . to raise the dish rack to its top position as shown in fig9 from the intermediate position shown in fig8 , a user may apply an upwardly directed force to the rack 105 and / or the rack mounting assembly 130 . as the rack mounting assembly 130 is raised , the geometry of the wedge portions 146 a - b will create a force that counteracts the pivoting force created by the biasing element thereby allowing the wedge portions 146 a - b to slide out of slots 118 a - b . once free of the slots 118 a - b , the wedge portions 146 a - b will be biased against the surface of the wheel mounting plate 112 and will slide against this surface as the rack mounting assembly 130 rises . upon reaching the top height position as determined by the upper locating edge 116 , the wedge portions 146 engage the upper locating edge 116 with the horizontal stop members 148 engaging the inner surface of the wheel mounting plate 112 . fig9 illustrates the height adjustment mechanism 100 in a top height position . in this position , the rack mounting assembly 130 and therefore the dish rack 105 is supported by the engagement of the lever 140 with the upper locating edge 116 of the wheel mounting plate 112 . in this embodiment , the rack mounting assembly 130 is prevented from traveling beyond a predetermined height by the interaction of the pins 122 a - b and the top of slots 115 a - b . in an alternative embodiment , the user applies a force to the handle portion 142 of the lever 140 against the biasing element 154 to disengage the wedge portions 146 a - b of the lever from the wheel mounting plate 112 and then raises the rack mounting assembly 130 and therefore the dish rack 105 to one of the plurality of height positions . to lower the rack from either the top height position or the intermediate height position , a user applies a force to the handle portion 142 of the lever 140 as generally shown in fig4 . this force counteracts the force created by the biasing element 154 and causes the wedge portions 146 a - b of the lever 140 to disengage the wheel mounting plate 112 . the dish rack 105 can then be positioned in a different height position . many modifications and other embodiments of the inventions set forth herein will come to mind to one skilled in the art to which these inventions pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings . for example , a single engagement arm may be employed or additional of slots may be defined by the wheel mounting plate . therefore , it is to be understood that the inventions are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims . although specific terms are employed herein , they are used in a generic and descriptive sense only and not for purposes of limitation .

US-85183307-A

an i . v . catheter assembly and needle safety device are disclosed which allow for the safe removal of a needle from a catheter assembly . the safety device includes a locking assembly which includes lock housing a rotatable locking member and a locking clip . the needle and the locking member are configured such that withdrawal of the needle from the catheter assembly effects rotation of the locking member . the locking clip is positioned and configured to obstruct rotation of the locking member after the needle has been retracted within the housing to obstruct re - advancement of the needle .

embodiments of the presently disclosed i . v . catheter assembly and needle safety device will now be described in detail with reference to the drawings wherein like reference numerals designate identical or corresponding elements in each of the several views . in this description , the term proximally is generally used to indicate relative nearness of a referenced item to a user of the device and the term distal is used to indicate relative remoteness of a referenced item to a user of the device . fig1 - 22 illustrate one embodiment of the presently disclosed i . v . catheter assembly and needle safety device (“ the device ”) shown generally as 10 . referring to fig1 and 2 , the device 10 includes a catheter assembly 12 including a catheter 14 and a catheter hub 16 , a safety device or lock assembly 18 including a rotatable locking member 20 , a locking clip 22 and lock housing 24 , and a needle assembly 26 including an elongated needle 28 and a needle hub 30 . as will be described in further detail below , needle 28 is positioned through lock assembly 18 and catheter assembly 12 such that in its extended position , a sharpened , tapered tip 28 a of needle 28 extends from the distal end of catheter 14 . as is known in the art , sharpened tip 28 a facilitates insertion of needle 28 and catheter 14 into the vasculature , e . g ., vein 32 ( fig1 ), of a patient . referring to fig2 , 10 and 11 , lock housing 24 defines a stepped bore 34 having a substantially cylindrical distal portion 36 , a substantially cylindrical central portion 38 and a proximal portion 40 . distal portion 36 is dimensioned to receive the proximal end of catheter hub 16 . in one embodiment , an annular rib 42 is formed about an inner wall of housing 24 in distal portion 36 and functions to releasably engage catheter hub 16 as will be described in further detail below . a first shoulder portion or step 44 is positioned between distal portion 36 and central portion 38 of stepped bore 34 . step 44 engages the proximal end of catheter hub 16 when catheter assembly 12 is secured to housing 24 ( fig1 ). central portion 38 of stepped bore 34 is dimensioned to rotatably receive locking member 20 of lock assembly 18 . a second shoulder portion or step 46 is positioned between central portion 38 and proximal portion 40 of stepped bore 34 . step 46 engages the proximal end of locking member 20 when member 20 is positioned in central portion 38 of bore 34 . proximal portion 40 includes a throughbore 48 . at least a portion 48 a of throughbore 48 has a non - circular shape , e . g ., truncated oval shape . the proximal end of throughbore 48 also includes an inwardly extending flange 48 b of reduced diameter which will be discussed in further detail below . non - circular portion 48 a functions to prevent rotation of needle 28 in relation to housing 24 and to lock needle 28 in a retracted position in relation to housing 24 as will be described in detail below . referring to fig2 - 9 , locking member 20 has a substantially cylindrical body 50 defining a non - circular throughbore 52 , e . g ., truncated oval shape , which is rotated or twisted along its longitudinal axis , e . g . partial helix . see fig6 - 9 . a distal end 50 a of locking member 20 includes a channeling surface 54 which will be discussed in further detail below . a proximal end 50 b of locking member 20 includes a stepped portion 56 with a series of cutouts 56 a formed along a circular track 58 formed about stepped portion 56 . an inner wall 60 defining central portion 38 of stepped bore 34 includes a cutout 62 . locking clip 22 includes a substantially circular member formed of a spring material including a first end having an outwardly extending finger 64 and a second end having an inwardly angled stop member 66 . finger 64 is configured and dimensioned to be received within cutout 62 to rotatably fix locking clip 22 about proximal end 50 b of locking member 20 . when finger 64 is positioned within cutout 62 , clip 22 is non - rotatably secured to housing 24 and stop member 66 is positioned to ride over circular track 58 of stepped portion 56 of locking member 20 as locking member 20 rotates within central portion 38 of stepped bore 34 . as locking member 20 rotates in relation to clip 22 and housing 24 , stop member 66 ratchets into and out of cutouts 56 a . because of the angled faces defining cutouts 56 a and the angle of stop member 66 , locking clip 22 will permit rotation of locking member 20 in a first direction but prevent rotation of locking member 20 in the opposite direction . referring to fig2 and 12 - 15 , as discussed above , needle assembly 26 includes a needle hub 30 and a needle 28 having a sharpened tip 28 a . sharpened tip 28 a defines a beveled surface configured to pierce body tissue to access vasculature of a patient . needle 30 further includes first and second non - circular portions 70 and 72 which are configured and dimensioned to be slidably received within throughbore 52 of locking member 20 and within non - circular portion 48 a of throughbore 48 of housing 24 . needle hub 30 is secured to the proximal end of needle 28 and provides a gripping surface to facilitate removal of needle 28 from catheter assembly 12 . needle hub 30 can be secured to needle 28 using any known fastening technique including adhesion , crimping , press - fitting . referring to fig1 and 17 , when device 10 is assembled , needle 28 is positioned through stepped bore 34 of housing 24 , through throughbore 52 of locking member 20 , and through catheter 14 of catheter assembly 12 . non - circular portion 72 of needle 28 is positioned within throughbore 52 of locking member 20 and locking member 20 is rotatably supported within central portion 38 of bore 34 of housing 24 . needle hub 30 is positioned adjacent a proximal end of housing 24 . as illustrated in fig1 , stop member 66 of locking clip 22 is positioned on circular track 58 . as discussed above , locking clip 22 is formed of a spring material such that stop member 66 is urged against circular track 58 . further , catheter hub 16 is positioned within distal portion 36 of stepped bore 34 such that annular rib 42 is positioned within an annular recess 76 formed in catheter hub 16 to releasably secure catheter hub 16 to housing 24 . the distal end of housing 24 is formed of a material , e . g ., plastic , having a degree of resiliency to facilitate disengagement of catheter hub 16 from housing 24 . the distal end of catheter hub 16 may include a grasping surface configured to further facilitate disengagement of catheter hub 16 from housing 24 . alternatively , catheter hub 16 and housing 24 may contain other releasably securing structures such as bayonet , press - fit , or any other suitable engagement structure for releasably securing catheter hub 16 to housing 24 . referring to fig1 , 19 and 19 a , when hub 30 is pulled in the direction indicated by arrow “ a ” in fig1 , needle 28 is withdrawn through cannula 14 and first non - circular portion 72 and then non - circular portion 70 pass through throughbore 52 of locking member 20 . since throughbore 52 has a non - circular bore which twists or rotates about the longitudinal axis to define a screw - like channel , as needle 28 is pulled proximally , locking member 20 is forced to rotate about the longitudinal axis in the direction indicated by arrow “ b ”. as locking member 20 rotates , stop member 66 on locking clip 22 moves along circular track 58 and ratchets into and out of cutouts 56 a ( fig1 a ). as discussed above , sloped surface 66 a of stop member 66 allows rotation of locking member 20 in the direction indicated by arrow “ b ” but prevents rotation of locking member 20 in an opposite direction . it is noted that when non - circular portion 72 of needle 28 enters non - circular throughbore 48 , needle 28 is prevented from rotating in relation to housing 24 . referring to fig2 and 21 , when needle 28 is retracted to the point non - circular portion 72 engages flange 48 b , needle 28 is prevented from further proximal movement . further , if an attempt is made to advance needle 28 , tip 66 b of stop member 66 of locking clip 22 , if not already engaged in a cutout 56 a , moves into engagement with a cutout 56 a , to prevent rotation of locking member 20 ( fig2 ). when this occurs , advancement of needle 28 is prevented because of the screw - like configuration of throughbore 52 . referring to fig2 , as illustrated , when needle 28 is in its locked , retracted position , sharpened tip 28 a of needle 28 is safely confined within distal portion 36 of stepped bore 34 . as discussed above , flange 48 b prevents proximal movement of needle 28 in relation to housing 24 of lock assembly 18 and since locking member 20 is prevented from rotating by locking clip 22 , needle 28 cannot be moved distally in relation to housing 24 . thus , distal end 28 a of needle 28 is safely confined within distal portion 36 of stepped bore 34 of housing 24 . at this time , housing 24 with needle 28 locked therein ( fig2 ) can be separated from catheter assembly 12 ( fig2 ) by pulling catheter assembly 12 apart from housing 24 in the direction indicated by arrow “ c ” to disengage annular rib 42 of housing 24 from annular recess 76 of catheter hub 16 . lock assembly 18 and needle assembly 26 can now be safely disposed of by medical personnel . fig2 - 35 illustrate another embodiment of the presently disclosed i . v . catheter assembly and needle safety device shown generally as 100 . i . v . catheter assembly and needle safety device 100 includes a catheter assembly 112 , a safety device or lock assembly 118 and a needle assembly 126 . catheter assembly 112 includes a catheter 114 and a catheter hub 116 supported on a proximal end of catheter 114 . safety device or lock assembly 118 includes a rotatable locking member 120 , a locking clip 122 and a lock housing 124 . needle assembly 126 includes an elongated needle 128 and a needle hub 130 . as will be discussed in further detail below , needle 128 is positioned through lock assembly 118 and catheter assembly 112 such that in its extended position , a sharpened tip 128 a of needle 128 extends from the distal end of catheter 114 . as is known in the art , sharpened tip 128 a facilitates insertion of needle 128 and catheter 114 into vasculature , e . g ., vein 132 ( fig2 ), of a patient . referring to fig2 and 27 , lock housing 124 defines a stepped bore 134 having a substantially cylindrical distal portion 136 , a substantially cylindrical central portion 138 and a proximal portion 140 . distal portion 136 is dimensioned to receive the proximal end of catheter hub 116 . a first shoulder portion or step 144 is positioned between distal portion 136 and central portion 138 of stepped bore 134 . step 144 includes a pair of cutouts 142 which are configured to receive projections or ears 116 a formed on the proximal end of catheter hub 116 when catheter assembly 112 is secured to housing 124 ( fig1 ). the receipt of projections 116 a in cutouts 142 prevents rotation of hub 116 in relation to lock housing 124 as will be discussed in further detail below . central portion 138 of stepped bore 134 is dimensioned to rotatably receive locking member 120 of lock assembly 118 and defines a longitudinal channel 141 . a second shoulder portion or step 146 is positioned between central portion 138 and proximal portion 140 of stepped bore 134 . step 146 engages the proximal end of locking member 120 when member 120 is positioned in central portion 138 of bore 134 . proximal portion 140 includes a throughbore 148 . at least a portion 148 a of throughbore 148 has a non - circular shape , e . g ., truncated oval shape . the proximal end of throughbore 148 also includes an inwardly extending flange 148 b of reduced diameter which will be discussed in further detail below . non - circular portion 148 a functions to prevent rotation of needle 128 in relation to housing 124 and to lock needle 128 in a retracted position in relation to housing 124 as will be described in detail below . referring to fig2 - 28 , locking member 120 has a substantially cylindrical body 150 defining a non - circular throughbore 152 , e . g ., truncated oval shape , which is rotated or twisted along its longitudinal axis , e . g . partial helix , in the manner described above with respect to throughbore 52 of locking member 20 . a distal end 150 a of locking member 120 includes a channeling surface 154 which will be discussed in further detail below . a longitudinally extending channel 156 is formed along an outer surface of rotatable locking member 120 . locking clip 22 is supported within channel 156 and includes a base portion 122 a , an angled resilient portion 122 b which extends outwardly from base portion 122 a , and a retaining portion 122 c which extends downwardly from resilient portion 122 b . as illustrated , base portion 122 a is secured within channel 156 with at least one screw 166 such that angled resilient portion 122 b extends outwardly of channel 156 in its undeformed state . when rotatable lock member 120 is positioned within central portion 138 of stepped bore 134 , angled resilient portion 122 h of locking clip 122 is urged to a deformed state by an inner wall of lock housing 124 . in the deformed state , locking clip 122 is positioned within channel 156 of rotatable locking member 120 such that locking member 120 can freely rotate within central portion 138 of stepped bore 134 . see fig2 . when locking member 120 is rotated to a position in which locking clip 122 is aligned with longitudinal channel 141 of lock housing 124 , angled resilient portion 122 b will return to its non - deformed state and move into longitudinal channel 141 and obstruct further rotation of locking member 120 within central portion 138 of stepped bore 134 . see fig3 . as illustrated in fig2 , when locking clip 122 is in the deformed state within channel 156 , retaining portion 122 c engages a top surface of a proximal rim 157 of hub 116 to releasably retain catheter assembly 112 within distal portion 136 of stepped bore 134 . when locking clip 122 rotates to a position aligned with longitudinal channel 141 and returns to the non - deformed state , angled resilient portion 122 b springs outwardly to disengage retaining portion 122 c from rim 157 of hub 116 to release catheter assembly 112 from within distal portion 136 of stepped bore 134 . see fig3 . referring to fig2 - 27 , as discussed above , needle assembly 126 includes a needle hub 130 and a needle 128 having a sharpened tip 128 a . sharpened tip 28 a defines a beveled surface configured to pierce body tissue to access vasculature of a patient . needle 130 further includes first and second non - circular portions 170 and 172 which are configured and dimensioned to be slidably received within throughbore 152 of locking member 120 and within non - circular portion 148 a of throughbore 148 of housing 124 . needle hub 130 is secured to the proximal end of needle 128 and provides a gripping surface to facilitate removal of needle 128 from catheter assembly 112 . needle hub 130 can be secured to needle 128 using any known fastening technique including adhesion , crimping , press - fitting . referring to fig2 - 28 a , when device 110 is assembled , needle 128 is positioned through stepped bore 134 of housing 124 , through throughbore 152 of locking member 120 , and through catheter 114 of catheter assembly 112 . non - circular portion 172 of needle 128 is positioned within throughbore 152 of locking member 120 and locking member 120 is rotatably supported within central portion 138 of bore 134 of housing 124 . needle hub 130 is positioned adjacent a proximal end of housing 124 . as illustrated in fig2 and 28 , locking clip 122 is positioned within channel 156 of rotatable member 120 such that retaining portion 122 c is engaged with rim 157 of catheter assembly 112 to releasably secure catheter assembly 112 within distal portion 136 of lock housing 124 . as discussed above , locking clip 22 is formed of a spring material such that angled resilient portion 122 c is urged outwardly against an inner wall of housing 124 . referring to fig2 and 30 , when hub 130 is pulled in the direction indicated by arrow “ d ” in fig2 , needle 128 is withdrawn through cannula 114 such that first non - circular portion 172 and then second non - circular portion 170 pass through throughbore 152 of locking member 120 . since throughbore 152 has a non - circular bore which twists or rotates about the longitudinal axis to define a screw - like channel , as needle 128 is pulled proximally , locking member 120 is forced to rotate about the longitudinal axis in the direction indicated by arrow “ e ”. as locking member 120 rotates , locking clip 122 moves in the direction indicated by arrow “ f ” from a position angularly offset , e . g . 90 °, from longitudinal channel 141 of lock housing 124 towards a position aligned with longitudinal channel 141 . engagement between projections 116 a and cutouts 142 prevent hub assembly from rotating with locking member 120 . referring to fig3 and 32 , when needle assembly 126 is retracted to a position to rotate rotatable locking member 120 to a position in which locking clip 122 is aligned with longitudinal channel 141 , angled resilient portion 122 b springs outwardly into longitudinal channel 141 . when this occurs , retaining portion 122 c disengages from rim 157 of catheter assembly 112 to release catheter assembly 112 from distal portion 136 of lock housing 124 . see fig3 . in this position , sharpened tip 128 a of needle 128 is positioned within distal portion 136 of lock housing 124 . further , since locking clip 122 is positioned within longitudinal channel 141 of lock housing 124 , rotatable locking member 120 is prevented from rotating . thus , needle 128 cannot be advanced or retracted in relation to lock housing 124 because of screw - like configuration of throughbore 152 and sharpened tip 128 a of needle 128 is safely retained within lock housing 124 . needle 128 also cannot be retracted from lock housing 124 because flange 148 b obstructs movement of non - circular portion 172 of needle 128 . at this time , housing 124 with needle 128 locked therein ( fig3 ) can be separated from catheter assembly 112 ( fig3 ) by pulling housing 124 apart from catheter assembly 112 in the direction indicated by arrow “ g ” in fig3 . lock assembly 118 and needle assembly 126 can now be safely disposed of by medical personnel . it will be understood that various modifications may be made to the embodiments disclosed herein . therefore , the above description should not be construed as limiting , but merely as exemplifications of preferred embodiments . those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto .

US-201113112140-A

the present invention provides an advanced water flosser utilizing a direct water source , such as , but not limited to , an attachment to a shower head , that also may embody a reservoir and / or compartment capable of introducing other desirable substances designed to enhance the teeth cleaning process , such as , but not limited to fluoride , antibiotics , mouthwash , whiteners and the like .

for clarity of disclosure , and not by way of limitation , the detailed description of the invention is divided into the following subsections that describe or illustrate certain features , embodiments or applications of the present invention . in one embodiment , the present invention provides an oral hygiene device comprising : i . a fitting for connection to a water supply further comprising a valve for engaging the water flow into said device ; ii . a hydro pulse module further comprising a paddle wheel and a water pulsing wheel contained within a housing wherein said paddle wheel and said water pulsing wheel rotate simultaneously when engaged along a central axis ; iii . a nozzle ; and iv . a nozzle valve . in another embodiment , the present invention provides an oral hygiene device as described further comprising a reservoir for delivery of desired substances into the water flow prior to said water flow through the nozzle . in one embodiment , the reservoir would be an interchangeable hydro - cassette containing fluid substances and introduced into the water line via a siphon and valve . in one embodiment , the reservoir may be encased within a larger housing encasing the entire oral hygiene device . in one embodiment , the reservoir would be integral with the overall housing design . in one embodiment , the reservoir would contain dry ingredients that would be dissolved into the water flow . in one embodiment , the reservoir would contain compartments for introduction of multiple substances at the choice of the operator . in one embodiment , the reservoir r would further comprise an adjustment valve for any or all of the substances to be introduced into the water flow to control the concentration of such substance in the water flow . in one embodiment , the reservoir would be a removeable squeeze bottle . in one embodiment , the device would further comprise a variable valve that controls water pressure and the flow of liquid from the water source and a two - part connector that splits the flow of water and injects the reservoir substance into one water line leading directly to the pulsing wheel chamber and allows water to pass directly to the turbine paddle wheel side of the hydro pulse chamber . this connector incorporates a reduced size orifice in the whitener side of the connector and connects at an angle resulting in reduced pressure where the whitener joins the main water line . the pressure drop at the end of the connector means the reservoir substance is injected into the water stream at reduced pressure , and goes directly to the pulse side of the hydro pulse module and ultimately pulsed onto the teeth and gums . in one embodiment , the hydro pulse module may be removed from the handset and located within the external reservoir squeeze bottle assembly thereby simplifying the hydraulic attachments and allowing the reservoir substance to be introduced after the hydro pulse module , thereby avoiding any negative effects associated with any particular reservoir substance passing through the hydro pulse module . in one embodiment , the oral hygiene device would have replaceable and / or rotatable tips . such tips may include various styles and / or end tips for use specifically with flossing , teeth whitening , and the like . in one embodiment , the water supply connection would be in an ordinary shower , said fitting adapted to fit between the water supply and the shower head . in one embodiment , the oral hygiene device would have a water off / on control such that once the water supply is turned on , the water flow would be controlled to the oral hygiene device . in one embodiment , the hydro pulse module would operate by having the water flow rotate the paddle wheel which in turn would rotate the water pulsing wheel which when aligned properly in the housing would allow water to flow through the nozzle and when misaligned would prevent water flow through the nozzle . in one embodiment , the hydro pulse module would have replaceable water pulsing wheels for different number of times of proper alignment allowing water flow through to the nozzle per 360 ° rotation . for example , in one embodiment the water pulsing wheel would have only one through hole that would align properly every 180 ° rotation and provide a water pulse twice per revolution . in one embodiment , the water pulse wheel through holes would contain an aeration function which would reduce the overall water required and increase the effectiveness of teeth cleaning . in one embodiment , such aeration would be introduced in the water pulse wheel by a fine screen . in one embodiment , the fine screen would be located in the nozzle or between the nozzle and the hydro pulse mechanism . in one embodiment , the screen would be of various mesh sizes for variable aeration . in one embodiment , such water aeration function would be variably adjusted . in one embodiment , the water in line is divided into two separate lines entering into the hydro pulse module wherein one line enters into the paddle wheel compartment and one line enters into the pulse wheel compartment . in one embodiment , the chamber within the hydro pulse module that contains the paddle wheel is completely separate from the chamber that contains the pulse wheel except that the paddle wheel and the pulse wheel are connected via an axle that penetrates both chambers , however , water is restricted from flowing between the chambers . in one embodiment , this water line division would occur prior to the delivery of the reservoir substances such that those substances are not wasted in the turning of the paddle wheel , but only delivered through the water pulse wheel . in one embodiment , the oral hygiene device would further comprise a splash guard to protect the face and eyes during operation . in one embodiment , parts of the oral hygiene device will be molded from plastic . in one embodiment , parts of the oral hygiene device will be molded from metal . in one embodiment , parts of the oral hygiene device may be made from any non - corrosive , hygienic material suitable for containing water pressure and delivering a precision stream of water and other substances as disclosed herein . in one embodiment , parts of the oral hygiene device may be made from any combination of materials . for clarity of disclosure , the following examples are based on this device being attached in a typical shower environment . one of ordinary skill in the art will appreciate the many embodiments of the device of the present invention , for example , and not by way of limitation , installation at a bathroom sink . in a typical installation , installation would require simply unscrewing a shower head from the shower nozzle and screwing the fitting of the device of the present invention in place and then screwing the shower head back on into a specially adapted fitting . thereafter , the device of the present invention would work by simply turning the shower water on and depressing a button on the device to make water flow through it and releasing the button to stop water from flowing through it . when this device is used in the shower , there would be no need for worry about the mess of spilled water or other messes . in a preferred embodiment , one or more reservoirs would contain one or more a liquid substances such as mouthwash , oral antiseptic , teeth whitener , gum health substances and the like , any or all of which can be siphoned into the water flow according to the foregoing description that will be delivered through the nozzle . the operator would then direct the nozzle tip at a space in the mouth for cleaning such as directly at the teeth or in between teeth or at the gums and then depress the button to begin the flow of treated water . at any time , the operator would simply release the button and the flow would stop . by turning off the shower , water flow to the inlet line would cease and release any pressure in the device . publications cited throughout this document are hereby incorporated by reference in their entirety . although the various aspects of the invention have been illustrated above by reference to examples and preferred embodiments , it will be appreciated that the scope of the invention is defined not by the foregoing description but by the following claims properly construed under principles of patent law . each and every feature described herein , and each and every combination of two or more of such features , is included within the scope of the present invention provided that the features included in such a combination are not mutually exclusive .

US-201414215698-A

a method of enabling a user to play an online fantasy sports game that provides an opportunity to play the game when the user visits a lottery site , provides a plurality of fantasy sports selections in a time window , the plurality of fantasy sports selections corresponds to an option to select a plurality of related actual sports games specified in the time window for that fantasy sport selection , receives the one or more fantasy sports selections that completes a lottery submission before the time window begins , determines a fantasy performance score for each of the plurality of corresponding actual sports games , determines which users have won the game based on each user &# 39 ; s selections and each of the determined corresponding fantasy performance scores , and transmits an electronic message indicating one or more winners of corresponding lottery submissions when certain users are identified to have won the game .

in accordance with some principles of the present invention , an online fantasy sports game system and method of playing that allows a user to make selections , such as professional teams , players , specific games , etc ., and potentially win an award if the selections made are correct can be provided . as shown in fig1 , the present invention may be implemented using hardware , software , or a combination thereof , and may be implemented in one or more computer systems or other processing systems . in one embodiment , the invention is directed toward one or more computer systems capable of carrying out the functionality described herein . fig1 shows a computer system 1 that includes one or more processors , such as processor 4 . the processor 4 is connected to a communication infrastructure 6 ( e . g ., a communications bus , cross - over bar , or network ). various software embodiments are described in terms of this exemplary computer system . after reading this description , it will become apparent to a person skilled in the relevant art ( s ) how to implement the invention using other computer systems and / or architectures . computer system 1 can include a display interface 2 that forwards graphics , text , and other data from the communication infrastructure 6 ( or from a frame buffer not shown ) for display on the display unit 30 . computer system 1 also includes a main memory 8 , preferably random access memory ( ram ), and may also include a secondary memory 10 . the secondary memory 10 may include , for example , a hard disk drive 12 and / or a removable storage drive 14 , representing a floppy disk drive , a magnetic tape drive , an optical disk drive , etc . the removable storage drive 14 reads from and / or writes to a removable storage unit 18 in a well known manner . removable storage unit 18 , represents a floppy disk , magnetic tape , optical disk , etc ., which is read by and written to removable storage drive 14 . as will be appreciated , the removable storage unit 18 includes a computer usable storage medium having stored therein computer software and / or data . in alternative embodiments , secondary memory 10 may include other similar devices for allowing computer programs or other instructions to be loaded into computer system 1 . such devices may include , for example , a removable storage unit 22 and an interface 20 . examples of such may include a program cartridge and cartridge interface ( such as that found in video game devices ), a removable memory chip ( such as an erasable programmable read only memory ( eprom ), or programmable read only memory ( prom )) and associated socket , and other removable storage units 22 and interfaces 20 , which allow software and data to be transferred from the removable storage unit 22 to computer system 1 . computer system 1 may also include a communications interface 24 . communications interface 24 allows software and data to be transferred between computer system 1 and external devices . examples of communications interface 24 may include a modem , a network interface ( such as an ethernet card ), a communications port , a personal computer memory card international association ( pcmcia ) slot and card , etc . software and data transferred via communications interface 24 are in the form of signals 28 , which may be electronic , electromagnetic , optical or other signals capable of being received by communications interface 24 . these signals 28 are provided to communications interface 24 via a communications path ( e . g ., channel ) 26 . this path 26 carries signals 28 and may be implemented using wire or cable , fiber optics , a telephone line , a cellular link , a radio frequency ( rf ) link and / or other communications channels . in this document , the terms “ computer program medium ” and “ computer usable medium ” are used to refer generally to media such as a removable storage drive 14 , a hard disk installed in hard disk drive 12 , and signals 28 . these computer program products provide software to the computer system 1 . computer programs ( also referred to as computer control logic ) are stored in main memory 8 and / or secondary memory 10 . computer programs may also be received via communications interface 24 . such computer programs , when executed , enable the computer system 1 to perform the features of the present invention , as discussed herein . in particular , the computer programs , when executed , enable the processor 4 to perform the features of the present invention . accordingly , such computer programs represent controllers of the computer system 1 . in an embodiment where the invention is implemented using software , the software may be stored in a computer program product and loaded into computer system 1 using removable storage drive 14 , hard drive 12 , or communications interface 24 . the control logic ( software ), when executed by the processor 4 , causes the processor 4 to perform the functions of the invention as described herein . in another embodiment , the invention is implemented primarily in hardware using , for example , hardware components , such as application specific integrated circuits ( asics ). implementation of the hardware state machine so as to perform the functions described herein will be apparent to persons skilled in the relevant art ( s ). in yet another embodiment , the invention is implemented using a combination of both hardware and software . now referring to fig2 , which is a communication system for use with the computer system of fig1 , in accordance with one embodiment of the present invention . the communication system 30 includes an accessor 31 ( also referred to interchangeably herein as a “ user ”) and a terminal 32 . in one embodiment , data for use in the computer system 1 is , for example , input and / or accessed by the accessor 31 via the terminal 32 , such as a personal computer ( pc ), minicomputer , mainframe computer , microcomputer , telephonic device , or wireless device , such as a hand - held wireless device coupled to a server 33 , such as a pc , minicomputer , mainframe computer , microcomputer , or other device having a processor and a repository for data and / or connection to a processor and / or repository for data , via , for example , a network 34 , such as the internet or an intranet , and couplings 35 , 36 . the couplings 35 , 36 include , for example , wired , wireless , or fiberoptic links . in another embodiment , the method and system of the present invention operate in a stand - alone environment , such as on a single terminal . for all data received or transmitted under the present invention , such as player statistics and team scores , may be calculated based on values input , which may be manually input or downloaded from a database at any location , preferably remote . the database itself can be online , stored in fixed memory , or disk - based . now referring to fig3 , which is an exemplary method 300 and steps of one embodiment of the present invention . at step 301 , implement an online fantasy sports game ( e . g ., a comparison based game ) in connection with real life sports games in which each fantasy player has to select for each member of his or her fantasy team or lineup the real life game in which that member will have a performance fantasy sports achievement relative to that member &# 39 ; s other real life games in a time window ( e . g ., less than a season comprising a set of near term games ). a game submission or time window may be a specific time period that is less than a full sports season . also , the game submission or time window may include consecutively played game of a player or non - consecutively played games . at step 302 , a user navigates to a lottery site to play a lottery game . examples of a lottery site includes , but is not limited to , nylottery . org , powerball , mega million , pick 5 , etc . it should also be appreciated that the lottery site could be a lottery mobile application downloaded to a mobile device . at step 304 , the user is provided the opportunity to play an online fantasy sports game . the lottery site may include a link or some other method to navigate to an online fantasy sports game . in one embodiment , the lottery mobile application or site may enable a user to play the online fantasy sports game through the application / site . the lottery mobile application / site may also direct the user to download a different mobile application that is directed towards the online fantasy sports game . the lottery mobile application or site may also enable the fantasy player or user to go back and check on the performance of his or her fantasy team or lineup during the time window . the online fantasy sports game may provide this functionality , as well . at step 306 , the user is directed to an online fantasy sports game . the online fantasy sports game may be presented to the user in many different ways including , but not limited to , a website and a mobile application . in one embodiment , the lottery site may present the online fantasy sports game within a frame directly on the lottery site . the online fantasy sports game may include many different options of sports games for the user to play . for example , the user may be presented with a selection for designating a particular sport to play , such as football , basketball , baseball , soccer , hockey , etc . the sports may also be designated between professional leagues ( e . g ., nba , nfl , nhl , mls , etc .) or college leagues . further , the user may be able to select different teams within each league , such as kansas city chiefs , missouri tigers , new york yankees , detroit redwings , etc . then the user may be presented with different players associated with the selected teams . also , the user may be presented with information about each player and team . at step 308 , the user is provided the opportunity to make fantasy sports selections ( e . g ., in a specific time window ). for example , if the user selects nba and then selects the new york knicks , the user may be presented with all of the players currently on the new york knicks . the specific time window is a designated set of time that the game ( s ) will be played . for example , the specific time window may be the next 3 , 5 , or n games scheduled for the team or player selected . in the case of football , the specific time window may be different because usually only one game is played in one week . the time window may also be less than a full season in whatever sport is chosen . if desired , each fantasy sports game can be for a short period of near term upcoming real life games in a sports league . also , the user may be able to select a fantasy lineup including at least two or more real life players . therefore , at step 308 the user may make selections about a particular team or player within the specific time window . in the example that the user selected the new york knicks , the user may want to select one or more players on the knicks that will have their best game on x night in the upcoming specific time window out of the other y games played in that time window . also , a user may want to choose to select which game a particular player will have his / her best game in the specific time window . also the fantasy sports game may give the option of only a limited number of players to select from and the lottery / fantasy players have to select a subset of the players to start . this feature may make the fantasy sports game more challenging . while one embodiment is directed towards a fantasy player competing against himself , another embodiment allows multiple fantasy players to play the game and compete against each other and themselves . in the embodiment where other fantasy players are playing , the other fantasy players may have the opportunity to select the same real life players to start in their fantasy game submissions . it should be appreciated both embodiments may be implemented at the same time . at step 310 , the user submits the fantasy sports selections . once the user has selected all the options for the time window and submits the selections with the online fantasy sports game , the user may not be able to revise or change the selections . also , the online fantasy sports game may prevent a user from making selections or changes to the selections after the specific time window has started . for example , if the specific time window is a wednesday through tuesday of the next week , the user will be prevented from revising the selections made after tuesday of the current week . at step 312 , it is determined whether the user is a winner of the fantasy sports game based on his / her selections ( e . g ., performance in the related actual sports games ). once the time window has lapsed , the online fantasy sports game would determine a fantasy performance score for each actual game played during the time window and a fantasy performance score for each player during the time window . for example , if the knicks played in the upcoming time window on night 1 , night 2 , and night 3 and the user selected that the knicks would have their best night on night 2 , then the online fantasy sports game system would determine a fantasy score for all three nights for the knicks and determine which night in that time window was the best night . the determination of the best night may be calculated using a fantasy scoring formulation . then , it would be determined if the user was a winner based on the selection ( s ) made by the user . in the situation where a user selects more than one selection , the online fantasy sports game may determine that each selection needs to be correct in order for the user to be considered a winner . at step 314 , the user is awarded with a lottery cash sum if it has been determined that the user is a winner based on his / her selection ( s ). it should be appreciated that the lottery cash sum may be many different types of awards , such as money , free future game plays , or other awards . in some embodiments , winning is based on or determined by comparing an individual real life player &# 39 ; s performance against his or her performance in the other games in the time window , and doing that for each player selected by the fantasy player for his or her fantasy team or lineup , and determining how many of the real life players the right game was selected in a game submission . if all of the games or some predetermined subset of games is selected correctly , the fantasy player wins . also , it may be determined for each player which game was his or her best and / or worst performance in each of the other games in that time window . now referring to fig4 , which is an exemplary system diagram for the system 400 , in accordance with the embodiments of the present invention . the system 400 may include an online fantasy sports game system 402 , a sports statistics and results database 412 , a lottery component 414 , wide area network ( wan ) 416 , a user &# 39 ; s computer 418 , and a user 420 . the online fantasy sports game system 402 may also include an interface 404 , a transaction engine 406 , a scoring engine 408 , and a game database 410 . the online fantasy sports game system 402 is not limited to only these components . the interface 404 may provide functionality that enables the system 402 to interact with the other components either within the fantasy sports game system 402 or outside of the fantasy sports game system 402 . the interface 404 may also provide a user interface that the user would view when visiting the fantasy sports game website or mobile application . the transaction engine 406 may provide many different functionalities , such as facilitating financial transactions between the fantasy sports game system 402 and the user 420 . for example , the user 420 may purchase a subscription or pay per use fee to make selections on the fantasy sports game website or mobile application . the transaction engine 406 may provide functionality to receive credit card information and / or other methods of payment ( e . g . paypal , wire transfer , etc .). also , if the user is determined to be a winner after making and submitting selections on the fantasy sports game website or mobile application , the transaction engine 406 may provide functionality to provide the award to the user 420 . for example , if the award is a cash prize , the transaction engine 406 may facilitate obtaining the user &# 39 ; s 420 mailing address , or information for a direct deposit into a bank account , etc . if the award is not cash prize , the transaction engine 406 may also help facilitate awarding the user 420 with the award in other ways . the scoring engine 408 may provide functionality for determining a fantasy performance score for each game or player with in a specific time window . the scoring engine 408 may be in communication with the sports statistics and results database 412 and the game database 410 . the game database 410 may be used to store information pertaining to past , present and future games within the fantasy sports game system 402 . the game database 410 may include user 420 information . the user 420 information may include , but is not limited to , past and present game submissions and results , financial information , personal preferences , etc . the sports statistics and results database 412 may include information pertaining to the actual real life sports games . the sports statistics and results database 412 may also receive and transmit data feed information pertaining to the relevant sports information . the scoring engine 408 may utilize information requested or received from the sports statistics and results database 412 to determine if a user is a winner , to create odds of a particular player , game , or team selection . determining the odds of a particular player , game , or team may influence the amount of the award that is awarded to user 420 in the situation that user 420 is a winner . the scoring engine 408 may also be in communication with the lottery component 414 to make these determinations about the odds . the scoring engine 408 may request information from the game database 410 to make the determination of whether the selection ( s ) of user 420 was correct . once the scoring engine 408 makes the determination about whether user 420 is a winner within the time window , the scoring engine 408 may communicate this information to the interface 404 or the transaction engine 406 , or both . the sports statistics and results database 412 may request or receive up to date information about relevant real life sports games . the lottery component 414 may provide functionality to facilitate communication between the fantasy sports game system 402 and a third - party lottery site or mobile application . the computer 418 and the fantasy sports game system 402 may be communicatively coupled to a wan 416 . for example , the wan 416 could be the internet . the wan may include wired , wireless networks and interconnection . if desired , the wan may be a private network . the sports statistics and results database 412 and the lottery component 414 may also be communicatively coupled to the wan 416 . the computer 418 may be any different types of computing devices , such as a personal computer , laptop , mobile device , tablet , etc . now referring to fig5 , which is an exemplary screenshot 500 of one embodiment of the online fantasy sports game website . it should be appreciated that online fantasy sports game website is not limited to the features and overall look illustrated in fig5 . also , the online fantasy sports game may be implemented as a mobile application . the screenshot 500 includes a menu 502 , a graphical representation of players 504 , and a fantasy sports game submission window 506 . the fantasy sports game website is not limited to only these features . the menu 502 may include many different options including but not limited to set lineup , standings , statistics , live scoring , iq scouring report , and rules . the set lineup menu option may provide a user with the ability to either view a potential lineup planned for a particular real life sports game or allow the user to select which players will play in which position . the standings and statistics menu options may provide information to the user pertaining to the rankings of the players and teams . the live scoring menu option may provide the user with up to the moment scores or statistics of the games the user is interested . the live scoring menu option may further provide functionality to direct the user to a website to watch the game live . the iq menu option may provide trivia or other valuable information about the players and teams . the scouting report menu option may provide the user with information about trades of players between teams or new players that may join the team in the future . the rules menu option may provide rule information about the particular sport or rule information about how the fantasy sports game is played and scored . the graphical representation of players 504 may provide different functionalities . for example , after selecting the set lineup menu option in menu 502 , the graphical representation of players may be displayed 504 . the graphical representation of players 504 may illustrate to the user which players will be playing in a particular game and the positions for the players for that particular game . the graphical representation of players 504 may also illustrate which players will be sitting on the bench ( or not playing ) in that particular game . also , the area that the graphical representation of players 504 may be a frame within the website that may change depending on a menu option selected ( from menu 502 ). for example , if the user selects the live scoring menu option , the area of screenshot 500 that graphical representation of players 504 resides may change to provide the live scoring information . in the mobile application example , the user may be presented with a different screen entirely when the user selects from one of the options of menu 502 . the game submission window 506 , which will be discussed in more detail below with respect to fig6 , provides the user the ability to select a game for each player . the user will select the game in which he or she believes that player will have his / her best game . the games are shown within a specific time window . now referring to fig6 , which is another exemplary screenshot of one embodiment of the online fantasy sports game website . as discussed above , the online fantasy sports game is not limited to only a website and may be implemented as a mobile application . game submission window 600 includes the following : a listing of players by position 602 , 604 , starter designation 606 , multiplier selection 608 , games 610 , 612 , 614 , season indicator 616 , and day of the week indicator ( s ) 618 . game selection window 600 may include more or less options and is not limited to only these examples . the listing of players by position 602 , 604 illustrates one way of listing the players . in this example , the players are listed by position that they will be playing in the upcoming games . the screenshot is showing an nhl hockey team and therefore , the players are organized by forwards , defensemen , goalies , etc . it should be appreciated that when the sport , team , or players change , the positions and names change accordingly . the listing of players may also be organized by starting players , alphabetical , etc . the starter designation 606 may provide a couple of different functionalities , such as letting a user decide whether the player should start in a fantasy game or the fantasy sports game system retrieves this information about the real life sports game . selecting a player to start may not dependent on whether that actual player ends up starting in the selected game or that player ends up not playing because of an injury , etc . starting a player by a fantasy player may essentially mean selecting a performance , if any , of that player at that game . the multiplier selection 608 may provide the user the option to make this selection in the situation that the user is very confident that the selections he / she will make about the players are correct . for example , if the multiplier selection 608 is selected and the user wins , then the amount of the award may be increased by a factor ( e . g . doubled , tripled , etc .). also , there may be an option for a player to select a mega selection within the game selection window . the mega selection may provide the functionality that a fantasy player has to select which player on his or her fantasy team or lineup that will have the best performance compared to all of the other player on his or her fantasy team or lineup . if the mega selection is selected , then the fantasy player has to select the correct player otherwise , the fantasy player will not win that game . the games 610 , 612 , 614 are listed for the upcoming time window . the number of games in a time window may vary based on the sport selected or the fantasy sport game system may also provide the user the ability to choose the time window . in this example , there are three hockey games coming up for a time window of five days ( monday - friday ). also , for each game it is noted who the team is playing and if the game is home or away . for example , “@ chi ” indicates that it is an away game against the chicago blackhawks . the “ bos ” indicates that it is a home game against the boston bruins . season indicator 616 illustrates at what point in the season that the specific time window the game submission window 600 is currently displaying ( e . g . week 1 ). the season indicator 616 may also provide the user to view future or past weeks by clicking or selecting the arrows on the left and right of “ week 1 .” although , the user may be able to view past weeks in the game submission window 600 , the fantasy sports game system can prevent the user from making changes to selections and submitting selections for past time windows . day of the week indicator ( s ) 618 may illustrate to the user the day of the week that each game within the time window will be played . even though it is not shown , either game submission window 600 or screenshot 500 of fig5 may include a submit button that a user may select after the selection ( s ) have been made . now referring to fig7 , which is a flowchart of one embodiment of the online fantasy sports game process ( 700 ). at step 702 , a list of real life players and their upcoming games within a specific time window are displayed in a game submission window . the list of players and their upcoming games will vary depending on the sport and / or league selected . at step 704 , a user is provided the opportunity to select one of the plurality of upcoming games for an individual player . the user may also be able to make selections for multiple players . the user may also be able to select a fantasy lineup that includes at least two or more players . at step 706 , the user selects one of the plurality of games for an individual . at step 708 , the user is blocked from being able to select another game for that individual player in the time window . the fantasy sports game system will also prevent the user from selecting all of the games within the time window . for example , if there are three games in a time window , then the user may be able to choose either one or two games but not all three . in other situations , the user may be able to only select one game in the time window . at step 710 , the user submits the selection ( s ) for each individual player as a lottery game submission for a time window . the user may submit several selections . at step 712 , the fantasy sports game system may prevent the user from revising selections in a game submission after submission and / or after the time window starts . once the user has submitted the game submission , the user should not be able to make changes to his / her selections . also , once a time window has started , the fantasy sports game system will no longer accept game submissions for that time window . at step 714 , a fantasy performance score is generated based on how each player played during the real life sports game ( s ) in the game submission window . the fantasy performance score may be determined using a fantasy scoring formulation . the fantasy performance score may be scored based on many different factors , such as total points scored , assists , yards , blocks , etc . the fantasy performance score may be calculated differently for different sports and / or leagues . also , a fantasy performance score for a game may be calculated differently than for player . this is not an exhaustive list but it should be appreciated that the information to determine how well a player played in a specific game may be multifaceted . at step 716 , it is determined for each real life player in the time window which game that player had his / her highest fantasy performance score . once the fantasy performance score has been calculated , then it is determined which game out of the time window was the best for each player . at step 718 , it is determined whether the user selected the real life game in which each player had his / her highest performance score . so once it is determined which game was the best for each player in a time window , that is compared against the game submission from the user . at step 720 , it is determined whether a game submission selected each player &# 39 ; s best game correctly in a time window . in one embodiment , a user can choose multiple selections about multiple players in one game submission , but each of the selections must be correct in order for the user to win an award . at step 722 , an award amount is determined for each game submission . each game submission may be treated differently . some selections may have better odds than others . therefore , the odds of winning based on the selections may also come into account to determine the amount of a possible award . at step 724 , the user is awarded an award amount upon determining that the user selected each player and game correctly in a game submission ( e . g ., send a message or signal , transfer cash , etc .). if desired , the fantasy sports game can be implemented as part of casino online gaming sites . if desired , the game can be configured to provide options other than a comparison - based selection , such as providing options to make selections against a sports line or performance threshold in a game . the options can be implemented using software and hardware as illustratively described here . if desired , the application and system may be used for enhancing performance measurement for training performances of athletes and sports teams . if desired , the fantasy game can be configured to allow a user to select a group of games for each real life player and use a comparison to an unselected group of games to determine whether the player own or selected correctly . if desired , the game can be configured to allow a user to select a team or a team &# 39 ; s subteam ( e . g ., offense , defense , etc .). the online fantasy sports game system , computing devices , databases , or other discrete software or hardware components can communicate and are arranged to carry out the illustrative processes and applications described herein by way of sending a signal such as a packet , digital message , or a command within a communication to or between components ( and act in response to the receipt of a signal to carry our processes ) and between or through supporting software or hardware such as communicating with an operating system , communicating with another resident application through an api or the like , communicating between network elements using an internet protocol or one or more layers of the osi model , or communicating through an intermediate component . the online fantasy sports game system may operate in coordination with application software running external to the computing device to carry out or provide the intended game experience . for example , the online fantasy sports website or mobile application may interact with another software to authenticate a user , check the status of a user &# 39 ; s account , or carry out financial transactions . providing software features that are subsidiary or are tangential to the game functionality can be incorporated into the online fantasy sports game system or can be provided in conjunction or coordination with other software if desired . a computing device can include a computer , computer system or other programmable electronic device , including a client computer , a server computer , a portable computer ( including a laptop and a tablet ), a handheld computer , a mobile phone ( including a smart phone ), a gaming device , an embedded controller and any combination and / or equivalent thereof ( including touchless devices ). moreover , the computing device may be implemented using one or more networked computers , e . g ., in a cluster or other distributed computing system . it is understood that the exemplary environment discussed and illustrated is not intended to limit the present disclosure , and that other alternative hardware and / or software environments may be used without departing from the scope of this disclosure . the present techniques can be applied to devices other than hand - held devices , such as laptops or desktop computers . further , the terms “ computing device ”, “ computer device ”, “ computer ” and “ machine ” are understood to be interchangeable terms and shall be taken to include any collection of computing devices that individually or jointly execute a set ( or multiple sets ) of instructions to perform any one or more of the methods discussed herein . the local storage can include volatile memory ( such as ram ) and / or non - volatile memory ( such as rom as well as any supplemental levels of memory , including but not limited to cache memories , programmable or flash memories and read - only memories ). the computing device or hand - held device can include one or more processing devices ( e . g ., one or more central processing units ( cpus ), one or more graphics processing units ( gpus ), one or more microprocessors ( μp ) and similar and complementary devices ) and optional media devices ( e . g ., a hard disk module , an optical disk module , etc .). additionally , any storage techniques used in connection with the presently disclosed method and / or system may invariably be a combination of hardware and software . one or more features illustratively described herein can be implemented individually or in various combinations . the present system , method , or related inventions also relate to a non - transient computer readable medium . the application can be set of instructions readable by a processor and stored on the non - transient computer readable medium . such medium may be permanent or semi - permanent memory , such as hard drive , floppy drive , optical disk , flash memory , rom , eprom , eeprom , etc ., as would be known to those of ordinary skill in the art . features or characteristics described in one context , process , or device are applicable to other context , process or devices described herein . the steps of the processes illustratively described herein can be performed in a different order , if desired . also , steps could be added or removed from the processes illustratively described herein . the processes or steps illustratively described herein can be implemented in software and data ( in computer readable medium , transient and / or nontransient ) using the described examples of hardware and network configurations . the terms and expressions which have been employed in the specification are used as terms of description and not of limitations , there is no intention in the use of such terms and expressions to exclude any equivalents of the features shown and described or portions thereof , but it is recognized that various modifications are possible within the scope of the claims to the invention .

US-201514956283-A

a system and method for passively testing a cardiac pacemaker in which sensing signal amplitudes and lead impedance values are measured and stored while the pacemaker is functioning in its programmed mode . the amplitude and impedance data may be gotten and stored periodically at regular intervals to generate a historical record for diagnostic purposes . sensing signal amplitudes may also be measured and stored from a sensing channel which is currently not programmed to be active as long as the pacemaker is physically configured to support the sensing channel . such data can be useful in evaluating whether a switch in the pacemaker &# 39 ; s operating mode is desirable .

the basic function of a modern pacemaker is to deliver pacing pulses to the heart in accordance with sensed cardiac signals . programmability of the pacemaker allows it to operate in a number of different pacing modes . the electronic circuitry for controlling the pacemaker can be either in the form of custom integrated circuits or a microprocessor based design with application specific software . because of its inherent flexibility and the ease with which additional functionality can be added , a microprocessor - based designs is the most widely used . in the description that follows , a microprocessor - based pacemaker will be referred to as incorporating the system and method which is the present invention . it should be appreciated , however , the invention could also be incorporated into a pacemaker controlled by custom logic circuitry either in addition to or instead of a programmed microprocessor . the term “ circuitry ” as used herein should therefore be taken to mean either custom circuitry or a microprocessor executing programmed instructions contained in a processor - readable storage medium along with associated circuit elements . fig1 shows a system diagram of a microprocessor - based dual - chamber pacemaker . a microprocessor 10 communicates with a memory 12 via a bidirectional data bus . the memory 12 typically comprises a rom for program storage and a ram for data storage . the microprocessor also has a port for communicating with the telemetry interface 40 which in turn receives programming data from and transmits telemetry data to an external programmer by a radio link . the pacemaker also has atrial sensing and pacing channels comprising electrode 34 , lead 33 , sensing amplifier 31 , pulse generator 32 , and an atrial channel interface 30 which communicates bidirectionally with a port of microprocessor 10 . the ventricular sensing and pacing channels similarly comprise electrode 24 , lead 23 , sensing amplifier 21 , pulse generator 22 , and a ventricular channel interface 20 . for each channel , the same lead and electrode are used for both sensing and pacing . the channel interfaces 20 and 30 include analog - to - digital converters for digitizing sensing signal inputs from the sensing amplifiers and registers which can be written to by the microprocessor in order to output pacing pulses , change the pacing pulse amplitude , and adjust the gain and threshold values for the sensing amplifiers . a cardiac pacemaker is basically a device that responds to sensed cardiac events and elapsed time intervals by changing its functional states so as to deliver pacing pulses to the heart at appropriate times and properly interpret sensed data . as such , the essential operation of a pacemaker can be usefully represented from a state machine perspective . a state machine is a computational device which transitions from one state to another based on a defined set of rules unique to each state regarding inputs and timer events . in the following description , the operation of a pacemaker incorporating the present invention is described as such a state machine . it should be realized , however , that this description refers to the external behavior of the device and not to any specific implementation by either the programming of the microprocessor or discrete logic circuitry . fig2 shows a state machine representation of a simplified pacemaker operating in ddd mode which has five basic states : state s 0 where interval timers are initialized , state s 1 indicating a ventricular sense , state s 2 indicating an atrial sense , state s 3 to pace the ventricle , and state s 4 to pace the atrium . the system moves from state to state based upon sensed events and the outputs of timers for two intervals : aei for atrial escape interval which defines the minimum rate at which the atria will be paced in the absence of spontaneous activity , and avi for atrioventricular interval which defines a minimum time interval in which a spontaneous ventricular depolarization must occur following an atrial sense or pace . if the avi expires following an atrial sense or pace , a ventricular pace is delivered . not shown are other time intervals used to define refractory periods for the sensing channels during which time the channels are closed so that inputs are ignored . ( the term “ refractory ” means a no sensing condition when applied to a sensing channel , to be distinguished from the physiological refractory period of excitable tissue .) sensing channels are rendered refractory both in order to prevent reentry into the system of an output pacing pulse ( in which case the sensing amplifiers are blanked ) and to prevent the misinterpretation of input data by the sensing of afterpotentials or by crosstalk between sensing channels . an actual ddd pacemaker may even use additional algorithms for interpreting input data , but it must still exhibit the functionality defined by fig1 if it is desired to perform passive testing in the device of fig2 in order to store a record of sense signal amplitudes and lead impedances , test states can be added to the operation of the pacemaker which allows the testing and recording to be done while the pacemaker is operating in its programmed mode . the non - test states of the device will be referred to a programmed states . in order to test a programmed sensing or pacing channel passively , there must be a corresponding test state for each such channel to be tested . for example , one test state is an amplitude storing state for storing signal amplitudes which is entered upon detection that a corresponding programmed sensing state has been entered due to receipt of a signal from a sensing channel which is not in its refractory period . another test state is a lead impedance measuring state which is entered after detecting that the pacemaker has entered a corresponding pacing state due to the occurrence of an event which triggers output of a pacing pulse according to the programmed mode . the lead impedance measuring state measures an impedance value of the lead through which the pacing pulse is delivered during output of the pacing pulse and stores the value in a memory . a test state has the same transition rules as its corresponding programmed state so that the programmed operation of the device is undisturbed by the passive testing . fig3 shows a state machine diagram of a pacemaker operating in vvi mode which has three basic states : state s 0 for initialization , state s 1 indicating a ventricular sense , and state s 3 for outputting a pacing pulse to the ventricle . the system moves from state to state based upon sensed ventricular events ( i . e ., r waves ) and the output of a lower rate interval ( lri ) timer that defines a minimum rate at which the ventricles will be paced in the absence of spontaneous activity . the ventricular sense signal amplitude and ventricular lead impedance can be measured passively with testing states as described above . if the vvi pacemaker is a dual - chamber one having the capability of operating in ddd mode and physically configured with an atrial lead and sensing channel , it would be desirable to be able to passively measure atrial signal amplitude as well . simply turning on the atrial sense amplifier ( which may be turned off when the pacemaker is in vvi mode to conserve power ) with an amplitude storing state is not enough because the operation of the pacemaker does not include an atrial sensing state in its current programming . this means that there are no transition rules that define how an atrial sensing state should be entered and exited . nor does the pacemaker have an atrial channel refractory period timer which is needed in order not to misinterpret a ventricular depolarization or a pacing pulse as an atrial sense signal . fig4 shows a state transition diagram of a pacemaker incorporating a testing system in accordance with the present invention . a virtual sensing test state vs corresponding to the currently unprogrammed sensing channel ( i . e ., the atrial channel in this case ) is added to the operation of the pacemaker where the pacemaker then operates as if programmed in a mode including that sensing state . the virtual sensing test state includes a refractory period timer in its transition logic in order to properly interpret sensing signals . the virtual testing state is thus transitioned to upon receipt of a sensing signal in the corresponding sensing channel , and an amplitude value corresponding to the sense signal is stored in memory . the term “ virtual ” in this context means that transition to the virtual sensing state results in no triggering or inhibition of pacing pulses as would be the case were the pacemaker simply programmed to operate with the atrial sensing channel active . the transition rule of the virtual sensing test state is to return to the state from which the virtual state was entered in order to leave the programmed operation of the device undisturbed . the testing states as described may be part of a passive measurement testing mode which when activated causes the testing states to persist until signal amplitudes and lead impedances for all available channels are stored . the microprocessor is thus programmed to maintain the testing mode until all testing has been performed and then deactivate the testing mode . an amplitude test interval timer can be used to set a limit on the time for which the system will wait for a sensing signal to store . upon expiration of the interval , the system aborts the test sequence . similarly , a lead test interval timer can be used to limit the time the system waits for a pacing pulse to occur through a lead in order to measure its impedance . upon expiration of that interval , however , instead of aborting the lead impedance test , a virtual pacing test state may be employed where “ virtual pacing ” in this context means the outputting of a pacing pulse to the chamber to which the lead is connected occurs shortly after a depolarization during the chamber &# 39 ; s refractory period . the impedance of the lead can then be measured and stored . similarly , a virtual pacing state may be used to measure the impedance of a shock lead in the case of an implantable cardioverter - defibrillator . the passive measurement testing mode as described can be initiated either by a telemetry command from an external programmer or by a timer which causes periodic testing at regular intervals in order to store a record of historical values . for example , the passive measurement testing mode can be set to activate once per day and store a week &# 39 ; s worth of signal amplitude and lead impedance values . an average taken over a selected number of most recent values can also be calculated and stored for later retrieval . the system and method as described above may be used in situations where it is desired to evaluate operating parameters of an implanted pacemaker which are not currently derivable in its current operating mode . such nonprogrammed parameters may be useful in planning a switch of operating modes . for example , atrial triggering modes such as ddd or vdd are desirable in chronotropically competent patients in need of ventricular pacing because they allow the pacing to track the physiologically normal atrial rhythm . atrial triggering modes are contraindicated , however , in patients prone to atrial fibrillation or flutter or in whom a reliable atrial sense cannot be obtained . in the former case , the ventricles will be paced at too high a rate . failing to sense an atrial p wave , on the other hand , results in a loss of atrial tracking which can lead to negative hemodynamic effects . this is because the pacemaker then reverts to its minimum ventricular pacing rate after failing to sense the p wave , and the next p waves may occur so early that they fall within the post - ventricular refractory period of the atrial channel . the minimum rate pacing may thus continue for several cardiac cycles until a p wave is again sensed . for such patients , a synchronous non - atrial triggered mode such as vvi or dvi set at an appropriate minimum rate is usually best . it may be the case , however , that with proper adjustment of parameters , such as amplifier gain and signal threshold , reliable atrial sensing could actually be accomplished . if it can be determined that such parameter adjustments are successful , the patient can be switched to the more desirable atrial triggered mode . the present invention allows periodic samples of atrial sensing signals to be taken and stored over time even while the pacemaker is operating in vvi , dvi , or any other non - atrial sensing mode . the atrial sensing data can then be used to decide if the atrial sensing is reliable enough to allow switching the patient to an atrial triggered mode . although the invention has been described in conjunction with the foregoing specific embodiment , many alternatives , variations , and modifications will be apparent to those of ordinary skill in the art . such alternatives , variations , and modifications are intended to fall within the scope of the following appended claims .

US-1097404-A

a surgical instrument for performing an anastomosis includes a housing having a proximal end and a distal end ; a shaft extending from the housing distal end ; and a disposable loading unit configured and dimensioned to retain a plurality of surgical fasteners , the disposable loading unit extending from the shaft and forming a juncture with the shaft , the disposable loading unit including : i ) opposed split - sections pivotably connected to facilitate movement of the opposed split - sections between open and closed configurations , the opposed split sections being movable through a firing stroke from a first position to a second position and back to the first position to form a plurality of surgical fasteners ; and ii ) a pivot lockout member including a latch portion which extends between the opposed split - sections , the latch portion including a contact surface which interacts with a corresponding surface formed on at least one of the opposed split - sections to retain the opposed split - sections in the closed configuration , wherein upon return of the fastener pusher member to the first position from the second position , the pivot lockout member is displaced relative to the opposed split sections to an unlocked configuration .

preferred embodiments of the surgical instrument and method disclosed herein will be described in terms of a minimally invasive direct coronary artery bypass ( midcab ) procedure wherein a vascular anastomosis is created by joining a section of a harvested vessel , e . g ., the internal memory artery ( ima ) to bypass an occlusion in a coronary artery , e . g ., the left anterior descending artery ( lad ). however , the presently disclosed surgical anastomosis instrument may also be utilized in performing anastomosis of other tubular luminal body structures . for example , the presently disclosed surgical anastomosis instrument may also be utilized to perform an a - v fistula to facilitate hemodialysis . this procedure consists of an end - to - side anastomosis joining an artery and a vein in the forearm or near the elbow . the a - v fistula allows a single puncture at the dialysis unit for blood cleansing . referring now in detail to the drawing figures in which like reference numerals identify similar or identical elements , one embodiment of the present disclosure is illustrated generally in fig1 and is designated therein as surgical instrument 100 . briefly , surgical instrument 100 includes a handle / actuator assembly 110 having a disposable loading unit 112 which is removably and rotatably attached to the handle / actuator assembly 110 by way of intermediate section 114 which extends from a distal end of housing / actuator assembly 110 . referring now to fig2 - 8 , disposable loading unit 112 includes a two - part fastener support member made up of split half - sections 116a and 116b which form a hinge and are connected to each other by hinge pin 118 . split half - section 116a includes an actuator barrel 120 which forms a bore that opens at a proximal end . actuator barrel 120 includes opposed longitudinal slots 122 and 124 to facilitate operation of an actuator member 126 which is slidably mounted in actuator barrel 120 . actuation member 126 is spring biased to a proximal - most orientation by a coil spring 128 . actuator 126 is further retained within actuator barrel 120 by a lock ring 130 which includes an annular groove 132 defined by proximal and distal flanges 134 and 136 , respectively . each of the proximal and distal flanges 134 and 136 include a pair of opposed slotted portions which are aligned to facilitate locking of ring 130 anterior portion of a mounting hub 138 . for example , by way of passing lock ring 130 over opposed extended tabs 140 and 142 , as best seen in fig8 at the rotating lock ring 130 one quarter turn such that the pairs of opposed slots formed in proximal flange and distal flange 134 and 136 , respectively , are rotated 90 ° with respect to tabs 140 and 142 . lock ring 130 is biased against the distal facing surfaces of extended tabs 140 and 142 by the force of compressed coil spring 128 which is disposed in the bore formed longitudinally within actuator 126 . in particular , a shoulder portion 144 of actuator 126 is biased against an annular lip 146 ( fig4 ) which is formed on the distal facing surface of lock ring 130 . actuator member 126 further includes a pair of opposed transversely extending slots 148 and 150 formed on the outer surface thereof which , as will be described in further detail herein , provide an engagement surface for a fastener pusher member . split half - sections 116a and 116b of the fastener support member are provided with fastener retaining sections 152 and 154 . each of fastener retaining sections 152 and 154 are provided with a plurality of longitudinal channels 156 which are configured and dimensioned to support a &# 34 ; c &# 34 ;- shaped surgical fastener or clip 158 therein by , for example , friction or partial compression of clips 158 . fastener retaining sections 152 and 154 are preferably arranged such that longitudinal channels 156 form an eccentric array radially about the outer surface of fastener support member 116 . this arrangement facilitates the efficacious formation of an angled connection or fistula between the vessels to be joined . such a connection facilitates better fluid flow through the anastomotic site . a fastener pusher member 160 is provided to facilitate deformation of clips 158 during firing of the instrument . fastener pusher member 160 is made up of split half - sections 160a and 160b which are secured to split half - sections 116a and 116b , respectively , by way of mounting plates 162 and 164 and screws 166 which are threaded into threaded holes formed in receiving posts 168 , 170 ; and 172 , 174 disposed on split half - sections 116a and 116b , respectively . mounting plates 162 and 164 are attached to split half - sections 116a and 116b in a manner to permit longitudinal sliding movement of split half - sections 160a and 160b of fastener pusher member 160 relative to fastener support member 116 . this sliding movement is facilitated by longitudinally aligned slots 176 , 178 ; and 180 , 182 which are provided on split half - sections 160a and 160b , respectively . split half - sections 160a and 160b are further provided with molded surfaces such as protrusions 184 and depressions 186 as shown on split half - section 160a which interfit with corresponding protrusions and depressions formed on split half - section 160a so as to prevent relative longitudinal movement of split half - sections 160a and 160b . stepped camming or pusher surfaces 188 are formed on the distal ends of each of split half - sections 160a and 160b and serve to cam a proximally oriented portion of clips 158 towards a distal oriented portion of clips 158 . this motion effects deformation of the clips upon firing of surgical instrument 100 . finally , a hinge lock 190 is mounted between mounting plate 162 and split half - section 160b . hinge lock 190 is provided with latch portions 192 and 194 which extend transversely across one side of disposable loading unit 112 to latch onto raised correspondingly shaped surfaces 196 and 198 , respectively , formed on the outer surface of split half - section 160a . hinge lock 190 is further provided with a pair of longitudinally oriented slots 200 and 202 which are radially aligned with slots 180 and 182 of split half - section 160b to facilitate relative longitudinal movement of hinge lock 190 with respect to both split half - section 160b and split half - section 116a . a flexible return lockout tab 204 extends proximally from the distal end of slot 202 and is cantilevered outwardly away from a plane defined by slots 202 and 204 such that it is positioned in a tab receiving recess 206 formed on the inner surface of mounting plate 162 when the dlu 112 is in a pre - fired condition . a lockout slot 208 is formed longitudinally aligned with tab receiving recess 206 and spaced distally therefrom such that upon distal movement of hinge lock 190 ( when split half - section 160b is moved distally ), return lockout tab will be deflected to a flattened condition and will extend into lockout slot 208 in order to prevent subsequent proximal movement of hinge lock upon proximal movement of split half - section 160b after firing of surgical instrument 100 . in this manner , after firing of surgical instrument 100 , latch portions 192 and 194 of hinge lock 190 will remain distal relative to raised surfaces 196 and 198 of split half - section of 160a by permitting the split half - sectioned dlu 112 to be opened by pivoting split half - sections 116b and 160a away from split half - sections 116a and 160b to facilitate removal of the vessel segment from within the vessel pathway formed through the distal end of dlu 112 and out through a lateral opening 210 formed by aligned molded recesses formed in each of split half - sections 116a , 116b ; and 160a and 160b of fastener support member 116 and fastener pusher member 160 , respectively . referring now to fig9 - 12 , the handle / actuator assembly 110 of surgical instrument 100 will now be described in detail . handle / actuator assembly 110 includes a housing formed of half - sections 212a and 212b which are preferably molded to have recessed inner surfaces and contours formed therein to house the various components which are contained within handle / actuator assembly 110 . in particular , handle / actuator assembly 110 includes a dlu mounting assembly which facilitates detachable mounting of a dlu 112 to the distal end of handle / actuator assembly 110 . the dlu mounting assembly includes an elongated holding tube 214 which is held longitudinally and rotationally fixed relative to housing half - sections 212a and 212b . this mounting arrangement may be accomplished for example , by way of an annular flange 216 formed adjacent the proximal end of holding tube 214 being held within an annular groove defined by partition wall segments 218 and 220 formed in each of housing half - sections 212a and 212b . holding tube 214 is further prevented from rotational movement by way of flattened sidewall portions 222 formed on opposing sides of holding tube 214 being retained within and abutting flat surfaces 224 and 226 formed long partition wall segments 218 and 220 , respectively , in each of housing half - sections 212a and 212b . dlu locking tube 215 is secured within a collar 228 formed on slide 217 . tube 215 may be secured in slide 217 by any suitable means , for example , friction fitting bonding , adhesives , or the like . coil spring 219 is interposed in housing half - sections 212a and 212b between partitioned segments 218 and the proximal end surface of collar 228 . in this manner , locking tube 215 is biased in a distal - most position which corresponds to a locked position to retain dlu 112 on the distal end of surgical instrument 100 . the distal end of dlu holding tube 214 is provided with a semi - annular groove 230 which is dimensioned to receive mounting hub 138 formed at the proximal end of dlu 112 . semi - annular groove 230 is dimensioned to permit dlu mounting hub 138 to rotate within the groove . handle and actuator assembly 110 further includes a firing assembly which facilitates movement of actuator 126 housed within the actuator barrel 120 . in the embodiment illustrated in fig9 - 15 , the firing assembly is a linkage mechanism which imparts reciprocating longitudinal movement in an actuator rod by way of movement of an actuator lever . however , it is within the scope of the present disclosure that the actuator rod may be reciprocatingly moved by any suitable known methods . the firing assembly basically includes an actuator rod 232 which is connected to an actuator lever 234 by way of links 236 pivotally attached at either end to actuator rod 232 and actuator lever 234 , respectively . actuator rod 232 is slidably disposed within a longitudinal bore formed through dlu holding tube 214 . actuator rod 232 is biased in a proximal - most position by way of a torsion spring 238 being mounted on a post 240 formed near the proximal end of housing half - section 212b . extended legs 238a and 238b are provided on torsion spring 238 to bias actuator lever 234 upwardly away from housing half - sections 212a and 212b thereby pulling actuator rod 232 toward its proximal - most position as determined by the abutment of annular shoulder 242 against partition 244 formed in each of housing half - sections 212a and 212b . to facilitate comfort and ease of operation for the user , a cover 246 is secured over actuator lever 234 and is independently pivotally mounted to housing half - sections 212a and 212b . cover 246 is provided with an ergonomic surface 248 which is contoured and configured to be comfortably actuated by the thumb of a user when handle and actuator assembly 210 is held in the palm of the user &# 39 ; s hand . a firing safety mechanism is also provided to prevent premature firing of surgical instrument 100 . in the illustrated embodiment , the firing safety assembly includes an inverted leaf spring 250 having a cut - out portion 252 formed therein which biases against a shoulder 254 formed on actuator rod 232 . spring 250 is further provided with a hook portion 256 formed at the proximal end thereof which latches onto a protruding surface 258 formed in housing half - sections 212a and 212b . in this manner , spring 250 prevents distal movement of actuator rod 232 when the safety mechanism is armed . a safety release slide 260 which includes an upwardly extending contact surface which is exposed from the upper surface of housing half - sections 212a and 212b to permit the user to operate the slide and forms a clevis on a lower portion thereof which receives a flattened section 266 of actuator rod 332 . safety release slide 260 is further provided with a camming surface 268 along the lower edge thereof which cams the spring 250 out of contact with shoulder 254 upon proximal movement of safety release slide 260 . in use , as shown in fig1 - 31 , surgical instrument 100 facilitates the performance of a vascular anastomosis without the need for manual suturing of the vessels . the method and usage described herein will be addressed in terms of minimally invasive vascular anastomosis performed on a beating heart such as in a midcab procedure . however , the presently disclosed surgical instrument may also be used in performing anastomoses of other tubular or luminal body structures without departing from the scope of the present disclosure . for example , surgical instrument 100 may be used in conventional open cabg procedures using a median sternotomy or other large incision without stopping the heart . alternatively , the thoracic &# 34 ; window &# 34 ; procedure may be used to achieve access to the heart . the &# 34 ; window &# 34 ; approach involves a smaller incision and less displacement of the ribs , and therefore is less traumatic to the patient . for this approach , conventional surgical techniques are used to determine the location of the incision to access the chest cavity . in particular , a surgical retractor assembly may be used to separate the ribs at the site of the incision as shown in fig1 . specifically , a base 270 is placed on the chest of the patient with the central opening defined by the base being positioned over the operative site . retractor assemblies 272 are mounted to the base at various locations . each of retractor assemblies 272 includes a blade having a hook to engage either a rib or the sternum therewith . the retractor assemblies are mounted and used to retract ribs until a sufficiently large opening in the chest cavity is defined to provide direct access to the heart . for example , the sternum and the fourth and fifth ribs can be split apart to create a window . other configurations of spreading the ribs and / or selectively cutting individual ribs away from the sternum may also be utilized for a particular procedure . once the desired access to the heart is achieved , the graft vessel , e . g ., the internal memory artery ( ima ) is dissected from the surrounding cartilage and muscle , in a free end of the vessel is exposed . the occluded coronary artery , e . g ., the left anterior descending artery ( lad ), is then prepared for receiving the ima graft . the heart is positioned in the desired orientation either by traction sutures passing through the pericardium or by manipulation with heart manipulation instruments which are held by the surgical personnel or clamped in a fixed orientation to a base such as the retractor assembly base . one such heart manipulating instrument is available from united states surgical corporation of norwalk , connecticut . blood flow through the lad can be restricted by cardiopulmonary bypass and pericardial cooling . alternatively , a damping instrument may be applied directly on the lad to restrict blood flow and reduce movement of the heart near the lad . such a heart stabilizing instrument is also available from united states surgical corporation of norwalk , connecticut . referring to fig1 , the free end of the ima is inserted through lateral opening 210 of dlu 112 and passed out the distal end opening of the dlu . the free end of the ima is then everted over the distal end of the dlu such that the end of the ima is retained by the distal end oriented portions of clips 158 as best shown in fig1 and fig1 . everting of the tissue may be achieved by any suitable known techniques such as y using graspers . with the ima loaded in dlu 112 , the dlu is manipulated preferably detached from the handle and actuator assembly 110 in approximation to an incision &# 34 ; i &# 34 ; formed in the lad , as shown in fig1 . referring to fig1 and 19 , the dlu with the everted ima is inserted into the incision &# 34 ; i &# 34 ; of the lad such that the walls of the lad surrounding the incision are retained between the everted end of the ima and the proximal ends of clips 158 , as shown in fig1 . as previously noted , the distal end of dlu 112 is configured with an angle relative to a transverse plane of the dlu in order to optimize the anastomosis and to facilitate optimal blood flow across the graft site from the ima to the lad . this junction creates &# 34 ; heel &# 34 ; and &# 34 ; toe &# 34 ; portions in which an acute or obtuse angle between the vessels is defined . once dlu 112 with the everted ima has been successfully inserted through the incision of the lad , the surgeon may then attach the handle / actuator assembly 110 to dlu 112 as shown in fig2 and 21 . in particular , the dlu lock slide 217 is moved proximally as indicated by arrow &# 34 ; a &# 34 ; in order to retract locking tube 215 and thereby expose the distal end of dlu holding tube 214 , and in particular , semiannular groove 230 . dlu 112 is inserted on the distal end of the handle and actuator assembly 110 by placing mounting hub 138 within semi - annular groove 230 and releasing the force applied on dlu lock slide 217 as indicated by arrow &# 34 ; b &# 34 ; in fig2 , to permit coil spring 219 to return lock slide 217 and locking tube 215 to their distal - most orientations thereby securing the dlu in place . referring to fig2 and 23 , when the surgeon is ready to complete the anastomosis , the safety release slide 260 is moved proximally as indicated by arrow &# 34 ; c &# 34 ; in fig2 thereby causing camming surface 268 to cam spring 250 downwardly away from shoulder 254 as indicated by arrow &# 34 ; d &# 34 ;. thereafter , the surgeon may depress cover 246 towards handle half - sections 212a and 212b , as indicated by arrow &# 34 ; e &# 34 ; in fig2 , causing actuator rod 232 to drive actuator 126 of dlu 112 distally as indicated by arrow &# 34 ; f &# 34 ;, thereby moving pusher member split half - sections 160 and 160b distally to deform clips 158 as shown in fig2 and 26 . as best illustrated in fig2 , one particularly advantageous feature of the presently disclosed surgical instrument is that upon actuation of handle / actuator assembly 110 , safety release slide 260 is urged back into its initial locked orientation by way of annular flange 216 of actuator rod 232 pushing the lower portion of safety release slide 260 during the distal movement of actuator rod 232 . in this manner , upon release of cover handle 246 , the potential energy created by the compression of torsion spring 238 will cause actuator rod 232 to be pulled back proximally thereby engaging shoulder 254 with cutout 252 of spring 250 . this will serve to prevent accidental re - firing action of surgical instrument 100 . referring to fig2 - 30 , a farther uniquely advantageous feature of surgical instrument 100 is hinge lock 190 and its operation . upon firing of surgical instrument 100 , return lockout tab 204 of hinge lock 190 , which extended into lockout slot 208 during distal movement of hinge lock 190 with split half - sections 160 and 160b , serves to retain hinge lock 190 distal of its original seated location in tab receiving recess 206 . by retaining hinge lock 190 at this position , latch portions 192 and 194 are released from raised surfaces 196 and 198 of split half - section 160a of the pusher member . in this manner , split half - section 116b and 160a may be pivoted away from split half - sections 116a and 160b as shown in fig3 to permit the removal of the ima from within the pathway of the dlu thereby completing the vascular anastomosis as shown in fig3 . referring to fig3 a , a portion of the vascular anatomy of an arm which may be an alternative utilized anastomosis site as illustrated wherein instead of joining the ima to the lad in a bypass procedure , an a - v fistula is performed utilizing surgical instrument 100 to join the radial artery end - to - side with the cephalic vein ( sometimes called the radial vein ). other a - v fistulas which may also be achieved utilizing surgical instrument 100 include joining the ulnar artery end - to - side with the basilic vein ( sometimes called the ulnar vein ). such a - v fistulas are performed to facilitate hemodialysis for end stage kidney disease to allow a single puncture at the dialysis unit for blood cleansing . the fistula allows a greater flow rate through the dialyzer ( not shown ). referring to fig3 - 39 , an alternative embodiment of the firing safety mechanism illustrated in fig2 - 24 is illustrated which also prevents the unintended firing of surgical instrument 100 . the firing safety mechanism includes a lock spring 350 and a safety release slide 360 . referring to fig3 and 33a , safety release slide 360 includes a pair of camming surfaces 360a and 360b which interact with cam follower surfaces 350d and 350e . lock spring 350 , as best illustrated in fig3 , includes a body portion 350a that defines a yoke , a pair a leaf spring portions 350b and 350c , and a pair of cam follower surfaces 350d and 350e formed along a top portion thereof . an actuator rod 332 , fig3 , is configured and dimensioned to pass through yoke portion 350a of lock spring 350 . in the initial ( pre - fired ) configuration , as shown in fig3 , safety release slide 360 is disposed above lock spring 350 such that camming surfaces 360a and 360b contact cam following surfaces 350e and 350e , respectively , when safety release slide 360 is in the distal - most position . in this orientation , leaf spring portions 350b and 350c serve to bias lock spring 350 upwardly within the instrument housing so that a shoulder portion 332a of actuator rod 332 abuts against a proximal facing lower surface 350f , as shown in fig3 , to prevent firing of the instrument . when the surgeon desires to fire the instrument , safety release slide 360 is moved proximally as indicated by arrow &# 34 ; g &# 34 ; in fig3 . in this manner , camming surfaces 360a and 360b travel over cam follower surfaces 350e and 350d , respectively , thereby urging lock spring 350 downwardly in the direction of arrows &# 34 ; h &# 34 ; to overcome the spring force of leaf spring portions 350b and 350c . this movement displaces proximal surface 350f below shoulder portion 332a thereby permitting actuator rod 332 to move distally . upon distal movement of actuator rod 332 as indicated by arrow &# 34 ; i &# 34 ; in fig3 , a second shoulder portion 332b formed proximal of shoulder portion 332a on actuator rod 332 contacts a rear wall portion 360c of safety release slide 360 thereby urging safety release slide distally in a direction of arrow &# 34 ; i &# 34 ; as well . upon release of actuator handle cover 246 , actuator rod 332 moves proximally as indicated by arrow &# 34 ; j &# 34 ; in fig . 39 thereby permitting lock spring 350 to move upwardly as indicated by arrow &# 34 ; k &# 34 ; in fig3 to reset the firing safety mechanism . it will be understood that various modifications may be made to the embodiment shown herein . for example , the instruments may be sized to perform an anastomosis for other vessels and luminal tissue . therefore , the above description should not be construed as limiting , but merely as exemplications of preferred embodiments . those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto .

US-25626099-A

a game assembly in the form of a puzzle comprising a plurality of pieces disconnected from one another but successively positioned and collectively movable along the length of a track structure . opposite exposed surfaces of the pieces are contrastingly designated such as by different colors or the like and wherein the pieces may be selectively positionable into a predetermined array , for purposes of solving the puzzle , by temporarily disconnecting segments of the track structure along with the pieces thereon and repositioning the track segments into a different operable position from an original operable position .

as shown in fig1 through 9 , the present invention relates to a toy assembly in the form of a puzzle structure generally indicated as 10 including an elongated track structure 12 of a continuous , closed configuration to define a continuous path of travel along the length thereof . as clearly shown in fig1 the track structure 12 is preferably in the form of a figure 8 construction defined by two end loops 14 and 16 removably secured together by a center assembly generally indicated as 18 . with references to fig1 through 4 , the track structure 12 comprises , along its length , two inwardly extending flanges 22 and 24 spaced apart in substantially coplanar relation to one another so as to define an elongated space therebetween . the space 26 extends along the entire length of the track structure 12 in a continuous uninterrupted fashion except for the center assembly 18 serving as an interconnection for the end loops 14 and 16 . similarly , the flanges 22 and 24 extend continuously along the length of the track 12 so as to define the longitudinal boundaries of the space 26 . another important feature of the present invention is the provision of a plurality of pieces 28 movable along the length of the track structure 12 by being slidably retained within the elongated groove 26 . as shown in fig1 a preferred embodiment of the subject puzzle structure 10 includes a sufficient number of pieces 28 to essentially be disposed in spaced apart , independent , and successive relation to one another along the length of the track structure 12 . accordingly , movement of any one of the pieces 28 along the length of the track structure 12 will in effect cause movement of the entire plurality of pieces 28 . also , it is noted that each of the pieces are equally dimensioned and congruently configured . while the configuration of each of the pieces may in fact vary from the multi sides pieces shown , a preferred embodiment thereof would again call for all the pieces being equivalently configured and dimensioned . further , each of the pieces 28 include a mid - portion 30 and oppositely disposed exposed surfaces 32 and 34 . the mid - portion 30 is of a sufficiently reduced transverse dimension to fit between the flanges 22 and 24 of the track structure 12 and into the elongated groove 26 for retaining travel therein as set forth above ( see fig2 and 4 ). the plurality of pieces 28 are divided into a plurality of groups wherein an equal number of pieces exist within each group . the pieces of each group may be determined by contrastingly designating the exposed surfaces 32 and 34 in such a manner that all the pieces of a specific group are of the same color on at least one of the exposed surfaces and wherein pieces of different groups are contrastingly designated by having a different color thereon . performance of the puzzle and its solution is therefore accomplished by first arbitrarily arranging all the pieces relative to one another in an uncoordinated manner . the eventual solving of the puzzle occurs by then rearranging all of the pieces 28 so that all of the pieces of the same group are consecutively positioned relative to one another with no intervening pieces of a contrasting color disposed therebetween . another feature of the present invention is the existence of a frame structure generally indicated as 40 comprising a main or primary support member in the form of elongated shaft 42 extending along the length of the puzzle structure 10 between opposite ends thereof . as clearly shown in fig1 and 2 , the shaft 42 has its opposite ends removably seated as at 44 within a recess formed in the inner surface of the track structure 12 . further , the approximate mid portion of the shaft 42 is connected to or extends through a mid portion 46 of the center assembly 18 . the frame structure 40 further includes a plurality of brace elements 48 having one end secured as at 49 to each of a plurality of track segments 50 , 52 , 54 , and 56 . their innermost end is secured by a slidable connector 52 to the elongated shaft 42 such that the brace elements 48 may be movable along at least a short distance of the shaft 42 as will be explained in greater detail hereinafter . in order to provide additional structural integrity to the track structure 12 and maintain the flanges 22 and 24 in fixed spaced apart relation to one another so as to form the elongated groove or channel 26 , connectors 55 are attached to the track structure at spaced apart locations relative to one another . further it is readily apparent that these connectors 55 are fixedly secured or attached to the brace elements 48 . with regard to fig1 it should be noted that the various track segments 50 , 52 , 54 , and 56 are separated from one another by junctions 58 . such junctions allow for the separation of the track segment 50 relative track segment 52 and track segment 54 relative to track segment 56 . further , as set forth above , the track segments 52 and 54 are each separable from the center assembly 18 . biasing means in the form of a plurality of strategically placed biasing springs 60 , 62 , 64 and 66 are mounted on the shaft 42 and positioned to normally bias the brace elements , through biasing engagement with the connectors 52 , into an operative position as pictured in fig1 . with reference to fig2 it should be apparent that the positioning of the spring elements 62 , 64 , 66 and 68 bias the brace elements 48 towards one another and more specifically collectively towards the center assembly 18 . however , removable interconnections are provided so as to allow separations of the various adjacently positioned track segments relative to one another and specifically wherein track segments 52 and 54 are separable relative to the center assembly 18 . these removable interconnections are accomplished by a plurality of outwardly extending fingers 70 cooperating with correspondingly positioned and mating apertures 70 &# 39 ; in which such fingers may be removably received . it should be apparent that any one of the track segments 50 , 52 , 54 , and 56 may be removed from its next adjacent track segment to which it is removably attached and effectively rotated 180 degrees about the longitudinal axis of the support shaft 42 by a manipulation and rotation of the respective brace element serving to interconnect the respective track segment to the support shaft 42 . this is accomplished due to the fact that the connectors 52 are both movable in a sliding fashion along the length of the support shaft 42 and rotatable thereabout . disconnection of the various track segments from one another is readily accomplished by moving the brace elements 48 and the attached connector elements 52 against the biasing force of the correspondingly positioned biasing springs 62 , 64 , 66 , and 68 until disconnection between adjacent track segments occurs . with reference to fig1 and 5 through 9 , the center assembly 18 ( see fig6 ) comprises a first track portion 74 and a second track portion 76 fixedly secured to one another and separated by mid portion 46 . further , each of the first and second track portions 74 and 76 are open to allow various pieces 28 to pass therethrough in directions which are transverse to one another as the pieces pass between track segments 52 and 54 . therefore , it should be readily apparent that a first end of each of the track segments 52 and 54 as at 52 &# 39 ; and 54 &# 39 ; communicate with opposite sides of the first track portion 72 and a second end 52 &# 34 ; and 54 &# 34 ; communicate with and allow pieces to pass through the second track portion 76 of the center assembly 18 . it should be obvious therefore that the various exposed faces 32 and 34 on each piece carried by any given track segment 50 , 52 , 54 and / or 56 may be reversed by rotating that particular track segment about the longitudinal axis of the support shaft 42 through 180 degrees . the various pieces can therefore be manipulated such that the exposed faces 32 and 34 themselves being of different colors , can be arranged into a predetermined array or grouping , as set forth above , to solve the above set forth problems . for purposes of simplicity , fig1 has been shown without a full cover portion 80 covering the interior or center section or more specifically the enlarged apertures of the opposite ends 14 and 16 . such a cover structure and its relative disposition to the frame structure 40 is clearly disclosed in fig1 and 7 .

US-4965487-A

a handle assembly for operating an articulatable surgical instrument is provided and includes a housing ; an actuation shaft translatably and rotatably supported in the housing ; a first trigger supported on the housing and connected to the actuation shaft , the first trigger being configured to translate the actuation shaft to operate a first function of the surgical instrument ; a second trigger supported on the housing and connected to the actuation shaft , the second trigger being configured to rotate the actuation shaft to operate a second function of the surgical instrument ; and a second - trigger release supported in the housing , the second - trigger release having a first position blocking actuation of the second trigger and a second position permitting actuation of the second trigger , where the second - trigger release is actuated from the first position to the second position upon and complete actuation of the first trigger .

the present disclosure relates to devices , systems and methods for endoscopic , laparoscopic , endoluminal , and / or transluminal suturing . in one embodiment , for example , such a device comprises a handle , handle assembly or other suitable actuating mechanism ( e . g ., robot , etc .) connected to a proximal end of a flexible , elongated body portion . a neck assembly operatively supported on a distal end of the flexible , elongated body portion allows an end effector , operatively supported at a distal end of the neck assembly , to articulate in response to actuation of articulation cables . the end effector includes a suture needle and a pair of jaws . in operation , the suture needle is passed back and forth through tissue from one jaw to the other . the device is adapted to be placed in a lumen of a flexible endoscope and then inserted into a natural orifice of a patient and transited endoluminally through the anatomy of the natural lumen to a treatment site within or outside the natural lumen . in the drawings and in the description which follow , the term “ proximal ”, as is traditional , will refer to the end of the device which is closest to the operator , while the term “ distal ” will refer to the end of the device which is furthest from the operator . referring now in specific detail to the drawings , in which like reference numbers identify similar or identical elements , fig1 - 11 illustrate an embodiment of a handle assembly , for an end effector of a stitching device , shown generally at 100 . exemplary end effectors of stitching devices , for use with handle assembly 100 , are shown and described in detail in u . s . patent application ser . no . 12 / 442 , 847 , filed on may 4 , 2009 , entitled flexible endoscopic stitching devices , the entire content of which is incorporated herein by reference . as seen in fig1 - 11 , handle assembly 100 includes a housing 102 having a right - half section 102 a and a left - half section 102 b joinable to one another by suitable fastening elements ( not shown ), such as screws . handle assembly 100 includes a first trigger 104 and a second trigger 105 , each operatively supported in / on housing 102 and extending therefrom . as will be described in greater detail below , triggers 104 , 105 are independently movable between a first un - actuated position , as seen in fig1 - 5 , and at least one second actuated position . in use , movement of triggers 104 , 105 between the first and second positions results in actuation and / or operation of the end effector ( not shown ). first trigger 104 is pivotally connected to housing 102 at a pivot point “ p 1 ” so as to rotate thereabout . first trigger 104 is operatively associated or otherwise connected to an actuation mechanism 110 ( see fig6 ) of handle assembly 100 . in use , movement of first trigger 104 between the first and second positions results in a first function , actuation and / or operation of the end effector . second trigger 105 is pivotally connected to housing 102 also at pivot point “ p 1 ” so as to rotate thereabout . second trigger 105 is operatively associated or otherwise connected to an actuation mechanism 110 of handle assembly 100 . in use , movement of second trigger 105 between the first and second positions results in a second function , actuation and / or operation of the end effector . it is contemplated that second trigger 105 is nested in first trigger and may include a lip 105 c ( see fig9 and 9a ) configured to engage first trigger 104 , when first trigger 104 is moved from an actuated position to an un - actuated position , lip 105 c of second trigger 105 is engaged by first trigger 104 thereby also moving second trigger 105 from an actuated position to an un - actuated position . first trigger 104 may be biased to the un - actuated position by a suitable biasing member , such as , for example a spring or the like ( not shown ). first trigger 104 includes a lever arm 104 a extending therefrom and into housing 102 . a free end of lever arm 104 a terminates in a head portion 104 b . lever aim 104 a extending from first trigger 104 is formed to have a flattened profile and of a resilient material ( e . g ., spring steel ) in order for lever arm 104 a to deflect in a direction transverse to a plane defined by the flattened lever arm . lever arm 104 a of first trigger 104 is curved or biased in a direction out of a plane defined by the plane in which first trigger 104 is actuated . as seen in fig3 - 6 , handle assembly 100 further includes a trigger latch 106 supported in housing 102 and located to selectively engage head portion 104 b . trigger latch 106 includes a first cam member 106 a projecting toward first trigger 104 . first cam member 106 a includes a first distal cam surface 106 a 1 configured and oriented to urge or bias head portion 104 b of lever arm 104 a to a non - biased position as first trigger 104 is moved from the un - actuated position to an actuated position . trigger latch 106 includes a second cam member 106 b projecting toward first trigger 104 . second cam member 106 b is spaced a proximal distance from first cam member 106 a . second cam member 106 b includes a distal cam surface 106 b 1 oriented in substantially the same direction as first distal cam surface 106 a 1 of cam member 106 a . in use , as first trigger 104 is actuated past an initial actuation to a fully actuated position , head portion 104 b of lever arm 104 a travels from distal cam surface 106 b 1 of cam member 106 a to distal cam surface 106 b 1 of second cam member 106 b . with continued reference to fig3 , first cam member 106 a includes a proximal notch 106 a 2 formed in a proximal surface of first cam member 106 a and spaced an axial distance from distal cam surface 106 b 1 of second cam member 106 b . in use , as first trigger 104 is released ( i . e ., moved in a direction away from the fully actuated position ), due to the bias of lever arm 104 a , head portion 104 b thereof is passed from distal cam surface 106 b 1 of second cam member 106 b to notch 106 a 2 formed in a proximal surface of first cam member 106 a , thereby stopping first trigger 104 from returning completely to the un - actuated position . with continued reference to fig3 , first cam member 106 a further includes a proximal cam surface 106 a 3 formed in a proximal surface of first cam member 106 a and located adjacent notch 106 a 2 . in use , first trigger 104 is re - actuated , thereby separating or lifting head portion 104 b of lever 104 from or out of notch 106 a 2 . as head portion 104 b of lever 104 is lifted out of notch 106 a 2 , the bias of lever 104 moved head portion 104 b out of registration with notch 106 a 2 and into registration with proximal cam surface 106 a 3 . in this manner , as first trigger is re - released or returned to the un - actuated position , head portion 104 b of lever 104 cams against proximal cam surface 106 a 3 and around first cam member 106 a . in this manner , when first trigger 104 is pulled once , upon release thereof , first trigger 104 is held by trigger latch 106 in a partially actuated position . then , when first trigger 104 is pulled a second time , upon release thereof , first trigger 104 is able to return to the fully un - actuated position . second trigger 105 includes a lever arm 105 a extending therefrom and into housing 102 . a free end of lever arm 105 a terminates in a head portion 105 b . head portion 105 b of lever arm 105 a of second trigger 105 is received in a slot 334 a formed in a gear rack 334 of a needle blade actuating assembly 330 ( see fig3 ). gear rack 334 is slidably supported in housing 102 . the structure and function of gear rack 334 will be described in greater detail below . handle assembly 100 includes , as seen in fig3 - 6 , 9 and 9 a , an actuation assembly 110 supported in housing 102 and connected to triggers 104 , 105 . in particular , actuation assembly 110 includes a drive or actuation shaft 312 rotatably and translatably supported in housing 102 . actuation shaft 312 may be rigid and includes a distal end connected to a flexible actuation cable or the like not shown . actuation assembly 110 includes a drive block 114 axially , translatably supported in housing 102 . actuation block 114 includes a lumen 114 a ( see fig8 ) through which actuation shaft 312 passes . actuation shaft 312 is rotatably disposed within actuation block 114 and is inhibited from axial translation relative to actuation block 114 as a result of any number of stops 312 a provided along the length thereof . exemplary stops 312 a include and are not limited to spring clips or ring clamps attached to actuation shaft 312 , a flange projecting from actuation shaft 312 and / or the like . actuation assembly 110 includes a drive link 116 inter - connecting first trigger 104 and actuation block 114 . as so configured , as first trigger 104 is actuated from the first un - actuated position to a second actuated position , first trigger 104 acts on drive link 116 which in turn acts on actuation block 114 to urge actuation block 114 in a proximal direction . as actuation block 114 is urged in a proximal direction , actuation block 114 moves actuation shaft 312 in a proximal direction , and in turn the actuation cable is moved in a proximal direction . as seen in fig4 - 5b , actuation assembly 110 further includes a second - trigger release 118 rotatably supported in housing 102 . second - trigger release 118 is biased to a locking condition wherein second - trigger release 118 engages and blocks movement of gear rack 334 of needle blade actuating assembly 330 . in use , as first trigger 104 is actuated to move actuation block 114 to the actuated position , actuation block 114 engages second - trigger release 118 to disengage second - trigger release 118 from gear rack 334 of needle blade actuating assembly 330 . handle assembly 100 includes an articulation assembly 170 supported on and / or in housing 102 . articulation assembly 170 may be operatively connected to the end effector in order to impart multiple articulations to the end effector or any other suitable movement or operation to the end effector . as seen in fig6 and 7 , articulation assembly 170 includes a pair of knobs or dials 172 a , 172 b rotatably supported on or in housing 102 , and a set of gears 174 keyed to and sharing a common rotational axis as dials 172 a , 172 b . the set of gears 174 includes a first gear 174 a keyed to first dial 172 a , via a rotation shaft 175 a , and a second gear 174 b keyed to second dial 172 b . articulation assembly 170 further includes two pairs of opposed racks 180 a , 180 b with each pair being operatively engaged with and disposed on opposed sides of respective first and second gears 174 a , 174 b . each pair of racks 180 a , 180 b is slidably supported within respective channels 182 a , 182 b formed in a support member 182 . support member 182 includes a central body portion 182 c , and a pair of opposed cap walls 182 d , 182 e secured to central body portion 182 c by suitable screw members 182 f , 182 g . screw members 182 f , 182 g are disposed one each on opposed sides of racks 180 a , 180 b . channels 182 a , 182 b are formed between central body portion 182 c and respective cap walls 182 d , 182 e . in operation , the dimensions ( i . e ., widths ) of channels 182 a , 182 b may be increased / decreased by adjusting screw members 182 f , 182 g to either increase / decrease the space between cap walls 182 d , 182 e and central body portion 182 c , and thus increase / decrease friction on racks 180 a , 180 b . each rack of the pair of racks 180 a , 180 b includes an articulation cable ( not shown ) secured thereto . in this manner , during operation , as each rack of the pair of racks 180 a , 180 b is displaced so to is each respective articulation cable . in operation , as first gear 174 a is rotated in a first direction , due to the rotation of first dial 172 a and first gear 174 a , the first pair of racks 180 a are displaced in opposite directions to one another , thus displacing respective articulation cables in opposite directions to one another . it is understood that rotation of first dial 172 a in an opposite direction and thus rotation of first gear 174 a in an opposite direction will result in movement and / or displacement of the respective pair of racks 180 a and articulation cables in opposite directions . rotation of first dial 172 b thus may impart an operation , movement or first articulation of the end effector . also , in operation , as second gear 174 b is rotated in a first direction , due to the rotation of second dial 172 b and second gear 174 b , the second pair of racks 180 b are displaced in opposite directions to one another , thus displacing respective articulation cables in opposite directions to one another . it is understood that rotation of second dial 172 b in an opposite direction and thus rotation of second gear 174 b in an opposite direction will result in movement and / or displacement of the respective pair of racks 180 a and articulation cables in opposite directions . rotation of second dial 172 b thus may impart an operation , movement or second articulation of the end effector . as seen in fig1 - 5a , handle assembly 100 includes friction adjustment assembly 173 . friction adjustment assembly 173 includes a slide switch 115 translatably supported on housing 102 , and a gear rack 116 connected to slide switch 115 and movable therewith . friction adjustment assembly 173 further includes a first gear 173 a treadably supported on screw member 182 f and in operative engagement with gear rack 116 , a second gear 173 b threadably supported on screw member 182 g , and a reversing gear 173 c operatively inter connecting first and second gears 173 a , 173 b . in use or operation , as slide switch 115 is actuated in a first direction , gear rack 116 is actuated in a first direction , and first and second gears 173 a , 173 b are actuated in first direction to tighten screws 182 f , 182 g and increase the friction on racks 180 a , 180 b . also in use or operation , as slide switch 115 is actuated in a second direction , gear rack 116 is actuated in a second direction , and first and second gears 173 a , 173 b are actuated in second direction to loosen screws 182 f , 182 g and decrease the friction on racks 180 a , 180 b . the friction on racks 180 a , 180 b may be increased or decreased as needed in order to assist in maintaining an articulated orientation of the end effector or to assist or enable the end effector to be articulated or un - articulated . as seen in fig3 - 5a , 6 and 8 - 9 a , handle assembly 100 further includes a needle loading assembly 300 including a knob 310 rotatably supported on a rear end of housing 102 and configured to enable loading of a surgical needle in the jaws of an end effector ( not shown ). knob 310 includes an indicator 310 a , for example , in the form of a rib extending from a side edge thereof , for cooperation with an indicator 102 c ( see fig1 and 2 ) formed on housing 102 . indicators 102 c and 310 a provide the user with an indication of a relative state of handle assembly 100 and / or the surgical device based on the relative position of indicators 102 c , 310 a to one another . knob 310 is coupled to a proximal end of actuation shaft 312 , which has been keyed for connection to knob 310 , via a keyed rotation hub 314 rotatably and slidably supported in housing 102 . keyed rotation hub 314 has a shaped outer surface for receipt in a complementary shaped recess formed in knob 310 such that rotation of knob 310 results in rotation of keyed rotation hub 314 . keyed rotation hub 314 defines a shaped lumen ( not shown ) for receipt of a complementary shaped outer surface of keyed shaft 312 such that rotation of knob 310 also results in rotation of keyed shaft 312 . rotation hub 314 is biased to an advanced or distal position by a biasing member 316 , in the form of a c - spring or the like . thus , in use , as knob 310 is pulled in a proximal direction relative to housing 102 , rotation hub 314 is also pulled in a proximal direction and biasing member 316 is biased . upon release of knob 310 , biasing member 316 is free to return to an un - biased condition and thus pull rotation hub 314 and knob 310 in a distal direction relative to housing 102 . as seen in fig4 , 6 , 8 and 11 , needle loading assembly 300 includes a clutch member 318 rotatably supported in housing 102 and selectively connectable to rotation hub 314 . clutch member 318 is rotatably disposed about keyed shaft 312 . clutch member 318 includes a non - circular shaped stem 318 a extending proximally therefrom and being configured for selective engagement in a complementary recess 314 a ( see fig3 , 3 a , 9 and 9 a ) formed in a distal surface of rotation hub 314 . clutch member 318 includes at least one rib 318 b formed on an outer surface thereof . as seen in fig4 , 6 , 8 and 11 , needle loading assembly 300 further includes a clutch driver 320 rotatably supported in housing 102 and selectively engageable by clutch member 318 . clutch driver 320 a body portion 320 a rotatably disposed about keyed shaft 312 , and a pair of opposed arms 320 b , 320 c extending radially therefrom . clutch driver 320 further includes a cam wall 320 d , 320 e supported on a respective end of arms 320 b , 320 c . cam walls 320 d , 320 e are spaced radially outward by an amount sufficient to at least partially surround clutch member 318 . cam walls 320 d , 320 e are also configured to selectively operatively engage the at least one rib 318 b of clutch member 318 . in this manner , as clutch member 318 is rotated in a first direction , the at least one rib 318 a thereof will engage either cam wall 320 d and / or 320 e and transmit rotation to clutch driver 320 . also , cam walls 320 d , 320 e are configured such that rotation of clutch member 318 in a second direction does not result in rotation of clutch driver 320 . needle loading assembly 300 further includes a spring arm 322 , secured to housing 102 , and in tangential contact with cam walls 320 d , 320 e of clutch driver 320 . spring arm 322 is arranged such that a free end thereof will ride over or across cam walls 320 d , 320 e of clutch driver 320 as cam driver 320 is rotated in the first direction due to the rotation of clutch member 318 , and will enter into and between cam walls 320 d , 320 e of clutch driver 320 as cam driver 320 is rotated in the second direction due to the rotation of clutch member 318 to thereby limit or block rotation of cam driver 320 . as seen in fig3 , 3 a , 5 , 8 , 9 and 9 a , handle assembly 100 further includes a needle blade actuating assembly 330 connected to second trigger 105 and to actuation shaft 312 . in particular , needle blade actuating assembly 330 includes a spur gear 332 supported on and keyed to body portion 320 a of can driver 320 . in this manner , rotation of cam driver 320 or spur gear 332 results in rotation of the other of cam driver 320 or spur gear 332 . needle blade actuating assembly 330 further includes a gear rack 334 slidably supported in housing 102 , as described above . gear rack 334 defines a slot 334 a for receipt of head portion 105 b of lever arm 105 a of second trigger 105 . gear rack 334 is positioned in housing 102 such that the gear teeth thereof engage with the gear teeth of spur gear 332 . accordingly , in use , following actuation of first trigger 104 and the release of gear rack 334 by second - trigger release 118 , as described above , as second trigger 105 is actuated from an un - actuated condition , lever arm 105 a thereof acts on gear rack 334 to translate gear rack 334 . as gear rack 334 is translated the gear teeth thereof cooperate with the gear teeth of spur gear 332 and thus cause spur gear 332 to rotate . as spur gear 332 is rotated , cam driver 320 is also rotated due to spur gear 332 being keyed thereto . as described above , rotation of cam driver 320 in one direction transmits rotation to clutch member 318 , on to rotation hub 314 and then to actuation shaft 312 . meanwhile , rotation of cam driver 320 in an opposite direction is limited or blocked by spring arm 322 . as can be appreciated , a distal end of keyed shaft 312 is fixedly secured to a proximal end of an actuation shaft ( not shown ), and a distal end of the actuation shaft may be connected to an actuation cable ( not shown ) extending in and connected to the end effectors . in use , in order to load a surgical needle into jaws of an end effector , knob 310 is pulled in a proximal direction relative to housing 102 ( to disengage rotation hub 314 from clutch member 318 ) and then rotated , thereby rotating keyed shaft 312 , the actuation shaft , and the actuation cable . as knob 310 is rotated , blades that are translatably supported in the jaws of the end effector are translated axially until the distal ends of the blades are out of registration with needle receiving recesses formed in the jaws , as evidenced by the alignment of indicator 310 a of knob 310 and indicator 102 c of housing 102 . with the distal ends of the blades out of registration with the needle receiving recesses of the jaws , a surgical needle is inserted into one of the receiving recesses . knob 310 is then rotated until the distal end of one of the blades engages the surgical needle to hold the surgical needle in the jaw . while the disclosure has been particularly shown and described with reference to particular embodiments , it will be understood by those skilled in the art that various modifications in form and detail may be made therein without departing from the scope and spirit of the invention . accordingly , modifications such as those suggested above , but not limited thereto , are to be considered within the scope of the invention .

US-89632410-A

the present invention relates to a connection arrangement and a method of assembly , for providing a substantially tamper resistant connection with at least a first medical device . the connection arrangement having a centre axis , the connection arrangement comprises ; a first connection member for connection to the first medical device by means of a rotational motion in a first direction , and a body . additionally the first connection member and the body are connected directly or indirectly together via at least one designated ruptureable retaining member , the designated ruptureable retaining member is arranged to rupture at a predetermined breaking force , wherein the first connection member , and thereby the first medical device after assembly , can be displaced with respect to the body after rupture . the present invention provides for a substantially tamper safe connection arrangement which disables accidents such as wrongly disengage a connected medical device . a safer handling is provided for the involved user .

the present invention will be described in greater detail and in a non limiting way with reference to the enclosed embodiments . fig1 shows a connection arrangement 1 having a centre axis a , according to a first embodiment of the present invention , in the form of a medical adaptor device 10 for connecting to a syringe , a vial or any other medical device having a luer lock connection , and e . g . a medical device from the carmel pharma ™ product range , using a double membrane coupling . a medical device using a double membrane coupling is described in the publication of wo 2008 / 115102a1 . the medical adaptor device 10 comprises a second connection site 11 for connecting with a medical device via a membrane coupling 12 having a neck element 13 and a first and a second guiding groove 14 , 15 for guiding corresponding parts of a membrane coupling between a locked position and an unlocked position with a rotational motion . a barrier member 16 provides for a gas and liquid tight seal around a piercing member which during use is intended to be inserted into the barrier member 16 to e . g . administrate drugs . the medical adaptor 10 further comprises a first connection site 20 to connect to e . g . an injection port or a port an infusion bag , via a luer lock type connection 20 . a supportive housing 30 is arranged to structurally support at least the second connection site 20 . fig2 shows the first and the second connection sites 20 , 11 and a body 60 , shown without the barrier member 16 . the first connection site 20 , i . e . the luer lock type connection , comprises a female cylinder 21 with an inner surface 22 and an outer surface 23 , female in the sense that the female cylinder 21 is arranged to receive a male counterpart . the inner surface 22 of the female cylinder 21 exhibit threads 25 as shown in fig4 - 5 . the female cylinder 21 has an upper and lower edge 26 , 27 . as can be seen a male tapered connection part 28 can be seen extending past the lower edge 27 of the female cylinder 21 , as such , the first connection site 20 is generally referred to as a male luer - lock . at least partly defining the upper edge 26 of the female cylinder 21 of the first connection site 20 is a groove 40 extending around the periphery of the female cylinder 21 and extending through the width of the wall of the female cylinder 21 . four designated ruptureable retaining members 41 ( only two of which are shown in fig2 ) hold the female cylinder 21 is a fixed position with respect to the second connection site 11 and the body 60 . the female cylinder 21 further ; comprises , is arranged to , or is optionally in working cooperation with means for preventing the female cylinder 21 from motion along the centre axis a and especially in a direction away from the second connection site 11 . in the shown embodiment , according to the present invention , the means comprises a stop flange 29 arranged in the proximity of the second end 27 of the female cylinder 21 and extending around the periphery of the female cylinder 21 , and which is arranged in working cooperation with the supportive housing 30 , as shown in fig1 . fig2 further show two of the four designated ruptureable retaining members 41 positioned symmetrically around the centre axis a at 90 ° intervals . each of the four designated ruptureable retaining members 41 are adapted to rupture when subjected to a predetermined shear force subjected to the designated ruptureable retaining members 41 preferably after the assembly with a first medical device , and preferably with a substantially planar fracture surface so that the friction forces between the body 60 and the female cylinder 21 is kept as low as possible to prevent the first medical device being unscrewed . the form and shape of the designated ruptureable retaining members 41 , and for the sake of the present invention , any at least one designated ruptureable retaining member ( s ), is preferably adapted to provide a fracture surface which minimizes the friction between the rotating parts , in the shown embodiment of fig2 , between the female cylinder 21 and the body 60 . this can preferably be done by providing the designated ruptureable retaining members with a notch to steer the location of the fracture surface . this is also preferable for all the embodiments described hereafter . in the embodiment , according to the present invention , shown in fig2 , the designated ruptureable retaining members 41 are formed having a tilting surface 42 , tilting towards the first end 26 of the female cylinder 21 . in this case , the notch is tangential to the first end 26 of the female cylinder 21 , providing a fracture surface at the first end 26 of the female cylinder 21 . furthermore , the manufacturing material is preferably chosen so that the fracture surface is substantially parallel with the first end 26 of the female cylinder 21 to minimize the friction there between . the tilting surface 42 is preferably arranged so that it provides for a slope towards the unscrewing direction to reduce the friction formed between the female cylinder 21 and the body 60 . this is of course applicable to all embodiments herein . fig3 a - 3 b show the supportive housing 30 in greater detail and separated from the other parts of the medical adaptor device 10 for the sake of clarity . the supportive housing 30 has a substantially cylindrical form having an upper and a lower end , equivalent to a first and a second end 31 , 32 and an inner and an outer surface 33 , 34 . a plurality of , in this embodiment four , wedge like protrusions 35 extend out from the inner surface 33 of the supportive housing 30 in the proximity of the first end 31 , although only two wedge like protrusions 35 are shown in fig3 a - 3 b . the wedge like protrusions 35 have a tapering surface , tapering towards the first end 31 of the supportive housing 30 . at the second end 32 of the supportive housing 30 is a circumferential stop flange 36 , which extends around the inner surface 33 and protrudes towards the centre axis a . the purpose of the circumferential stop flange 36 and the wedge like protrusions 35 will be described in greater detail below . fig4 shows a cross section of the medical adaptor device 10 shown in fig1 . more specifically , fig4 shows the second connection site 11 with the barrier member 16 , the first connection site 20 and a fluid channel 50 extending there between . a body 60 defines the fluid channel 50 and the male tapered connection part 28 as can be seen extending past the lower edge 27 of the female cylinder 21 . the supportive housing 30 encloses the female cylinder 21 of the first connection site 20 . during assembly , the supportive housing 30 is slid onto the female cylinder 21 until the wedge like protrusions 35 snap onto a lock flange 61 , which extends around the periphery of the body 60 . the wedge like protrusions 35 and the lock flange 61 of the body 60 prevent the supporting housing 30 from movement along the centre axis a . in addition , the second connection site 11 can be arranged to be positioned adjacent the upper end 31 of the supportive housing 30 to prevent the supportive housing from movement along the centre axis a , at least in one direction . as can further be seen in fig4 , the circumferential stop flange 36 of the supportive housing 30 is , after assembly , positioned substantially adjacent the corresponding stop flange 29 of the female cylinder 21 . optionally part of the second end 27 of the female cylinder 21 can be used to cooperate with the circumferential stop flange 36 . the supportive housing 30 permits the female cylinder to rotate around the centre axis a , after the designated ruptureable retaining members 41 are ruptured . it further keeps the female cylinder 21 from motion in the longitudinal direction of the centre axis a . this enables the medical adaptor device 10 to be tamper resistant in the meaning of that any device which is attached with the medical adaptor device 10 can , after the at least one designated ruptureable retaining member is / are ruptured , freely rotate . in practice , the effect of this is that the second connection site 11 uses a rotational motion to fasten a medical device , for the sake of this example ; an injector . the same rotational motion can be used to rupture the designated ruptureable retaining members 41 whereafter the friction between the female cylinder 21 and the body 60 and the supportive housing 30 is so low that a counter rotational motion does not unscrew the injector . this function and effect will be described in greater detail with reference to fig5 a - 5 b . fig5 a - 5 b show the medical adaptor device 10 as shown in fig1 and fig4 after connection with a female catheter connection part 70 . the female catheter connection part 70 has been screwed onto the threads 25 of the female cylinder 21 until the male tapered connection part 28 of the body 60 engages the inner surface 71 of the female catheter connection part 70 . when continuing the rotational motion , i . e . the threading , the friction between the male tapered connection part 28 and the inner surface 71 of the female catheter connection part 70 is sufficiently high to provide for a good connection and a substantially liquid tight seal therebetween . as the rotational motion is continued , the designated ruptureable retaining members 41 rupture . as can be seen in fig5 a , the designated ruptureable retaining members 41 are formed integrally with the body 60 and the female cylinder 21 of the medical adaptor device 10 , for example by form molding with a termoplastic material . in other embodiments , according to the present invention , the at least one designated ruptureable retaining member ( s ) 41 can be made form different material ( s ), combinations of integrally formed designated ruptureable retaining members 41 and designated ruptureable retaining members 41 made from different materials are of course also possible , each embodiment having its own advantage . for instance , if the medical connector device is manufactured from a metal material it might be advantageous to have the designated ruptureable retaining members 41 manufactured in a termoplastic material . further , the at least one designated ruptureable retaining member ( s ) can be manufactured from a substantially elastic material . this could be advantageous since a user could be warned or informed of when the designated ruptureable retaining members 41 are about to break by an indication on the connector , in this case the medical adaptor device 10 , corresponding to the required rotational distance before rupture , which can be calculated or evaluated . fig5 b shows the female catheter connection part 70 after being connected to the luer lock type connection of the medical adaptor device 10 . the female catheter connection part 70 can now be connected to a medical device having a double membrane bayonet coupling via the medical adaptor device 10 . as can further be seen , the designated ruptureable retaining members 41 have ruptured , thereby permitting the female cylinder 21 to be freely rotated around the centre axis a , while being substantially prevented from motion in a longitudinal direction of the centre axis a , i . e . in a motion along the centre axis a . as the female cylinder 21 can be freely rotated , the second connection site 11 can also be freely rotated , with respect to the first connection site 20 , i . e . the luer lock connection and the female catheter connection part 70 . hence , the medical adaptor device 10 in principle cannot be removed from the female catheter connection part 70 . it is further notable that the risk of leakage between the inner surface 71 of the female catheter connection part 70 and the male tapered connection part 28 is very low . in fact , the male tapered connection part 28 can be rotated inside of the female catheter connection part 70 without leakage . should it be desirable for any reason to further improve the leakage preventive properties of the medical adaptor device 10 , the medical adaptor device 10 can be provided with at least one leakage barrier , preferably in the near proximity of the root of the male tapered connection part 28 , such as an o - ring , which after assembly is intended to be positioned adjacent the attached medical device , in the shown embodiment , the top of the female catheter connection part 70 . the connection arrangement 1 , in this case the medical adaptor device 10 , can be coated with a leakage preventing coating such as a silicone based coating . in this case the coating would be applied onto the male tapered connection part 28 . it is further notable that the supportive housing 30 can be arranged with means to prevent it from rotation with respect to the second connection site 11 . such means may be in the form of a protrusion and a corresponding groove . this feature would improve the handling of the medical adaptor device 10 by providing a larger grip area . the present invention will be further described with reference to a second embodiment according to the present invention . in this embodiment , the connection arrangement 1 is applied to a piercing member protection device 99 for providing at least a first medical device with a substantially tamper resistant connection . suitable piercing member protection device which can be utilized is disclosed in the patent application publication of wo2008 / 115102 in the name of carmel pharma ab . fig6 shows the piercing member protection device 99 with a longitudinal centre axis a extending in the longitudinal direction of the piercing member protection device 99 and in the centre of the piercing member protection device 99 . generally the piercing member protection device 99 exhibits a first cylindrical member 100 which is at least partly encompassed by a second cylindrical member 200 , which in turn is at least partly encompassed by a third cylindrical member 300 . a piercing member ( not shown ) is connected to the third cylindrical member 300 and extends into a protection chamber defined by the interior of the first cylindrical member 100 . a first barrier member 101 , which after connection with a connection port on e . g . an infusion bag is intended to provide a double membrane coupling , seals the protection chamber of the first cylindrical member 100 to provide a closed environment for at least the tip of the piercing member of the piercing member protection device 99 . this position is also referred to as the unexposed state , as the piercing member is unexposed inside the protective chamber . a first locking arrangement 250 is provided between the first cylindrical member 100 and the second cylindrical member 200 . the first locking arrangement 250 can be arranged in a first position in which the first cylindrical member 100 is enabled to be turned with respect to the second cylindrical member 200 and a second position in which the first cylindrical member 100 is disabled form turning with respect to the second cylindrical member 200 . the second locking device can be alternated between the first and the second position by means of connecting the piercing member protection device 99 to the connection port . a second locking arrangement provides a first position in which the piercing member , and the third cylindrical member 300 , is enabled to move along the centre axis a with respect to the first barrier member 101 , and a second position in which the piercing member , and the third cylindrical member 300 , is prevented from moving along the longitudinal centre axis a with respect to the first barrier member 101 . the second locking arrangement 350 is alternated between the first position and the second position by means of turning the first cylindrical member 100 and the third cylindrical member 300 with respect to the second cylindrical member 200 . as the piercing member is moved along the longitudinal centre axis a it can be moved to an exposed state at which parts of the piercing member are exposed outside of the protective chamber and the first barrier member 101 , for example in order to transfer a drug from a vial to a syringe . the second locking arrangement is enabled by an l - shaped groove on the third cylindrical member 300 and a corresponding protrusion on the second cylindrical member 200 . as can further be seen in fig6 , the third cylindrical member 300 comprises a first connection site 111 having a threaded female connection part 112 for connection with a male luer lock connection on e . g . a syringe . the first connection site 111 is connected to the third cylinder member 300 via at least one ruptureable retaining member 141 , in the shown embodiment of fig6 , five designated ruptureable retaining members 141 , although only four can be seen . this permits the first connection site 111 to freely rotate around the centre axis a , after the designated ruptureable retaining members 141 are ruptured . it further prevents the first connection site 111 from motion in the longitudinal direction of the centre axis a . this enables the piercing member protection device 99 to be tamper resistant in the meaning of that any device which is attached to the piercing member protection device 99 can , after the at least one designated ruptureable retaining member is / are ruptured , freely rotate . in practice , the effect of this is that since the first connection site 111 uses a rotational motion to fasten a medical device , for the sake of this example ; a syringe . the same rotational motion can be used to rupture the designated ruptureable retaining members 141 whereafter the friction between the first connection site 111 and the third cylinder member 300 is so low that a counter rotational motion does not unscrew the medical device , in this case a syringe . in the embodiment shown in fig6 , the designated ruptureable retaining members 141 are assembled to the piercing member protection device 99 via a ring body 160 having an inner and an outer ring member 161 , 162 , as seen in greater detail in fig7 . by the terms inner and outer rings , is meant with reference to the centre axis a . fig7 shows further that the outer ring member 161 comprises a plurality of deformable lock flanges 163 which are arranged to , during assembly , deform so that the deformable lock flanges 163 can be positioned to engage and lock the ring body 160 to the third cylinder member 300 at a plurality of corresponding lock grooves 310 ( shown in fig9 ). each deformable lock flange 163 comprises a lock protrusion extending from the distal end of the deformable lock flanges 163 towards the centre axis a . the ring body 160 also exhibits a first and a second end 165 , 166 , equivalent to the upper and the lower end 165 , 166 as seen in fig7 . in the near proximity of the first end 165 of the ring body 160 , five designated ruptureable retaining members 141 attach the inner ring member 161 to the outer ring member 162 preventing the inner ring member 161 from substantially any motion with respect to the outer ring member 162 before the designated ruptureable retaining members 141 are ruptured by a predetermined shear force . each of the designated ruptureable retaining members 141 exhibit a tilting surface 142 serving the purpose of reducing the friction forces and minimizing the risk for reengagement of the fractured parts , between the inner and outer ring member 161 , 162 after the designated ruptureable retaining members 141 have been ruptured . the designated ruptureable retaining members 141 are made integrally with the cylindrical body 160 . however , as mentioned earlier , they can be made from different materials or combinations thereof . the inner ring 161 comprises attachment flanges 170 to provide a snap on connection between the first connection site 111 and the inner ring 161 . fig8 shows the first connection site 111 in greater detail . as can be seen , the first connection site 111 comprises a threaded female connection part 112 equipped with threads 113 for a rotational connection with a medical device ( not shown ) such as a syringe . the threaded female connection part 112 comprises a distal end 114 and a proximal end 115 . the proximal end 115 of the threaded female connection part 112 is arranged on a cylindrical base 120 having a first and a second locking flange 121 , 122 for providing a snap on connection with the inner ring 161 and the corresponding attachment flanges 170 . furthermore , the cylindrical base 120 comprises a circumferential channel 125 extend around the periphery of the cylindrical base 120 permitting , after assembly , free rotation of the cylindrical base 120 with respect to the third cylinder 300 of the piercing member protection device 99 . as is noticed , the cylindrical base 120 and the inner ring member 161 of the ring body 160 forms the body while the outer ring 162 and optionally the third cylinder member 300 forms a first connection member . fig9 shows the third cylinder member 300 in greater detail without any other components attached . as can be seen , the third cylinder member 300 comprises a plurality of lock grooves 310 for connection with the ring body 160 and the deformable lock flanges 163 of the outer ring 162 of the ring body 160 . wedge like protrusions 311 are arranged on the inside of the third cylinder member 300 in the proximity of an upper end 301 of the third cylinder member 300 , and extending towards the centre axis a enabling a snap on connection with the circumferential channel 125 of the cylinder base 120 . fig1 shows a cross section of the third cylinder member 300 , the ring body 160 and the first connection site 11 after assembly and before rupture of the designated ruptureable retaining members 141 . an infusion tube 400 is threaded onto the threaded female connection part 112 of the first connection site 111 . as the infusion tube 400 is connected by a rotational motion , the luer lock connection provides for a liquid tight seal between the first connection site 111 and the infusion tube 400 . as the rotational motion continues , the connection is tightened and a predetermined threshold of stress , in this case about 25 ncm , the shear force imparted from the infusion tube 400 ruptures the designated ruptureable retaining members 141 of the cylindrical body 160 . as the designated ruptureable retaining members 141 of the cylindrical body 160 rupture , the inner ring 161 of the cylindrical body 160 is permitted to freely rotate around the centre axis a , disabling any attempts to disconnect the infusion tube 400 . in a third embodiment according to the present invention , the connection arrangement is utilized on an infusion bag connection system 500 for a tamper resistant connection to an infusion bag 501 . as is seen in fig1 , the infusion bag connection system 500 comprises a second connection site 503 , as described earlier with reference to fig4 and 5 a - 5 b . that is , a body , a first connection member 505 , in the form of a female cylinder 521 having a threaded inner surface 522 , is fixedly connected to the body 504 by means of at least one designated ruptureable retaining member , which after subjected to a predetermined shear force is arranged to rupture . after rupture the female cylinder 521 can be freely rotated around the centre axis a with respect to the body 504 . a fluid transfer channel 550 is arranged in the body 504 . as has been shown , the connection arrangement 1 according to present invention can advantageously be used as a male luer lock connection . additionally the connection arrangement 1 can be used on , i . e . as the connection arrangement on a medical device e . g . a syringe , such as a disposable syringe , a medical fluid container , a medical waste container or the like . it is also within the boundaries of the present invention that the connection arrangement 1 is used as a female luer lock connection , as is shown in fig1 a - 12 b exemplified with a disposable syringe ( only a part of the syringe is shown for the sake of clarity and without its plunger ). fig1 a shows a cross section of a syringe 600 with a centre axis a and adapted for a tamper resistant connection with a first medical device , such as a piercing member protection device . fig1 b shows the syringe as seen in perspective . the syringe 600 is preferably of the disposable type . with reference to both fig1 a and 12 b , the syringe 600 comprises a fluid housing 601 in which drugs can be temporarily contained before administration trough a dispensing opening 602 , arranged in the end of the fluid housing 601 . the fluid housing 601 further comprises a second opening ( not shown ) through which a plunger can be inserted for volumetric control of the fluid housing . the dispensing opening 602 comprises a dispensing channel housing 603 with a dispensing channel and with a slightly tapered inner surface 604 , so as to be able to tightly mate with the male tapered connection part of a male luer lock connection , see for example the male tapered connection part 28 in fig2 or fig4 . the dispensing channel housing 603 exhibit a distal end 605 , and a proximal end 606 wherein the proximal end is arranged on the fluid housing 601 of the syringe 600 . a cylinder 620 having an outer and an inner surface 621 , 622 and a first and a second end 623 , 624 is arranged on the dispensing channel housing 603 . the outer surface 621 facing away from the centre axis a . threads 625 are arranged on the outer surface 621 of the cylinder 620 for connection with a male luer lock connection . the distal end 605 of the dispensing channel housing 603 comprises a circumferential lock flange 607 to substantially prevent the cylinder 620 from motion in a direction along the centre axis a , at least in a direction away from the fluid housing 601 , the fluid housing 601 being a natural stop in the other direction . as is noted , the dispensing channel housing 603 form together with the fluid housing 601 a body while the cylinder 620 form a first connection member . a connection site 610 is formed by the dispensing channel housing 603 and the cylinder 620 . the cylinder 620 is attached to the circumferential lock flange 607 via a plurality of designated ruptureable retaining members 641 . the designated ruptureable retaining members 641 prevent the rotation of the cylinder 620 with respect to the fluid housing 601 and thereby enabling the connection to a male luer lock connection . as the syringe is screwed on to the medical device and a tight connection is reached , the threshold shear force of each of the designated ruptureable retaining members 641 is surpassed , fracturing the ruputureable retaining members 641 . as the designated ruptureable retaining members rupture , the cylinder 620 of the syringe 600 can rotate freely , with respect to the fluid housing 601 of the syringe , without risking that the syringe and the medical device is disconnected . the fluid housing 601 , the designated ruptureable retaining members 641 , the cylinder 620 , the circumferential lock flange 607 and the dispensing channel housing 603 can be formed integrally from the same material . optionally , the designated ruptureable retaining members can be formed from another material ; the cylinder 620 can be e . g . adhered to the dispensing channel housing 603 to form the designated ruptureable retaining members . in the embodiments described above the rupture of the designated ruptureable retaining members is accomplished by a rotational motion in the same rotational direction as the connection of the first medical device . one major advantage of using this configuration of the connection arrangement , according to the present invention , is of course that it disables any attempt to counter - rotate the medical device after the designated ruptureable retaining members are ruptured . however , it is well within the boundaries of the present invention that the rupture of the designated ruptureable retaining member ( s ) can be done by means of pressing , pulling , tilting or otherwise manipulating e . g . the connected first medical device . the triggering mechanism for rupturing the designated ruptureable retaining member ( s ) are in some embodiments less relevant , although the rotational triggering is preferable since it can be combined with a rotational attachment of a medical device . furthermore , the connection of the first medical device does not have to be by a rotational motion , instead is it possible to use e . g . a snap on connection . preferable material for manufacturing a connection arrangement according to the present invention as described above is polypropylene , polyethylene , pvc , polyurethane , acrylonitrile butadiene styrene ( abs ), polystyrene , polyoxymethylene , polyethylene terephthalate , similar plastics or mixtures thereof , although other materials such as metal e . g . aluminum , steel , iron , brass , or alloys thereof are possible . combinations of these materials are of course also possible .

US-33520708-A

a conjugate is disclosed . the conjugate comprises an isolated or a synthetic targeting peptide of less than 15 amino acid residues in length , comprising an amino acid sequence having at least 90 % identity to a sequence selected from the group consisting of seq id nos : 1 - 8 ; and a component conjugated to the targeting peptide , the component being selected from the group consisting of a drug delivery vehicle , an anti - cancer drug , a micelle , a nanoparticle , a liposome , a polymer , a lipid , an oligonucleotide , a peptide , a polypeptide , a protein , a cell , an imaging agent , and a labeling agent . methods of treating lung cancer and detecting lung cancer cells are also disclosed .

the present invention is more particularly described in the following examples that are intended as illustrative only since numerous modifications and variations therein will be apparent to those skilled in the art . various embodiments of the invention are now described in detail . referring to the drawings , like numbers indicate like components throughout the views . as used in the description herein and throughout the claims that follow , the meaning of “ a ”, “ an ”, and “ the ” includes plural reference unless the context clearly dictates otherwise . also , as used in the description herein and throughout the claims that follow , the meaning of “ in ” includes “ in ” and “ on ” unless the context clearly dictates otherwise . moreover , titles or subtitles may be used in the specification for the convenience of a reader , which shall have no influence on the scope of the present invention . additionally , some terms used in this specification are more specifically defined below . the terms used in this specification generally have their ordinary meanings in the art , within the context of the invention , and in the specific context where each term is used . certain terms that are used to describe the invention are discussed below , or elsewhere in the specification , to provide additional guidance to the practitioner regarding the description of the invention . for convenience , certain terms may be highlighted , for example using italics and / or quotation marks . the use of highlighting has no influence on the scope and meaning of a term ; the scope and meaning of a term is the same , in the same context , whether or not it is highlighted . it will be appreciated that same thing can be said in more than one way . consequently , alternative language and synonyms may be used for any one or more of the terms discussed herein , nor is any special significance to be placed upon whether or not a term is elaborated or discussed herein . synonyms for certain terms are provided . a recital of one or more synonyms does not exclude the use of other synonyms . the use of examples anywhere in this specification including examples of any terms discussed herein is illustrative only , and in no way limits the scope and meaning of the invention or of any exemplified term . likewise , the invention is not limited to various embodiments given in this specification . 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 this invention pertains . in the case of conflict , the present document , including definitions will control . as used herein , “ around ”, “ about ” or “ approximately ” shall generally mean within 20 percent , preferably within 10 percent , and more preferably within 5 percent of a given value or range . numerical quantities given herein are approximate , meaning that the term “ around ”, “ about ” or “ approximately ” can be inferred if not expressly stated . the term “ drug delivery vehicles ” refers to a vehicle that is capable of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others . drug delivery vehicles includes , but not limited to , polymeric micelles , liposomes , lipoprotein - based drug carriers , nano - particle drug carriers , dendrimers , cells , polypeptides , etc . an ideal drug delivery vehicle must be non - toxic , biocompatible non - immunogenic , biodegradable , and must avoid recognition by the host &# 39 ; s defense mechanisms . the term “ treating ” or “ treatment ” refers to administration of an effective amount of the compound to a subject in need thereof , who has cancer , or a symptom or predisposition toward such a disease , with the purpose of cure , alleviate , relieve , remedy , ameliorate , or prevent the disease , the symptoms of it , or the predisposition towards it such a subject can be identified by a health care professional based on results from any suitable diagnostic method ( see u . s . patent application ser . no . 14 / 499 , 201 , which is incorporated herein by reference in its entirety ). the term “ treating ” or “ treatment ” refers to administration of an effective amount of the compound to a subject in need thereof , who has cancer , or a symptom or predisposition toward such a disease , with the purpose of cure , alleviate , relieve , remedy , ameliorate , or prevent the disease , the symptoms of it , or the predisposition towards it . such a subject can be identified by a health care professional based on results from any suitable diagnostic method . the term “ an effective amount ” refers to the amount of an active compound that is required to confer a therapeutic effect on the treated subject . effective doses will vary , as recognized by those skilled in the art , depending on rout of administration , excipient usage , and the possibility of co - usage with other therapeutic treatment . the “ guidance for industry and reviewers estimating the safe starting dose in clinical trials for therapeutics in adult healthy volunteers ” published by the u . s . department of health and human services food and drug administration discloses a “ therapeutically effective amount ” may be obtained by calculations from the following formula : in this study , we used a phage - displayed peptide library and biopanning technique to isolate lung cancer - specific peptides . we identified three novel peptides hsp1 , hsp2 and hsp4 that were able to bind to several types of nsclc ( including lcc , adenocarcinoma , and scc ) and sclc in both cell lines and clinical surgical specimens , but not normal pneumonic tissue . in vivo study further proved the enhanced therapeutic efficacy and bioavailability of these hsp1 , 2 , or 4 peptide - mediated drug delivery systems . these data demonstrated a promising potential for these three novel peptides in theranostics applications . iron oxide - binding peptides have been disclosed in u . s . patent publication nos . 20100158837 and us20090208420 . superparamagnetic iron oxide ( uspio )- based liposomes have been disclosed by frascione det al . ( int j nanomedicine . 2012 ; 7 : 2349 - 59 ). the term “ a labeling agent ” includes , but not limited to , “ a fluorescent labeling agent ”. imaging agents are designed to provide more information about internal organs , cellular processes and tumors , as well as normal tissue they can be used to diagnose disease as well as monitor treatment effects . without intent to limit the scope of the invention , exemplary instruments , apparatus , methods and their related results according to the embodiments of the present invention are given below . note that titles or subtitles may be used in the examples for convenience of a reader , which in no way should limit the scope of the invention . moreover , certain theories are proposed and disclosed herein ; however , in no way they , whether they are right or wrong , should limit the scope of the invention so long as the invention is practiced according to the invention without regard for any particular theory or scheme of action . nci - h460 , nci - h661 , nci - h1993 , nci - h441 , nci - h520 , nci - h1688 , a549 human lung cancer cell lines and nl20 human bronchial epithelial cells were purchased from american type culture collection ( atcc ®) and were authenticated by atcc based on dna profile , cytogenetic analysis and isoenzymology . these cells were cultured by atcc &# 39 ; s protocols and had been passaged for fewer than 6 months after resuscitation , cl1 - 5 cells were established and were verified routinely by growth , morphology and mycoplasma - free . the human normal nasal mucosal epithelial ( nnm ) cells were a primary culture derived from a nasal polyp and were grown in dmem . human lung large cell carcinoma cell line h460 cells were incubated with uv - treated inactive control helper phage ( insertless phage ). the phage - displayed peptide library , which initially contained 5 × 10 10 plaque - forming units ( pfu ) was then added . after washing , the bound phages were eluted with a lysis buffer ( 150 mm nacl , 50 mm tris - hcl , 1 mm edta , 1 % np - 40 , 0 . 5 % sodium deoxycholate , 0 . 1 % sds , ph 7 . 4 on ice . this eluted phage pool was amplified and titered in an escherichia coli er2738 culture . recovered phages were used as input for the next round of panning . in the fourth and fifth round of biopanning the phage clones were randomly selected to culture for elisa screening ( manuscript submitted for publication , which is incorporated herein by reference in its entirety ). identification of phage clones using cellular enzyme - linked immunosorbent assay ( elisa ) ninety - six - well elisa plates were seeded with either cancer or control nnm cells . individual phage clones were added to the cell - coated plates and were incubated with horseradish peroxidase ( hrp )- conjugated mouse anti - m13 monoclonal antibody , followed by incubating with the peroxidase substrate o - phenylenediamine dihydrochloride . the reaction was stopped and absorbance was measured at 490 nm using an elisa reader . the selected phage clones were further analyzed using dna sequencing with the primer 5 ′- ccctcatagttagcgt aacg - 3 ′ ( seq id no : 12 ) corresponding to the piii gene sequence . the synthetic targeting peptide hsp1 ( gamhlpwhmgtl ; seq id no : 1 ), hsp2 ( npweeqgyrysm ; seq id no : 2 ), hsp4 ( nnpwremmyiei ; seq id no : 3 ) and control peptide ( 12 amino acid sequence from bsa protein , kateeqlktvme ; seq id no : 13 ) were prepared by fmoc spps using a cem liberty automated microwave peptide synthesizer and purified using reverse - phase high - performance liquid chromatography to 95 % purity . conjugation of these peptides with fluorescein isothiocyanate ( fitc ) was performed through the addition of fitc to the peptide c - terminus . peptide synthesis , conjugation , and purification were performed by peptide synthesis core facility of the institute of cellular and organismic biology , academia sinica ( taipei , taiwan ). the lung cancer cell lines or control cells were collected using enzyme - free cell dissociation buffer , and then were incubated with 20 μg / ml fitc - conjugated hsp1 , 2 , 4 or control peptide at 4 ° c . for 1 hour . after washing , cells were analyzed by flow cytometer . h460 and h1993 cells were seeded and grown to about 50 % confluence on cover slips . after the cells had been fixed with 2 % paraformaldehyde , they were incubated with 10 μg / ml fitc - labeled hsp1 , 2 , 4 or control peptides . then the slides were counterstained with 4 ′, 6 - diamidino - 2 - phenylindole ( dapi ), mounted and examined under a leica universal fluorescent microscope . the images were merged using the metamorph image analysis software . eleven cases of lung adenocarcinoma and ten cases of lung squamous cell carcinoma paraffin tissue section were obtained from tissue bank of national taiwan university hospital ( ntuh ) with approval from the institutional review board in ntuh . to increase the case number and histopathological subtypes of lung cancer specimens , we also obtained commercial tissue microarray sections consisted of a total of 120 cases of lung adenocarcinoma , squamous cell carcinoma , large cell carcinoma , small cell carcinoma , etc . with approval of the as - irb03 - 102103 . for localization of phages binding to the lung cancer tissues , the tissues were incubated with hpc1 , hpc2 , hpc4 or control phages ( 2 ˜ 5 × 10 8 pfu / μl ). after washing with pbs , sections were treated with anti - m13 mouse mab ( ge healthcare ) for 1 hour at room temperature . following washing steps , a biotin - free super sensitive polymer - hrp detection system was used to detect immunoreactivity . the slides were lightly counterstained with hematoxylin , mounted with aquatex ® ( merck ) and examined by light microscopy . scid mice were injected subcutaneously in the dorsolateral flank with 5 × 10 6 h460 cells . the mice bearing size - matched lung cancer xenografts ( approximately 300 mm 3 ) were intravenously injected with 2 × 10 9 pfu of the targeting phage or control phage . after eight minutes of phage circulation , the mice were sacrificed and perfused with 50 ml pbs to wash out unbound phage . subsequently , xenograft tumors and mouse organs were dissected and homogenized . the phages bound to each tissue sample were recovered through the addition of er2738 bacteria and titered on iptg / x - gal agar plates . for the in vivo whole body imaging , hpc1 , 2 , 4 and control phages were labeled with the fluorescence dye , hilyte ™ fluor 750 acid nhs ester ( hl750 ), by nhs functional group . same h460 xenograft model were intravenously injected with 5 × 10 9 pfu of the hl750 - labeled targeting phages or control phages . fluorescence imaging of mice and tissues was captured using xenogen ivis200 imaging system ( excitation 710 / 760 nm ; emission : 810 / 875 nm ) at indicated time points . and the fluorescence intensity of tissues was calculated by subtracting background using living image software ( xenogen ). the peptide was coupled to nhs - peg - dspe [ n - hydroxysuccinimido - carboxyl - polyethyleneglycol ( mw , 3400 )- derived distearoylphosphatidyl ethanolamine ] in a 1 . 1 : 1 molar ratio . the pegylated peptide - peg - dspe conjugates were purified by sephadex ® g - 15 ( ge healthcare ) gel filtration chromatography , and were then dried through lyophilization . the conjugates were also analyzed by hplc quantitatively and by maldi - tof - ms ( bruker microflex ™) qualitatively . a lipid film hydration method was used to prepare pegylated liposomes composed of distearoylphosphatidylcholine , cholesterol , and peg - dspe , which were then used to encapsulate doxoruhicin , vinorelbine or to incorporate sulforhodamine b - dspe with the particle size ranging from 65 to 75 nm in diameter . hsp1 , 2 , or 4 - peg - dspe was subsequently incorporated into pre - formed liposomes by co - incubation at 60 ° c ., the transition temperature of the lipid bilayer , for 1 hour with gentle shaking . after incubation , the surface of each liposome displayed about 500 peptide molecules . sephadex ™ g - 25 gel filtration chromatography was used to remove released free drug , unconjugated peptides , and unincorporated conjugates . doxorubicin and vinorelbine concentrations m the fractions of eluent were determined by measuring excitation / emission wavelengths of fluorescence at 485 / 590 and 520 / 570 nm , respectively , using spectrofluorometer ( spectra max m5 , molecular devices ). uptake of targeting peptide - conjugated lsrb or ld by human lung cancer cells h460 and h1993 cells were grown on a 24 - well plate to 90 % confluency , and 20 , 10 , 5 , 2 . 5 , 1 . 25 , 0 . 625 μm hsp1 , 2 , 4 - liposomal sulforhodamine b ( lsrb ) or lsrb in complete culture medium was added . the cells were incubated at 37 ° c ., at the following time periods : 10 , 30 min , 1 , 2 , 4 , 8 , 16 and 24 hours . at the indicated time point , cells were washed with pbs , and non - internalized lsrb on the cell surface was removed by adding 0 . 1 m glycine , ph 2 . 8 for 10 min . cells were then lysed with 200 μl 1 % triton x - 100 . uptake of ld at low concentration in h1993 cells was performed using same protocol . for extraction of srb or doxorubicin , 300 μl ipa ( 0 . 75 n hcl in isopropanol ) was added to the lysate and shaken for 30 min . after the lysate was centrifuged at 12 , 000 rpm for 5 min , the amount of uptakes were determined by measuring excitation / emission wavelengths of fluorescence at 520 / 570 nm for srb and 485 / 590 nm for doxorubicin using , a spectrofluorometer ( spectramax ® m5 , molecular devices ). the concentration of srb and doxambicin were calculated by interpolation using a standard curve . h460 cells were incubated with hsp1 , hsp2 , hsp4 - lsrb or lsrb for 10 min at 4 ° c . and 37 ° c . after being washed with pbs , the cells were fixed by 4 % paraformaldehyde , blocked by 1 % bsa , and then stained with wga - alexa fluor ® 467 and dapi for cell membrane and nucleus . all fluorescence images were obtained by confocal microscopy . h460 cells were seeded in 96 - well plates ( 5000 cells / well ) in complete culture media and were incubated overnight . next day , cells were treated with varying concentration ( 0 - 100 μm ) of hsp1 - ld , hsp2 - ld , hsp4 - ld or ld at 37 ° c . for 24 hours ; after removal of the excess drug , the cells were washed once with pbs and continued to incubate with fresh culture medium for 48 h at 37 ° c . the cell viability was measured by adding 50 μl of mtt ( thiazolyl blue tetrazolium bromide ; sigma - aldrich ) to each well of the plate . after 3 . 5 hours mtt incubation , 150 μl of dimethyl sulfoxide ( dmso ; mallinckrodt baker ) was added to each well for 10 min , and the absorbance was determined with microplate reader ( spectramax ® m5 , molecular devices ) at 540 nm . female scid mice 4 - 6 weeks of age were injected subcutaneously in the dorsolateral flank with human nsclc cells . mice with size - matched tumors ( approximately 75 mm 3 for small tumor ; 300 or 500 mm 3 for large tumor ) were then randomly assigned to different treatment groups , and were injected intravenously with liposomal doxorubicin ( ld ), liposomal vinorelbine ( lv ), targeting peptide ( hsp1 , hsp2 or hsp4 )- conjugated ld or lv , free doxotubicin ( fd ), free vinorelbine ( lv ) or equivalent volumes of saline . the dosages of drugs and administration time courses were described in figure legends depend on different experiment design . mouse body weights and tumor sizes were measured twice a week . tumor volumes were calculated according to this formula : length ×( width ) 2 × 0 . 52 . animal care was carried out in accordance with guidelines of academia sinica , taipei , taiwan . the protocol was approved by the committee on the ethics of animal experiments of academia sinica . scid mice ( 6 - week - old ) were anesthetized with isofloruance mixed with oxygen and placed in the right decubitus position . the skin overlying the left chest wall in the mid - axillary line was prepared with alcohol , and the underlying , chest wall and intercostal spaces were visualized . luciferase - overexpressed h460 or a549 cells ( 5 × 10 5 cells ) in 50 μl serum - free medium plus matrigel ® matrix ( 2 : 1 ) were injected into the left lateral thorax , at the lateral dorsal axillary line . after tumor injection , the mice were turned to left decubitus position and observed for 45 to 60 min until fully recovered . luciferase - expressing cancer cells were imaged and quantified using ivis200 system ( xenogen corporation , alameda , calif .) at 10 minutes after i . p . injection of lucwerin ™ ( caliper life sciences ) before drug administration each time . scid mice bearing h460 lung cancer xenografts (˜ 300 mm 3 ) were injected in the tail vein with either free drug doxorubicin ( fd ), liposomal doxorubicin ( ld ), or targeting ( hsp1 , hsp2 or hsp4 ) ld at a single dose of 2 mg / kg . at 1 hr and 24 hr post - injection , blood samples were collected through submaxillary punctures before mice were anaesthetized and sacrificed ( three mice in each group ). then the mice were perfused with 50 ml pbs through heart , xenograft tumors and organs ( brain , lung , heart , liver , and kidney ) were dissected , weighted , and homogenized to calculate amount of doxorubicin in tissues . total doxorubicin was quantified by measuring fluorescence at λ ex / em = 485 / 590 nm using a spectrofluorometer ( spectramax ® m5 , molecular devices ) two - sided unpaired student &# 39 ; s t - test was used to calculate p values . p & lt ; 0 . 05 was considered significant for all analyses . identification of three novel peptides that bind to several types of human lung cancer cells in this study , we used a phage - displayed random peptide library to isolate phages that were able to bind to h460 non - small cell lung carcinoma ( nsclc ) cells . after five rounds of affinity selection ( biopanning ), the titer of bound phage increased by up to 9 - fold . ninety - four phage clones were randomly selected from both the fourth and the fifth rounds of biopanning for cellular elisa screening . forty - seven clones of these selected phages possessed higher affinity to h460 cells . we then further tested the binding activity of these h460 bound clones to other cell lines , including human lung adenocarcinoma h1993 , cl1 - 5 , a549 , murine lewis lung carcinoma 3ll or human normal nasal mucosal epithelial nnm cells . by sequencing phage clones with the highest lung cancer binding but the faintest normal cell reactivity , we identified thirteen phage clones , which displayed two distinctive groups of consensus sequences ( table 1 ). its interesting that hpc1 , 5 and 13 displayed identical sequence “ gamhlpwhmgtl ” ( seq id no : 1 ). table 1 shows alignment of phage - displayed peptide sequences selected by h460 cells . from 47 random selected phage clones in the fifth round of biopanning , 13 phage clones with higher h460 binding affinity were identified and the displayed - peptide sequences were aligned . * phage - displayed consensus amino acids are shown in the box . to investigate whether these similar peptide - displayed phages exhibited similar binding , patterns to different lung cancers , we compared the binding intensity of these two groups of phages to h460 , h1993 , cl1 - 5 , a549 and 3ll by cellular elsa ( manuscript submitted for publication , which is incorporated hereby by reference in its entirety ). the data revealed that although hpc2 , 3 and 4 displayed similar sequences containing npw - e ( seq id no : 14 ) motif , hpc 3 , 4 and 6 exhibited more similar binding patterns in various lung cancers . this suggested that w - emm ( seq id no : 15 ) mimetic motifs may play more important role than npw - e motif in binding to lung cancers , since hpc3 and 4 consist both of these two motifs but behaved as hpc6 , which contains only w - emm mimetic motif . the other group of phages all displayed mhl - w ( seq id no : 16 ) consensus sequence with similar binding patterns to lung cancers . based on these findings , we chose to focus on hpc1 , hpc2 and hpc4 for further study since they typified mhl - w motif , npw - e motif , and w - emm motifs , respectively . to determine whether the peptide sequences displayed on hpc1 , hpc2 and hpc4 have lung cancer binding function , we synthesized hsp1 , hsp2 , and hsp4 peptides , which have the amino acid sequences gamhlpwhmgtl ( seq id no : 1 ), npweeqgyrysm ( seq id no : 2 ) and nnpwremmyiei ( seq id no : 3 ), respectively . the words “ sp ” in “ hsp ” represented the “ synthetic peptide ” displayed by hpc phage . hsp1 , hsp2 or hsp4 synthetic peptides or their fluorescein isothiocyanate ( fitc ) conjugates would be used in the following experiments . to verify whether hsp1 , 2 , and 4 peptides would bind to target molecules expressed on the surface of lung cancer cells , the surface binding activities of each fitc - conjugated peptides was analyzed by flow cytometry and immunofluorescent staining ( fig1 a ). in the facs data , all of these three fitc - labeled peptides exhibited prominent binding to several pathological subtypes of human lung cancer cell lines , including large cell carcinoma ( h460 and h661 ), adenocarcinoma ( h1993 , h441 , cl1 - 5 and a549 ), squamous cell carcinoma ( h520 ) and small cell carcinoma ( h1688 ), but not to human normal bronchial epithelial cell ( nl20 ). furthermore , hsp1 , 2 , and 4 show different binding patterns of fluorescence intensity in various lung cancer cells , suggesting that these peptides might target different molecules on the cell surface . in cell ifa experiments ( fig1 a ), fitc - labeled hsp1 , 2 or 4 can bind to a major group of h460 large cell carcinoma cells and h1993 adenocarcinoma cells while fitc - labeled control peptide cannot . the fitc - positive cells represent the peptide target molecules expressing cells . thus , we calculated the percentages of positively stained h460 and h1993 cells by these three peptides ( fig1 b ). based on the statistic table and fluorescence pictures , we found out the proportions of target - expressing cells relative to the entire populations and the receptor densities on cell surface . it is worth noting that hsp4 showed higher receptor density on the cell surface as indicated by its stronger fluorescent intensity despite having lower positive rate in h1993 cells . in addition , hsp4 peptides showed the best reactivity to h460 cells , both in terms of percentage of positive cells and receptor density . these results suggest that hsp1 , 2 , and 4 are able to bind to both nsclc and sclc cells in vitro with different binding patterns . to investigate the targeting ability of the selected phage clones in vivo , we intravenously injected each clone into mice bearing h460 - derived tumor xenografts . after perfusion , we measured the phage titers in the tumor and normal organs . the tumor homing ability was estimated by the phage titer ratio of tumor to normal organs , comparing to control phage . in the first group of phages with consensus sequence ( hpc2 , 3 , 4 , 6 ), hpc2 , 3 and 4 showed prominent tumor homing ability , whereas hpc6 exhibited only recessive tumor localization iii vivo ( fig2 a ). that was another reason why we chose hpc2 and hpc4 , but not hpc6 , to typify npw motif and w - emm motif for further study . in the other group of phages with consensus sequence of mhl - w , hpc1 , but not hpc9 , exhibited notable tumor homing ability ( fig2 a ). further , we labeled phages with hilyte ™ fluor 750 ( hl750 ) fluorescence dye , which can be used for whole body imaging at specific ranges of excitation and emission wavelength ( excitation : 710 / 760 nm : emission : 810 / 875 nm ). scid mice beating size - matched h460 xenografts were i . v . injected with hpc1 - hl750 , hpc2 - hl750 , hpc4 - hl750 or control phage - hl750 and serially monitored by ivis200 . the hl750 - labeled phages were visible under ivis200 imaging system while systemic circulating through the mice . after 6 hr post - injection , the targeting phages , which accumulated in tumor tissue , became obvious and could be easily seen . at 24 hr post - injection , fluorescence imaging of mice and the dissected tissues were captured ( fig2 c ). the tumor fluorescent intensities in the targeting phage groups were about 3 to 4 - fold higher than that in the control phage group ( fig2 b ). these results indicate that all of hpc1 , hpc2 and hpc4 possess significant tumor - homing ability . hsp1 , 2 and 4 synthetic peptides improved liposomal drug binding , intracellular delivery and cytotoxicity since “ receptor - mediated endocytosis ” is crucial for targeting drug delivery due to improved drug penetration , release and efficacy , we next examined whether hsp1 , hsp2 or hsp4 could promote liposomal drug internalization to human lung cancer cells . for materials preparation hsp1 , his2 and hsp4 were conjugated to nhs - peg - dspe before inserted to the external surface of liposomal nanoparticles by phospholipid dspe . these nanoparticles contained sulforhodamine b ( srb : fluorescence reagent ) or doxorubicin . unlike chemotherapeutic drugs , fluorescence dye srb wound not cause cell death even at high concentration , making it an ideal tool for measuring the uptake efficiency of living cells . in the time course experiment , we found targeting peptide ( hsp1 , 2 or 4 )— conjugated liposomal srb ( lsrb ) enhanced liposome internalization in h460 ( fig3 a ) and h1993 cells compared to non - targeting lsrb . interestingly , we also observed that hsp2 exhibited prominent intracellular delivery at low lsrb concentrations , while no difference from non - targeting lsrb at high concentration in h460 cells was observed ( fig3 a ). on the contrary . hsp1 and hsp4 showed better uptake ability at higher doses . one possible explanation for this phenomenon is that the receptors of hsp2 on h460 cell surface were saturated at high concentration . this phenomenon suggests that hsp1 , 2 , or 4 may target different receptors on the cell surface due to the different receptor densities . for visual imaging , we also examined the targeting peptide - conjugated lsrb in lung cancer cells using confocal microscopy . we observed a large amount of lsrb in the cytoplasm of h460 cells incubated with hsp1 - lsrb , hsp2 - lsrb or hsp4 - lsrb at 37 ° c ., whereas little srb fluorescence was detectable in cells incubated with non - targeting lsrb . at 4 ° c ., all of the lsrb conjugated these three targeting peptides bound to the outer membrane of the h460 cells . it is worth noting that hsp1 peptide exhibited stronger ability at binding than internalization , compared to hsp2 and hsp4 , as evident by its stronger binding intensity at 4 ° c . but weaker srb fluorescence in cytosol at 37 ° c . furthermore , we examined whether hsp1 , 2 , and 4 - mediated liposomal drugs enhanced the therapeutic efficacy of drugs due to their proven targeting and endocytosis abilities . we performed in vitro cytotoxicity assays for hsp1 , 2 , or 4 - conjugated liposomal doxorubicin ( ld ) in h460 cells ( fig3 b ). compared to ld , all of these three targeting peptide - ld significantly enhanced the cytotoxicity of the drug to cancer cells . hsp1 , hsp2 and hsp4 , at its optimal peptide ratio , decreased the half maximal inhibitory concentration ( ic 50 ) in h460 cells by 12 . 5 -, 13 - and 9 . 4 - fold , respectively ( fig3 b ). in brief , hsp1 , 2 and 4 targeting peptides not only bind to lung cancer cell with high specificity , but they also trigger liposomal drug internalization and enhance therapeutic efficacy in vitro . therapeutic efficacy of hsp1 , hsp2 and hsp4 - mediated drug delivery systems in human large cell carcinoma and adenocarcinoma xenograft models further , to determine whether hsp1 , 2 and 4 could improve the chemotherapeutic efficacy of anticancer drugs in vivo , we formulated targeting drug delivery systems by coupling these peptides with pegylated liposomal doxorubicin ( ld ). in the first experiment , scid mice bearing h460 human lung large cell carcinoma xenografts were administered intravenously with hsp1 - ld , hsp2 - ld , hsp4 - ld , non - targeting ld , free doxorubicin ( fd ) or equivalent volumes of pbs ( fig4 a - f ). we examined the therapeutic efficacies of these targeted - lds in both small tumor ( average tumor size of ˜ 75 min 3 ) ( fig4 a ) and large tumor ( average tumor size of 500 mm 3 ) ( fig4 b - d ), respectively . anticancer efficacy was evaluated by determining the average tumor volumes while the side - effects were estimated by measuring body weight changes throughout the period of treatment . the mice bearing small tumor were treated with 1 mg / kg of doxorubicin once a week for 4 times . the tumor volume decreased significantly in targeting - ld groups ( fig4 a ). in the mice beating large tumor treatment , the targeting peptides hsp1 , 2 , and 4 significantly improved therapeutic efficacy of ld in h460 large tumor , especially hsp2 and hsp4 - ld , which showed a decrease in tumor volume by half compared to the ld group ( fig4 b - e ). the result of in vivo biodistribution and pharmacodynamics study could support this finding that hsp2 and hsp4 exhibited better drug delivery efficacy of ld to h460 tumor tissues . the prolonged overall survival rates were observed ( fig4 f ) and body weight had not changed significantly during the course of treatment . we also examined the therapeutic effect of hsp1 , 2 , and 4 - ld in h1993 human lung adenocarcinoma xenograft model ( fig5 a - f ). mice hearing size matching h1993 large tumor were injected intravenously with 1 mg / kg of hsp1 - ld , hsp2 - ld , hsp4 - ld , ld , fd or equivalent volumes of pbs twice a week for three weeks . fig5 e showed that administration of hsp1 , 2 , and 4 - ld did not cause an appreciable reduction in body weight as compared to the ld group , hsp4 - ld showed the best therapeutic effect , as measured by tumor volume since the tumor size was significantly decreased as early as 10 . 5 days after treatment ( after 3 injections ) ( fig5 b - d ). however , in terms of overall survival rate , mice treated with hsp1 and hsp2 - ld lived 50 - 60 days longer than that treated with ld ( fig5 f ). these data indicate that decrease in tumor volumes does not translate into prolonger overall survival rates . one of the possible explanations for this was that although hsp4 had the highest receptor number on h1993 cell surface ( fig1 a ) compared to the other two peptides , there were only 55 . 93 % of h1993 cells expressing the receptor of hsp4 , which was less than that of hsp1 and 2 ( fig1 b ). this might provide more chances for those hsp4 - negative cells , which would be selected to become drug - resistant cells during hsp4 - ld treatment in h1993 model . hsp1 , 2 and 4 targeting peptides enhanced minor drug delivery in vivo by biodistribution assay to explore the mechanisms underlying the enhanced anticancer effects of hsp1 , 2 , or 4 - conjugated liposomal drugs in vivo , we performed a pharmacodynamics and biodistribution study to measure the drug accumulation in tumor tissues . mice bearing h460 xenograft tumor were intravenously injected with a single dose of 2 mg / kg fd , ld , hsp1 - ld , hsp2 - ld or hsp4 - ld . after 1 hr and 24 hr systemic circulation , the doxorubicin concentration in serum , tumors and normal organs were estimated by measuring fluorescence signal of doxorubicin after purification steps . the mean intra - tumor doxorubicin concentrations in the hsp1 , hsp2 , and hsp4 - ld groups were about 1 . 5 -, 2 - and 2 - fold higher than that in the ld group , respectively . this data provided evidence and explanation for the superior tumor inhibitory effects exhibited by hsp2 and 4 in the previous experiment comparing h460 large tumor treatment using targeting - ld ( fig4 b - f ). since doxorubicin worked by intercalating dna , the drugs accumulated in cancer nuclei were also measured . the results generally paralleled those in the tumor . liposomal formulation drugs ( ld , hsp1 - ld , hsp2 - ld , and hsp4 - ld ) displayed similar biodistribution profiles in plasma and normal organs , whereas free form of doxorubicin exhibited much shorter half - life in plasma . the results from this experiment demonstrated that hsp1 , 2 , and 4 elevated the penetration of anticancer drugs into tumor and resulted in higher accumulation of the drugs at their intracellular target sites , thereby enhancing the therapeutic efficacy of doxorubicin . in addition , these targeting peptides did not increase doxorubicin accumulated in normal organs such as brain , heart , lungs , liver and kidney in animal models . given the genomic instability and genetic heterogeneity of cancer biology , single - drug monotherapy often strengthens the redundant signaling pathways , accelerating chemoresistant mutations and recurrence . the use of multiple chemotherapeutics with different mechanisms of actions in combination has become the primary strategy to treat drug , resistant cancers . therefore , we co - delivered hsp4 - ld and hsp4 - conjugated liposomal vinorelbine ( lv ), which acts as a microtubule inhibitor at a 1 : 2 combinatorial ratio , to treat h460 xenograft model ( fig6 a - d ). the administration regimen of these two drugs had been tested and optimized by therapeutic synergism in vivo ( data not shown ). fig6 c - d showed that hsp4 - mediated combinatorial targeting liposome - treated group had a much longer overall survival than non - targeting liposome - or free drug - treated groups . the combinatorial targeting liposome - treated group prolonged median survival compared to non - targeting liposome - treated group by up to 11 days ( 74 vs . 63 days ). we also investigated this 1 : 2 ld and lv combinatorial regimen in h460 large cell carcinoma fig7 a - e ) and a549 adenocarcinoma ( fig8 a - e ) orthotopic models , which successfully recapitulated tumor - microenvironment interactions . in h460 orthotopic model , luciferase - expressing tumor mass decreased significantly in hsp4 - mediated combinatorial liposome - treated group ( fig7 a - b ) compared to free drug - treated group , while non - targeting liposome - treated group showed no significant differences to free drugs group . since h460 orthotopic model was highly aggressive , all mice underwent severe body weight loss due to cancer cachexia syndrome ( fig7 c ). however , the prolonged median survival time was observed by 6 . 5 days in targeting liposome group compared to nontargeting liposome group ( 77 . 5 vs . 71 days ). in terms of a549 orthotopic model , hsp4 - mediated combinatorial liposome - treated group significantly prolonged overall survival rate and increased median survival times by up to 47 days compared to non - targeting liposome - treated group ( 131 vs 84 days ) ( fig8 d - e ). we can demonstrate that hsp4 targeting peptide not , only improved the therapeutic efficacy of nanodrugs ( fig8 a - b ), but also reduced adverse effect by decreasing body weight loss ( fig8 c ). binding activities of hpc1 , 2 , and 4 to clinical surgical specimens of human lung cancer the response rate of a targeting drug to biopsies or surgical specimens of cancer patients is one of the most difficult challenges facing clinical drug development . here , we examined whether hsp1 , 2 or 4 would react to several different types of human lung cancer specimens , including adenocarcinoma . papillary adenocarcinoma , bronchioloalveolar carcinoma ( bac ), squamous cell carcinoma ( scc ), large cell carcinoma , and small cell carcinoma . since m13 phage particles consisted of many coat proteins , the signals were amplified under immunostaining steps and were more visible than using peptides themselves . for this reason , we used hpc1 , 2 , and 4 phages for human tissue staining . table 2a lists the percentages of the positive rates of hpc1 , 2 , and 4 for cancer detections in several different types of lung cancers . in general , hpc4 displayed the best reactivity (& gt ; 80 %) in almost all types of lung cancers , which was followed by hpc1 (& gt ; 50 %). moreover , hpc1 , 2 and 4 also recognized metastatic adenocarcinoma or scc from lung ( table 2b ), but exhibited no reaction for normal lung tissue or cancer adjacent normal lung tissue ( table 2c ). fig9 shows examples of immunohistochemistry staining obtained on consecutive sections from individual tumors . these data demonstrate that hpc1 , 2 , and 4 can recognize not only nsclc but also sclc surgical specimens , but do not cross - react to normal pneumonic tissues tables 2a - c show detection of human lung cancer surgical specimens by hpc1 , 2 and 4 using immunohistochemistry . several histopathological subtypes of clinical human lung cancer biopsies were immunostained by hpc1 , 2 or 4 and compared to control phage ( table 2a ). the positive response percentages were calculated and compiled ihc data of metastatic adenocarcinoma and scc from lung ( table 2b ). normal pneumonic tissue and cancer adjacent normal pneumonic tissue were confirmed for hpc1 , hpc2 and hpc4 tumor specificity ( table 2c ). reaction area : +++, & gt ; 50 %; ++, 50 - 20 %; & lt ; 20 %; −, 0 %. in contrast to monoclonal antibodies , which exhibit large size , poor tumor penetration , and high immunogenicity when used as targeting ligands ( cheng and allen , 2010 ), peptide ligands are the better choice for payload delivery because of smaller size , less immunogenicity , higher tumor penetration , more cost - effective for synthesis and production . in this study , we identified three novel peptides hsp1 , 2 and 4 that could selectively bind to several types of human lung cancer , but not normal pneumonic tissue in vitro , in vivo , and among clinical samples . thirteen phage clones ( hpc1 - 13 ) with higher lung cancer binding in vitro were divided into two major categories by distinct consensus sequences , in which the first group displayed “ mhl - w ” motif ( hpc1 ) while the other displayed “ npw - e or w - emm ” motif ( hpc2 and 4 ). although hpc2 and 4 displayed more similar sequences , they showed different binding patterns and distinct functional behaviors in serial experiments , such as cellular elisa binding assay , facs analysis , cell ifa staining ( fig1 a - b ), dose - dependent and time course lsrb uptake assay ( fig3 a ), and even human surgical specimens detection ( fig9 ; table 2 ). these findings imply that hsp1 , 2 , and 4 may target different protein molecules on the cell surface of lung cancers due to their different positive - stained rates , reactive intensities , or receptor densities . hsp1 , 2 , and 4 - mediated dds can specifically bind to lung cancer cells , which in turn trigger “ receptor - mediated endocytosis ” to discharge payloads to their intracellular target site ( for example , dna for doxorubicin ), resulting in about 10 - fold reduction in ic 50 in vitro ( fig3 a - b ). likewise , hsp1 , 2 , and 4 - mediated liposomal drugs significantly improved drug bioavailability in vivo , leading to increased therapeutic index ( fig4 - 8 ). it should be noted that hsp2 and 4 performed better in ld delivery by increasing both tumor accumulation and therapeutic efficacy ( fig4 b - c ) by up to 2 - fold in h460 xenograft model . unlike its consensus sequence - displayed member hsp2 , hpc4 , which positively stained nearly all types of nsclc and sclc surgical specimens , exhibited the best clinical reactivity ( table 2 ). in addition , preclinical data also highlight the advances of hsp4 - mediated combinatorial liposomes in overall survival ( fig6 - 8 ), this strategy promises a novel and better tailored combinatorial regimen to overcome clinical chemoresistance and delay cancer relapse . ihc data ( fig9 ; table 2 ) also revealed that w - emm motif of hsp4 might contribute more significantly to this effect than npw - e motif , thus was vital for clinical application . more advanced studies are needed to investigate the detailed functions of each motif in order to choose the appropriate motifs for endocytosis and for other clinical detections . hence , we can modify the peptide sequences into perfection and multi - functions . further research would be necessary to elucidate the receptor proteins expressed on lung cancer cell surface targeted by hsp1 , hsp2 and hsp4 and to investigate their respective downstream intracellular signals critical to the transport of the cargos released . target protein identification will also provide information on safety and toxicity profiles , which are crucial for the development of targeting drugs for clinical use . based on our research , hsp1 , 2 and 4 lung cancer targeting peptides bear significant potential to be developed into “ theranostics nanoparticles ” with broad clinical applications including targeting therapy , companion diagnostics and non - invasive imaging . the foregoing description of the exemplary embodiments of the invention has been presented only for the purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise forms disclosed . many modifications and variations are possible in light of the above teaching . the embodiments and examples were chosen and described in order to explain the principles of the invention and their practical application so as to enable others skilled in the art to utilize the invention and various embodiments and with various modifications as are suited to the particular use contemplated . alternative embodiments will become apparent to those skilled in the art to which the present invention pertains without departing from its spirit and scope . accordingly , the scope of the present invention is defined by the appended claims rather than the foregoing description and the exemplary embodiments described therein . some references , which may include patents , patent applications and various publications , are cited and discussed in the description of this invention . the citation and / or discussion of such references is provided merely to clarify the description of the present invention and is not an admission that any such reference is “ prior art ” to the invention described herein . all references cited and discussed in this specification are incorporated herein by reference in their entireties and to the same extent as if each reference was individually incorporated by reference .

US-201514599291-A

this invention generally relates to a set of parallelepipedal bodies capable of matingly compatible engagement for interconnection with substantially similar cubes or matingly conformed rails , so as to allow up to three degrees of freedom in the sliding movement of an individual cube or grouping of cubes about a grouping of other interconnected cells from the set . each cube is constructed from six plates with an interior physical configuration adapted for connection and that lends itself to monolithic injection molding . the exterior physical configuration of all plates are substantially similar . when a number of cubes are assembled into a cubic array , there can be slab movement , row movement or solo cube movement .

there has thus been outlined , rather broadly , the more important features of the invention in order that the detailed description thereof that follows may be better understood and in order that the present contribution to the art may be better appreciated . there are , of course , additional features of the invention that will be described hereinafter and which will form the subject matter of the claims appended hereto . in this respect , 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 to the arrangements of the components set forth in the following description or illustrated in the drawings . the invention is capable of other embodiments and of being practiced and carried out in various ways . also , it is to be understood that the phraseology and terminology employed herein are for the purpose of descriptions and should not be regarded as limiting . looking at fig1 , an exploded view of the basic assembly concept of a cube can best be seen . ( here the exterior faces 12 have had all t posts 8 and ½ t posts 10 removed for visual clarity .) the physical configuration of the interior faces 20 are identical . here base cube 1 can be seen as assembled from six substantially similar base face plates 3 . the interior faces 20 of the base face plates 3 have two substantially similar linear assembly members 24 extending normally therefrom . assembly members 24 are parallel and reside on opposite peripheral edges of interior face 20 . referring to fig1 and 2 a - c it can be seen that both linear assembly members 24 of one base face plate 3 are designed to contact one linear assembly member 24 of all four adjacent base face plates 3 at 90 ° ( with respect to the linear axes of the members ) so as to allow for a surface for adhesion ( or other method of affixation ) between the adjacent plates . in this manner the linear assembly members 24 of six base face plates 3 can be engaged to form a cube 1 as illustrated . fig2 a shows the front , right , and top views of a single base face plate 3 . fig2 b shows the front , right , and top views of two joined base face plates 3 , and fig2 c shows the front , right , and top views of three base face plates 3 joined to make half a cube 1 . looking at fig3 , an exploded view of the preferred embodiment of the cube 2 , it can best be seen that in this design there is a first face plate 4 and second face plate 6 , which , when viewing their exterior faces 12 , are mirror images . ( this is an assembly requirement because of stearic hindrance caused by the overhang of the t posts 8 and ½ t posts 10 .) it is to be noted that the arrangement of all first face plates 4 is such that there is a common corner shared by all three of these and at the diagonal corner of the cube resides the common corner for the three second face plates 6 . in fig4 , looking at all six views of a face plate ( either of 4 or 6 ) it can be seen that each face plate has one t post 8 and ½ tee post 10 ( formed upon the exterior face 12 thereof so as to form an inverted t slot 14 and an inverted ½ t slot 16 respectively adjacent the ½ t post 10 and t post 8 . the inverted t slot 14 is complementary to the t post 8 , while the inverted ½ t slot 16 is complementary to the ½ t post 10 . this configuration allows for sliding engagement between all face plates when they are oriented correctly . when matingly engaged the off - set design of the face plates allows the plates to slide parallel to the longitudinal axis of the posts or slots . the longitudinal axis of the posts and slots on any exterior face on an assembled cube lies perpendicular to the longitudinal axis of the posts and slots on any and all adjacent faces . it is known that the ts and ½ t posts ( see fig1 ) can be tapered to further facilitate the sliding engagement between face plates of neighboring cubes . it is to be noted that both ends of the t post 8 are cantilevered or extend beyond the edges of face plate 4 or 6 . the amount of cantilever of each end is not equal . it is this feature of the design that forces the use of two sets of three each , mirror image plates . if there were no cantilever , the assembly of the cube 2 would require but six substantially similar face plates . it is this cantilever feature that allows for a truer alignment between the faces of adjacent cubes . in this fashion , sliding cubes will always remain guided by the t posts thereby avoiding jamming . since the first face plate 4 and the second face plate 6 are mirror images of each other , they have substantially similar length and width dimensions and are rectangular , but are not square . the length of each face plate is defined as the dimension parallel to the longitudinal axis of the slots and ts thereon and is the largest single physical dimension of the face plates . the width of each face plate is defined as the dimension perpendicular to the longitudinal axis of the ts and slots thereon . the width of each face plate is shorter than the length of each face plate by two times the thickness of the face plate . this allows for the cube 2 to be a regular hexahedron with each visible face having a square configuration when all face plates are assembled into a monolithic structure as the length dimension of each face plate resides adjacent to the width dimension of each adjacent face plate at all edges of the cube 2 . the alternate embodiments have differing methods of connection and alignment dictated by the different configurations of their interior faces . all cube embodiments have substantially similar exterior faces and are virtually indistinguishable when assembled . the interior face of the face plates of the first alternate embodiment as illustrated in fig5 a - 5c deviates from the preferred embodiment face plates with two structural differences . on the interior face 23 of first alternate embodiment plates 9 and 11 resides a raised rectangular platform 26 having a smaller surface area than the exterior face 13 . in the platform 26 there are two detents 28 formed on opposite sides of the rectangular platform 26 non - adjacent to the modified linear members 30 . each modified linear member 30 has a tab 32 located at the member &# 39 ; s midpoint that is matingly conformed to the detent 28 . in assembly , the tabs 32 are engaged into the detents 28 in the following manner : from each first plate 9 one tab 32 is inserted into a detent 28 of an adjacent first plate 9 and one tab 32 is inserted into the detent 28 of an adjacent second plate 11 ; and from each first plate 9 one detent 28 is filed with a tab 32 from an adjacent first plate and one detent is filled with a tab 32 from an adjacent second plate 11 . although discussed as rectangular in shape so as to maximize the gluing surfaces , the platform 26 may be of any shape that supports a detent configuration of a modified linear member 30 . as discussed earlier , if the exterior configuration uses t posts that cantilever beyond the edge of the exterior face , then it will be necessary to have a cube assembled wherein half of the plates have mirror image exterior post configuration . if the t post ends even with the plate edge or less than the plate edge then all six of the plates used to assemble the cube will be identical . the interior face of the face plates of the second alternate embodiment as illustrated in fig6 differs from the preferred embodiment with one structural difference . on the interior face 21 of second alternate embodiment plates 5 resides a raised lip rectangular platform 34 with an exterior lip 36 formed about its perimeter so as to create a groove 38 between the lip 34 and the plate &# 39 ; s interior face 21 on two parallel sides . this groove 38 is dimensioned ( in depth and width ) to accept the linear assembly members 25 . the rectangular platform 34 has a smaller surface area than the exterior face 15 . there still are two parallel linear members 25 that reside along the edges of the plate ( 5 or 7 ) in a similar fashion to that of the preferred embodiment . these linear members 25 reside perpendicular to the grooves 38 . in assembly , four of the second alternate embodiment first plates 5 are assembled to form a right cylinder ( two of these plates have mirror image exterior face configuration ) and one of each of the mirrored image preferred embodiment plates 5 and 7 . it is to be noted that the length of linear assembly members 25 may be varied in this second alternate embodiment for ease of assembly or material costs as illustrated in fig7 a - 7c . the interior face of the face plates of the third alternate embodiment as illustrated in fig1 employs an offset raised platform 31 . on the interior face 33 , of third alternate embodiment plates 17 . the offset raised platform 31 has a smaller surface area than the exterior face 19 . the offset raised platform 31 and third alternate embodiment plate 17 share a common edge 35 such that there is symmetry about their width axis . assembly of a complete cube requires six plates 17 . fig1 illustrates the offset raised platform interior design of the third alternate embodiment with t posts and ½ t posts on the exterior faces . the interior face of the face plates of the fourth alternate embodiment is illustrated in fig1 . the fourth alternate embodiment employs the same offset design of the third alternate embodiment but instead uses offset parallel linear members 37 instead of an offset raised platform 31 . on the interior face 41 of the fourth alternate embodiment plates 39 reside a first offset linear member 37 extending normally from interior face 41 and a second offset linear member 49 also extending normally from interior face 41 . said first offset linear member shares a common edge 43 with fourth alternate embodiment plate 39 such that there is symmetry about their width axis . assembly requires six plates 39 . with the aforementioned design and embodiments , it is possible to fabricate the face plates as monolithic components with such methods as injection molding . this greatly reduces the cost of fabrication as compared to prior art designs . it is also known that a matingly engageable dovetail formation of a dovetail t post 50 , dovetail ½ t post 52 , dovetail t slot 54 and dovetail ½ t slot 56 may be utilized as an optional embodiment to any of the plates illustrated and described herein ( see fig8 ). looking at fig8 the effect of having a t post that is cantilevered can be seen , as adjacent plate &# 39 ; s t posts create a unitary linear member therein reducing jamming was the cubes are slidingly engaged along that longitudinal direction . this provides and overlapping joint when two , three , or four cubes meet at their common edge . this overlap means that the cubes are already aligned with each other before they begin to move . looking at fig1 , it can be seen that a matingly engageable l post 62 formation with linear post 64 is another optional embodiment to any of the plates illustrated and described herein . fig9 illustrates another optional embodiment click stop exterior face plate configuration that can be utilized with any of the interior face plate configurations discussed herein . this click stop design has the same effect of alignment of the cube that is accomplished utilizing a cantilevered t post . the click stop face plate 44 employs at least one ( preferably two ) sets of complimentary alignment buttons 40 and recesses 42 on the two edges 46 of the click stop face plate 44 that reside perpendicular to the longitudinal axis of the dovetail t post 48 . when the adjacent cubes are closely aligned , the recesses 42 will tightly draw the buttons 40 into a precise location that finely tunes or aligns the cubes edges and longitudinal axes of t posts , therein eliminating the need for cantilevered t posts . in this embodiment the click - stop would serve as the primary bearing surface for movement . as another embodiment of the click stop , fig1 illustrates an offset button 60 . this facilitates the sliding of cubes without interference between buttons . in the previous embodiment , the cubes must separate slightly as the buttons pass over each other . the above description will enable any person skilled in the art to make and use this invention . it also sets forth the best modes for carrying out this invention . there are numerous variations and modifications thereof that will also remain readily apparent to others skilled in the art , now that the general principles of the present invention have been disclosed .

US-1240908-A

apparatus wherein tobacco is dried in several successive units each of which contacts a continuous stream of tobacco with hot air . the moisture content of tobacco is measured between a preceding unit and the next - following unit , and the temperature of hot air which is supplied by the next - following unit is respectively increased and reduced when the monitored moisture content of tobacco respectively rises and decreases . the temperature of air which is admitted by the preceding unit is maintained at a constant value . the temperature of air which is supplied by the next - following unit is further influenced , when necessary , in dependency on measurement of such temperature and in dependency on differences between the final moisture content of tobacco and a preselected optimum moisture content . the detector which monitors the moisture content between the preceding and next - following units is built directly into the conveyor which transports the tobacco stream through the drying units .

the apparatus of fig1 and 2 comprises a first heating or drying unit 1 and a second heating or drying unit 3 . the first drying unit 1 comprises a dryer 2 wherein the particles 69 of tobacco are relieved of moisture while floating in currents of ascending hot drying fluid . the second drying unit 3 comprises a second dryer 4 wherein the particles of tobacco are relieved of moisture in the same way as in the dryer 2 . the drying unit 3 is followed by a further treating unit 6 wherein the particles of tobacco are cooled by a device 7 wherein ascending currents of a fluid whose temperature is lower than the temperature of particles issuing from the unit 3 not only cool the particles but also cause them to float during travel through the unit 6 . the exact nature of the dryers 2 , 4 and cooling device 7 forms no part of the invention . reference may be had to commonly owned u . s . pat . nos . 3 , 799 , 176 and 3 , 877 , 469 . the means for transporting a continuous tobacco stream through the dryers 2 , 4 and the cooling device 7 comprises a vibratory conveyor 8 which is mounted on pivotable arms 9 and is agitated by a suitable motor through the medium of an eccentric in a manner as disclosed in the aforementioned patents . the conveyor 8 is permeable to fluids so that it allows hot and cool fluids to pass therethrough and to agitate and intimately contact the particles of the tobacco stream which are fed onto and advance along the upper side of the conveyor 8 . the means for contacting tobacco with a hot fluid ( e . g ., air ) in that portion of the tobacco path which is adjacent to the drying unit 1 comprises a chamber 11 below a foraminous screen 12 serving to uniformize the pressure of air between its upper side and the underside of the conveyor 8 . the conveyor 8 comprises a lower portion 13 ( see particularly fig2 ), a trough 14 and an upper portion having divergent side walls 16 , 17 flanking a foraminous screen 18 which prevents particles of tobacco from entering air evacuating pipes 31 . the vibratory movements of the conveyor 8 are synchronized with the speed of ascending currents of hot air ( such speed decreases while the currents rise in the space between the upwardly diverging side walls 16 and 17 ) in such a way that the particles of tobacco float in the space immediately above the upper side of the cconveyor 8 and are intimately contacted by hot air from all sides . the channel 11 receives air from the outlet of a blower 21 which admits air into a pipe 22 containing a heating device 23 . some air which issues from the blower 21 bypasses the heating device 23 via pipe 24 and is admitted into heated air that flows in a pipe 51 connecting the outlet of the heating device 23 with the chamber 11 . the pipes 22 and 24 respectively contain adjustable valves in the form of flaps 28 , 27 ( the flap 28 is mounted in that portion of the pipe 22 which is located downstream of the locus where some of the air enters the bypass pipe 24 ). the positions of the flaps 27 , 28 can be adjusted by a reversible electric motor 26 when the latter receives appropriate signals from an amplifier 78 . by changing the positions of the flaps 27 , 28 , the motor 26 regulates the temperature of air in the pipe 51 , i . e ., the ratio of air which is heated during passage through the heating device 23 to the air which enters the pipe 51 via bypass pipe 24 . the aforementioned pipes 31 discharge spent air into a collecting pipe 33 whose outlet is connected to the intake of the blower 21 . a further conduit 32 discharges some air which issues from the outlet of the blower 21 . such air is replaced by air which is admitted by the collecting conduit 33 . the latter is further connected to the treating unit 6 . the means for admitting heated air to the chamber below that portion of the tobacco path which is adjacent to the heating unit 3 comprises a pipe 52 which receives air from the outlet of a second blower 36 . the blower 36 admits air into a pipe 37 which contains a flap 42 and discharges air into a heating device 39 which , in turn , admits heated air into the pipe 52 . a bypass pipe 38 contains a flap 43 . the flaps 42 , 43 are adjustable by a reversible electric motor 44 which receives signals from an amplifier 91 . the intake of the blower 36 draws air from the evacuating pipes 41 of the drying unit 3 and also from the treating unit 6 . a pipe 46 for spent air receives some air which is discharged by the blower 36 . the reference character 47 denotes a further pipe which receives air from the treating unit 6 and admits such air into the intake of the blower 36 . the parts 42 - 44 constitute and adjustable regulating device for the temperature of hot air which contacts the particles of tobacco in the dryer 4 . the pipes 51 and 52 respectively contain detectors 53 and 54 which monitor the temperature of heated air streams and transmit appropriate signals to transmitters 56 and 57 . the outputs of the transmitters 56 , 57 respectively transmit electric signals to signal comparing stages 77 and 87 . the detectors 53 and 54 are heat - sensitive semiconductors of known design . the drying units 1 and 3 are separated by a gap 61 . a first moisture detector 63 is installed in the gap 61 to monitor the moisture content of the tobacco stream which advances from the unit 1 into the unit 3 , and a second moisture detector 64 monitors the moisture content of tobacco downstream of the cooling device 7 . as shown in fig3 and 4 , the moisture detectors 63 and 64 are immediately adjacent to tobacco in the trough - shaped portion 14 of the conveyor 8 . each of these detectors comprises an insulating plate 66 which is mounted in the bottom panel of the trough 13 and an electrode 67 which is recessed into the insulating plate 66 . the trough - shaped portion 14 constitutes the second electrode of each of the detectors 63 and 64 . the two electrodes form part of a high - frequency oscillator circuit . the arrows 68 denote the field lines of the capacitor which includes the electrodes 14 and 67 . such lines extend into the path of tobacco particles 69 on the conveyor 8 . the direction in which the particles of tobacco advance when the conveyor 8 is in motion is indicated by the arrow 70 . the illustrated moisture detectors 63 and 64 can be replaced with other types of moisture detectors , for example , capacitive detectors of the type known as hwk produced by the assignee of the present application . it is further possible to employ infrared moisture detectors , for example , detectors of the type known as sm 2 ( produced by infrared - engineering ltd .). the cooling device 7 comprises a blower 71 whose outlet admits cool atmospheric air into a pipe 72 connected to the chamber below that portion of the conveyor 8 which is adjacent to the treating unit 6 . some air which is admitted via pipe 72 and is heated on contact with tobacco particles 69 in the treating unit 6 is admitted into the pipe 33 , and the remaining preheated air is admitted into the pipe 47 . such air replaces those air streams which are discharged via pipes 32 and 46 . the control circuit for the heating unit 1 comprises a source 74 of reference signals which is connected to the aforementioned signal comparing stage 77 . the signal at the output of the stage 77 indicates the difference between the actual temperature of hot air in the pipe 51 ( detector 53 ) and the desired temperature ( reference signal from 74 ). such output signal is transmitted to the amplifier 78 which adjusts the positions of the flaps 27 , 28 via motor 26 whenever the intensity or another characteristic of the signal at the output of the transmitter 56 deviates from the same characteristic of the reference signal . thus , the control circuit insures that the temperature of hot air which is admitted into the chamber 11 remains constant . the character 79 denotes a second source of reference signals which is activatable by a device 81 ( shown three times in fig1 ) serving to measure the rate of tobacco admission . the source 79 transmits a reference signal to the signal comparing stage 77 instead of the source 74 when the admission of tobacco to the conveyor 8 is interrupted . it will be noted that the tobacco flow monitoring device 81 is connected with the source 79 as well as with the source 74 . a third source 82 of reference signals is connected with the signal comparing stage 77 during starting of the apparatus . at such time , the outputs of the sources 74 and 79 are disconnected from the stage 77 . the signal comparing stage 87 receives signals from the transmitter 57 and from the moisture detectors 63 , 64 . the output of the stage 87 transmits an adjusting signal to the amplifier 91 for the motor 44 when the intensity or another characteristic of the signal from 63 changes , when the intensity of signal transmitted by 64 deviates from the intensity of reference signal supplied by a source 88 , or when the sum or another combination of just mentioned signals deviates from that transmitted by the device 57 . the part 89 is a pid circuit which is connected between the stage 87 and a further signal comparing stage 86 . one input of the stage 86 is directly connected with the source 88 and another input of this stage is connected with the output of the moisture detector 64 . the sources 92 and 93 of reference signals are analogous to the sources 79 and 82 . the device 81 in the control circuit section for the drying unit 1 is indentical with the similarly numbered part between the sources 88 and 92 . the output of the moisture detector 63 is directly connected to the stage 87 . the broken lines indicate that the sources 79 , 82 , 92 and 93 are active only when the operation of the apparatus is not automatic . as mentioned above , the sources 79 and 92 transmit reference signals when the admission of tobacco particles 69 is interrupted , and the sources 82 and 93 transmit reference signals during acceleration of moving parts of the apparatus to normal operating speed . the stage 87 and the amplifier 91 adjust the regulating means 42 - 44 in response to signals from detector 63 , 64 and / or 54 . the adjustment is such that the temperature of air in the pipe 52 is caused to rise in response to a rise of moisture content of tobacco in the gap 61 and vice versa . when the left - hand end portion of the conveyor 8 ( as viewed in fig1 ) receives tobacco , the device 81 activates the sources 74 and 88 which transmit reference signals to the signal comparing stages 77 and 86 . successive increments of the continuous tobacco stream on the conveyor 8 advance through the drying unit 1 and the particles of tobacco are caused to float in the currents of hot air which ascend from the chamber 11 and pass through the sieve 12 and the perforations of the conveyor 8 . such hot air is supplied by the pipe 51 which receives hot air from the heating device 23 and cool air from the bypass pipe 24 . the speed of air which rises above the conveyor 8 decreases between the divergent side walls 16 and 17 ; this insures that the ascending currents of air cannot entrain the lighter particles of the tobacco stream . hot air thereupon passes through the sieve 18 and is conveyed to the intake of the blower 21 via pipes 31 and 33 . the outlet of the blower 21 discharges a certain percentage of air into the atmosphere via pipe 32 . as mentioned above , the air stream which is admitted via pipe 33 is preheated due to admission of hot air via pipes 31 . the source 74 of reference signals insures that the temperature of hot air in the pipe 51 is at least substantially constant . thus , when the temperature which is monitored by the detector 53 deviates from the temperature denoted by the reference signal which is transmitted by the source 74 , the signal comparing stage 77 transmits a signal to the motor 26 via amplifier 78 whereby the motor changes the ratio of cool air to hot air in the pipe 51 by appropriate adjustment of angular positions of the flaps 27 and 28 . the nature of adjustment is such that the flap 27 moves toward its fully open position when the flap 28 moves toward its fully closed position and vice versa . the moisture detector 63 in the gap 61 measures the moisture content of tobacco which issues from the drying unit 1 . its signal is transmitted to the signal comparing stage 87 . thus , the intensity of such signal influences the signal which the stage 87 transmits to the amplifier 91 for the motor 44 . the circuit for the drying unit 3 is dominated by the signal from 63 . the detector 64 transmits signals to the stage 86 which compares such signals with the reference signal from 88 and transmits a signal to the stage 87 ( via pid circuit 89 ) when the measured final moisture content of tobacco deviates from the desired final moisture content . the stage 87 further receives signals from the detectors 54 ( via transmitter 57 ) and 63 . if the intensity of signal from 57 deviates from the intensity of signals from 63 and 89 , the amplifier 91 starts the regulating motor 44 so as to adjust the flaps 42 , 43 in a direction to increase or reduce the temperature of hot air in the pipe 52 and hence the drying action of the unit 3 . hot air which leaves the unit 3 is admitted to the blower 36 via pipes 41 . relatively cool air which is admitted to the blower 36 via pipe 47 compensates for air which is discharged into the atmosphere via pipe 46 . the delay with which the circuit for the second drying unit 3 adjusts the temperature of air in the pipe 52 ( and hence the final moisture content of tobacco ) is very short . this is due to the fact that the signal comparing stage 87 receives signals from the moisture detectors 63 and 64 . thus , the temperature of air in the pipe 52 is changed in immediate response to detection ( by 63 ) that the moisture content of tobacco leaving the first drying unit 1 deviates from the anticipated moisture content ( i . e ., when the intensity of signal which is transmitted by the detector 63 deviates from the average intensity . this insures that , in most instances , the moisture content of tobacco in the second drying unit 3 is changed to correspond to the desired final moisture content even before the tobacco batch whose moisture content on leaving the unit 1 is unsatisfactory reaches the second moisture detector 64 . in other words , the second moisture detector 64 merely constitutes a safety device which normally influences the drying action only in response to long - range deviations of final moisture content from the desired optimum final moisture content . tobacco which leaves the second heating unit 3 enters the treating unit 6 and is cooled by air currents which are admitted by the pipe 72 . heated air which issues from the unit 6 is admitted in part to the collecting pipe 33 ( i . e ., to the intake of the blower 21 ) and in part to the intake of the blower 36 . an important advantage of the improved apparatus is that the deviations of moisture content from desired moisture content can be detected before the respective portion of the tobacco stream leaves the drying units , and that such deviations can be eliminated before the respective batch reaches the detector 64 . this reduces the percentage of tobacco which leaves the apparatus with a moisture content that deviates from the optimum moisture content . 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 prior art , fairly constitute essential characteristics of the generic and specific aspects of our contribution to the art and , therefore , such adaptations should and are intended to be comprehended within the meaning and range of equivalence of the claims .

US-90675378-A

a dice game uses six - sided die . the object of the game is achieved with random dice rolls and is a game of chance . the simplicity of the game requires only numerical recognition of the values 1 to 6 . since no other prior knowledge is required , this game effectively eliminates the age and knowledge gap among players , hence creating an unbiased starting point for players of different age ranges .

the game of joma is for 2 to 4 players of all age range . each player has two dice of a color that is unique to the player and a notepad used to tally dice rolls . the tally notepad is preprinted with numbers 1 to 6 ( representing each possible dice roll ) vertically on the left hand side of each sheet . a game board for two players is shown on figure one . the dice 10 for player one may be placed on the board , and the dice for player two may be placed on the board . the tally sheet for player one and 12 and the tally sheet for player two 13 may be placed on the board . a roll area defined on the board may be imprinted on the board as a rectangular area , or as a picture of a cartoon character , or other artwork . the goal of the game is to be the first player to gather 10 tally marks for all six possible dice rolls in each set of the game . players continue to roll dice until this goal is reached . the first player to gather 10 tally marks is the winner of the set and receives a joma — a token with an imprinted character . there are four sets in a game and the player with the most jomas at the end of four sets wins the entire game . a tie score is resolved by a play - off set between all the players who hold equal number of tokens , or “ jomas .” the single winner of the play - off set is the winner of the entire game . each player is provided with a set of two dice with a color ( such as red and green ) that is unique to the player and a tally notepad . a tally notepad is pad of paper upon which the tallied score is kept . the dice is a six face dice , with each face presenting a number between 1 to 6 . each sheet of the tally notepad is preprinted with the player number and the color of dice for the respective players . the numbers 1 to 6 are listed below the title of each player , representing each possible dice roll . a round constitutes one series of dice rolling by every participating player . a set constitutes a series of rounds in which 10 tallies on each of the six numbers is obtained . each of the 4 sets begins with determining the order of each player by a dice roll . each player rolls one die once . the player with the higher dice roll precedes player ( s ) with lower dice rolls . the highest possible dice roll is 6 and the lowest possible is 1 . any tie dice roll should be resolved as follows : if two players roll the same number , they will position themselves among other players with their current tie value . thereafter these two players will roll the die once more to decide the order between them . the two players will then resume to the order where their original dice roll placed them . after the order among all players has been established , each player will roll two dice simultaneously . the roll of the two dice will be accounted as two individual numbers ( tally ). for example , a dice roll of 2 and 3 will be recorded with a tally mark next to the number 2 and number 3 , not the sum of the two numbers ( as shown in fig2 ). rule 1 : at the beginning of each individual set , the first player is awarded two turns in the first round of the set . rule 2 : if a player rolls a number that already has 10 tally marks , the player will lose a turn in the next round . the maximum amount of turns to be lost is 1 , even if the player rolls two numbers that already have 10 tallies . scenario 1 : player 1 already has 10 tally marks for the number 4 . if player 1 gets a dice roll of 2 and 4 , player 1 will add a tally mark to number 2 but not number 4 , and will lose a turn in the next round . scenario 2 : player 1 already has 10 tally marks for the number 4 and rolls two 4 &# 39 ; s . he will not add any tally marks to the number 4 and will lose a turn in the next round . ( optional ) rule 2 : if a player rolls a number that already has 10 tally marks , the player will lose a turn in the next round . if two numbers are rolled that already have ten tally marks then the player will lose his or her turn in the next two rounds . scenario 1 : player 1 already has 10 tally marks for the number 4 . if player 1 gets a dice roll of 2 and 4 , player 1 will add a tally mark to number 2 but not number 4 , and will lose a turn in the next round . scenario 2 : player 1 already has 10 tally marks for the number 4 and rolls two 4 &# 39 ; s . he will not add any tally marks to the number 4 and will lose a turn in the next two rounds . rule 3 : the player who rolls after a player has lost a turn will get an additional roll , even if it carries over into the next round . scenario 1 : player 1 has 10 tally marks for the number 4 . player 1 gets a dice roll of 2 and 4 . player 2 , who rolls after player 1 , will therefore get an extra roll in this round . scenario 2 : player 4 has 10 tally marks for the number 4 . player 4 gets a dice roll of 2 and 4 . player 4 therefore will lose a turn in the next round , and player 1 who begins the new round will gain an extra roll . rule 4 : if a player , who has gained an extra roll , rolls a number that already has 10 tally marks , that player will lose his or her extra roll and his or her turn in the next round . scenario : player 2 has been awarded an extra roll because player 1 has lost a turn . player 2 has 10 tally marks for the number 4 . on the first roll , player 2 gets a dice roll of 2 and 4 . player 2 will add a tally mark to the number 2 , but will lose the extra roll and a turn in the next round . rule 5 : if a player rolls a number that already has 10 tally marks on their extra turn , that player will lose a turn in the next round . scenario : player 2 has been awarded an extra roll because player 1 has lost a turn . player 2 has 10 tally marks for the number 4 . on the first roll , player 2 gets a dice roll of 2 and 6 . player 2 will add a tally mark to the numbers 2 and 6 . on the extra roll , player 2 rolls a 2 and a 4 . player 2 will add tally to the number 2 but will lose a turn in the next round . the foregoing describes the preferred embodiments of the invention . modifications may be made without departing from the spirit and scope of the invention as set forth in the following claims .

US-44597803-A

this invention relates to a biopsy device consisting of an inner cannula and an outer hollow tube , a handle which may be removably attached to the outer hollow tube , a locking system to secure the inner cannula and / or the attenuator in the outer hollow tube , and characterized in that the tip of the outer hollow tube is ellipse shaped and extends beyond the inner cannula , the latter ending in a blunt edge . the blunted tip of the outer hollow tube together with the sharpened ending of the inner cannula determines the cutting edge of the device . in combination the distal ends of inner cannula and outer hollow tube determine the biopsy depth size and shape of the biopsy sample in a reproducible way . in one embodiment of the present invention , the length of the inner cannula can be controlled , allowing varying the aforementioned sample parameters as desired .

the biopsy device of the present invention solves the problems associated with the aforementioned prior art devices in that it provides : 1 ) the ability to control and select the biopsy length ( shape and size ) in relation to the defect size ; 2 ) the ability to standardized biopsy harvesting at all locations in the knee joint , with in particular the lateral and medial intercondylar notch ; 3 ) the ability to avoid osteochondral defects for reasons of patient safety and product contamination with non - chondrogenic cells ; 4 ) a cartilage insertion into the biopsy needle with minimal tissue damage ; 5 ) a capturing chamber for the biopsy sample to minimize risk of loss ; 6 ) a measurable and visible positioning of the device ; 7 ) a user - friendly and safe use ; 8 ) a single - use to reduce the risk of contamination and / or infection and to maintain its sharpness . the invention relates to a biopsy device as shown in fig2 a , 2 b , 7 , 8 a , 8 b , 9 b , 12 and 13 comprising an inner cannula ( 4 ) and an outer hollow tube ( 1 ), a handle ( 7 ) which can be removably attached to the outer hollow tube , a locking system ( 14 ) to close the handle when in use and to secure the inner cannula or the attenuator ( 15 ), optionally having a handle ( 20 ), in the biopsy device , and characterized in that the tip ( 2 ) of the outer hollow tube is ellipse shaped and extends beyond the inner cannula ( fig3 ), the latter having a cutting edge ( 5 ), such as for example a truncated cone or truncated pyramid ( fig6 ). the biopsy device of the present invention is particularly well suited for autologous chondrocyte implantation ( aci ) treatment or any other biopsy scraping technique . as such , the present invention provides a system for a biopsy device comprising an inner cannula having a cutting edge , such as a truncated cone or a truncated pyramid and an outer hollow tube extending beyond said inner cannula , said outer hollow tube having an ellipse shaped cutting edge . as used herein , the inner cannula and outer hollow tube consist of needles that are typically made of metal , e . g . stainless steel or a non - ferrite metal . it is preferred that the inner cannula and outer hollow tube as a whole are provided out of stainless steel or other rust - free metal , e . g . medical grade stainless steel . fig4 shows an embodiment of the outer hollow tube according to the invention . the outer hollow tube ( 1 ) is between and about 15 . 0 to 20 . 0 cm long , in particular about 17 . 0 cm , measured between the tip of the outer hollow tube and the handle . the outer hollow tube has an outer diameter of about and between 4 . 0 - 6 . 0 mm and in inner diameter of about and between 3 . 0 - 5 . 0 mm . in a particular example , the outer needle has an outer diameter of about 5 . 0 mm and in inner diameter of about 4 . 0 mm . optionally the outer hollow tube comprises at the outer surface a grading system ( 9 ) to measure the advancement of the device during harvesting . in a particular embodiment a laser - marking is applied every 10 mm ( fig5 ). the extended ellipse shaped tip ( 2 ) of the outer hollow tube ( 1 ) is further characterized in that it is blunt at the most distal end ( 3 ) and has a bevel angle of about 10 - 30 °, in particular 15 ° or 20 ° ( 19 ). this tip ( 3 ) of the outer hollow tube , together with the sharpened edge ( 6 ) of the inner cannula will compose the cutting edge ( 3 , 5 ) of the device ( see fig4 and 6 ). as such , these elements will determine the biopsy depth , size and shape of the biopsy samples . the tip of the outer hollow tube assists in the correct positioning of the device at the site of harvesting . it is accordingly important that the tip of the outer hollow tube is shaped with high precision such that the outer beveled surface ( 10 ) has a higher angle than the inner surface at its distal end . the angle of the outer beveled surface is suitably 115 ° but may vary from about 100 ° to 120 °, and is in particular 117 °. fig6 shows an embodiment of the inner cannula ( 4 ) according to the invention . like for the blunt tip of the outer hollow tube , the angle of the outer beveled surface ( 11 ) at the cutting edge of the inner cannula ( needle ) is suitably 20 ° but may vary from about 17 to 25 °. the angle of the inner beveled surface ( 13 ) of the inner cannula ( needle ) is suitably 5 °, but may vary from about 3 to 8 °. as such the cone / pyramidal part of the inner cannula ( needle ) ( 13 ) has a bevel angle of about 3 - 8 °, and is in particular 5 °. the position of the cutting edge of the inner cannula together with the tip of the outer hollow tube , determines the cutting depth of the biopsy device . when the tip ( cutting edge ) of the inner cannula is more retracted when compared to the tip of the outer hollow needle , the cutting depth will decrease . when the tip ( cutting edge ) of the inner cannula is more advanced , the cutting edge will increase . in the particular aci application of the present invention , the inner cannula is proximally fixed at between and about 3 . 0 to 5 . 0 mm from the most distal tip of the outer hollow needle , more in particular at about 3 . 4 or 4 . 0 mm . in said embodiment the cutting depth is between and about 2 . 0 to 2 . 5 mm ; in particular about 2 . 4 mm thick . in one embodiment of the present invention , such as for example shown in fig7 , 8 a and 8 b , 9 a , 9 b , 9 c and 13 , the back end of the device will have a locking system ( 14 ) for positioning and fixing the inner cannula and / or the attenuator ( 15 ) in respect to the outer hollow tube and to close the handle when in use . depending on the design of the locking system , the device may further contain a fixation pin ( 21 ) and / or a screw ( 22 ) for positioning and / or attaching the locking system ( 14 ) onto the device , as shown in fig1 . preferably , in this embodiment , and as for example shown in fig8 b , 10 and 11 , the inner cannula and outer hollow tube form an integrated part with one another , i . e . consist of a single piece . in an alternative and further embodiment of the present invention the inner cannula is controllably positioned within the device , such that the length of the inner cannula within the outer hollow tube can be adjusted as desired but never extends beyond the most distal tip of the outer hollow tube . through adjustment , such as for example by means of a turning knob , of the position of the tip of the inner cannula , the cutting depth can range between and about 1 . 0 to 4 . 0 mm , and is typically between and about 1 . 2 to 2 . 8 mm thick , in a particular embodiment 2 . 1 mm ( fig7 ). the outer diameter of the inner cannula ( needle ) ( 4 ) should be such that it closely fits the inner surface of the outer hollow tube . it will accordingly range between and about 4 . 0 to 6 . 0 mm , and in particular has an outer diameter of about 4 . 0 mm . the inner diameter of the inner cannula ( needle ) ranges between and about 3 . 0 to 5 . 0 mm , and in particular has an inner diameter of about 3 . 0 mm . as the biopsy samples are captured inside the inner cannula ( needle ), an opening ( 8 ) ( fig9 a , 9 b ) needs to be at the top of said cannula ( needle ) to allow pressure release ( so that there is minimal pressure on the biopsy material in the tube ) during the harvesting procedure , and to allow recovery of the collected samples after harvesting . this opening is typically an integrated part of the handle at the proximal end of the inner cannula ( needle ). in a particular embodiment the handle provides a valve for pressure release from the inner cannula ( needle ). fig8 b illustrates an embodiment of a biopsy device according to the invention providing a valve ( 18 ) applied to the handle ( fig8 c for detail ). in a further embodiment , the handle provides a perforated indentation ( 17 ) to control pressure release from the inner cannula ( needle ) with the fingertip of the manipulator . at said back end of the device a locking system ( 14 ) is provided on the one hand and as explained hereinbefore , to secure the inner cannula ( 4 ) or attenuator ( 15 ) in the biopsy device when entering the device into the body ; and on the other hand to close the handle when in use . any art known locking system to lock a cannula in a tube can be used . examples of an inner cannula knob that fits in the outer hollow tube handle , are provided in fig8 a , 9 a , 9 b , 9 c and 13 . the handle ( 7 ) of the device is designed to fit ergonomically into the hand . in one embodiment , as shown in fig2 a , the round side is to be placed into the palm of the hand so that the flat sides are embraced with the fingers and the thumb . in another embodiment of fig2 b , the handle has a flatter shape , and may comprise a perforated indentation ( 17 ) to allow pressure release ( so that there is minimal pressure on the biopsy material in the tube ) during the harvesting procedure . the material should be such that it feels warm and comfortably in the hand . also and preferably the material should be able to resist steam temperatures during sterilization . the sterilizable material is preferably made of a plastic material , for example a polycarbonate or a polyacetal such as ertacetal . the present invention further provides a method for performing a biopsy , comprising the following steps : a ) positioning an attenuator within or cap on the biopsy device of the present invention ; b ) entering the biopsy device into the body ; c ) positioning the tip of the biopsy device to the sampling surface ; d ) removing the attenuator or cap from the biopsy device and optionally replacing the attenuator with the inner cannula ; e ) sliding the tip of the outer hollow tube over the sampling surface to cut the biopsy sample with the tip of the inner cannula ; f ) harvesting the biopsy sample within the inner cannula , while releasing pressure from said inner cannula ; g ) retracting the biopsy device from the body ; and h ) opening the biopsy device at the back to push the biopsy samples out of the biopsy device . it will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrated embodiments and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof . the present embodiments are therefore to be considered in all respects as illustrative and not restrictive , the scope of the invention being indicated by the appended claims rather than by 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-201013201686-A

the invention relates to a method and an apparatus for spatially displaying a region to be examined of an examination object , which has an x - ray emitter which can be rotated about the examination object in order to generate an x - ray beams and an x - ray detector which can be rotated about the examination object in order to record a part of the x - ray beam penetrating the examination object , with a facility having an opening for fading - in a split beam being arranged at a distance from the x - ray emitter . by being able to adjust the opening and / or the distance of the fade - in facility , a method and an apparatus can be provided , with which the radiation exposure for an examination object is reduced .

fig1 shows a device for spatially displaying a region b to be examined of an examination object in the form of an angiography apparatus 10 . the angiography apparatus 10 features an x - ray recording facility 11 , which comprises an x - ray emitter 20 , in which an x - ray source 21 is permanently arranged . an x - ray detector 22 is arranged opposite the x - ray emitter 20 , said x - ray detector 22 detecting an x - ray beam arriving at the x - ray detector 22 . the x - ray emitter 20 and the x - ray detector 22 cannot be moved relative to one another . however , the recording facility 11 is mounted in a rotatable manner about an examination object u which can be positioned on a support 60 , said examination object u being arranged between the x - ray emitter 20 and the x - ray detector 22 . the x - ray source 21 generates an x - ray beam x , which is essentially radiated in the direction of an x - ray detector 22 , and comprises a beam centerline s x . if an examination object u is arranged on the support 60 between the x - ray emitter 20 and the x - ray detector 22 , the examination object u is x - rayed by an x - ray beam x when the x - ray source 21 is operating . the arrangement of the x - ray emitter 20 and the x - ray detector 22 can be designed here in a different manner , e . g . as an upper table system , as shown in fig1 , or also as a lower table system ( not shown ). the recording facility 11 comprises a fade - in facility 30 , which is arranged between the examination object u and the x - ray source 21 . the fade - in facility 30 serves to fade the x - ray beam x generated by the x - ray source 21 into a split beam x ′. to this end , the fade - in facility 30 features an aperture 31 s , which is designed as a slit . the fade - in facility 30 is essentially manufactured from x - ray - absorbent material , in this case lead . the slit 31 s features a slit width b , which can be adjusted by means of regulating means in the form of diaphragm elements ( not shown ). in addition , the slit features a slit length which does not however restrict the expansion of the x - ray beam x emitted by the x - ray source 21 , said expansion being predetermined by a beam limiting surface . a distance d is provided between the x - ray source 21 and the fade - in facility 30 . this distance d of the slit 31 s from the x - ray source 21 can be adjusted here by means of a telescope arm 40 . the adjustment of the distance d and the slit width b can be carried out manually or automatically . the slit 31 s is arranged between the x - ray source 21 and the examination object u such that the beam centerline s x passes through the slit 31 s in a point symmetrical manner . the x - ray beam x emitted by the x - ray source 21 is faded - in through the gap 31 s in a wedge - shaped fashion onto a split beam x ′. a configuration featuring two essentially flat partial areas ∂ x ′ restricting the x - ray beam is caused by fading - in the x - ray beam x onto the split beam x ′. these partial areas ∂ x ′ of the beam limiting surface are inclined towards one another . the adjustments of the fade - in facility 30 , which comprise the distance d and the slit width b , are adjusted such that the partial areas ∂ x ′ of the beam limiting surfaces rest closely against the region b to be examined . in the present case , a human stomach b of a child u is to be examined . to keep the radiation exposure for the child u as minimal as possible , the x - ray emitter 20 is arranged above the child u positioned on the support such that the smallest possible slit width b of the fade - in facility 30 can be selected , in order to allow both partial areas ∂ x ′, of the beam limiting surfaces to rest closely against the stomach b . the slit width b of the fade - in facility 30 can also be selected with regard to the age , size and stature of the child u . a data processing system 52 is used to create a spatial display of the stomach b of the child u . the plurality of two - dimensional projection data sets of the stomach b recorded by means of the faded - in split beam x ′ is fed to the data processing unit 52 and is stored there . a spatial representation of the stomach b is determined from the plurality of two - dimensional projection data sets , by means of a reconstruction method , said spatial display being shown on an input / output unit 53 . the fade - in facility 30 can be adjusted by way of regulating means , in this instance a drive facility 51 . the adjustment encompasses the slit width b of the fade - in facility 30 as well as its distance from the x - ray source 21 . the size of these parameters can be predefined by way of an input / output unit 53 . this can be carried out by directly inputting values , or instead by marking the region to be examined on a patient model output to the input / output device 53 and present in the data processing system 52 . by marking the region b to be examined on the patient model , the fade - in facility 30 is adjusted by the control facility 50 in conjunction with the regulating means 51 such that the partial areas ∂ x ′ of the beam limiting surface of the x - ray beam x ′ rest closely against the region b to be examined . while recording the two - dimensional projection data sets , the x - ray emitter 20 and the x - ray detector 22 facing the x - ray emitter 20 are rotated about the region b to be examined . while rotating about the stomach b , projection data sets of stomach b are recorded at specific time intervals . the projection direction of the projection data sets determined by the beam centerline s x of the faded - in x - ray split beam x ′ lies in one of the examination planes ex penetrating the stomach b , said examination plane being vertical to the sheet plane in fig1 and the vertical projection of which coincides on the sheet plane with the beam centerline s x indicated in fig1 . the beam centerline s x of the recorded projection data sets form concurrent lines with a common point . the common point is in this way identical to an examination center z x . the examination center z x is intersected by all beam centerlines s x of the faded - in x - ray split beam x ′ when the recording facility 11 is rotated about the examination object u . expediently , the examination center z x lies in the center of the region b to be examined , i . e . in this case in the central point of the stomach . this ensures the best possible imaging of the region b to be examined in the projection data set and thus in the spatial display to be determined . fig2 shows a front view of the recording facility 11 illustrated schematically in fig1 . the x - ray emitter 20 with the x - ray source 21 is connected to the x - ray detector 22 with a c - arm 23 . the c - arm 23 is affixed to a stand ( not shown ). to enable a controlled rotation of the x - ray emitter 20 and the x - ray detector 20 about the examination object u by means of the control device 50 illustrated in fig1 , a drive facility 24 , which is designed as an orbital drive system 24 , is provided . the orbital drive system 24 rotates the recording facility 11 at an angular speed ω about the examination object u . the rotation of the recording facility 11 comprises two top dead centers , between which the recording facility 11 is rotated . furthermore , fig2 illustrates that with the fade - in facility 30 designed as a slit 31 s , the whole width of the child is x - rayed using the faded - in split beam x ′, which features the same spatial dimensions in this direction as the x - ray beam x . a layer of the child u is thus radiated . by using an adjustable aperture 31 r designed as a rectangle , see fig3 , the beam limiting surface shown in fig2 can also be adjusted in the direction of the region b to be examined such that this beam limiting surface also closely surrounds the stomach b , thereby not x - raying the whole width of the child u . fig3 shows a fade - in facility 30 , comprising different adjustable apertures . in particular , in addition to a slit 31 s , the fade - in facility 30 comprises an adjustable rectangular aperture 31 r , a circular aperture 31 k which can be adjusted using an iris diaphragm ( not shown ) as well as an ellipsoid , adjustable aperture 31 e . as a function of the shape and size of the region b to be examined of the examination object u , a corresponding diaphragm can be selected and adjusted to the region to be examined . the dashed and drawn - through markers for the respective apertures 31 s or 31 r or 31 e or 31 k within the fade - in facility 30 show two of several possible control positions of the respective apertures 31 s or 31 r or 31 e or 31 k . a fade - in facility 30 of this type does not require a manual exchange of diaphragms with associated apertures . a drive facility , for instance the drive facility 51 mentioned in fig1 , allows the apertures 31 s or 31 r or 31 e or 31 k arranged on the fade - in facility 30 to be moved and adjusted in the radiation path of the emitted x - ray x , see fig1 , such that the diaphragm elements restricting the x - ray beam x generate a beam limiting surface ∂ x ′, see fig1 , which closely surrounds the region b to be examined , see fig1 .

US-70442507-A

the present invention relates to an apparatus for fitting the protecting femoral neck device . the said apparatus includes a clamping base . a fixation element whose circumference size can be adjusted according to the size of the femoral neck is mounted on an end of the said clamping base and a locating element is mounted on the other end of the said clamping base . an element for shaping the bone can be fixed on the said locating element .

please refer to fig1 and 2 for an apparatus for fitting a protecting femoral neck device according to the present invention . the apparatus comprises a clamping base 10 , and the clamping base 10 has a fixation element 20 , and the fixation element 20 is in a tapered shape and comprised of two symmetrical semicircular rings 21 , and the semicircular rings 21 has an upwardly extending flange 211 disposed at an inwardly contracted end , and a pivotal member 22 for movably coupled the semicircular rings 21 is disposed at one end of the flanges 211 , and thus the connection of the semicircular rings 21 by the pivotal member 22 can couple the semicircular rings as well as providing the opening and closing functions . further , an embedding body 23 and a corresponding serrated bar 24 are disposed on the surface of an edge at the other end of the semicircular rings 21 ; wherein the serrated bar 24 is comprised of a plurality of equidistant serrations 241 , so that the embedding body 23 can be embedded into one of the serrations 241 of the serrated bar 24 according to the size of the femoral neck when the apparatus is in use . then , the fixation element 2 can be mounted closely to the femoral neck and cannot be rotated freely as shown in fig4 . further , one of the semicircular rings 21 of the fixation element 20 is pivotally coupled with a movable support rod 31 at a predetermined position , and the support rod 31 is coupled with a pivotal base 212 of the semicircular ring 21 by the insertion of an insert pin only , so that the support rod 31 can be inclined to an angle to be fixed onto the fixation element 20 and also moved outward . the support rod 31 has a locating element 30 on the other end corresponding to the fixation element 20 , and the locating element 30 is a cup structure for this embodiment . the locating element 30 comprises an indented plane 32 , an open groove 33 disposed on the indented plane 32 , an embedded groove 321 disposed on the periphery of the indented plane 32 , a locating member 34 disposed on plane 32 and attached onto the embedded groove 321 , and a through hole disposed on the locating member 34 corresponding to the open groove 33 as shown in fig5 . please refer to fig7 and 9 . the clamping base comprises a broach 40 , a support rod 41 disposed on the broach 40 , a locating member 44 disposed on the support rod 41 , a rotary base 42 coupled to an end of the support rod 41 , a sleeve 43 disposed on the other end of the support rod 41 , and a serration 431 disposed at the periphery of an open end of the sleeve 43 . please refer to fig3 to 10 for using . the connected ends of the semicircular rings 21 of the fixation element 20 are opened first as shown in fig3 , and the fixation element 2 is sheathed onto the femoral neck , and the embedded body 23 on one semicircular ring 21 is latched into the serration 241 of the serrated bar 24 of another semicircular ring 21 according to the size of the injured femur , so that the fixation element 20 can be secured onto the femur as shown in fig4 , and then the locating member 34 is embedded on the locating element 30 as shown in fig5 . a boring head 50 passes through a through hole 341 and implanted deeply into the surface of the femur , so that the boring head 50 can rotate at a fixed position under the limitation of the through hole 341 and drill a hole at the center of the femur to a predetermined depth as shown in fig6 . later , the boring head 50 is withdrawn from the femur to move the locating element 30 outward as shown in fig7 and the sleeve 43 of the broach 41 connects to the periphery of the femoral neck , and the locating element 30 returns to its original position to move the locating member 44 on the support rod 42 to a position corresponding to the locating element 30 . in the meantime , the locating member 44 embedded in the plane 32 of the locating element 30 , so that the broach 40 can used the center of the locating element 30 for carrying out the grinding and rotate the sleeve 43 under the limitation of the open groove 33 of the locating element 30 . as a result , the serrations 431 at the sleeve 43 disposed on the periphery of femur cut and grind the femur into a required shape as shown in fig8 . then , the clamping base 10 and the broach 40 are removed from the femur as shown in fig9 to allow the surgeon to fit the protecting femoral neck device 60 onto the femur as shown in fig1 . the present invention has the simple - to - use and easy - to - install functions . in summation of the description above , the present invention overcomes the shortcomings of the prior - art and enhances the performance than the conventional structure and further complies with the patent application requirements and is submitted to the patent office for review and granting of the commensurate patent rights . while the invention has been described by way of example and in terms of a preferred embodiment , it is to be understood that the invention is not limited thereto . to the contrary , it is intended to cover various modifications and similar arrangements and procedures , and the scope of the appended claims therefore should be accorded the broadest interpretation so as to encompass all such modifications and similar arrangements .

US-49964104-A

a secondary dispenser readily attachable to a standard toilet - tissue dispenser of a roll type for positioning next to the primary toilet - tissue dispenser for dispensing supplemental materials such as pre - wetted toilet sheets . the sheets can be withdrawn from an open door . a compact auxiliary device providing wetted or self - wetting sheets for releasable proximate mounting in conjunction with a conventional toilet - tissue dispenser of dry sheets ; comprises an inexpensive container or magazine component pre - loaded with the supplemental sheets . the magazine can be snapped into functional position rapidly . it serves an improved health care and cleanliness function .

detailed descriptions of one or more preferred embodiments are provided herein . it is to be understood , however , that the present invention may be embodied in various forms . therefore , specific details disclosed herein are not to be interpreted as limiting , but rather as a basis for the claims and as a representative basis for teaching one skilled in the art to employ the present invention in any appropriate system , structure or manner . referring to the figures in general , in one embodiment is provided a supplementary dispenser 10 is provided for storing and dispensing folded tissue sheets 250 from a toilet paper dispenser 100 , the supplemental dispenser 10 having extending and retracting support arms 400 , 500 , a container 200 , and an interior volume 210 . fig2 is a side view of supplemental dispenser 200 with folding arms 400 , 500 attached to and hanging from a spindle 150 of a toilet paper dispenser 100 , and a positioning bracket 300 being opened ( indicated by angle 322 ) to place the dispenser container 200 in a non vertical position relative to the wall as schematically indicated by angle 34 . positioning bracket 320 can be pivotally connected to container 200 . container 200 can include recess 310 to that , when closed , positioning bracket 320 is substantially if not completely recessed relative to bottom 300 of container . fig3 is a perspective view of conventional toilet paper dispenser 100 with supplemental dispenser 10 attached to the spindle 150 , where the supplemental dispenser 10 has been rotated to a non - vertical position and the door 220 opened . in one embodiment supplemental dispenser 10 can be provided for dispensing pre - moistened or dry tissue sheets 250 from a container housing 200 . in one embodiment , various types of sheets 250 can be dispensed from supplemental dispenser 10 , such as dry or pre - moistened tissues . in one embodiment , supplemental dispenser 10 can dispense individual stacked interfolded sheets — either dry or pre - moistened . such stacked configurations for dry or pre - moistened sheets are well known to those of ordinary skill in the art . referring particularly to the figures , container housing 200 can have has a configuration with a width and a depth to contain conventionally available pre - moistened wipes . container housing 200 can include an interior volume 210 in which the tissue sheets 250 are stored and dispensed from . container housing 200 may take on any shape or configuration , and the rectangular box - type configuration shown in the figures is for illustrative purposes only . top 205 of container 200 can include dispensing opening 208 ( to interior volume 210 ) which can be sealed / closed by door 220 . in different embodiments dispensing opening 208 may be included on any side of container housing 200 . for example , in the illustrated embodiment , the dispensing opening 208 is shown on the top 205 . in various embodiments dispensing opening 208 may take on any suitable shape or configuration . the container housing 200 may be formed of any conventional material , and may be a relatively inexpensive plastic disposable material , paperboard material , paper , cardboard , and the like . it may be desired to form the container housing 200 of a liquid impermeable material if it is desired to contain and dispense premoistened tissue sheets 250 . in one embodiment , container housing 250 may be formed of any type of material , including a liquid absorbent , and the pre - moistened tissue sheets 250 may be encased in a liquid impermeable film . alternatively , interior volume 210 may be lined with the film . the premoistened sheets 250 may be provided in a refill package or cartridge that may be placed into the interior volume 210 , the refill package including the liquid impermeable film . in this configuration , the container 200 can have a resealable wall , lid , or other member that may be opened to allow a refill cartridge of tissues to be inserted into the interior volume 210 . it may further be desired that interior volume 210 include a door 220 over a dispensing opening 208 . in the case of pre - moistened sheets 250 , door 220 may be hinged with hinge 224 and when door 220 is closed , it prevents significant loss of moisture from sheets 250 and prevents undesired drying out . in one embodiment door can be snap closed on top 205 with lock 226 . in on embodiment door 220 can be frictionally locked with a rim of opening 208 . in one embodiment supplemental dispenser 10 can be supported on toilet paper dispenser 100 by a plurality of arms 400 , 500 . in one embodiment the support arms 400 , 500 can be foldably connected to container 200 by hinges 402 , 502 . in one embodiment supplemental dispenser 10 can be attached to a conventionally available toilet paper dispenser 100 having a roll of toilet paper 170 . such fixtures 100 are well known and a typical fixture 100 is shown in fig1 through 3 , with a frame 110 , support arms 120 , and recesses 130 , along with a telescoping spindle 150 . each of the support arms 120 typically includes a recess 130 . a conventional spindle 150 having tabs 160 on each end is typically inserted through a hollow core of a roll of toilet paper 170 ( not shown ) and received in the recesses 130 . fig1 is a perspective view of an alternative version of a supplemental dispenser 200 ′ with folding / pivoting arms 400 , 500 which arms are also telescopically extendable ( respectively via telescoping sections 470 , 570 ) to vary the depth from which the dispenser will hang vertically from a spindle 150 of a toilet paper dispenser 100 . fig2 is a schematic view of one of the arms 500 shown in fig1 taken from the external side of the arm 500 . fig2 is a side view of arm 500 taken from the internal side , where arm 500 is in a retracted position ( with telescoping section 570 in its lowermost position ) and locked in place in such retracted position ( via locking button 574 locking into the lowermost opening of plurality of openings 568 ), and schematically the length of such upper portion is indicated as l 1 . fig2 is a side view of arm 500 taken from the internal side , where telescoping section 570 arm is in an extended position and locked in place in such extended position ( via locking button 574 locking into the uppermost opening of plurality of openings 568 ), and schematically the length of such upper portion is indicated as l 2 where l 2 is larger than l 1 . any intermediate telescoping position for telescoping section 570 can be selected via locking button 574 into one of the intermediate openings of plurality of openings where the length of such upper section will be between l 1 and l 2 . arm 400 can be constructed substantially similar to arm 500 . fig2 is a top view of arm 400 , where telescoping section 470 arm is in a retracted position and locked in place in such retracted position ( via locking button 474 locking into the lowermost opening of plurality of openings 468 ). arrow 490 schematically indicates that locking button 474 can be pushed in to unlock arm and move to another position . fig2 is an internal side view of the telescoping section 470 of arm 400 , and fig2 is a perspective view of the telescoping section 470 . telescoping section 470 can include second end 476 , locking button 474 , and stopping tables 478 . locking button 474 can be biased outside of telescoping section via biased section 480 . fig2 is a side view of the alternative supplemental dispenser 200 ′ with folding arms 400 , 500 attached to and hanging vertically from a spindle 150 of a toilet paper dispenser 100 . gap 30 indicates the distance between dispenser bottom 30 and wall 20 . the distance of the upper section of container 200 to the bottom of the roll of toilet paper 170 can be varied by changing the amount of telescoping ( e . g ., l 1 , l 2 , or some other length ) of the two telescoping sections 470 and 570 . fig2 is a side view of alternative supplemental dispenser 200 ′ with folding arms 400 , 500 attached to and hanging from a spindle 150 of a toilet paper dispenser 100 , and a positioning arm / spacer 350 being attached to place the dispenser container 200 ′ in a non vertical position relative to the wall as schematically indicated by angle 34 . positioning arm 350 can be threaded to container 200 ′ all measurements disclosed herein are at standard temperature and pressure , at sea level on earth , unless indicated otherwise . all materials used or intended to be used in a human being are biocompatible , unless indicated otherwise . it will be understood that each of the elements described above , or two or more together may also find a useful application in other types of methods differing from the type described above . 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 prior art , fairly constitute essential characteristics of the generic or specific aspects of this invention set forth in the appended claims . the foregoing embodiments are presented by way of example only ; the scope of the present invention is to be limited only by the following claims .

US-201615391054-A

the present invention proposes a domestic appliance and specifically an electrical household appliance for preparing turkish coffee by way of using encapsulated turkish coffee packets . the apparatus comprises a main housing having an inner receptacle part and a removable coffee pot receiving coffee to be prepared . said removable coffee pot is in electrical communication with a housing extension part comprising control electronics and electrical heating means . temperature change data in said removable coffee pot is monitored to determine boiling point and transferred heat energy is then reduced in a timely manner whereby overflowing of the content is

the following numerals are assigned to different parts demonstrated in the drawings : 1 main housing 2 main housing base 3 main housing top surface 4 main housing extended portion 5 water receptacle 6 water receptacle top portion 7 water receptacle cover 8 coffee pot 9 coffee pot base 10 coffee pot handle 11 coffee pot outer surface 12 thick film 13 thick film sealing means 14 ntc sensor 15 thermic switch 16 connector 17 position switch 18 capsule housing cover 19 operating button 20 visual indicators 21 pump 22 conduit 23 nozzle 24 water receptacle slot 25 electronic control unit 26 transformator 27 on / off switch 28 cable connector 29 mains cord 30 cover unlocking button 31 capsule 32 capsule housing 33 perforator adaptor 34 capsule perforating water outlet referring now to the figures outlined above , the present invention proposes an electrical household appliance for preparing turkish coffee by way of using encapsulated turkish coffee packets . a main housing ( 1 ) having a base ( 2 ) and a top surface ( 3 ) is provided with an electrical connection cord ( 29 ) as seen in the enclosed figures . the apparatus comprises a main housing ( 1 ) with a water receptacle ( 5 ) therein receiving water to be served into a removable coffee pot ( 8 ) placeable on a coffee pot base ( 9 ) integral to said main housing ( 1 ). said base ( 9 ) comprises an electrical connector ( 16 ) for effecting power transfer to a thick film ( 12 ) base . the apparatus further comprises an extended portion ( 4 ) of the main housing , said portion extending over said coffee pot &# 39 ; s ( 8 ) upper portion . said water receptacle ( 5 ) also has an openable cover ( 7 ) over a top portion ( 6 ) thereof . said coffee pot ( 8 ) typically has a handle ( 10 ). said turkish coffee preparation apparatus according to the present invention comprises a heating element ( 12 ) in the form of a thick film ( 12 ), which has the known advantage of instant heating and cooling , i . e . operating without accumulating heat energy to be radiated after switching off . this might be inconvenient since accumulated heat energy could initiate overflowing of the coffee ingredients even after deenergization of said heating element ( 12 ). thick film heaters are commercially available in the market under different trade names . the present invention further features a turkish coffee capsule housing ( 32 ) for accommodating encapsulated turkish coffee packets , i . e . capsules ( 31 ). this arrangement provides that a capsule ( 31 ) accommodated as such is perforated by a perforator ( 34 ) longitudinally extending within a water outlet designated as the perforator adaptor ( 33 ) according to the invention , said perforator ( 34 ) designed as integral to a capsule housing cover ( 18 ). perforation process provides that water transferred from said water receptacle ( 5 ) directly reaches said capsule as said perforator ( 34 ) is provided coaxially within said water outlet . said capsule housing cover ( 18 ) is not freely openable but opening thereof is effected by way of pushing a front button , designated as the cover unkicking button ( 30 ). to this end , the apparatus of the invention functions as follows : water is added to said water receptacle ( 5 ) and a turkish coffee capsule ( 31 ) is placed in the respective housing ( 32 ). said removable coffee pot ( 8 ) is also optionally filled with sugar in the desired amount . upon switching on of the apparatus by the respective on / off button ( 27 ), said thick film ( 12 ) is energized and a certain amount of water as preset by the user is transferred to said coffee pot ( 8 ) with the help of a pump ( 21 ) and a conduit ( 22 ) in this effect . transfer of water form said water receptacle ( 5 ) to said coffee pot ( 8 ) can also be effected without a pump ( 21 ) but with siphoning action through a bidirectional valve , i . e . by the pressure from the expanded steam . in this case , a heating arrangement is implemented to heat water in said receptacle ( 5 ). power transfer to said thick film ( 12 ) is interrupted at a certain temperature around a preset boiling temperature . temperature in the coffee pot is monitored by means of a sensor in the form of a ntc thermistor ( 14 ) in electrical communication with an electronic control unit ( 25 ). the ntc sensor ( 14 ) used herein is a negative temperature coefficient thermistor element , wherein resistance of the sensor decreases as the temperature increases . temperature values detected by means of the ntc sensor ( 14 ) are sent to the electronic control unit ( 25 ) and said electronic unit ( 25 ) enables keeping temperature of the coffee ingredients within the coffee pot ( 8 ) at values lower than said preset boiling temperature . a thermal switch ( 15 ) functions to disconnect the coffee pot ( 8 ) from the mains power upon detection of excess heat generated by the heating element ( 12 ) when coffee liquid within the coffee pot ( 8 ) runs out for any reason ; thus , preventing damage to the surrounding area and to the device by effecting termination of the heating process . it is worthy of note that temperature monitoring in the apparatus of the invention may be undertaken by other suitable sensors as practiced in the art and the ntc sensor ( 14 ) as such is not the only option but one within a plurality of equally effective alternatives . this same also applies to the bimetal thermal switch ( 15 ). the apparatus may conventionally comprise a user informative screen with visual indicators ( 20 ) and a control panel . in a nutshell , the present invention proposes a turkish coffee preparation apparatus comprising a main housing ( 1 ) having a water receptacle ( 5 ) for containing water . therefore , water at a certain amount for a certain number of cups to be served as determined by the user is transferred to said coffee pot ( 8 ) with the help of said pump ( 21 ) and said conduit ( 22 ). in the meantime , dry coffee ingredients provided in encapsulated form are mixed with water in said capsule housing ( 32 ) and cold coffee liquid is poured into said removable coffee pot ( 8 ). coffee liquid poured into said coffee pot ( 8 ) continually in small amounts is hence being homogenized in this process and then heated in said removable coffee pot to be ready for consumption . said removable coffee pot ( 8 ) placeable on said coffee pot base ( 9 ) that is integral to said main housing ( 1 ) receives coffee ingredients mixed with water as poured thereon from a nozzle ( 23 ). said main housing ( 1 ) with said extended portion ( 4 ) incorporating said nozzle ( 23 ) spray cold coffee liquid over said coffee pot ( 8 ), said portion ( 4 ) extending over said coffee pot &# 39 ; s ( 8 ) open upper portion . said removable coffee pot ( 8 ) being in electrical communication with the main housing ( 1 ) and comprising electrical heating means ( 12 ) therefore effects heating of the coffee liquid . said removable coffee pot ( 8 ) is electrically connected to said main housing ( 1 ) only when it is properly placed on said coffee pot base ( 9 ) to be electrically coupled with said connector ( 16 ) of said base ( 9 ). a position switch ( 17 ) communicates proper positioning of said coffee pot ( 8 ) to said electronic control unit ( 25 ). to this end , coffee liquid is heated by said electrical heating means ( 12 ) and heating process is monitored by said electronic control unit ( 25 ), which is in electrical communication with said ntc sensor ( 14 ).

US-201314443100-A

the present invention relates to an illuminating device for an operating microscope comprising two observation beam paths for a first observer and two observation beam paths for a second observer , having an illuminating system for providing two parallel illuminating beam paths and a deflecting device , for deflecting the parallel illuminating beam paths onto an object that is to be observed , the deflecting device comprising a first semitransparent deflector element which is associated with a first observation beam path of the first observer and a first observation beam path of the second observer , and a second semitransparent deflector element , which is associated with a second observation beam path of the first observer and a second observation beam path of the second observer , the first illuminating beam path acting exclusively on the first deflector element and the second illuminating beam path acting exclusively on the second deflector element .

in fig1 and 2 , a preferred embodiment of the illuminating device according to the invention , comprising a main objective 150 and , downstream thereof , a magnification system ( including the requisite tubes and eyepieces ) 160 of a microscope 300 , is generally designated 100 . the microscope 300 is an operating stereomicroscope which provides two observation beam paths 152 , 154 for a main surgeon and two further observation beam paths 156 , 158 for an assistant . the observation beam paths running in corresponding observation channels are represented in fig1 as circles and in fig2 by means of the observation axes 152 a , 154 a , 156 a , 158 a associated therewith . there is no need to go into detail about specific items of equipment ( such as e . g . lenses and zoom systems ) for providing four such observation channels within the scope of the present invention relating to an illuminating device . the illuminating device 100 according to the invention first of all has a light source 102 . two parallel illuminating beam paths 106 , 108 are generated by means of a beam splitter 104 ( diagrammatically shown in fig1 ), which may be configured as a köster prism , for example . as will be self - explanatory , these illuminating beam paths 106 , 108 may be regarded as light beams emanating from ( virtual ) light sources 106 a , 108 a . it is also possible to provide two ( actual ) light sources 106 a , 108 a instead of the light source 102 and beam splitter 104 . the use of fibre illuminating devices is also possible . the illuminating device 100 also comprises two deflector elements 118 , 120 as a deflector device . the first deflector element 118 , which the illuminating beam path 106 strikes first , is configured as a semitransparent element ( physical beam splitter ), particularly a semitransparent mirror . the second deflector element 120 that the illuminating beam path 108 strikes is of corresponding construction , for example again in the form of a semitransparent mirror . it is possible to construct areas of the deflector elements 118 , 120 , for example regions located outside or in the edge region of the observation beam paths , with a full mirror finish . it is also possible for example to construct small areas of the deflector elements in the centre of the observation beam paths , i . e . substantially within the region of the observation axes , with a full mirror finish . this measure allows the red reflex to be influenced , for example . the deflector elements 118 , 120 or their longitudinal axes which can be defined as the connecting lines between the observation axes of their associated observation beam paths , are oriented diagonally or at an angle of 45 ° to the main surgeon &# 39 ; s stereo base ( imaginary connecting line between the observation axes 152 a , 154 a of the main surgeon ) or the assistant &# 39 ; s stereo base ( imaginary connecting line between the observation axes 156 a , 158 a of the assistant ). the deflector elements are arranged in the immediate vicinity of the optical axis 151 of the main objective 150 and thus close to the observation axes 152 a , 154 a , 156 a , 158 a , and therefore provide a 0 ° or 2 ° illumination of the object 200 for each observation beam path . the illuminating device also comprises another deflector element 170 which is acted upon by another light source 172 . the deflector element 170 is arranged at a greater distance from the optical axis 151 of the main objective 150 and serves to provide a 6 ° illumination for the observation beam paths 152 , 154 , 156 , 158 , which is advantageous for increasing the contrast for users of the microscope . for operating techniques in which the red reflex is not required , it may be sufficient to use only the 6 ° illumination . the deflector element 170 is preferably configured as a fully mirrored reflector , and also arranged at an angle of 45 ° to the preferably horizontally extending additional illuminating beam path 174 . it is possible to combine the light sources 102 , 172 to form a single light source , and to produce the illuminating beam paths 106 , 108 , 174 by means of suitable beam splitter devices and / or light conducting systems ( fibre optics ). it is also possible to make the deflector element 170 semitransparent , so that an additional observation beam path 179 ( shown by dashed lines ) can be illuminated . a documentation device , for example , may be connected to this observation beam path 179 . for the observation beam path 179 , a 0 ° to 2 ° illumination is thus provided , for example , rendering the red reflex visible even within the scope of the documentation , as no light whatsoever has to be coupled out of the observation beam paths for the documentation . the core of the invention lies in the particular arrangement of the deflector elements 118 , 120 relative to the observation beam paths 152 , 154 of the main surgeon and 156 , 158 of the assistant : as can be seen from the figures , the first deflector element 118 is associated with the first observation beam path 154 of the main surgeon , and the first observation beam path 156 of the assistant . this means that the horizontal projection of the deflector element 118 , as shown in fig1 , at least partially overlaps the first observation beam path 154 of the main surgeon and the first observation beam path 156 of the assistant . this overlap can be selected as desired , while in particular a total overlap is also possible . the illuminating beam path 106 is partly deflected through 90 ° by the first deflector element 118 in the direction of the main objective 150 ( partial beam paths 106 ′), and partly transmitted without any deflection ( partial beam path 106 ″). the partial beam path 108 strikes the second deflector element 120 analogously , this second deflector element being associated with the second observation beam path 152 of the main surgeon and the second observation beam path 158 of the assistant . the second deflector element 120 is also of semitransparent construction . the partial beam path deflected through 90 ° in the direction of the main objective is designated 108 ′, and the transmitted partial beam path is designated 108 ″. the transmitted partial beam paths 106 ″, 108 ″ expediently strike a light trap 171 ( not shown in detail ) to minimise unwanted reflections . the illuminating system shown thus provides both the main surgeon and the assistant with an optimum red reflex , and achieves this with only two deflector elements 118 , 120 and preferably only one light source 102 . according to the embodiment shown in fig1 and 2 , the two deflector elements 118 , 120 are arranged at the same height relative to the optical axis 151 . the same is true of the additional deflector element 170 . this measure advantageously makes it possible to minimise the overall height of an operating microscope equipped with the illuminating device according to the invention . it is also possible to mount the deflector elements 118 , 120 in an offset position relative to the optical axis 151 , i . e . at different heights . two deflector elements thus offset from one another in the vertical direction can also be acted upon by only a single light source using a corresponding beam splitter . the deflector elements 118 , 120 may be provided in a coherent glass block ( not shown ). in this way the number of glass - air surfaces can be reduced , thus further reducing unwanted reflections . the deflector elements 118 , 120 may also be constructed as a single reflecting element , while opaque regions may be provided between the deflector elements 118 , 120 which are of semitransparent construction according to the invention . these opaque regions may be configured to be fully absorbent or fully mirrored . using these measures , the illuminating beams striking the object that is to be observed can be delimited from one another or shaped in any desired manner . it is possible for example to provide illuminating beam paths of rectangular , square or round cross - section . cross - sections of illuminating beam paths of this kind may also be obtained by a suitable choice of the lighting medium of the light source , with particular reference to halogen lamps , leds , etc . fig3 is a plan view of a particularly preferred embodiment of the illuminating device according to the invention viewed in schematic plan view . the same or similar components have been given the same reference numerals here . beam paths emanating from a light source 102 are split by a beam splitter element 104 into illuminating beam paths 106 , 108 . the element 104 is embodied here as a semitransparent mirror . the illuminating beam path 106 is deflected again from another , fully mirrored element 104 a , so that the illuminating beam paths 106 , 108 then run parallel to one another again . the illuminating beam path 106 strikes the first semitransparent deflector element 118 , the illuminating beam path 108 strikes the second semitransparent deflector element 120 . the respective observation beam paths which are substantially overlapped by these deflector elements 118 , 120 are not shown here . another light source for providing illumination of the surrounding area is designated 172 . this acts on an additional deflector element 180 , which may be semitransparent or fully mirrored , with another illuminating beam path 174 . the embodiment shown in fig3 is characterised in that both the illuminating beam paths 106 , 108 needed for the red reflex illumination and the illuminating beam path 174 used for illuminating the surrounding area are irradiated from substantially the same direction , i . e . substantially parallel to one another . this results in a particularly compact construction .

US-201113053268-A

a storage device includes a generally enclosed body including inner and outer areas . the inner area includes axially adjustable shelves for dividing the inner area into adjustable compartments , and the outer area includes a plurality of pockets disposed along a periphery of the body for facilitating storage of shoes within the pockets . a release mechanism provides and prevents access to the inner area when in respective opened and closed configurations . a connection mechanism is disposed adjacent a top of the body and affixable to a complementary connector to allow the storage device to be hung and thereby permit axial extension of the body when in a hung configuration and otherwise permit collapse of the body . in other configurations , instead of adjustable shelves , the storage device may include an independently rotatable inner body including a plurality of pockets , or individual shoe storage bodies mounted on rails .

referring now to the drawings wherein like reference numerals designate corresponding parts throughout the several views , fig1 - 6 illustrate a first embodiment of a shoe and accessory carousel storage device with adjustable compartments ( hereinafter “ storage device ”), according to the present invention , generally designated 10 . referring to fig1 storage device 10 may include a tubular body 12 having respective top and bottom ends 14 and 16 , and including a plurality of circumferentially disposed pockets 18 . the structure of body 12 may be formed of a breathable mesh material and / or a flexible material for permitting predefined expansion thereof under its own weight or under the weight of shoes and other articles . likewise , as illustrated in fig2 the flexible material for body 12 may be chosen for facilitating a predefined collapsed configuration for storage device 10 . pockets 18 may include longitudinal edges 22 at two or more comers thereof , which may be formed as extensions of the material for pockets 18 and sewn and / or otherwise affixed to body 12 . those skilled in the art will appreciate in view of this disclosure that the bottom - most edge 24 of pockets 18 may be sewn onto body 12 to form an enclosed pocket , or instead , may be left open to allow the toe of a shoe to protrude therethrough . pockets 18 may be uniformly and / or randomly disposed around the circumference of storage device 10 for facilitating storage of shoes and other such articles of various sizes and shapes . pockets 18 may be formed of the same material as body 12 , or instead , may be formed of materials such as clear vinyl , a polyester mesh , cotton , canvas , khaki and the like . storage device 10 may further include respective top and bottom rigid support members 26 and 28 for maintaining body 12 in a predefined expanded and collapsed configuration . support members 26 and 28 may be formed of metal , or other suitable material for providing sufficient rigidity to storage device 10 . it is apparent that although rigid support members 26 and 28 are illustrated in a circular configuration for the embodiment of fig1 square , rectangular , oval or various other geometric shapes may be used for rigid support members 26 and 28 . moreover , for a square support member for example , body 12 may be formed of a complementary configuration , as with the other geometric shapes discussed above . support members 26 and 28 may be affixed to body 12 by being sewn thereto , or alternatively , may be glued or otherwise affixed to body 12 . in another configuration ( not shown ), support members 26 and 28 may include a velcro strip and / or another device such as a zipper and the like for removable connection thereof to body 12 . in order to provide an aesthetic appearance for storage device 10 , support members 26 and 28 may be covered by material similar to that of body 12 . in order to facilitate the hanging of storage device 10 to a closet rail for example , top support member 26 may include a swivel hook 32 affixed thereon by means of wires 34 tied onto support connections 36 . support connections 36 may be of the form of standard hooks and / or other connection means , as would be apparent to those skilled in the art . in another configuration ( not shown ), wires 34 may include hooks and / or other means at the lower ends thereof for releasably connecting to support connections 36 so as to facilitate the disconnection of wires 34 from body 12 . swivel hook 32 may be configured to include a standard dampener ( not shown ) within swivel mechanism 38 to control the rotation speed thereof and also provide 360 ° rotation capability for storage device 10 . in order to control the maximum expandable length of storage device 10 , cords 30 may be affixed within body 12 to each support connection 36 of top support member 26 and likewise affixed to complementary opposite support connections 42 on bottom support member 28 . it is apparent that additional cords 30 may be provided as needed for controlling the maximum extension of storage device 10 and / or for providing additional rigidity . cords 30 may be made of nylon or other flexible material having a predetermined elasticity and / or a semi - rigid material to control the maximum extendable length of storage device 10 . in addition to outer pockets 18 for storage of shoes and the like , storage device 10 may further include adjustable inner compartments 44 for storage of shoes and other such articles such as socks and the like . inner compartments 44 may be accessible by opening zipper 50 and may be formed by a plurality of shelves 46 whose location may be axially raised or lowered along the longitudinal length of body 12 . for example , the lower most inner compartment 44 may be formed by axially moving shelf 48 toward or away from bottom support member 28 . each shelf 46 may include a central hole 40 through which a cord 31 made of nylon or other suitable material may pass through . cord 31 may be appropriately affixed to the respective top and bottom ends 14 and 16 of body 12 so as to provide guidance for axial movement of each shelf 46 . cords 30 may each include a plurality of knots 33 sewn or otherwise affixed thereon at predetermined intervals in order to facilitate the axial adjustment of shelves 46 relative to bottom support member 28 . additional shelves 46 may be added into body 12 to form additional compartments 44 . as shown in fig4 the additional shelves 46 may include a slot 47 to facilitate insertion of pre - attached cord 31 into hole 40 of the additional shelf 46 . referring next to fig5 in an alternative configuration , instead of a shelf 46 being adjustably disposable within body 12 by means of knots 33 , shelves 46 may be provided with circumferentially affixed velcro strips 58 for affixation with complementary velcro strips ( not shown ) within body 12 . the complementary velcro strips within body 12 may be provided at predetermined intervals in a similar manner as with knots 33 on cords 30 . thus in order to adjust the dimensions of compartments 44 , shelves 46 including velcro strips 58 may be detached from and thereafter reattached to the complementary velcro strips within body 12 as needed . for a body 12 provided with velcro strips therein , it is apparent that instead of shelves 46 , complementary pockets ( not shown ) having velcro strips ( not shown ) may be provided for attachment with the velcro strips within body 12 , thus providing a storage device 10 with internal and external pockets . in yet another alternative configuration , as illustrated in fig6 each shelf 46 may include holes 52 which cords 30 may be threaded through . each cord 30 may be provided with a conventional cord restraint 54 , such as the one illustrated in fig3 disposed at the bottom of each shelf 46 to facilitate axial adjustment and retention of shelves 46 . alternatively , instead of the use of cord restraints 54 , each cord 30 may be inserted into holes 52 in shelves 46 and frictionally retained therein such that shelves 46 remain at a predetermined height and are movable axially only under a predetermined force . in yet another configuration , each shelf 46 may be provided with a plurality of circumferentially affixed hooks ( not shown ) which may then be attached within complementary reinforced holes ( not shown ) in the structure of body 12 in order to support shelves 46 at a predetermined distance from bottom support member 28 . for the configuration with circumferentially affixed hooks , the reinforced holes in body 12 may be disposed at predetermined intervals along the axial length of body 12 to provide an adequate guide for adjusting the height of shelves 46 . referring to fig3 it should be noted that although cord 30 is illustrated with a knot 33 and a cord restraint 54 mounted thereon , knots 33 and cord restraints 54 may be used in combination or exclusively for retaining a shelf 46 at a predetermined height . it should also be noted that even though shelves 46 are disclosed herein as being adjustable , if needed , shelves 46 may be sewn in place onto body 12 , or otherwise glued or bonded in order to provide fixed shelves within body 12 . in the particular embodiment of fig1 storage device 10 may include three rows of eight circumferentially disposed pockets 18 , thus providing storage for twelve pairs of shoes . additionally , storage device 10 may include three adjustable compartments 44 for facilitating storage of large shoes and / or other articles . shelves 46 may be formed of a twelve inch diameter and body 12 may include an expanded length of three feet and a collapsed height of approximately three inches . it should be noted that although only a single zipper 50 is disclosed for access to compartments 44 of storage device 10 , additional zippers ( not shown ) may be placed along the circumference of body 12 to provide access to compartments 44 from various locations . the second embodiment of storage device , generally designated 60 , will now be described in detail . referring to fig7 storage device 60 may include a frame 62 including support rods 64 each including a shoe support body 66 . each shoe support body 66 may include respective top and bottom ends 68 and 72 , and further include a plurality of pockets 74 disposed at opposite sides 70 and 71 thereof . the structure of each shoe support body 66 may be formed of a breathable mesh material and / or a flexible material for permitting predefined expansion thereof under its own weight or under the weight of shoes and other articles . likewise , as illustrated above for storage device 10 in fig1 and 2 , the flexible material for each shoe support body 66 may be chosen for facilitating a predefined collapsed configuration for storage device 60 . pockets 74 may include longitudinal edges 76 at two or more comers thereof , which may be formed as extensions of the material for pockets 74 and sewn and / or otherwise affixed to each shoe support body 66 . those skilled in the art will appreciate in view of this disclosure that the bottom - most edge 78 of pockets 74 may be sewn onto each shoe support body 66 to form an enclosed pocket , or instead , may be left open to allow the toe of a shoe to protrude therethrough . pockets 74 may be uniformly and / or randomly disposed on each side of each shoe support body 66 for facilitating storage of shoes and other such articles of various sizes and shapes . pockets 74 may be formed of the same material as shoe support body 66 , or instead , may be formed of materials such as clear vinyl , a polyester mesh , cotton , canvas , khaki and the like . storage device 60 may further include a rigid support member 82 at the lower end thereof for maintaining each shoe support body 66 in a predefined expanded and collapsed configuration . support member 82 may be formed of metal , or other suitable material for providing sufficient rigidity to storage device 60 . it is apparent that although rigid support member 82 is illustrated in a rectangular configuration for the embodiment of fig7 circular , square , oval or various other geometric shapes may be used for rigid support member 82 . moreover , for a circular support member for example , each shoe support body 66 may be formed of a complementary configuration , as with the other geometric shapes discussed above . support member 82 may be affixed to each shoe support body 66 by being sewn thereto , or alternatively , may be glued or otherwise affixed to shoe support body 66 . in another configuration ( not shown ), support member 82 may include a velcro strip and / or another device such as a zipper and the like for removable connection thereof to shoe support body 66 . in order to provide an aesthetic appearance for storage device 60 , support members 82 may be covered by material similar to that of shoe support body 66 . it should be noted that the top end 68 of each shoe support body 66 may be affixed to rods 64 in the manner discussed above for the affixation of support member 82 to shoe support body 66 . in order to facilitate the hanging of storage device 60 to a closet rail for example , frame 62 may include a swivel hook 84 affixed thereon . swivel hook 84 may be configured to include a standard dampener ( not shown ) within swivel mechanism 86 to control the rotation speed thereof and also provide 360 ° rotation capability for storage device 60 . in the particular embodiment of fig7 storage device 60 may include four shoe support bodies 66 , each including three rows of pockets 74 on each side thereof , thus providing storage for thirty - six pairs of shoes . additionally , shoe support body 66 may include an extended length of three feet and a collapsed height of approximately three inches . the third embodiment of storage device , generally designated 100 , will now be described in detail . referring to fig8 and 9 , storage device 100 may include a tubular body 102 having respective top and bottom ends 104 and 106 , and including a plurality of circumferentially disposed pockets 108 . the structure of body 102 may be formed of a breathable mesh material and / or a flexible material for permitting predefined expansion thereof under its own weight or under the weight of shoes and other articles . likewise , as illustrated in fig2 for storage device 10 , the flexible material for body 102 for storage device 100 may be chosen for facilitating a predefined collapsed configuration thereof . pockets 108 may include longitudinal edges 112 at two or more comers thereof , which may be formed as extensions of the material for pockets 108 and sewn and / or otherwise affixed to body 102 . those skilled in the art will appreciate in view of this disclosure that the bottom - most edge 114 of pockets 108 may be sewn onto body 102 to form an enclosed pocket , or instead , may be left open to allow the toe of a shoe to protrude therethrough . pockets 108 may be uniformly and / or randomly disposed around the circumference of storage device 100 for facilitating storage of shoes and other such articles of various sizes and shapes . pockets 108 may be formed of the same material as body 102 , or instead , may be formed of materials such as clear vinyl , a polyester mesh , cotton , canvas , khaki and the like . storage device 100 may further include respective top and bottom rigid support members 116 and 118 for maintaining body 102 in a predefined expanded and collapsed configuration . support members 116 and 118 may be formed of metal , or other suitable material for providing sufficient rigidity to storage device 100 . it is apparent that although rigid support members 116 and 118 are illustrated in a circular configuration for the embodiment of fig8 square , rectangular , oval or various other geometric shapes may be used for rigid support members 116 and 118 . moreover , for a square support member for example , body 102 may be formed of a complementary configuration , as with the other geometric shapes discussed above . support members 116 and 118 may be affixed to body 102 by being sewn thereto , or alternatively , may be glued or otherwise affixed to body 102 . in another configuration ( not shown ), support members 116 and 118 may include a velcro strip and / or another device such as a zipper and the like for removable connection thereof to body 102 . in order to provide an aesthetic appearance for storage device 100 , support members 116 and 118 may be covered by material similar to that of body 102 . in order to facilitate the hanging of storage device 100 to a closet rail for example , top support member 116 may include a swivel hook 122 affixed thereon by means of wires 124 tied onto support connections 126 . support connections 126 may be of the form of standard hooks and / or other connection means , as would be apparent to those skilled in the art . in another configuration ( not shown ), wires 124 may include hooks and / or other means at the lower ends thereof for releasably connecting to support connections 126 so as to facilitate the disconnection of wires 124 from body 102 . swivel hook 122 may be configured to include a standard dampener ( not shown ) within swivel mechanism 128 to control the rotation speed thereof and also provide 360 ° rotation capability for storage device 100 . in order to control the maximum expandable length of storage device 100 , cords 120 may be affixed within body 102 to each support connection 126 of top support member 116 and likewise affixed to complementary opposite support connections 132 on bottom support member 118 . it is apparent that additional cords 120 may be provided as needed for controlling the maximum extension of storage device 100 and / or for providing additional rigidity . cords 120 may be made of nylon or another flexible material having a predetermined elasticity and / or a semi - rigid material to control the maximum extendable length of storage device 100 . in addition to outer pockets 108 for storage of shoes and the like , storage device 100 may further include rotatably mounted inner pockets 134 provided in a generally horizontal configuration as opposed to the generally vertical configuration for outer pockets 108 . in the embodiment of fig8 pockets 134 may be uniformly and / or randomly sewn and / or otherwise affixed to inner body 136 . inner body 136 may be hung by means of a cord 138 within body 102 to thereby permit independent rotation thereof relative body 102 . thus pockets 134 may be utilized for the storage of shoes and other such articles of various sizes and shapes . as with pockets 108 , inner pockets 134 may be formed of the same material as body 102 , or instead , may be formed of materials such as clear vinyl , a polyester mesh , cotton , canvas , khaki and the like . in the particular embodiment of fig8 storage device 100 may include three rows of eight circumferentially disposed outer pockets 108 , thus providing storage for twelve pairs of shoes . additionally , storage device 100 may include three rows of four oppositely disposed inner pockets 134 , thus providing storage for additional shoes and / or other articles , and body 102 may include an extended length of three feet and a collapsed height of approximately three inches . as discussed above for the embodiment of fig1 it should be noted that although only a single zipper 140 is disclosed for access to inner pockets 134 of storage device 100 , additional zippers ( not shown ) may be placed along the circumference of body 102 to provide access to inner pockets 134 from various locations . although particular embodiments of the invention have been described in detail herein with reference to the accompanying drawings , it is to be understood that the invention is not limited to those particular embodiments , and that various changes and modifications may be effected therein by one skilled in the art without departing from the scope or spirit of the invention as defined in the appended claims .

US-44519403-A

blood is stored under refrigeration at a temperature of about 4 ° c . when it is utilized on a relatively rapid basis within a surgical theater it is transported by tubing through a blood warming apparatus which , while warming the blood , causes an outgasing of entrained air . this air is trapped in an air trap receptacle having a drip chamber within which a gas - blood interface is developed . to assure that the capacity of the trap is not exceeded , an improved technique of gas removal and interface level setting is provided wherein access is achieved essentially through the entrance region of the gas trap receptacle .

referring to fig1 an assemblage of components typically employed within a surgical theater for administering fluids such as blood to a patient is revealed generally at 10 in partially schematic fashion . the administration of blood fluids involves a procedure wherein a unit of the blood is removed from refrigerated storage where it is retained at 4 ° c . and is brought to the surgical theater . the blood typically is retained in a disposable polymeric bag referred to as a &# 34 ; blood bag &# 34 ; as represented at 12 . blood bag 12 is shown carrying a quantity of blood 14 which is administered to the patient by hydrostatic pressure evolved by elevating the bag 12 a desired distance above the patient from an iv rack having a hook as at 16 . alternately the bag may be compressed by a pressuring assembly . the disposable blood bags as at 12 are generally configured having one or more fluid release ports as are represented at 18 and 20 , duplicate ports being provided , inter alia , for the purpose of providing a redundancy desirable with respect to the intensity of cognizance or metal concentration within the surgical theater and , additionally , to provide an alternate injection port for the administration of medicines into the fluid 14 itself . access port 18 is shown pierced by a hollow piercing spike 22 , such insertion of the spike 22 being facilitated by an integrally formed flange 24 . the opposite side of spike 22 and flange 24 is coupled in fluid communication to a length of transparent tubing 26 which extends to one input of a pump - filter assembly 28 . input to the assembly 28 may be turned off at tubing 26 by the manual movement of the roll 30 along a corresponding ramp within a roll clamp 32 . assembly 28 includes a duplicate input 34 which may be employed for attaching duplicate sources of fluid to the assemblage 10 . the upwardly - disposed portion of assembly 28 at 36 functions as a manual pump which includes a ball stop 38 . with the arrangement , in the course of surgery , should additional pressure be required above and beyond the hydrostatic pressure available , the portion 36 is manually grasped and squeezed , the ball 38 blocking upward movement of fluid while the pressure manually applied forces fluid downwardly into and through a filter portion of assembly 28 represented at 40 . the filter 40 functions , for example , to remove any clotting blood from the system as the fluid then progresses into a next tubing component 42 . ball stop 38 serves a second function in connection with the movement of fluid through the assembly 28 . in the event all fluid is utilized , the ball will drop to position 44 and block movement of air or the like into the system from the position of filter 40 . tube 42 is somewhat lengthy , typically having an extent of about 7 feet . thus , in the drawing , this region of tubing retained fluid flow is represented by the symbolic flow line 46 . in this flow line several implements may be provided , including roller clamps as at 48 and y - ports as at 50 and 52 . these ports 50 and 52 are configured to normally pass the fluids within the flow path 46 but additionally incorporate a straight channel section having a soft protective cap thereon through which a typical hypodermic needle may be inserted . thus , the ports may be employed for the purpose of adding medicaments in conjunction with the normal fluid flow from the supply 12 . tubing or flow path 46 is seen to terminate in a stopcock valve represented generally at 54 . these valves are manually actuated by a small lever as represented at 56 to provide , for example , three - way valving activity . for example , one such path will extend from the input of the valve at 58 and pass through its normal output 60 . on the other hand , an additional flow path may be developed at port 62 for receiving medicaments from the hollow stem portion of a typical hypodermic syringe . these medicaments are inserted into the normal flow of fluids which pass , as before , from the normal output 60 . output 60 is seen coupled to the dual input 64 of a blood or fluid warming assembly represented generally at 66 . some assemblages provide a single rather than a dual input as shown . assembly 66 includes a dual path heat exchange fluid flow component 68 through which the fluid of the system passes in delay fashion , whereupon it exits at a next tubing component 70 . generally , the component 68 is retained within a blood warmer , preferably of the &# 34 ; dry heat &# 34 ; variety which is represented in phantom by block 72 . in its general operation , the warming device 72 is formed of thermostatically controlled heated plates held at about 37 ° c .- 40 ° c . thus , the fluids passing through component 68 are warmed as they exit at tube 70 . however , an outgasing occurs in conjunction with this warming , particularly in the case of blood fluid . for example , blood contains dissolved oxygen and carbon dioxide and when rapidly warmed toward body temperature , the resulting temperature of about 37 ° c . is accompanied by changes in solubility coefficients of such gases . the resultant air bubbles or gas bubbles must be removed to avoid any infusion thereof into the patient . thus , the tubing component 70 is seen directed to the input region 74 of a gas trap receptacle 76 . recepacle 76 includes an entrance surface 78 at region 74 and extends to an exit region 80 including an exit surface 82 . intermediate the surfaces 78 and 82 there is defined a drip chamber within which fluid or blood accumulates at the lower region and gas is accumulated above that region to define a gas - liquid fluid interface 84 . interface 84 will assume various levels within the drip chamber of the receptacle 76 generally in dependence upon the amount of outgasing occuring in connection with the warming arrangement 66 . generally , the side surfaces of receptacle 76 are transparent and the dripping of fluid or blood from tube 70 thereinto provides an indicia to the practitioner that fluid is indeed flowing . as the amount of outgasing increases , however , the interface 84 will descend within receptacle 76 and , should it fall below the exit region 80 or surface 82 , a resultant infusion of gas into the patient may result with the noted consequences . thus , the practitioner observes interface 84 and as it falls below a level deemed acceptable , removal of the air component within the drip cavity must be carried out . it may be observed that the fluid flow path continues from the bottom region 80 of receptacle 76 as represented at tubing 86 . this last length of tubing 86 may be of an extent amounting , for example , to about 7 feet and will include several components , for example , three y - ports , one of which is shown at 88 , a three - way stopcock valve ( not shown ) a roll clamp as at 90 , and slide clamps as at 92 as may be appropriate . the tubing 86 terminates at a place of infusion 94 shown located at the upper hand portion 96 of a patient . prior to the procedure of the instant invention , the technique for controlling the interface level or amount of gas build - up within the drip cavity or chamber of receptacle 76 involved the steps of pinching off flow to the patient 94 at some position below y access port 88 ; manually upturning the receptacle 76 so that the air or gas component therein now confronts lower region 80 ; inserting a hyopdermic syringe needle into the access leg of y - port 88 ; and observing the movement of air or gas now exiting as a long bubble from lower region 80 through tubing 86 . as the moving gas in tube 86 reaches the point of aspiration at port 88 , negative pressure ( suction ) is applied from the hypodermic syringe and an appropriate amount of air or gas is removed , whereupon the receptacle 76 is returned to its upright position . because it is desirable to observe the dripping of blood into the drip chamber of receptacle 76 , not all of the gas or air is removed during this procedure . it may be apparent that the procedure is quite cumbersome and inexact . with the procedure of the instant invention , accurate positioning of the level of interface 84 is available along with an improved technique for removing the noted gas products of the warming procedure . with the technique , flow through the upper portion of tubing 70 is stopped either by manually pinching the tubing at that location or by carrying out that same blocking function with , for example , a slide clamp as at 110 . access is made to the upper region 74 of receptacle 76 and this is shown in the figure as being provided by a y - access port 112 . with the instant procedure , the flow from the warming device 66 is terminated by activating the clamp 110 to close the tube 70 upper region and a hypodermic syringe as at 114 is inserted in the access port of y - port 112 . by withdrawing the plunger of syringe 114 , negative pressure may be asserted from the access port at 112 to remove the gases above the interface 84 . additionally , positive pressure may be applied from the syringe 114 to adjust the level of the interface 84 to a desired starting level . a small amount of blood or fluid as will be contained within tubing 70 below clamp 110 is aspirated by syringe 114 with this procedure . as an alternative , an access conduit can be provided directly within the receptacle 76 . the y - port 112 may be replaced with a stopcock similar to that at 54 to provide an arrangement wherein the needle component of syringe 114 need not be utilized . in this regard , the hollow plastic stem portion of the syringe may be inserted within the access port as at 62 of such a stopcock . it has become desirable in the surgical theater to avoid sharp needles and the like and , thus , by employing such a device as a stopcock valve , the needles may be eliminated . looking to fig2 another embodiment for gas trap receptacles which may employ the technique of the invention is revealed generally at 130 . device 130 includes an upper disposed entrance region 132 as well as a lower disposed exit region 134 which may be coupled within the tubing string in the manner of receptacle 76 . accordingly , tubing component 70 is shown being directed through the entrance surface 136 of upper region 132 , while , correspondingly , tube component 86 is shown being coupled in fluid flow communication with the exit surface 138 of region 134 . with the instant embodiment , direct access to the upper region 132 of the drip chamber within recetacle 130 is provided by a conduit 138 located as extending through entrance surface 136 somewhat in adjacency with tubing component 70 . the conduit 138 is capped at 140 such that , alternately , it may be accessed by the needle component of a hypodermic syringe as at 114 or may be accessed by the hollow stem portion thereof without employment of needles . for the latter utilization , the cap 140 is removed and access by removable association between a hypodermic hollow stem portion and component 138 is effected . to assure that no draw - down effects or the like are occasioned through component 70 , the procedure in adjusting the gasfluid interface within receptacle 130 involves pinching off tubing 70 . for this purpose , a conventional slide clamp as at 142 may be provided . in similar fashion , conduit 138 may be sealed by such a slide clamp as at 144 . in addition to conduit structures as at 138 , of course , two - way valves may be employed having a particular utilization in conjunction with hypodermic stem components as opposed to the needles thereof . referring to fig3 the device 130 again is reproduced as having an upper disposed entrance region 132 , as well as a lower disposed exit region 134 which may be coupled within the tubing string in the manner of receptacle 76 . in the latter regard , the tube component 86 is seen extending from lower disposed region 134 . for one embodiment quite similar to that of fig2 tubing component 70 extends through the entrance surface 136 of upper region 132 . as before , a slide clamp 142 may be employed to pinch off tube 70 during level adjustment procedures . for the instant embodiment , such level adjustment procedures are provided by a valve similar to that described above in general at 54 but for the present embodiment not having an upper input port 58 . the valve is seen coupled to tubing component 138 at its normal output 60 &# 39 ;. one input to the valve at 62 &# 39 ; is shown coupled to a hypodermic syringe 114 &# 39 ; which is applied to the valve without a needle . thus , the interface level within the container 130 may be adjusted at this location . as an alternate arrangement , the additional input represented at tubing component 70 and slide 142 is not provided and , as shown in phantom in the figure , the input to the valve is provided as at 58 &# 39 ; and this input is coupled to the tubing component 70 as represented in phantom at 70 &# 39 ;. with this arrangement , by manipulating the lever 56 &# 39 ;, input port 58 &# 39 ; is cut off , input port 62 &# 39 ; is then communicated with output port 60 &# 39 ; to permit level adjustment by the application selectively of negative or positive pressure from the syringe 114 &# 39 ;. since certain changes may be made in the above apparatus and method without departing from the scope of the invention herein involved , 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 .

US-20733388-A

the present invention relates to composition and method for inhibiting growth or propagation of spoilage or pathogen microorganisms in vegetables . microorganisms , bacteria or yeasts , that can be naturally found or introduced into vegetables before or during their processing , such as fermentation , can be inhibited by treatment with a solution containing hydrolyzed chitosan - lactate . in this way , unprocessed and processed vegetable foods can be preserved for a longer period of time without deterioration .

the present invention now will be described more fully hereinafter with reference to the accompanying drawings , in which preferred embodiments of the invention are shown . this invention , may , however , be embodied in many different forms and should not be construed as limited to the embodiments set forth herein ; rather , these embodiments are provided so that this disclosure will be thorough and complete , and will fully convey the scope of the invention to those skilled in the art . in accordance with the present invention , there is provided hydrolyzed chitosan - lactate that is a molecule showing efficacy for use as a preservative in acidic foods such as fermented vegetables . antimicrobial activities of chitosan - lactate are greatly modulated by the degree of hydrolysis , the target organisms and the composition of the media . another embodiment of the present invention is to provide a method of preserving foods , processed or not , which is broadly effective to prevent foods from deterioration and from denaturation caused by microorganisms , including yeast and / or bacteria , even in the use of small amount of antimicrobial agents . preferably , the food products targeted for applying the method invention concern fresh fruits or vegetables , processed fruits or processed vegetables . the present invention relates to a method of preserving foods which comprises adding at least one kind of a natural antimicrobial agent hydrolyzed chitosan - lactate to foods , and storing or processing the food . hydrolyzed chitosan - lactate can be added to a food product before , during or after processing , such as fermentation , of the food products . particularly interesting food products that can be preserved with the method and composition of the present invention are vegetables . the vegetables can be treated with a composition containing hydrolyzed chitosan - lactate as whole , or after processing , or even after having been transformed into pastes or juices . the present invention will be more readily understood by referring to the following examples , which are given to illustrate the invention rather than to limit its scope . antimicrobial action of hydrolyzed chitosan against spoilage yeast and lactic acid bacteria of fermented vegetables hydrolysates and native chitosan - lactate were obtained from ism biopolymer inc . ( sherbrooke , canada ). this 40 - g / l chitosan preparation contained 2 . 5 % of food grade dl lactic acid ( 88 %) and had a deacetylation level of 90 % ( manufacturer &# 39 ; s data ) ( ph 5 . 5 ). native and hydrolyzed chitosan - lactate of different molecular weights were tested in chitosan concentration of 0 . 5 , 1 , 2 , 5 and 10 g / l . the mean molecular weights of the molecules and degree of polymerization ( dp ) are presented in table 1 . all samples were sterilized by filtration through 0 . 22 μm nitrocellulose membranes ( millipore , milford , mass ., u . s . a .). microbial strains used in this study included three species of lactic acid bacteria ( lab ) used as sauerkraut starter ( blac 1 ™, caldwell biofermentation canada inc , compton , canada ) and two spoilage yeasts . lab were lactobacillus plantarum nk 312 ( lallemand , st - simon , france ), pediococcus acidilactici aferm 772 ( quest , lachine , canada ) and leuconostoc mesenteroides blac ( crda , st - hyacinthe , canada ). yeast strains were isolated with method known in the art , from spoiled fermented vegetables and identified as saccharomyces unisporus y - 42 and saccharonzyces bayanus y - 43 . lab strains were maintained on mrs agar ( bdh , montréal , canada ) at ph 5 . 6 and yeast strains on ym agar ( bdh , montréal , canada ) at ph 3 . 5 acidified with 5n hcl . the antimicrobial activity was first examined on methylene blue agar ( mba ) as described by walker et al . ( fems microbiol . lett ., 127 : 213 - 222 ). mba was distributed in aliquots of 15 ml then autoclaved at 121 ° c . for 15 min and cooled to 45 ° c . before addition of lab or yeasts at a final cell number of 1 × 10 5 per petri dish . target cells were seeded into the molten mba , mixed gently and then poured in petri dishes . five mm diameter punctures were made with a stainless steel punch in the solidified agar in order to obtain wells . sterile native and hydrolyzed chitosan solutions ( 50 μl ) at concentrations of 0 . 5 , 1 , 2 , 5 and 10 g / l were distributed into 5 - mm diameter wells . lactate ( 2 . 5 %) was used as a negative control . in mba , test organisms grew as a background lawn and inhibitory activity was evidenced by a clear zone surrounding the well , which could itself be surrounded by blue - stained line ( dead ) colonies if fungicidal or bactericidal activity was present . plates were incubated at 30 ° c . for 72 h and kept at 4 ° c . for two weeks . three independent assays were performed in duplicate and diameter of inhibition ( clear ) zones delimited by the blue line was measured in millimeters . data obtained with agar - based media were compared to those obtained on vegetable juice media ( vjm ) liquid media by automated spectrophotometer ( as ) using a bioscreen ™ apparatus ( labsystems , helsinki , finland ). the vjm was composed of 61 % carrot juice , 12 % cabbage juice , 3 % onion juice and 24 % brine containing 20 g / l sea salt and was prepared according to gardner et al . ( int . j . food microbiol ., 66 : 261 - 275 ). the initial ph of the blend was 6 . 34 . to determine the inhibitory potential of chitosan in fermented vegetables , vjm was acidified at ph 3 . 8 with lactic acid 85 %. vjm was supplemented with hydrolyzed chitosan - lactate at 0 . 5 , 1 , 2 , 5 or 10 g / l and distributed in a 200 - well microplate . wells were inoculated with test strains in triplicate at 0 . 1 % ( vov / vol ) of 72 h yeast preculture ( ym broth , 30 ° c . for 72 h ). for each sample , control conditions without chitosan were made in triplicate and blanks with chitosan without yeasts were subtracted from the mean value obtained for the test wells . experiments were conducted on three independent assays in triplicate . incubation of the microplates was carried out at 26 ° c . for 28 h and the optical density ( od ) at 600 nm was measured every 15 min . the bioscreen ™ unit is designed to shake the microplates and set intervals and , in this study , the microplates were shaken for 20 s prior to and after od readings . samples were examined after four treatments at two ph values ( 3 . 8 and 6 . 0 ) in order to evaluate the effect of chitosan in function of ph . saccharomyces unisporus y - 42 and sc . bayanus y - 43 were pre - incubated at 30 ° c . for 48 h in ym broth ( control ). intermediate hydrolyzed chitosan ( dp25 ) was added at a concentration of 2 g / l and samples were taken after 1 h or 5 h of incubation ( first and second treatments ). chitosanase ( ism biopolymer inc . sherbrooke , canada ) was mixed with chitosan - lactate dp25 in the third treatment to confirm the nature of the aggregate and all of them were compared to control without chitosan and chitosanase ( control treatment ). after incubation , samples were centrifuged at 4000 - x g for 15 min at 4 ° c . and yeast cells embedded in 4 % softened agar ( bacteriological agar , difco laboratories , detroit , mich . u . s . a .) ( ph 6 . 0 or 3 . 8 , 45 ° c .). the remaining gel was cut in small pieces of about 1 mm . samples were then fixed in 2 % glutaraldehyde / cacodylate buffer 0 . 1 m ph 7 . 3 for 2 . 5 h at room temperature , rinsed several times in the same buffer for a total of 1 . 5 h and postfixed overnight in 2 % osmium tetroxide / water at 4 ° c . afterwards samples were rinsed three times within 1 . 5 h , dehydrated in a graded ethanol series ( 30 , 50 , 70 and 100 %), infiltrated with spurr resin and polymerized for 24 h at 60 ° c . thin sections were obtained , stained with uracyl acetate and lead citrate and observed on a transmission electron microscope at 80 kv ( philips model 420 , eindhoven , the netherlands ). the antimicrobial activities of native and hydrolyzed chitosan - lactate were first assessed on mba agar . fig1 and 2 illustrate the level of inhibition for sc . bayanus y - 43 ( fig1 - a ), sc . unisporus y - 42 ( fig1 - b ) and for lactic acid bacteria ( fig2 ). the highly degraded chitosan ( dp3 ) showed the greatest inhibitory activity with all microorganisms . inhibition decreased with increasing molecular weight . trimers ( dp3 ) were the most potent inhibitor , followed by octamers ( dp8 ). intermediate molecular weight chitosans ( dp25 and dp42 ) showed little activity and no growth inhibition could be observed with polymers of up to 10 kda . however , inhibitory activities of the different oligomers were a function of the concentration and the target organism . no growth inhibition was observed with concentrations of 0 . 5 , 1 and 2 g / l for sc . bayanus y - 43 , which needed a minimum of 5 g / l to show inhibition ( fig1 - a ). for sc . unisporus y - 42 , a similar inhibitory pattern was observed even though this strain was more sensitive to chitosan hydrolysates ( p & lt ; 0 . 002 , t - test ). inhibition was also observed on lactic acid bacteria with a minimal inhibitory concentration of 2 g / l and lactobacillus plantarum was the most resistant of the three strains ( fig2 ). control conditions with only lactic acid at 2 . 5 % did not shown inhibitory activities . based on these results , inhibitory activity of chitosan - lactate was higher with low and intermediate molecular weight hydrolysates and was directly proportional to the concentration added to mba . inhibitory activity is lost with hydrolysates between dp8 and dp42 depending on the target organism . these data are consistent with the fact that low molecular weight chitosan was more inhibitory than intermediate and higher molecular weight chitosan in agar systems , although the molecular weight was not specified . therefore , the fact that lactic acid bacteria were also affected by chitosan implies that chitosan - lactate should not be added at the beginning of vegetable fermentation . however , the mba agar test was carried out at ph 4 . 5 and it remains to be determined if a similar inhibition pattern would occur at the higher ph levels encountered at the beginning of vegetable fermentation the antimicrobial activities of native and hydrolyzed chitosan - lactate in liquid medium were assessed only on yeast strains , since , at the ph of 3 . 8 used with vjm , growth of the lactic acid bacteria was critically inhibited and no increase in od values could be obtained during the recording time ( 28 h ) ( data not shown ). vjm was used as a complex medium representative of conditions encountered following a lactic fermentation . fig3 shows the growth curves of sc . bayanus y - 43 in presence of dp3 ( a ), dp8 ( b ), dp25 ( c ) and dp42 ( d )) at different concentrations . in contrast to data obtained in agar - based media , all hydrolysates were inhibitory and hydrolysates of intermediate molecular weight became the most potent inhibitors . with sc . bayanus y43 , all concentrations tested were effective against this yeast but complete growth inhibition was not obtained in this medium with concentrations as high as 10 g / l . nevertheless , the inhibition was concentration dependent . as shown in fig4 , saccharomyces unisporus y - 42 ( the most sensitive strain in agar - based media ) showed complete growth inhibition at 0 . 5 g / l except for the trimer ( dp3 ), which did not reduce the growth of this yeast as compared to the control . interestingly , it has been observed before that sc . unisporus is more resistant to low ph and acid than sc . bayanus . this resistance is generally conferred by more effective proton pumping at the cell wall and a more acidic internal cytoplasmic ph . these characteristics are linked with anionic charges on the cell wall and could explain the high sensitivity to the polycationic charge of chitosan - lactate . the inhibition pattern in liquid medium ( vjm ) differed from those obtained in solid media ( mba ). hydrolysates of low molecular weight chitosan - lactate were less toxic than hydrolysates of intermediate molecular weight . this confirms that the media composition and the degree of hydrolysis influenced the inhibitory activity of hydrolysates . the discrepancies observed between liquid and solid media can be explained by the fact that particulate nature of solid media restricted mass transfer of the relatively large , polymeric chitosan molecules , which reduced the chance of contact with a microbial cell in the agar . another possibility is a dilution factor related to the number of molecules in a static medium . chitosan stock solutions are prepared with 40 g / l and chitosan is then degraded with chitosanase . for the same initial number of molecules , the most hydrolyzed chitosan showed a higher relative number of molecules than the native one . fig5 and 6 show transmission electron micrographs of sc . unisporus y - 42 . treatments with chitosan - lactate were examined in ym at ph 3 . 8 and 6 . 0 but no differences could be observed between either values , probably because these ph were below the pka of chitosan ( 6 . 34 ). for this reason , only micrographs of ym at ph 3 . 8 were presented . for sc . unisporus y - 42 , a thick sheath of refractive substances could be observed around the cell wall after 1 h exposure to chitosan - lactate dp25 ( fig5 - b ) and the thickness of the layer increased with the term of exposure to chitosan - lactate ( fig5 - c ). the adsorption pattern was irregular but often covered the entire cell wall surface . the material had the appearance of a “ heap of needles ” as shown in fig6 - a . the placement of these heaps seemed to be linked at some specific sites of the cell wall ( fig6 - b ). these refractive substances could be hydrolyzed by chitosanase . furthermore , sc . bayanus y - 43 , the less sensitive strain to chitosan hydrolysates vjm broth ( fig3 ), did not show this coating ( fig7 ). the results obtained with sc . unisporus y - 42 reveal an irregular coating and support the phenomenon of “ cell suffocation ”. this is based on the ability of the reactive amino groups in chitosan to interact with a multitude of anionic groups on the yeast cell surface , thereby forming an impervious layer around the cell , and causing a loss of active transport and a modification of membrane permeability which could become irreversible after a certain point . therefore , this phenomenon does not exclude the possibility that chitosan causes a more direct disturbance of the membrane function by the leakage of proteinaceous and uv - absorbing materials . the fact that no coating could be observed on sc . bayanus y - 43 , which also demonstrated a chitosan - lactate sensitivity in both solid and liquid media suggests that the chitosan could have multiple mechanisms of action at the same time that do not necessarily implicate the cell wall or the membrane . it is reported that chitosan could bind a range of heavy metals and trace elements and suggested that the antimicrobial activity of chitosan was principally linked to chelating properties conferred by the polycationic nature of chitosan . this hypothesis could apply to our results but further investigation is needed to verify if this is also the case for sc . bayanus y - 43 . our results suggest therefore a multiple mechanism of action of chitosan . while the invention has been described in connection with specific embodiments thereof , it will be understood that it is capable of further modifications and this application is intended to cover any 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 and as may be applied to the essential features hereinbefore set forth , and as follows in the scope of the appended claims .

US-50414705-A

method and device for digital x - ray tomosynthesis . tomographic and / or three - dimensional images of an object are obtained with an x - ray source and a digital x - ray image sensor . the source , object and sensor are positioned relative to each other and attenuation data is obtained for a large number of rays of x - radiation through the object . a special algorithm is provided to convert the data into images . to calculate the images the algorithm uses iterative processes with a least squares type technique but with generalized functions . the algorithm solves for the functions which are the images . preferred embodiments include a system having an x - ray point source with a cone of diverging x - rays , a two - dimensional digital x - ray image sensor , two linear translation stages to independently move both the x - ray source and the digital x - ray image sensor , two rotation mechanisms to rotate the two linear translation stages , a microprocessor to control the data acquisition , and a computer programmed with a special algorithm to calculate the tomographic images . a plurality of sets of digital data are acquired by the digital x - ray image sensor , with the x - ray source and the digital x - ray image sensor located at different positions and angles relative to the object . the digital data representing the x - ray attenuation images is stored in the computer . special mathematical algorithms then compute multiple images of the object using the acquired digital data . these images could include multiple tomographic images , a three - dimensional image , or a multiple three - dimensional images .

preferred embodiments of the dxt system hardware are displayed in fig2 . x - ray source 120 is attached to linear translation stage 85 which is attached to pivot assembly 90 . this enables the x - ray source 120 to be selectively positioned along a plane at the top of the dxt system so that x - ray source assembly 121 can be move left and right from its central position show in fig1 . in addition , the x - ray source 120 can be selectively tilted about pivot point 119 for each position of the x - ray source along the dimension of the translation stage 85 , in order to direct the cone of x - rays directly at the object to be imaged . digital x - ray image sensor 115 is positioned on linear translation stage 105 which is attached to pivot assembly 110 . this enables the digital x - ray image sensor 115 to be selectively positioned along a plane at the base of the dxt system . the source - to - image distance ( sid ) is adjustable in the range of 50 – 100 cm by the use of telescopic pillars 95 supplied by skf magnetics with offices in bethlehem , pa . the object to be imaged is placed on platform 100 that is transparent to x - rays . platforms can be placed at any of five vertical levels and then positioned vertically at different heights ( 0 – 50 cm ) with pillars 95 relative to the digital x - ray image sensor 115 . the preferred x - ray sensor 115 is an indirect detection sensor based on a thin - film transistor ( tft ) technology that involves the fabrication of a two - dimension array of amorphous silicon - based electronic circuit pixels on large ( 30 cm × 40 cm , for example ) glass sheets . the tft array is sensitive to visible radiation ( 400 nm – 700 nm ). this array is coated or covered with a material that converts incident x - rays to visible light and the visible light is recorded by the pixelated tft array and digitized to provide a two - dimensional digital image of the incident x - rays . typical x - ray to light converters include gadolinium oxisulfide ( gd 2 o 2 s : tb ) phosphor screens or dendritic cesium iodide scintillator coatings . preferred x - ray to light converters include high x - ray attenuation characteristics ( pi - 200 gd 2 o 2 s : tb , 436 microns thick , 200 mg / cm 2 ; kasei opthonix , for example ), these converters provide very good detective quantum efficiency ( dqe ) and very good special resolution . alternate sensor embodiments include direct detection x - ray sensors ; such as amorphous selenium coated tft arrays , for example . incident x - ray photons are converted directly into electronic charge in the amorphous selenium layer , and the charge is collected at each pixel . indirect detection x - ray sensors available from canon , thales , and varian and direct detection x - ray sensors are available from general electric and hologic . the preferred x - ray source 120 features a tungsten non - rotating anode with a 50 – 160 kvp tube potential range , and a 0 – 0 . 5 ma tube current . a microprocessor subsystem controls the position of x - ray source 120 and x - ray sensor 115 by controlling translation stages 85 and 105 and rotation stages 90 and 110 . the microprocessor subsystem also controls the technique factors ( tube voltage , tube current , and exposure time ) of x - ray source 120 . the dxt system incorporate a computer and software to acquire , store , and display projection radiographs ; provide digital tomosynthesis image reconstruction calculations ; and display tomographic images . the preferred geometrical arrangement for the invention is displayed in fig3 . the positioning of x - ray source 120 is constrained to positions 210 ( i . e ., x i , y i , h ) on x - ray source plane 200 , and the positioning of x - ray sensor 115 is constrained to x - ray sensor plane 230 that is parallel to x - ray sensor plane 200 at a distance h = sid . the system produces tomographic images located in tomographic image plane 220 that is parallel to x - ray sensor plane 120 at distances h and a tomographic slice thickness dh . a plurality of tomographic images are calculated , each image at different distances h from x - ray sensor plane 210 . typical x - ray 223 is emitted at angle ( θ , φ ) [ representing dimensions ( elevation , azimuth )] by x - ray point source 120 that is located at position ( x i , y i , h = sid ) in x - ray source plane , and travels a straight line trajectory that intercepts tomographic image plane 220 at position ( x tomo , y tomo , h ) and is then incident on x - ray sensor 115 , located at x - ray sensor plane 120 , at pixel position ( x , y , h = 0 ). the primary objective of digital tomosynthesis is to provide an x - ray attenuation image that is isolated to a single tomographic slice , so that spatially varying x - ray attenuation from other slices does not clutter the image . a second objective is to help identify features by finding the three - dimensional positions of the features . previous dxt methods have implemented a simple shift - and - add technique that basically emulates the motional blurring described by the gt method , in order to visualize the single image plane at the fulcrum of motion of the x - ray source and image sensor . we describe the important features of our method which include positioning of the source and sensor relative to the object being imaged and a special algorithm for constructing images using the acquired data : 1 ) optimal positioning of the x - ray source : this feature describes a preferred total number of digital projection radiographs , and total x - ray dose to produce image reconstruction with minimal image aliasing artifacts . these constraints depend on aliasing and spatial frequency range considerations , as well as the source - to - image distance ( sid ). a ) aliasing : there is a minimum preferred angular positioning step of the x - ray source required to discriminate planes for desired spatial frequencies of the image . this step is such that the spatial shift of the highest spatial frequency from the top slice to the bottom slice is approximately 1 line pair . if a larger minimum step were to be used , there would be some ambiguity in the reconstruction as to which plane the feature was in ( known as aliasing ) which would increase the noise in the image . for the preferred system , we specify f max = 1 . 5 lp / mm , object thickness = 300 mm , which results in a minimum step of 2 milliradians ( 0 . 23 degrees ). b ) spatial frequency range : a large angular positioning range results in a reduction of the image slice thickness for the lowest spatial frequencies . the angular positioning range is approximately the ratio of this low spatial frequency to the image slice thickness . very low spatial frequencies cannot be well localized without scanning through large angles . the preferred angular positioning range is 1 . 0 radian ( 57 . 32 degrees ), depending on the features of interest . c ) source - to - image distance ( sid ): the preferred sid is chosen based on geometrical requirements , clearance requirements , and spot size requirements . if a 600 micron diameter x - ray spot tube is used , then a reasonable specification of 200 micron blur requires a 3 : 1 ratio of sid to subject depth . this translates into a preferred sid = 900 mm for a 300 mm typical subject . a 300 micron diameter spot tube will have lower x - ray exposure capability but places less constraints on the sid . from a geometrical perspective , there is a magnification effect for objects away from the detector , which becomes more extreme for small sids . a ratio of 2 : 1 magnification or less should cause little impact on the reconstruction process . the preferred range of sid is between 750 mm and 1000 mm . d ) one dimensional positioning of the x - ray source : the key to simultaneously resolving the constraints of aliasing and range is to let the positioning step length of the x - ray source be small near the center of the positioning range ( so that small features do not alias ) and larger as the tube moves away from the center ( so that the low spatial frequencies are well localized ). if constant sized steps were used , the number of image angles taken would be impractical . a preferred positioning of the x - ray source , in one scan dimension is displayed in fig4 . the positioning is symmetric around ( x center , y center ), defined as the center of x - ray source plane 200 , with 21 x - ray source positions , and a sid = 900 mm . the positions of x - ray source 120 are described by x i - x center = ± d [ exp ⁡ ( ⅈ ⁢ ⁢ a ) - 1 a ] eq . ⁢ ( 1 ) where d = 5 mm , a = 0 . 15 , and i = 0 , . . . , 10 ; so that the positions x i - x center = 0 , ± 5 . 4 mm ,± 11 . 7 mm , ± 18 . 9 mm , ± 27 . 4 mm , ± 37 . 2 mm , ± 48 . 7 mm , ± 61 . 9 mm , ± 77 . 3 mm , and ± 95 . 1 mm . the total positioning range for the preferred embodiment is 2 * 116 . 1 mm = 232 . 2 mm and degrees . e ) two - dimension positioning of the x - ray source : most prior implementations of digital tomosynthesis so far have used positioning of the x - ray source in only one dimension , as shown in fig4 . while acceptable for some applications , there is a serious drawback , namely , it is impossible to localize the slice height of objects running parallel to the positioning direction . the best way around this is to position x - ray source 120 in two dimensions , thereby removing any sensitivity to object orientation . the preferred embodiment for this two dimension positioning , displayed in fig5 , is x i - x center = ± d ⁡ [ exp ⁡ ( ⅈ ⁢ ⁢ a ) - 1 a ] ⁢ ⁢ and ⁢ ⁢ y i - y center = ± d ⁡ [ exp ⁡ ( ⅈ ⁢ ⁢ a ) - 1 a ] eq . ⁢ ( 2 ) where d = 5 mm , a = 0 . 15 , and i = 0 , . . . , 9 . eq . ( 2 ) gives the positions x i − x center = 0 , ± 5 . 4 mm , ± 11 . 7 mm , ± 18 . 9 mm , ± 27 . 4 mm , ± 37 . 2 mm , ± 48 . 7 mm , ± 61 . 9 mm , ± 77 . 3 mm , ± 95 . 1 mm , and ± 116 . 1 mm , with the y - axis of x - ray source 120 positioned at y center ; and positions y i − y center = 0 , ± 5 . 4 mm , ± 11 . 7 mm , ± 18 . 9 mm , ± 27 . 4 mm , ± 37 . 2 mm , ± 48 . 7 mm , ± 61 . 9 mm , ± 77 . 3 mm , and ± 95 . 1 mm , with the x - axis of x - ray source 120 positioned at x center . the total number of positions of x - ray source 120 is 41 . the total angular positioning range is θ = 2 * arc tan ( 232 . 2 mm / 900 mm )= 0 . 52 radians = 30 degrees . f ) x - ray source positioning accuracy : the required accuracy of the translation stage is a fraction of the spot size of x - ray source 120 . this translates to roughly 200 micron positioning accuracy for a spot size of 600 microns for x - ray source 120 , which can be reasonably achieved . 2 ) optimal positioning of the x - ray sensor : fig6 a ( 1 ) and ( 2 ) show that the preferred x - ray sensor 115 is positioned , for each x - ray source 120 position , so that the field of view of the object is maximized . this is accomplished by positioning x - ray sensor 115 in a direction opposite to x - ray source 120 position so that a line 300 between x - ray source 120 and the center of x - ray sensor 115 has a virtual fulcrum of motion 310 that is approximately 20 cm above x - ray sensor 115 ; this provide a 30 cm field - of view . fig6 b ( 1 ) and ( 2 ) show that a 42 cm fulcrum of motion 310 only provides a 12 cm field of view and fig6 c ( 1 ) and ( 2 ) show that a 0 cm fulcrum of motion 310 only provides a 22 cm field of view . 3 ) linear image reconstruction algorithm : a preferred reconstruction algorithm takes input digital projection radiograph image data of an object with the x - ray source at multiple positions and angles relative to the object , and transforms the input data into tomographic images . a number of techniques have been demonstrated to date , such as the simple shift - and - add approach and iterative techniques . we have developed an image reconstruction algorithm that we believe outperforms the other approaches while being computationally manageable . a ) mathematical description of reconstruction algorithm : the geometry of the mathematical problem is displayed in fig3 . x - ray point source 120 ( stet ) is positioned at different n separate positions 210 ( x i , y i ); i = 1 , n in x - ray source plane 200 located at h = sid . the x - ray sensor is located in the x - ray sensor plane located at h = 0 . the the three - dimensional object that is imaged is represented by a scalar function d ( x tomo , y tomo , h ) in the dimension of hounsfield units we calculate d ( xyh ). the hounsfield unit is the common metric for computer axial tomography ( cat ) scan images . one hounsfield unit equals a 0 . 1 % difference in the density of water and the range of hounsfield units is from − 1000 ( air ) to 1000 ( bone ) with 0 hounsfields as the density of water . the attenuation of x - rays directed along the line 223 ( trajectory s ) is given by a i ⁡ ( s ) = a i ⁡ [ ∫ 0 s ⁢ d ⁡ ( x tomo , y tomo , h ) ⁢ ⅆ s ′ ] eq . ⁢ ( 2 ) where ( x tomo , y tomo ) are the coordinates where the trajectory s crosses the tomographic plane at z = h . the functional form of a i ( s ) is nearly exponential and depends on the x - ray spectrum of the x - ray source . the coordinates ( x tomo , y tomo ) = ( x ⁡ [ 1 - h sid ] + hx i sid , y ⁡ [ 1 - h sid ] + hy i sid ) eq . ⁢ ( 3 ) we can combine equations 2 – 5 and express the log of the attenuation of x - rays along the trajectory s from the x - ray source position ( x i , y i , h = sid ) to the position ( x , y , h = 0 ) in the plane of the x - ray sensor as the log of the pixelated digital x - ray images acquired by the digital x - ray image sensor are represented by m i ( x , y )= m 0 i ( x , y )+ n i ( x , y ) eq . ( 7 ) m 0 i ( x , y )= w ( x , y ) a i ( s ){ circle around (×)} psƒ ( x , y ) eq . ( 8 ) are the noise - free measurements for each the n source positions ( x i , y i ); i = 1 , n , n i ( x , y ) is the noise , w i ( x , y ) is the white field image acquired during calibration , and psƒ ( x , y ) is the point spread function . in equation 8 , the symbol { circle around (×)} denotes a two - dimensional convolution operation over variables ( x , y ). the white field will be measured directly for each x - ray source position and not calculated so as to calibrate other effects such as angular variations of the x - ray source pattern and x - ray anti - scatter grid effects , for example . by combining equations 6 and 8 , we have we need to invert equation 9 to express the tomographic slice image data d ( x , y , h ) in terms of the acquired noise free data m 0 ( x , y ). we invert equation 9 by minimizing the following generalized chi - squared function versus the function d ( x tomo , y tomo , h ) χ 2 = ∑ i ⁢ ∫ ∫ ( m i ⁡ ( x o , y o ) - m0 i ⁡ ( x o , y o ) ) ⁡ [ ( n ⁡ ( x 0 , y 0 ) ⁢ n ⁡ ( x 1 , y 1 ) ) avg ] - 1 ⁢ ( m i ⁡ ( x 1 , y 1 ) - m0 ⁡ ( x 1 , y 1 ) ) ⁢ ⅆ x o ⁢ ⅆ y o ⁢ ⅆ x 1 ⁢ ⅆ y 1 + ɛ ⁢ ∫ ∫ d ⁡ ( x , y , h ) 2 ⁢ ⅆ x ⁢ ⅆ y ⁢ ⅆ h eq . ⁢ ( 10 ) where e is a regularization parameter chosen so that the first term averages 1 per measurement and m 0 is implicitly a function of d . we simplify equation 9 by first remapping d to the function d d ⁡ ( x , y , h ) = d ⁡ ( x ⁢ sid sid - h , y ⁢ sid sid - h , h ⁢ sid sid - h ) ⁢ ( sid sid - h ) 2 eq . ⁢ ( 11 ) the integrals in equations 6 and 10 are then transformed to the noise correlation is generated from the noise power spectrum ( nps ) function ( n i ( x 0 , y 0 ) n i ( x 1 , y 1 )) avg =∫ nps ( x 0 − x , y 0 − y , x 1 − x , y 1 − y , x , y ) dxdy eq . ( 17 ) we assume at the noise is slowly varying over the region integrated ( a common approximation ), so we can approximate ∫ nps ⁡ ( x o - x , y o - y , x 1 - x , y 1 - y , x , y ) ⁢ ⅆ x ⁢ ⅆ y = ⁢ nps ⁡ ( x o - x 1 , y o - y 1 ) ⁢ noise i ⁡ ( x o , y o ) ⁢ noise i ⁡ ( x 1 , y 1 ) eq . ⁢ ( 18 ) where nps is the noise power spectrum correlation function normalized to 1 at 0 lp / mm , and “ noise ” is more slowly varying 0 lp / mm noise . the assumption restated is that the noise varies too slowly to matter much which parameter x is used in its argument . we next define an “ integrated hounsfield ” measurement m and its noise free version m 0 , which is a transform of the raw measurement m 0 by using a first order taylor expansion ( which is appropriate for the low noise regime we will operate in ), and bringing the slowly varying white field term w i ( x , y ) outside of the convolution , the difference of m and m 0 is a transformed noise term m i ⁡ ( x , y ) - m0 i ⁡ ( x , y ) = ⁢ ( m i ⁡ ( x , y ) - m0 i ⁡ ( x , y ) ) ⊗ ( psf - 1 ⁡ ( x , y ) ) sec ⁢ ⁢ θ i ⁡ ( x , y ) ⁢ w i ⁡ ( x , y ) ⁢ a ′ ⁡ ( m i ⁡ ( x , y ) ⁢ sec ⁢ ⁢ θ i ⁡ ( x , y ) ) ⁢ ⁢ where ⁢ ⁢ a ′ ⁡ ( v ) = ⅆ ⅆ v ⁢ a ⁡ ( v ) . eq . ⁢ ( 21 ) notice that the term in the denominator w i ( x , y ) a ′( m i ( x , y ) secθ i ( x , y )) is the derivative of the signal versus thickness which we will call “ dsignal ” and which can calculated or measured . using this expression m i ( x , y )− m 0 i ( x , y )=[( m 0 i ( x , y )− m i ( x , y )) dsignal i ( x , y ) sec θ i ( x , y )]{ circle around (×)} psƒ ( x , y ) eq . ( 22 ) the convolution in the middle is , by definition , the detective quantum efficiency noise dsignal 2 = δ ⁢ ⁢ t2 eq . ⁢ ( 25 ) which is the “ thickness noise ” squared . since noise is a strong function of thickness , and a weak function of angle , we can treat δt 2 as a function only of thickness . this function , like dsignal , can be calculated or measured . σ i ⁡ ( x , y ) = noise i ⁡ ( x , y ) dsignal i ⁡ ( x , y ) ⁢ sec ⁢ ⁢ θ i ⁡ ( x , y ) - 1 ⁢ ⁢ = sec ⁢ ⁢ θ i ⁡ ( x , y ) - 1 ⁢ δ ⁢ ⁢ t2 ⁡ ( m i ⁡ ( x , y ) ⁢ sec ⁢ ⁢ θ i ⁡ ( x , y ) ) eq . ⁢ ( 26 ) we can solve equation 27 by calculating the derivative of χ 2 versus d ( x 0 , y 0 , z 0 ) and calculating where this derivative equals 0 the problem with this expression is that d is a continuous variable of z , and divisions into z - slices will lead to inaccuracy and / or increased computational burden . there is a solution to this problem , however , which is to let d be defined from a generator that is discrete equation 30 can only be true if the individual elements in the i - summation are identically equal to zero we can simplify equation 31 further by defining a function c as in equation 31 , z max is determined by the height of the object that is imaged , and the integral excludes absorption below the detector or above z max in the solution . equation 31 can be expressed as this is the final equation to be solved for g , then we get d from g and finally d from d . if s were constant , then equation 33 could be inverted using fourier transforms because the convolutions become products ℑ ( dqe ) ℑ ( m i )= ℑ ( dqe ) ℑ ( c ij ) ℑ ( g j )+ εσ i 2 ℑ ( g i ) eq . ( 34 ) where ℑ denotes a fourier transform . equation 33 is then expressed as ℑ ( g i )=( ℑ ( dqe ) ℑ ( c ij )+ εσ i 2 δ ij ) − 1 ℑ ( dqe ) ℑ ( m i ) eq . ( 35 ) in equation 35 , the inverses are performed individually over each spatial frequency . note that these inverse matrices can be computed once and stored as a look - up table for improved computational speed . the stored data is required for each noise level and each value of z max , so this data will require a large storage capacity . the technique that we use to solve equation 33 for a non - constant s involves treating the problem in multiple iterations with a constant σ trial , solving equation 33 using the fourier transform method ( equation 34 ), calculating an error term , then iterating by reconstructing for the error term but using successively different values for the trial σ value σ trial . first calculate the error term dqe { circle around (×)}( c ij { circle around (×)} δ g i )+ εσ trial 2 δg i = error eq . ( 37 ) then repeat with a different value of σ trial . eventually , the “ error ” becomes sufficiently small and we have our solution . we start with the largest value s for s , and then gradually decrease . boundary conditions are handled by reflection conditions with tapering . the minimization function in this terminology is so , the first term should equal (# of tube positions )×(# of pixels ) when ε is set correctly . 1 ) transform the measurements m into the “ integrated hounsfield ” form m 2 ) repeat on : a . calculate error term using non - constant s b . select trial value strial c . invert the error term with strial d . update g e . change strial 3 ) for a given slice selection , calculate d from g 4 ) calculate d from d this section provides the computational flow chart for the linear image reconstruction algorithm . data taken over all of the pixels , one shot for each tube location i . nominal 41 tube locations , 2304 by 3072 pixels . map of dead pixels , assumed constant for all i . if not , then must have a map for each i . bins image data into n × n units . nominal choices are n = 4 ( fine ) and n = 8 ( coarse ). m bin i ( x , y )= bin ( mraw i ( x , y )* dead ( x , y ), n )/ bin ( dead ( x , y ), n ) dark field , assumed constant for all i . this assumption must be verified , may not be constant . white field , definitely not constant vs . i , due to geometrical , grid , and other effects . needs to be recalibrated every time tube settings are changed , either in output or position . white i ( x , y )= mbin i ( x , y )− dark ( x , y ) for an exposure with no subject ( or a small amount of plastic plate ). compute mcal i ( x , y ) for various thicknesses t of water equivalent plastic plate , to give mthick i ( x , y , t ). fit to the following function : m thick i ( x , y , t )= c 0 i ( x , y )* exp ( t *( c 1 i ( x , y )+ c 2 i ( x , y )* t )/( c 3 i ( x , y )+ t ) where c 0 , c 1 , c 2 , and c 3 are slowly varying functions , probably a low order polynomial fit in x and y for each i . m lin i ( x , y )={− c 1 + ln ( m cal / c 0 )+[( ln ( m cal / c 0 )− c 1 ) 2 + 4 * c 2 * c 3 * ln ( m cal / c 0 )] 1 / 2 }/( 2 * c 2 ) where i have dropped the ( x , y ) and i notation for simplicity . this parameter was called m i in solver algorithm write - up . the 1 / secθ i ( x ) term in the write up is implicitly included in our linearization calibration because we use flat plates , which already have the effect built in . let source be at ( xs i , ys i , sid ) and detector be at ( x , y , 0 ) then secθ i ( x , y )=[( xs − x ) 2 +( ys − y ) 2 + sid 2 ] 1 / 2 / sid ( the ratio of pixel distance from source to sid ) functional relationship that estimates noise from thickness of water traversed , found by modeling : δ t 2 e ( t )= 1 . 487 * 10 − 5 mm 4 * exp ([( t / 4 . 385 cm )* 38 . 6 cm +( t / 5 . 481 cm )* t ]/[ 38 . 6 cm + t ])/( pixel area ) the output has units of length 2 , which corresponds to the error squared of the length estimate . σ i ( x , y )={ δ t 2 e [ m lin i ( x , y )* secθ i ( x )]} 1 / 2 / secθ i ( x ) this is the estimate of the error in mlin i ( x , y ). it should be very close to a computation of the variance from the region around each pixel for uniform subjects , and can be checked in this way . as an alternative , we can try using a 3 × 3 nearest neighbor box and computing the variance within this box as an estimate for σ i ( x , y ). the output of this method should be clipped on the low side by a minimum value . this is a global constant parameter that determines how smooth the solution is . we will try reconstructions for different values until we understand what is preferable . compute the c i , j ( k x , k y ) cholesky matrices : these will be described separately , as it is the most involved portion of the algorithm . we will compute generators g i ( x , y ) as the output to the main algorithm , which is then put into a simple quick slice algorithm to recover the slice image . the generators are computed on an array the size of mbin , but are imbedded in a larger padded array , and use reflection or zero padding as boundary conditions . the height from the detector is described by h , but the algorithm uses a modified height variable that i have called z , but will start calling z eff to prevent confusion . the relationship is as follows : z eff =( sid * h )/( sid − h ), with inverse h =( sid * z eff )/( sid + z eff ) we use h max to denote the maximum object height from the detector . the algorithm assumes that there is nothing above this height . the corresponding z max =( sid * h max )/( sid − h max ). the pivot point is placed at h piv = 1 /( 2 / h max − 1 / sid ). the corresponding z piv = z max / 2 . each tube position has angles ( θx i and θy i associated with it . the formula for these angles is : the images are first computed for a scaled slice that we call d : d ( x , y , z eff )= sum i { g i [ x − θx i *( z eff − z piv ), y − θy i *( z eff − z piv )]} or in other words , the generator images are shifted by an amount that depends on height , then added together . the value of z eff given height is described above . to recover the actual image d ( x , y , h ), we must zoom and scale d : d ( x , y , h )= d ( x * zoom , y * zoom , z eff )* zoom 2 , where zoom = sid /( sid − h )= z eff / h . we are ignoring the dqe effects for this first version of the algorithm . err i ( x , y )= m lin i ( x , y )− sum j { c ij ( x , y ){ circle around (×)} g j ( x , y )}− eps * σ i ( x , y ) 2 * g i ( x , y ) the error is computed over the detector area . the convolution operation { circle around (×)} will be described later . the convolution requires that the array be imbedded in a larger working area , and before the convolution takes place the data is padded either by reflection or just zeroing outside the detector area . the choice of boundary conditions must be the same as that used to generate the slice images . next invert this error value : δ g i ( x , y )=[ c ij ( x , y )+ eps * σ0 2 * δ ( x , y )* δ ij ] − 1 { circle around (×)} err i ( x , y ) where σ 0 is a constant , at least for a particular iteration . then each iteration can either use the same choice for σ 0 or can vary to improve convergence . a good starting value is the maximum of σ i ( x , y ). the total rms of [ err i ( x , y )/ σ i ( x , y )] is used to decide if convergence is adequate . in order to efficiently compute the forward and backward convolutions while minimizing data storage , a number of complications must be introduced : 1 ) the convolutions , as is usual are computed using fft &# 39 ; s 2 ) since the matrix operations take place in fourier space , c ij ( x , y ) is never actually computed or stored but rather c ij ( k x , k y ). 3 ) in fourier space the convolutions become just simple matrix multiplications . 4 ) since the generator functions are real , and their fourier transform are symmetrical , a normal fft has a factor of 2 redundancy . we therefore use a 2d real fft instead . 5 ) due to the fact that c ij ( x , y ) is real , c ij ( k x , k y ) is symmetrical . we therefore only need to compute for half of the spatial frequencies , say k x ≧ 0 . 6 ) since we picked the pivot point z piv at exactly half of z max , the c ij ( x , y ) turn out to be symmetrical ( in x , y ), and therefore c ij ( k x , k y ) is real . 7 ) the c ij ( k x , k y ) are also symmetrical , and in fact positive definite , in i , j . the positive definiteness follows from the definition of c , which will be discussed later . this allows c to be factored into a cholesky decomposition , that is into a product of a lower triangular matrix l with itself c = l * l t . 8 ) only l is stored , and only the triangle of data values are saved and not the zeros . 9 ) to be more precise , we use l * l t = c ij ( k x , k y )+ eps * σ 0 2 * δ i , j 10 ) in the forward operation we need to subtract σ 0 2 back out from the σ i ( x , y ) 2 because we added it into the cholesky matrices 11 ) the inverse operation can be computed almost as efficiently as the forward operation due to the properties of cholesky matrices . therefore we do not need to save separate matrices for each operation . 12 ) we need to write a special code to take the packed l matrices and perform the forward and inverse vector multiply operation . this is pretty easy , i will write it up . 13 ) we need to get a real fft code and implement it . a site called fftw . org seems to have this for free , but we will need to change it to single precision . 14 ) the fft &# 39 ; s use padded arrays , which need to approximately add at least the size of the convolution kernels of c ij ( x , y ). the array plus padding also must be a nice size for the fft , such as a power of 2 times some small prime number ( 2 , 3 , 5 ). 15 ) the padding rules will have to be evaluated , but either zero padding or reflection padding will probably be best . it should make the most difference when the subject is sticking off the edge . c ) numerical operation count : this section provides computational operation count as follows : assumptions : 41 measurements , each with 2000 × 2000 pixels , and reconstruct 20 slices input fft &# 39 ; s : 28 * 10 ^ 9 real multiplies matrix operations : 13 * 10 ^ 9 real multiplies output fft &# 39 ; s : 14 * 10 ^ 9 real multiplies total : 55 gops the computation time is therefore 1 min on a 1 gflop processor . note the assumptions are conservative and much faster processing times are possible with smaller data sets . d ) rationale for image reconstruction algorithm : the preferred linear image reconstruction algorithm , described by the χ 2 minimization equation ( 10 ), is derived using equation ( 18 . 4 . 9 ) and ( 18 . 4 . 11 ) in numerical recipes in fortran 77 ; the art of scientific computing ”, chapter 18 . 4 “ inverse problems and the use of a priori knowledge ”, cambridge university press , pg . 795 – 799 ( 1986 – 1992 ). χ 2 = ∑ ij ⁢ [ c i - ∑ μ ⁢ r i ⁢ ⁢ μ ⁢ u ⁡ ( x μ ) ] ⁢ s ij - 1 [ c j - ∑ μ ⁢ r j ⁢ ⁢ μ ⁢ u ⁡ ( x μ ) ] + λ ⁢ ∑ μ ⁢ u 2 ⁡ ( x μ ) eq . ⁢ ( 40 ) where c i ≡ m i ( x 0 , y 0 ) are the measurements , ∑ μ ⁢ r i ⁢ ⁢ μ ⁢ u ⁡ ( x μ ) ≡ m o ⁡ ( x o , y o ) are the unknown model data convolved with the response function of the measurements system , and s ij ≡( n ( x 0 , y 0 ) n ( x 1 , y 1 )) avg is the covariance noise function . eq . ( 40 ), and therefore eq . ( 10 ), is the functional generalization of the conventional chi - squared fitting algorithm that fits a straight line , for example , to a measured set of data points ( x i , y i ); the best fit seeks to minimize the function ( eq . 15 . 1 . 5 in numerical recipes ) χ 2 = ∑ i ⁢ ( y i - y ⁡ ( x i ; a 1 , … ⁢ , a m ) σ i ) eq . ⁢ ( 41 ) where σ i is the uncertainty , or noise , associated with each data point . the fit is constrained to functional form ( straight line or quadratric function , for example ) and constants ( a 1 , . . . , a m ) are determined by the fit . equations ( 40 ) and ( 10 ) seek to minimize an equivalent χ 2 function but do not constrain the problem to a specific functional form . the optimal three - dimensional function d ( x tomo , y tomo , h ), representing the tomographic images , is calculated by the minimization routine . equation ( 40 ), and equation ( 10 ), is constrained by the second term that imposes a certain amount of “ smoothness ” to the solution , depending on the value of the regularization paerameter λ ( or ε ). the preferred embodiment uses a value ε = 0 . 01 for regularization parameter . e ) non - linear reconstruction algorithms : we assume that optimal reconstruction algorithm is the best that can be done with no assumptions about the nature of the subject being imaged . the proposed dxt system incorporates non - linear algorithms that incorporate additional information : minimization of the effect of overlaying tissue by tailoring sidelobe artifacts to be lower from regions with strong features and higher from featureless areas . techniques developed for sonar and radar may be applicable . these basically work by weighing projections more heavily which pass through “ windows ” in the subject . sharpening of slice thickness by “ concentrating ” features . some spatial frequencies can be located in depth better than others , so we can increase the probability that a feature at one spatial frequency lies together with the same feature measured at a different spatial frequency . imposing an outer boundary of the subject , so we can numerically constrain zero tissue outside of this boundary . a computer simulation of a preferred linear reconstruction algorithm is displayed in fig7 and 8 . the object is a thick walled cone with an “ x ” in the very center of the object ; this object was taken to be a combination of low and high spatial frequencies to demonstrate various aspects of the algorithm , and present a reasonably challenging case . the simulated cone is made up of 100 separate slices to ensure accuracy . multiple digital projection radiographs of the cone viewed from various positions of the x - ray source 120 are displayed in fig7 . fig8 through 10 displays original tomographic images ( left ) and images reconstructed from the digital projection radiographs of the cone model ( right ) in steps of 10 % of the thickness from 0 % to 100 %. fig8 shows the bottom 4 slices 0 %, 10 %, 20 %, and 30 %. fig9 shows slices 40 %, 50 %, 60 %, and 70 %. fig1 shows slices 80 %, 90 %, and 100 %. notice that there is only a faint hint of the center 50 % slice cross which spilled over into the 40 % and 60 % reconstruction slices . notice also the preservation of both the high resolution from the center cross and the lower spatial frequencies from the wall of the cone . an alternate embodiment of the invention involves the use of multiple x - ray sources in order to provide faster imaging times , and therefore higher throughput . fig1 displays the side views and fig1 the front views of a dxt system that incorporates a line of five x - ray sources 350 in a line that sequentially expose digital x - ray sensor 365 and provide five separate projection radiographs . conveyor belt 370 re - positions object 360 in a direction perpendicular to the line of x - ray sources 350 to a plurality of positions ( 8 positions preferred ) where x - ray sources 350 provide five digital projection radiographs at each position of object 360 in order to provide a total of 40 projection radiographs ; this data is used to reconstruct tomographic images of object 360 . this system is useful for luggage inspection . it uses the same basic algorithm as described above . while there have been shown what are presently considered to be preferred embodiments of the present invention , it will be apparent to those skilled in the art that various changes and modifications can be made herein without departing from the scope and spirit of the invention . for example , prior art techniques can be incorporated for fast readout of data to enable good images of moving parts such as the heart and lungs of people . the invention can be applied to a variety of uses in addition to medical imaging and luggage screening . the invention can be made portable for use by emergency teams and battlefield conditions . known techniques can be incorporated for automatic recognition of items such as weapons and explosives based on shape and attenuation information . many modifications could be made to the specific algorithm which has been described in detail without departing from the basic concepts of the present invention . for example other least square techniques other than the one specifically described can be used with generalized functions to turn x - ray data into images . thus , the scope of the invention is to be determined by the appended claims and their legal equivalents .

US-7766605-A

a surgical instrument handle includes adaptations for improved ergonomics , such as broad , rounded hand - contacting surfaces and physiologic range of motion for instrument actuation . the handle may be mostly enclosed by the hand in use , and may be stabilized by the palm , ring finger , and little finger . one example includes a ratchet mechanism and release button .

standard medical planes of reference and descriptive terminology are employed in this specification . a sagittal plane divides a body into right and left portions . a mid - sagittal plane divides the body into bilaterally symmetric right and left halves . a coronal plane divides a body into anterior and posterior portions . a transverse plane divides a body into superior and inferior portions . anterior means toward the front of the body . posterior means toward the back of the body . superior means toward the head . inferior means toward the feet . medial means toward the midline of the body . lateral means away from the midline of the body . axial means toward a central axis of the body . abaxial means away from a central axis of the body . the following disclosure is made in the context of a manual arthroscopic instrument for the purposes of illustration . the principles of the disclosed technology are applicable to a variety of other tools and instruments outside the scope of manual arthroscopic instruments . referring to fig1 , a surgical instrument 10 includes a working portion 12 and a handle portion 14 . the working portion 12 in this example includes a pair of opposed jaws 16 , 18 for grasping or biting a substance such as tissue . other working portions and / or end effectors may be substituted : rongeurs , scissors , suture graspers , suture passers , knot tiers , implant manipulators , implant actuators , and the like . the handle portion 14 includes a handle body 20 and a lever 22 mounted to the handle body 20 . the handle body 20 includes a finger loop 24 . the lever 22 includes a finger loop 26 and a finger rest 28 . the working portion 12 is operatively assembled to the handle portion 14 so that movement of the lever 22 relative to the handle body 20 causes actuation of the working portion 12 . in this example , the working portion 12 is carried by , or supported by , the handle body 20 . the lever 22 is pivotally mounted to the handle body 20 , and is connected to at least one sub - component of the working portion 12 , as will be discussed in more detail below . as the lever 22 pivots relative to the handle body 20 , the working portion 12 is actuated . in this example , the jaws 16 , 18 open and close as the lever 22 pivots relative to the handle body 20 . the jaws 16 , 18 may be said to move between a first state and a second state as the lever 22 pivots relative to the handle body 20 . in other examples , a different working portion may perform a different action in response to movement of the lever 22 . some examples of basic actions are opening , sliding , rotating , protruding , locking , cutting , vibrating , oscillating , reciprocating , heating , electrifying , magnetizing , illuminating , imaging , and the like . each action and its opposite action may be considered a pair of first and second states . it will be appreciated that , in some examples , multiple actions may occur in response to movement of the lever 22 in one direction , and their opposites may occur in response to movement of the lever 22 in an opposite second direction . in one specific example , a stationary jaw , such as jaw 18 , may be coupled to a first end 31 of a tube 30 . an opposite second end 33 of the tube 30 may be coupled to a first end 21 of the handle body 20 . a movable jaw , such as jaw 16 , may be opposably hinged to the stationary jaw 18 , and may also be connected to a first end of a shaft 32 ( not shown ), the first end of the shaft 32 adjacent the first end 31 of the tube 30 . the shaft 32 may be slidably and / or rotatably received within the tube 30 . an opposite second end of the shaft 32 may be connected to the lever 22 , the second end of the shaft 32 adjacent the first end 21 of the handle body 20 . the lever 22 may be pivotally mounted to the handle body 20 . in this example , when the lever 22 is pivoted toward the handle body 20 as shown in fig1 , the jaws 16 , 18 close . when the lever 22 is pivoted away from the handle body 20 ( not shown ), the jaws 16 , 18 open . the arrangement of the handle portion 14 may permit one or more of a user &# 39 ; s digits ( fingers ) to be inserted into the finger loops of the handle body 20 and lever 22 , as shown in fig9 . for example , an index finger 990 may be inserted into the lever finger loop 26 , a middle finger 992 may contact the finger rest 28 , and a thumb 998 may be inserted into the handle body finger loop 24 . while some users may find this “ fingertip grip ” to be satisfactory in terms of comfort , instrument control , mechanical advantage , efficiency , and the like , other users may find the fingertip grip to be unsatisfactory for continual use , or unsatisfactory right from the start . it has been observed that some users avoid inserting their digits into the finger loops . instead , these users may support the handle body 20 in the palm of the hand , with one or more fingers resting on the lever 22 . in other words , the hand wraps around the outside of the handle portion 14 . this “ palm grip ” may be preferred , at least by some users , because the wrist remains in an ergonomically neutral position , the instrument 10 tends to sit lower in the hand , the instrument 10 feels more stable , the fingers are unconfined by the finger loops 24 , 26 , and / or the instrument 10 is supported by portions of the hand other than the index and / or middle fingers 990 , 992 , so that support is independent of instrument actuation by these fingers . the following disclosure sets forth examples of instrument handle portions that may be adapted for the palm grip . the example handle portions are also adapted for actuation by the index and / or middle fingers , which are the so - called power fingers of the hand . the examples may be perceived by users as being better balanced than fingertip grip designs . the examples illustrate that the handle portion may be oriented relative to the working portion so that the user &# 39 ; s wrist remains in an ergonomically neutral position as the instruments are being used . an example with a ratchet mechanism is disclosed . the examples may be cost competitive relative to existing fingertip grip instruments . referring to fig2 a - 2b , a surgical instrument 40 includes a working portion 42 and a handle portion 44 . the working portion 42 in this example includes a pair of opposed jaws 46 , 48 for grasping or biting a substance such as tissue . other working portions and / or end effectors may be substituted : rongeurs , scissors , suture graspers , suture passers , knot tiers , implant manipulators , implant actuators , and the like . the handle portion 44 includes a handle body 50 and a lever 52 mounted to the handle body 50 . the instrument 40 includes a tube 60 between the working portion 42 and the handle portion 44 , and a shaft 62 ( not shown ) inside the tube . the surgical instrument 40 of fig2 a - 2b may share some of the characteristics set forth below for the surgical instrument 70 of fig3 a - 3b . the following description for instrument 70 also applies to instrument 40 of fig2 a - 2b , except as noted with regard to the ratchet link 100 , button 102 , button hole 85 , and pin hole 88 . referring to fig3 a - 3b , another surgical instrument 70 includes a working portion 72 and a handle portion 74 . the working portion 72 in this example includes a pair of opposed jaws 76 , 78 for grasping or biting a substance such as tissue . other working portions and / or end effectors may be substituted : rongeurs , scissors , suture graspers , suture passers , knot tiers , implant manipulators , implant actuators , and the like . the handle portion 74 includes a handle body 80 and a lever 82 mounted to the handle body 80 . the instrument 70 includes a tube 90 between the working portion 72 and the handle portion 74 , and a shaft 92 ( fig4 ) inside the tube . the surgical instrument 70 of fig3 a - 3b may share some or all of the characteristics set forth above for the surgical instrument 40 of fig2 a - 2b . unlike the surgical instrument of fig2 a - 2b , the example of fig3 a - 3b includes a ratchet link 100 and a button 102 . in the examples of fig2 a - 3b , the working portion is operatively assembled to the handle portion so that movement of the lever relative to the handle body causes actuation of the working portion . in these examples , the working portion is carried by , or supported by , the handle body . the lever may be pivotally mounted to the handle body , and may be connected to at least one sub - component of the working portion . as the lever pivots relative to the handle body , the working portion is actuated . in these examples , the jaws open and close as the lever pivots relative to the handle body . in other examples , the working portion may perform some other action , as listed above , in response to movement of the lever . in the example of fig3 a - 3b , a stationary jaw , such as jaw 78 , may be coupled to a first end 91 of a tube 90 . an opposite second end 93 of the tube 90 may be coupled to a first end 81 of the handle body 80 . in this example , the second end 93 is fixed in a hole 84 of the handle body ; thus tube 90 may be described as a stationary shaft . a movable jaw , such as jaw 76 , may be opposably hinged to the stationary jaw 78 , and may also be connected to a first end ( not shown ) of a shaft 92 ( fig4 ), where the first end of the shaft 92 is adjacent the first end 91 of the tube 90 . the shaft 92 may be slidably and / or rotatably received within the tube 90 ; thus shaft 92 may be described as a movable shaft . an opposite second end 94 ( fig4 ) of the shaft 92 may be connected to the lever 82 , where the second end 94 of the shaft 92 is adjacent the first end 81 of the handle body 80 . in this example , the second end 94 of the shaft 92 is coupled to the lever 82 by a series of links , as will be discussed in more detail below . in another example of the present technology , an outer tube may be the movable shaft and an inner shaft may be the stationary shaft . in yet another example , the stationary and movable shafts may both be tubes . in yet another example , the stationary and movable shafts may lie side by side , and may be solid or tubular . a solid shaft may have one or more inclusions , such as an inner conductive core surrounded by insulation . in further examples , multiple stationary and / or movable shafts may be included . the handle portion 74 may be shaped and sized to substantially fill the user &# 39 ; s palm . the size of the handle portion 74 may take into account published anthropometric data and human factors recommendations for grip span . as one example , the handle portion 74 may have a grip span of 5 . 5 cm at the lever pivot point ( pin 99 , fig3 a ), 7 cm at the center of the lever 82 , and 6 . 5 cm at the lever tip 83 . other grip span dimensions are contemplated in order to fit the natural distribution of hand sizes in the human population . the handle portion 74 may be shaped and sized so that the palm and the lesser two fingers , and optionally the thumb , are used to hold the handle portion 74 , leaving the index and middle fingers free to actuate the lever 82 . the lever 82 may be pivotally mounted to the handle body 80 , such as by pin 99 as shown in fig3 a . pin 99 may be referred to as a lever pivot point 99 . pin 99 is transversely offset from a central longitudinal axis of the tube 90 by about a handbreadth . the transverse offset may be between 6 cm and 10 cm ; other transverse offset dimensions are contemplated in order to fit the natural distribution of hand sizes in the human population , and in order to accommodate different design intents with regard to the amount of handle portion 74 covered by a user &# 39 ; s hand . when the lever 82 is pivoted away from the handle body 80 , the jaws 76 , 78 may be open , as shown in fig3 a . when the lever 82 is pivoted close to the handle body 80 , the jaws 76 , 78 may be closed , as shown in fig3 b . the instrument 70 of fig3 a - 3b may include a multi - link mechanism which cooperates with the handle body 80 , lever 82 , and pin 99 to provide the desired actuation stroke length and force magnification , also known as mechanical advantage . by positioning the lever pivot point 99 at a distance from the central longitudinal axis of the tube 90 , each finger moves through an anatomically and ergonomically appropriate actuation stroke length . the longer , stronger index and middle fingers can move farther than the smaller , weaker ring and little fingers . referring to fig4 - 5 , the handle portion 74 of the surgical instrument 70 of fig3 a - 3b has been cross sectioned along a plane of bilateral symmetry , also known as a center plane , mid - plane , or mid - sagittal plane . fig4 shows the instrument 70 in the open , resting , or non - actuated position and fig5 shows the instrument in the closed , active , or actuated position . while the following description points out specific characteristics of individual component parts , one of skill in the art will recognize that at least some of these characteristics may be altered , varied , or omitted without sacrificing the salient principles of the technology . referring to fig4 - 5 and 7 , the handle body 80 may be a thin - walled , hollow component that may be the primary structural element of the instrument . an aperture 96 may extend through the handle body 80 ; this example includes three apertures 96 of various shapes and sizes . the handle body 80 may present broad , rounded surfaces for contact with the palm of the hand . the palm - contacting surfaces , or backstrap , may be textured or may include high friction inserts to improve grip security . an extension , tang , or beavertail 95 may be present . the handle body 80 may be economically manufactured using a casting process , as one example . secondary operations may be performed , for example after casting , to form a shaft hole 84 and pin holes 98 , 101 , 103 , 104 , 105 . the handle body 80 may be simplified as a triangle , with apices at the center points of holes 98 , 101 , 103 , and line segments connecting the points . the center point of hole 98 may be referred to as a main pivot point because it forms a main pivot joint in combination with point 89 of the lever 82 . with reference to fig4 - 5 and 8 , the lever 82 may be a thin - walled , hollow component that is the location where the user applies actuation forces to the instrument 70 . the lever 82 may house a ratchet mechanism , as may be seen in fig3 a - 5 . the lever 82 may present broad , rounded surfaces for contact with the fingers of the hand . the lever 82 may be manufactured using a casting process , as one example . secondary operations may be performed , for example after casting , to form a button hole 85 and pin holes 87 , 88 , 89 . the lever 82 may be hinged to the handle body 80 by a pin through holes 89 and 98 . the lever 82 may be simplified as a line segment extending between the center points of holes 87 and 89 . the lever 52 of the surgical instrument 40 of fig2 a - 2b may be similar to lever 82 , but may lack the button hole 85 and / or pin hole 88 . with reference to fig4 - 5 , a main spring 86 may bias the instrument in the open position , although in other examples , the main spring 86 may bias the instrument in a closed position . the main spring 86 may be free - floating within the hollow sections of the handle body 80 and lever 82 . the position of the main spring 86 may be constrained in the handle body 80 and lever 82 by a retention pin 97 in each component . referring to fig4 - 6b , the first link 110 may be a connecting link . the first link 110 connects the lever 82 to the second link 112 , described below . the first link 110 may include an aperture 111 , and pin holes 117 , 119 in opposite ends of the first link 110 for connection to the lever 82 and second link 112 , respectively . the first link 110 may be hinged to the lever 82 at a first joint by a pin through holes 87 and 117 . the first link 110 may be simplified as a line segment extending between the center points of holes 117 , 119 . the second link 112 may be the force magnification link . the second link 112 receives input forces from the first link 110 and transfers the forces to the third link 114 . the magnitude of the force magnification , or mechanical advantage , can vary with the motion of the mechanism and / or the dimensions of the second link 112 . the magnification can increase as the mechanism moves from the open to the closed position . the second link 112 includes holes 120 , 123 , 124 for connection to the first link 112 , the handle body 80 , and the third link 114 , respectively . the second link 112 may be hinged to the first link 110 at a second joint by a pin through holes 119 and 120 , and hinged to the handle body 80 at a third joint by a pin through holes 101 and 123 . the second link 112 may also provide a connection point , or hole 122 for the ratchet link 100 as well as features to constrain the overall range of motion , such as a pin in slot 115 and hole 104 , which may form a sliding joint . the second link 112 may include an aperture 113 ; this example includes two apertures 113 . the second link 112 may also include a hole 121 for a drag plug ( not shown ). the second link 112 may be simplified as a triangle , with apices at the center points of holes 120 , 123 , and 124 , and line segments connecting the points . the mechanical advantage of the second link 112 may be at least partially determined by dividing the length of the line segment between points 123 and 120 by the length of the line segment between points 123 and 124 . the third link 114 may be another connecting link . the third link 114 connects the second link 112 to the jaw drawbar , or shaft 92 . the third link 114 may include pin holes 125 , 126 in opposite ends of the third link 114 for connection to the second link 112 and shaft 92 , respectively . the third link 114 may be hinged to the second link 112 at a fourth joint by a pin through holes 124 and 125 . the third link 114 may be simplified as a line segment extending between the center points of holes 125 , 126 . the fourth link 116 may be a control link that modulates , adjusts , or aligns the force vector from the third link 114 to match or align with the center longitudinal axis of the drawbar 92 , or a center longitudinal axis of the hole 84 through which the drawbar 92 passes . this may minimize load - induced deflections in the mechanism . the fourth link 116 may include pin holes 127 , 128 in opposite ends of the fourth link 116 for connection to the third link 114 and handle body 80 , respectively . the fourth link 116 may be hinged to the third link 114 at a fifth joint by a pin through holes 126 and 127 , and hinged to the handle body 80 at a sixth joint by a pin through holes 103 and 128 . the fourth link 116 may be simplified as a line segment extending between the center points of holes 127 , 128 . the actuation linkage is shown in the open position in fig4 and 6a , and in the closed position in fig5 and 6b . as the lever 82 rotates toward the handle body 80 , the center point of hole 126 of the third link 114 moves away from the first end 81 of the handle body 80 . the center point of hole 126 of the third link 114 moves along an arcuate path controlled by the fourth link 116 . the arcuate path includes a linear component acting along the center longitudinal axis of the hole 84 in the handle body 80 which receives the second end 93 of the tube 90 and / or the second end 94 of the shaft 92 , or other instrument components suitable for rongeurs , scissors , suture graspers , suture passers , knot tiers , implant manipulators , implant actuators , and the like . the arcuate path also includes a transverse component acting normal to the center longitudinal axis of the hole 84 in the handle body 80 ; this transverse component may be a small percentage of the linear component , and in some examples may be zero . the lever 82 receives an input force / rotation from the hand of a user , and by means of the linkage , transforms the user input to an output force / displacement at the center point of hole 126 of the third link 114 . in the example illustrated , the output is primarily a linear force / translation along the center longitudinal axis of the hole 84 in the handle body 80 , and secondarily a force / motion acting transverse to the center longitudinal axis of the hole 84 . the center point / axis of hole 126 of the third link 114 may be referred to as an actuation point , a drive point , or an output point of the handle portion 74 . the center longitudinal axis of the hole 84 may be referred to as an actuation axis , a drive axis , or an output axis of the handle portion 74 . the components of the actuation linkage may be manufactured using traditional machining processes or formed by casting with minimal secondary operations to the pin holes and clevis widths . alternate examples of the multi - link mechanism will now be discussed . these alternatives are contemplated for instruments 40 and 70 . the first link 110 may be replaced with a sliding connection between the lever 82 and the second link 112 . in this arrangement , lever 82 and second link 112 may be directly connected . the sliding connection may be a pin - in - slot arrangement , as illustrated elsewhere in the mechanism above , or it may be a shaft - in - collar arrangement , or the like . in one example , lever 82 may be modified to include a fixed extension with a forked end for engagement with a pin in hole 120 of the second link 112 . the orientation and extent of the fork may be selected to guide the pin in hole 120 along a path between the open and closed positions . the path may be similar or identical to a path between the open and closed positions followed by a pin through holes 119 and 120 in the mechanism of fig3 a - 5 . the third link 114 may be replaced with two or more individual links . this arrangement may be useful in situations where the linkage detours around an obstacle , such as another component in the handle portion 74 . some or all of the individual links which replace the third link 114 may be hinged together , or may include sliding connections , or they may bear against an internal part of the handle portion 74 , or they may be constrained by one or more control links similar to the fourth link 116 . the fourth link 116 may be replaced with a sliding connection between the third link 114 and the handle body 80 . the sliding connection may be like the ones described previously . the handle portion 74 may also be modified to include a transducer to convert the planar ( arcuate , quasi - linear , linear , etc .) motion of the center point of hole 126 of the third link 114 ( the output point of the handle portion 74 ) to rotational movement of a shaft , such as shaft 92 . in one example , motion of the output point may be mechanically converted to rotational motion by modifying the handle portion 74 to include an intermediate shaft between the third link 114 and the shaft 92 . in this arrangement , the shaft 92 may be proportionately shortened . a first end of the intermediate shaft may be hinged to the third link 114 at hole 126 , and optionally hinged to the fourth link 116 , if present , at hole 128 . an opposite second end of the intermediate shaft may include one or more transverse protrusions , such as posts , tabs , ears , bosses , and the like . the second end 94 of the shaft 92 may be modified to include a socket shaped and sized to receive the second end of the intermediate shaft . the interior of the socket may include one or more helical grooves shaped , sized , and positioned to receive the one or more transverse protrusions ; the number of grooves is equal to or greater than the number of transverse protrusions . as the center point of hole 126 of the third link 114 moves along its path in response to movement of the lever 82 , the intermediate shaft moves accordingly . the transverse protrusions interact with the helical grooves to force the socket , and therefore shaft 92 , to turn . this example provides alternating rotational motion as the handle portion moves between the open and closed positions . in a further development of this example , a clutch and / or flywheel may be added so that the shaft 92 may be driven in a single rotational direction , and may build up speed with each actuation of the lever 82 . returning to fig3 a - 5 , the ratchet link 100 may connect to the second link 112 in the same general area as the first link 110 . hole 130 of the ratchet link 100 is shown connected to hole 122 of the second link 112 by a hinge pin , forming a joint . this connection location exhibits the largest displacement during actuation in this example . the ratchet link 100 may be tied to , or connected to , the ratchet button 102 via a sliding connection of a pin in slot 129 and hole 136 of the ratchet button 102 . the ratchet link 100 may include a friction zone 132 with teeth , serrations , grooves , ridges , coating , or other high friction means for discrete or infinitely variable engagement with the button 102 , as will be discussed below . hole 134 of the ratchet button 102 may be rotationally pinned to hole 88 of the lever 82 at a joint . hole 136 of the ratchet button 102 may carry a pin for connection to the ratchet link 100 via sliding joint with slot 129 . the button 102 may include a friction zone 138 with teeth , serrations , grooves , ridges , coating , or other high friction means for discrete or infinitely variable engagement with the ratchet link 100 . the button 102 may be spring biased to protrude out from the front of the lever 82 through hole 85 . as the button 102 is depressed , the pin in the sliding joint pushes the ratchet link 100 away from the button 102 , separating the friction zones 132 , 138 , which are mating tooth patterns in this example . when the handle portion 74 is grasped by a hand of a user , the output axis is adjacent a thumb of the hand , the main pivot joint is adjacent a small finger of the hand , and a finger of the hand may rest on the button . this is similar to the palm grip illustrated in fig1 . with reference to fig3 a , it will be appreciated that a ring finger of a hand may be positioned to rest on the button 102 when the hand grips the handle normally . however , in other examples , a button may be positioned for normal contact by the index , middle , ring , and / or small finger . because the ratchet button 102 may be located in the normal finger contact area of the lever 82 , the ratchet mechanism may be selectively overridden using a normal grip . as a result , no separate ratchet lockout feature is included in this example , although a ratchet lockout feature may be included in other examples . a ratchet spring 118 may be captured in a slip fit keyway in the ratchet button 102 . the ratchet spring 118 may be maintained in its position by the internal walls of the lever 82 . the ratchet spring 118 may bias the button 102 to protrude through hole 85 of the lever 82 , and at the same time may bias the button friction zone 138 to engage the ratchet link friction zone so that the ratchet mechanism is normally engaged . the ratchet link 100 can function as an automatic one - way brake or locking device to hold the instrument 70 in a closed or partially closed position without user effort . the ratchet link 100 may resist the action of a biasing member , such as spring 86 , which may tend to urge the instrument 70 to an open position . the button 102 can function to temporarily disengage the ratchet link 100 so that the instrument 70 can move toward the open position . the components disclosed herein may be fabricated from metals , alloys , polymers , plastics , ceramics , glasses , composite materials , or combinations thereof , including but not limited to : peek , titanium , titanium alloys , commercially pure titanium grade 2 , astm f67 , nitinol , cobalt chrome , stainless steel , ultra high molecular weight polyethylene ( uhmwpe ), biocompatible materials , and biodegradable materials , among others . different materials may be used for different parts . different materials may be used within a single part . any component disclosed herein may be colored , coded or otherwise marked to make it easier for a user to identify the type and size of the component , the setting , the function ( s ) of the component , and the like . it should be understood that the present systems , kits , apparatuses , and methods are not intended to be limited to the particular forms disclosed . rather , they are to cover all combinations , modifications , equivalents , and alternatives falling within the scope of the claims . the claims are not to be interpreted as including means - plus - or step - plus - function limitations , unless such a limitation is explicitly recited in a given claim using the phrase ( s ) “ means for ” or “ step for ,” respectively . the term “ coupled ” is defined as connected , although not necessarily directly , and not necessarily mechanically . the use of the word “ a ” or “ an ” when used in conjunction with the term “ comprising ” in the claims and / or the specification may mean “ one ,” but it is also consistent with the meaning of “ one or more ” or “ at least one .” the term “ about ” means , in general , the stated value plus or minus 5 %. the use of the term “ or ” in the claims is used to mean “ and / or ” unless explicitly indicated to refer to alternatives only or the alternative are mutually exclusive , although the disclosure supports a definition that refers to only alternatives and “ and / or .” the terms “ comprise ” ( and any form of comprise , such as “ comprises ” and “ comprising ”), “ have ” ( and any form of have , such as “ has ” and “ having ”), “ include ” ( and any form of include , such as “ includes ” and “ including ”) and “ contain ” ( and any form of contain , such as “ contains ” and “ containing ”) are open - ended linking verbs . as a result , a method or device that “ comprises ,” “ has ,” “ includes ” or “ contains ” one or more steps or elements , possesses those one or more steps or elements , but is not limited to possessing only those one or more elements . likewise , a step of a method or an element of a device that “ comprises ,” “ has ,” “ includes ” or “ contains ” one or more features , possesses those one or more features , but is not limited to possessing only those one or more features . furthermore , a device or structure that is configured in a certain way is configured in at least that way , but may also be configured in ways that are not listed . in the foregoing detailed description , various features are grouped together in several embodiments for the purpose of streamlining the disclosure . this method of disclosure is not to be interpreted as reflecting an intention that the embodiments of the invention require more features than are expressly recited in each claim . rather , as the following claims reflect , inventive subject matter lies in less than all features of a single disclosed embodiment . thus , the following claims are hereby incorporated into the detailed description , with each claim standing on its own as a separate embodiment .

US-201313761019-A

novel beverage emulsions using pectin as an emulsifier are disclosed , along with finished beverages and processes for their preparation .

as used herein , the term “ cola type beverage ” refers to a beverage comprising an oil phase and an aqueous phase in a stable emulsion . preferably , the cola type beverage comprises caramel . such beverages will have a typical brown appearance . however , the term cola type beverage also comprehends beverages not including caramel , such as clear ( colourless ) beverages . preferably , the cola type beverage comprises caffeine . optionally , the cola type beverage comprises kola nut or extract of kola nut . as used herein , the term “ cola - type beverage emulsion ” refers to an emulsion suitable for the preparation of a cola type beverage . preferably , the cola type is prepared from the cola type beverage . emulsion by dilution with an aqueous component , particularly carbonated water . the present invention provides stable oil in water emulsions employing pectin as an emulsifier . a surprising finding of the invention is that in order to obtain oil in water emulsions which are stable towards long term storage both as concentrates and as finished ( i . e . diluted ) beverages , whilst utilising pectin as an emulsifier , it is necessary to balance the emulsifying capacity of pectin with the possibility that the pectin may trigger flocculation by depletion . it has also been found that it is important to control the incorporation of the caramel . as used herein , the term “ oil phase ” refers to a composition which is substantially immiscible with an aqueous phase when present as the oil component of an oil - in - water emulsion . preferably , the oil phase comprises one or more of the group comprising : flavour oils , antioxidants , and pigments . the term “ flavour oil ” as used herein means any water - immiscible liquid that serves to impart flavour or aroma or both to the oil phase containing it . suitable flavours include : fruit flavours , such as guava , kiwi , peach , mango , papaya , pineapple , banana , strawberry , raspberry , blueberry , orange , grapefruit , tangerine , lemon , lime , lemon - lime , etc . ; cola flavours ; tea flavours ; coffee flavours ; chocolate flavours ; dairy flavours ; root beer and birch beer flavours , such as methyl salicylate ( wintergreen oil , sweet birch oil ), and oils including nutmeg , bergamot cinnamon , cassia , neroli , coriander and lavender . in citrus - flavoured beverage products the flavour oil typically contains several citrus oils of different types so that a well - balanced flavour is produced . citrus oils may contain more than 90 % by weight mono - terpenes and a smaller amount of sesqui - terpenes . both are carriers of the oxygenated . terpenoids , specifically the alcohols , aldehydes , ketones , acids , and esters , that are responsible for the characteristic aroma and flavour profile of the oil . the term “ weighting agent ” as used herein refers to a water immiscible component which is soluble or miscible in the oil phase , which has a density of greater than 1 . 00 gcm − 3 at 20 ° c . cola - type beverages generally do not comprise weighting agents , although their use is known . examples of weighting agents for adjusting the density of the oil phases of the invention include ester gum , damar gum , brominated vegetable oil ( bvo ) sucrose acetate iso - butyrate ( saib ), glycerol tribenzoate and decaglycerol esters . the oil phase of the invention may comprise one or more than one weighting agent . ester gum is produced by esterification of pale wood rosin with food grade glycerol . wood rosin , a solid resinous material found in the oleoresin of pine trees , contains about 90 % by weight resin acids , primarily abietic acid and pimeric acid , and about 10 % by weight non - acidic neutral components . ester gum is prepared by esterification of the wood rosin with glycerol , which produces a mixture of mono -, di -, and triglycerides . after removal of the excess glycerine by vacuum distillation and steam sparging , the wood rosin typically has a specific gravity of about 1 . 08 at 25 ° c . currently , ester gum is approved by the united states and a number of other countries as a food additive . damar gum refers to a group of water - insoluble natural exudates from shrubs of the genus dammar , especially the caesalpinaceae and dipterocarpacae families , which are indigenous to malaysia , indonesia , and the east indies . it is highly soluble in essential oils and is typically used as a weighting agent in cloud emulsions . damar gum typically has a specific gravity of about 1 . 04 to 1 . 08 at 20 ° c . brominated vegetable oil ( bvo ) refers to unsaturated vegetable oil that has been reacted with elemental bromine . brominated vegetable oil typically has a specific gravity of 1 . 23 - 1 . 33 at 20 ° c . sucrose acetate isobutyrate ( saib ) is a mixture of sucrose esters containing about 2 mol of acetate and 6 mol of isobutyrate per mol of sucrose , primarily 6 , 6 ′- diacetyl - 2 , 3 , 4 , 1 ′, 3 ′, 4 ′- hexa - isobutyryl sucrose . it is produced by esterification of sucrose with acetic anhydride . sucrose acetate isobutyrate is a tasteless , odourless , and colourless viscous liquid with a specific gravity of about 1 . 146 at 20 ° c . the term “ clouding agent ” as used herein refers to a water immiscible component which is soluble or miscible in the oil phase as defined above , which serves to increase the “ cloudiness ” or turbidity of the emulsion comprising said oil phase . preferred clouding agents include vegetable oils ( such as rapeseed , peanut , corn , flaxseed , soybean , sunflower , cottonseed and combinations and blends thereof ), partially and fully hydrogenated vegetable oils , and oil replacements such as esterified epoxide extended polyols ( eeeps ). in one embodiment , between 0 . 5 to 40 . 0 % w / w of clouding agents may be used based on the total weight of the oil phase . the term “ antioxidant ” as used in this context refers to a water immiscible component which is soluble or miscible in the oil phase as defined above and serves to prevent the oxidation and / or rancidification of said oil phase . as the skilled person will appreciate , the oil phase may include one or more other components which are immiscible with the aqueous phase but are miscible or soluble within the said oil phase , and serve to provide desirable functional characteristics to the oil phase , the beverage emulsion comprising said oil phase , or the finished beverage of the invention . the term “ density ” as used herein refers to the mass per unit volume of a particular composition . density is measured by a densitometer ( density meter dma 38 , anton paar ) according to protocol 2 below . measurement is conducted at 20 ° c . throughout ( unless otherwise specified ), density is expressed in gcm − 3 . for the avoidance of doubt , term “ density of the oil phase ” refers to the density of the oil phase in isolation ( i . e . not the density when present in an emulsion ). preferably , the density of the oil phase is at least 0 . 75 gcm − 3 . more preferably , the density of the oil phase is at least 0 . 80 gcm − 3 . more preferably , the density of the oil phase is at least 0 . 84 gcm − 3 . more preferably , the density of the oil phase is at least 0 . 87gcm − 3 . preferably , the density of the oil phase is below 1 . 00 gcm − 3 . more preferably , the density of the oil phase is below 0 . 95 gcm − 3 . more preferably , the density of the oil phase is below 0 . 90 gcm − 3 . more preferably , the density of the oil phase is below 0 . 89 gcm − 3 preferably , the density is in a range between any of the preferred limits referred to above . more preferably , the density is between 0 . 84 and 1 . 00 gcm − 3 . more preferably , the density is between 0 . 85 and 0 . 90 gcm − 3 . more preferably , the density is between 0 . 87 and 0 . 89 gcm − 3 . the skilled person will appreciate that in a multi - component system such as the oil phase of the invention , it is not always possible to predict the viscosity and density based on the identity of the components . a degree of routine trial and error will be required . detailed procedures for the determination of viscosity and density are given in examples 1 and 2 respectively . the skilled person will moreover appreciate that although the properties discussed above relate to those of the isolated oil phase , in practice it may be unnecessary or undesirable to prepare the isolated oil phase ; it may be more convenient to prepare an emulsion comprising such an oil phase : the term “ emulsion ” as used herein refers to a mixture of two immiscible ( unblendable ) substances . one substance ( the dispersed phase ) is dispersed in the other ( the continuous phase ). preferably , the aqueous phase is the continuous phase , and the oil phase is the dispersed phase ; that is , the emulsior is an oil - in - water emulsion . as used herein , the term “ aqueous phase ” refers to a water - based composition which is substantially immiscible with the oil phase when present as the continuous component of a beverage emulsion of the invention . cola - type beverages preferably comprise caramel in the aqueous phase of the emulsion . an advantage of the present invention is that the cola type beverage emulsions obtained are stable even when large amounts of caramel are present . the aqueous phase may contain one or more ingredients customary in the production of beverage emulsions . preferably , the aqueous phase may comprise one or more of the following : low calorie sweeteners including acesulfame k , alitame , aspartame , cyclamate , neohesperidin dihydrochalcone , tagatose , neotame , saccharin , stevioside , and sucralose ; reduced calorie sweeteners including erythritol , hydrogenated starch hydrolysates and maltitol syrup , isomalt , maltitol , lactitol , sorbitol and mannitol , xylitol , crystalline fructose , high - fructose corn syrup , isomaltulose , trehalose , fructooligosaccharides and polydextrose ( such as litesse ®); acids including citric acid , malic acid and phosphoric acid , and the food acceptable salts thereof ; water soluble preservatives including sorbic acid , benzoic acid and the food acceptable salts thereof , especially the sodium and potassium salts additional emulsifiers including gum arabic , modified starch , xanthan gum , lecithin and other polysaccharides . preferably , the aqueous phase comprises citric acid . more preferably , the aqueous phase comprises citric acid in an amount of between 0 . 1 % w / w and 0 . 5 % w / w based on the weight of the emulsion . preferably , the aqueous phase comprises sodium benzoate . more preferably , the aqueous phase comprises sodium benzoate in an amount of between 0 . 05 % w / w and 0 . 1 % w / w based on the weight of the emulsion . in an alternative preferred embodiment , the aqueous phase comprises both sodium benzoate and potassium sorbate in a combined amount of between 0 . 05 % w / w and 0 . 18 % w / w based on the weight of the emulsion . preferably , the ph of the aqueous phase is between 1 and 7 . more preferably , the ph of the aqueous phase is between 2 . 5 and 4 . more preferably , the ph of the aqueous phase is between 3 . 2 and 3 . 8 . preferably , the aqueous phase is present in an amount of from 95 . 0 to 99 . 7 % w / w based on the weight of the beverage emulsion . more preferably , the aqueous phase is present in an amount of from 98 . 0 to 99 . 7 % w / w based on the weight of the beverage emulsion . more preferably , the aqueous phase is present in an amount of from 98 . 5 to 99 . 5 % w / w based on the weight of the beverage emulsion . preferably , the oil phase is present in an amount of from 0 . 3 to 5 . 0 % w / w based on the weight of the beverage emulsion . more preferably , the oil phase is present in an amount of from 0 . 3 to 2 . 0 % w / w based on the weight of the beverage emulsion . more preferably , the oil phase is present in an amount of from 0 . 5 to 1 . 5 % w / w based on the weight of the beverage emulsion . the aqueous phase of the emulsions of the invention comprises at least a pectin . the term “ pectin ” as used herein , unless otherwise specified , may refer to pectin of one specific origin or more than one origin . pectin is a structural polysaccharide , a polymeric carbohydrate of a high molecular weight , commonly found in the form of protopectin in plant cell walls . pectin has an eu - number e 440 and us fda reference 184 . 1588 ( gras ). pectin molecules typically have a molecular weight of up to 150 , 000 and a degree of polymerisation of up to 800 units . pectin has an important influence on plant cells , since it is protopectin and cellulose that form the structure of the cell walls . the backbone of pectin comprises α - 1 - 4 linked galacturonic acid residues which are interrupted with a small number of 1 , 2 linked α - l - rhamnose units . in addition , pectin comprises highly branched regions with an almost alternating rhamno - galacturonan chain . these highly branched regions also contain other sugar units ( such as d - galactose , l - arabinose and xylose ) attached by glycosidic linkages to the c3 or c4 atoms of the rhamnose units or the c2 or c3 atoms of the galacturonic acid units . the long chains of α - 1 - 4 linked galacturonic acid residues are commonly referred to as “ smooth ” regions , whereas the highly branched regions are commonly referred to as the “ hairy regions ”. preferably , the pectin used in the emulsion of the invention has a galacturonic acid content of between 50 and 85 %. more preferably , the pectin has a galacturonic acid content of between 65 and 80 %. commercial pectin is commonly derived from the peel of citrus fruits ( lemon , lime , orange and grapefruit ), or from apple pomace , all of which releasing pectin of superior quality for the purposes of gel formation . sugar beet pectin is extracted from sugar beet pulp subsequent to sugar extraction . it is generally considered inferior in terms of gelation properties when compared with citrus or other pectins . various chemically or enzymatically modified pectins are also contemplated within the term “ pectin ”. for example , the pectin may be a high ester pectin . “ high ester pectin ” refers to a pectin in which the degree of esterification or de is greater than or equal to 50 %. high ester pectins are also known as “ he pectin ”. alternatively , the pectin may be a low ester pectin . “ low ester pectin ” refers to a pectin in which the degree of esterification or de is less than 50 %. low ester pectins are also known as “ le pectin ”. preferably , the pectin of the composition has a degree of esterification ( de ) of between 55 and 60 %. preferably , the pectin of the composition has a degree of acetylation of between 5 and 50 %. more preferably , the pectin of the composition has a degree of acetylation of between 10 and 50 %. more preferably , the pectin of the composition has a degree of acetylation of between 10 and 40 %. most preferably , the degree of acetylation is between 15 and 35 %. preferably , the pectin comprises at least sugar beet pectin . more preferably , the pectin consists essentially of sugar beet pectin . still more preferably , the pectin consists essentially of sugar beet pectin as the sole emulsifier . preferably , the average molecular weight of the pectin is above 10 kda . more preferably , the average molecular weight of the pectin is above 15 kda . still more preferably , the average molecular weight of the pectin is above 20 kda . still more preferably , the average molecular weight of the pectin is above 25 kda . still more preferably , the average molecular weight of the pectin is above 30 kda . still more preferably , the average molecular weight of the pectin is above 35 kda . still more preferably , the average molecular weight of the pectin is above 40 kda . most preferably , the average molecular weight of the pectin is above 45 kda . preferably , the average molecular weight of the pectin is below 100 kda . more preferably , the average molecular weight of the pectin is below 90 kda . still more preferably , the average molecular weight of the pectin is below 80 kda . still more preferably , the average molecular weight of the pectin is below 70 kda . most preferably , the average molecular weight of the pectin is below 65 kda . preferably , the average molecular weight of the pectin is in a range between any of the preferred limits referred to above . more preferably , the average molecular weight of the pectin is in a range between 15 and 100 kda . still more preferably , the average molecular weight of the pectin is in a range between 30 and 100 kda . still more preferably , the average molecular weight of the pectin is in a range between 15 and 70 kda . still more preferably , the average molecular weight of the pectin is between 10 and 60 kda . still more preferably , the average molecular weight of the pectin is in a range between 15 and 100 kda . still more preferably , the average molecular weight of the pectin is in a range between 30 and 70 kda . still more preferably , the average molecular weight of the pectin is between 45 and 70 kda . still more preferably , the average molecular weight is between 30 and 65 kda . most preferably , the average molecular weight is between 45 and 65 kda . preferably , the beverage emulsion comprises between 0 . 05 and 1 . 00 % w / w of pectin based on the total weight of the emulsion . more preferably , the beverage emulsion comprises between 0 . 05 and 0 . 50 % w / w of pectin based on the total weight of the emulsion . more preferably , the beverage emulsion comprises between 0 . 05 and 0 . 30 % w / w of pectin based on the total weight of the emulsion . more preferably , the beverage emulsion comprises between 0 . 05 and 0 . 10 % w / w of pectin based on the total weight of the emulsion . preferably , the beverage emulsions of the invention are stable upon storage . in this context , “ stable ” means that the stored emulsion passes the “ ringing test ” described by tan and holmes , “ stability of beverage flavour emulsions ”, perfumer and flavourist 1988 , 13 , 23 - 41 ( see protocol 3 ). the cola - type beverage emulsions of the invention are suitably prepared by a process comprising : ( i ) bringing into association the constituents of the oil phase and an aqueous phase comprising a mucilage component to form a mixture ; the step of bringing the oil phase and aqueous phase may be accomplished in any one of a number of ways . for example , the oil phase may be added to the aqueous phase ; alternatively , the aqueous phase may be added to the oil phase . however , it is not necessary to prepare the oil phase or aqueous phase prior to bringing them into association , and in an alternative process the constituents of the aqueous phase and the constituents of the oil phase may be added together in any convenient order . in one preferred embodiment of the invention , however , the oil phase and the aqueous phase are prepared separately before being combined . homogenising , as used herein , refers to a process whereby the aqueous phase and oil phase are transformed into a stable emulsion of oil phase particles within the continuous water phase . preferably , the homogenising process is conducted in two steps , namely preliminary homogenisation and final homogenisation . preferably , final homogenisation is conducted after preliminary homogenization . preliminary homogenisation is a process step which results in the oil phase particles obtaining a particle size of from 0 . 5 to 1 . 2 μm , more preferably from 0 . 5 to 1 . 0 μm . preliminary homogenisation may be achieved in a variety of ways known to those in the art . suitable methods for achieving preliminary homogenisation include the use of a high speed mixer , a hydroshear mixer , a homomixer , or single pass homogenisation at a pressure of between 0 and 50 bar . final homogenisation is a process step which results in the oil phase particles obtaining a particle size of from 0 . 3 to 1 . 0 μm . final homogenisation may be achieved in a variety of ways known to those in the art . preferably , the emulsion obtained as a result of preliminary homogenisation above is passed through a homogeniser at a pressure of between 150 to 300 bar , more preferably at a pressure of between 200 and 250 bar . preferably , said emulsion is passed through the homogeniser more than once . more preferably , said emulsion is passed through the homogeniser 2 or 3 times . most preferably , said emulsion is passed through the homogeniser 2 times . as is known in the art , pectin may form a gelatanous gum or mucilage component in solution . this component may also include other components such as citric acid and preservatives . the beverage emulsions of the present invention may be combined with water and one or more ingredients customary in the art to give a beverage in a form suitable for consumption (“ finished beverage ”). preferably , the finished beverages comprise between 0 . 01 and 1 . 00 % w / w of the beverage emulsions of the invention based on the weight of the finished beverage . more preferably , the finished beverages comprise between 0 . 02 and 0 . 40 % w / w of the beverage emulsions of the invention based on the weight of the finished beverage . more preferably , the finished beverages comprise between 0 . 10 and 0 . 40 % w / w of the beverage emulsions of the invention based on the weight of the finished beverage . more preferably , the finished beverages comprise between 0 . 10 and 0 . 20 % w / w of the beverage emulsions of the invention based on the weight of the finished beverage . the finished beverage may be still . alternatively , the finished beverage may be carbonated . suitably , the finished beverage is carbonated in the range of 0 to 4 . 5 % v / v . the finished beverage may contain alcohol . preferably , the finished beverage contains alcohol in an amount of between 0 . 01 and 15 % v / v based on the volume of the finished beverage . preferably , the finished beverage may comprise one or more of the following ( in addition to those components present in the beverage emulsion ): low calorie sweeteners including acesulfame k , alitame , aspartame , cyclamate , neohesperidin dihydrochalcone , tagatose , neotame , saccharin , stevioside , and sucralose ; reduced calorie sweeteners including erythritol , hydrogenated starch hydrolysates and maltitol syrup , isomalt , maltitol , lactitol , sorbitol and mannitol , xylitol , crystalline fructose , high - fructose corn syrup , isomaltulose , trehalose , fructooligosaccharides and polydextrose ( such as litesse ®); fruit juices including guava , kiwi , peach , mango , papaya , pineapple , banana , strawberry , raspberry , blueberry , orange , grapefruit , tangerine , lemon , lime , lemon - lime and apple ; acids including citric acid , malic acid and phosphoric acid , and the food acceptable salts thereof ; water soluble preservatives including sorbic acid , benzoic acid and the food acceptable salts thereof , especially the sodium and potassium salts additional emulsifiers including gum arabic , modified starch , xanthan gum , lecithin and other polysaccharides . preferably , the finished beverage comprises citric acid . more preferably , the finished beverage comprises citric acid in an amount of between 0 . 1 % w / w and 0 . 5 % w / w based on the weight of finished beverage . preferably , the finished beverage comprises sodium benzoate . more preferably , the finished beverage comprises sodium benzoate in an amount of up to 350 ppm . in an alternative preferred embodiment , the finished beverage comprises both sodium benzoate and potassium sorbate in a combined amount of up to 350 ppm . the finished beverages may suitably be prepared according to the postmix or premix methods . after formulation , the finished beverage may suitably be pasteurized using a method known in the art . for example , the finished beverage may be treated at between 85 and 87 ° c . for between 20 and 30 seconds . the finished beverages thus produced exhibit excellent , stable levels of cloudiness . additionally , they are stable for extended periods with no evidence of ringing or sedimentation . according to a further aspect , there is provided a cola - type beverage comprising sugar beet pectin . preferably , the cola type beverage comprises sugar beet pectin as an emulsifier and / or stabiliser . more preferably , the cola type beverage comprises sugar beet pectin as the sole emulsifier . more preferably , the cola type beverage comprises sugar beet pectin as the sole stabiliser . preferably , the cola type beverage comprises sugar beet pectin in an amount of between 0 . 005 and 0 . 200 % w / w based on the total weight of the beverage . more preferably , the cola type beverage comprises sugar beet pectin in an amount of between 0 . 005 and 0 . 100 % w / w based on the total weight of the beverage . more preferably , the cola type beverage comprises sugar beet pectin in an amount of between 0 . 05 and 0 . 10 % w / w based on the total weight of the beverage . the cola type beverage will preferably include one or more ingredients typical of such comestibles . these include : flavours , especially flavour oils , such as cola , lemon , lime and vanilla ; also including liquorice flavour ; low calorie sweeteners including acesulfame k , alitame , aspartame , cyclamate , neohesperidin dihydrochalcone , tagatose , neotame , saccharin , stevioside , and sucralose ; reduced calorie sweeteners including erythritol , hydrogenated starch hydrolysates and maltitol syrup , isomalt , maltitol , lactitol , sorbitol and mannitol , xylitol , crystalline fructose , high - fructose corn syrup , isomaltulose , trehalose , fructooligosaccharides and polydextrose ( such as litesse ®); acids including citric acid , malic acid and phosphoric acid , and the food acceptable salts thereof , especially phosphoric acid ; water soluble preservatives including sorbic acid , benzoic acid and the food acceptable salts thereof , especially the sodium and potassium salts according to a further aspect , there is provided the use of sugar beet pectin as an emulsifier and / or stabiliser in a cola - type beverage . in a further aspect , the cola - type beverages are clear , non - cloudy beverages that comprise an emulsion comprising particles of an oil phase that have an average particle size of less than 300 nm . the present invention will now be described in further detail in the following examples . a cola - type beverage emulsion was prepared using an cola flavoured oil as given in table 1 . this cola flavoured oil was used to prepare a cola integrant as given in table 2 . this cola integrant was used to prepare a cola - type beverage emulsion as given in table 3 . the cola - type beverage emulsion of example 1 is combined with further ingredients in the quantities and order indicated in table 4 to provide a syrup , which further diluted into a carbonated finished drink . a cola - type beverage emulsion was prepared using an cola flavoured oil as given in table 5 . this cola flavoured oil was used to prepare a cola flavour emulsion as set out in table 6 . this cola flavour emulsion was used to prepare a cola type beverage emulsion as set out in table 7 . the viscosity of the oil phase is measured by rotational viscosimetry ( viscometer model lvf , brookfield , usa ). samples were placed in a thermostated measurement ( 20 ° c .) room . the inner cylinder was driven at a constant torque or stress and the resultant strain was measured as the speed at which the inner cylinder rotated . this speed is governed by the viscosity of the fluid between the plates so that the faster it spins at a given torque , the lower the viscosity of the liquid being analyzed . viscosity was computed from the shear stress / strain record according to the dimensional parameters of the inner cylinder . the oil phase viscosity was measured with a speed of 30 rpm at 20 ° c . using a lv spindle ( lv 2 ). the density of the oil phase is measured by a densitometer ( density meter dma 38 , anton paar ™). the sample to be analysed is pomped in a glass u - tube , which is forced to oscillate sinusoidally by the application of an alternating mechanical force . the density of a fluid is determined by measuring the resonant frequency of the u - tube and relating it to the density using an appropriate mathematical equation . the instrument is calibrated with two fluids of accurately known density . the “ ringing test ” is the most popular method to evaluate the stability of beverage flavor emulsions in soft drink . it is a test in which bottles of soft drink containing the beverage emulsion are held in an upright position at 4 , 20 and 35 ° c . +/− 2 for visualization of ringing or sedimentation during a period of at least 2 moths . ringing test is performed as described by tan and holmes ( 1988 ): stability of beverage flavour emulsions , perfumer and flavourist , 13 : 23 - 41 . all publications mentioned in the above specification are herein incorporated by reference . various modifications and variations of the described methods and system of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention . although the invention has been described in connection with specific preferred embodiments , it should be understood that the invention as claimed should not be unduly limited to such specific embodiments . indeed , various modifications of the described modes for carrying out the invention which are obvious to those skilled in chemistry or related fields are intended to be within the scope of the following claims .

US-63565506-A

an upright bicycle for supporting a handicapped or infirm person in a generally vertical position while providing a self - propelled ambulatory capability is disclosed . a pyramidal - shaped frame is comprised of a plurality of generally vertical telescoping members mounted on a flat , generally horizontal platform . two large side wheels are rotationally mounted to the frame and easily rotated by a person positioned on an aft portion of the platform . the platform is provided with foot pads on the upper surface thereof for enhanced user support , with rollers / casters provided on the lower side thereof for increased platform stability . a sternal support in combination with a removable tray is mounted to an upper portion of the frame , while to an intermediate portion thereof is mounted a strap / buttocks support adapted to extend around and encompass the lower , rear portion of the torso of the person . positioned beneath the strap / buttocks support on the frame are a pair of concave pads for engaging and providing support for the lower legs of the person . hand - operated , positive locking brakes are mounted on each side of the frame for firmly engaging a respective one of the two large side wheels with a minimal amount of effort . all of the aforementioned support elements are adjustable , as is the telescoping frame itself , to accommodate user growth or a number of different persons of various sizes . in addition , side wheel size may be changed by changing only a minimal number of frame components .

referring to fig1 there is shown a front lateral perspective view of an upright bicycle 10 in accordance with the present invention . the upright bicycle 10 includes a lower , generally horizontal platform 12 which supports an upright , generally pyramidal frame 14 extending upward therefrom . the rearward portion of the upright bicycle 10 as shown in fig1 is generally on the right in the figure . viewing the upright bicycle 10 from the rear , it includes left and right wheels 16 , 18 rotationally mounted on each end of an axle 48 which , in turn , is securely mounted to the upright frame 14 . securely mounted to an upper portion of the upright frame 14 is a sternal support 20 . right and left manually operated brake mechanisms 22 , 24 are mounted to respective right and left hand portions of the upright frame 14 immediately adjacent the right and left wheels 18 , 16 . a person using the upright bicycle 10 of the present invention is positioned on an aft portion of the horizontal platform 12 , just to the rear of the upright frame 14 , and leans forward against the sternal support 20 . the upright frame 14 includes a plurality of adjustable , telescoping members 30 for fixing the height of the sternal support 20 above the platform 12 as desired . this adjustment will , of course , depend upon the height of the person using the upright bicycle and should be such that the sternal support 20 is in contact with a forward , upper portion of the user &# 39 ; s torso . the hands of a person thus positioned will be located immediately adjacent an upper portion of a respective wheel permitting the person to manually rotate the wheels in moving the upright bicycle 10 . in addition , the hand brake mechanisms are within the easy grasp of a person thus positioned on the upright bicycle 10 . a detailed description of the structure and configuration of the upright bicycle 10 , including the operation of the hand brake mechanisms , is provided in the following paragraphs . referring to fig1 as well as to fig4 which is a partially cut away perspective view of the upright frame 14 , the structure and configurarion of the upright bicycle will now be described in greater detail . the upright frame 14 is comprised of four telescoping , generally upright members 30 each pivotally mounted to the platform 12 by means of a connecting pin combination 32 . as used throughout the present description , a connecting pin , or connecting pin combination , refers to a conventional means for coupling elements such as a nut and bolt combination , a screw , etc . because the present invention contemplates the use of such conventional coupling means , connecting elements are generally referred to as connecting pins which is intended to encompass those means for connecting structural elements well known to those skilled in the art . as shown in fig1 and 4 , each telescoping upright member 30 is positioned within a respective slot 33 in the upper surface of platform 12 . as shown in the cutaway portions of platform 12 , each telescoping upright member 30 is free to pivot with respect to platform 12 . this permits the upright frame 14 to be extended or lowered , as desired . this is accomplished by means of the several components of each telescoping upright member 30 . each telescoping upright member 30 is comprised of a lower element 30a , an upper element 30b , and a tube clamp collar 34 including a clamp screw 36 inserted therein . the tube clamp collar 34 is positioned at the upper end of the lower element 30a of the telescoping upright member 30 . the diameter of the upper element 30b is less than that of the lower element 30a of each telescoping upright member 30 , permitting the upper element 30b to be displaced along and within a respective lower element 30a . when the upper element 30b is extended to the desired length , the clamp screw 36 in the tube clamp collar 34 positioned on the respective lower element 30a is tightened for securely engaging the upper element 30b and maintaining its position within lower element 30a . because the upper portion of each upper element 30b of the telescoping upright members 30 is coupled by means of a connecting pin 62 to a mounting rib 60 on the lower surface of the sternal support 20 , when the telescoping upright members 30 are extended each telescoping upright member 30 will pivot about the connecting pin 32 which couples it to the platform 12 . thus , the telescoping nature of the upright members 30 as well as the pivotal coupling of each telescoping upright member 30 to platform 12 permits the height of the upright frame 14 to be easily adjusted to accommodate a wide range of user sizes . the upright frame 14 is shown in an extended , or upraised , configuration by broken lines in fig4 . to the lower surface of platform 12 are mounted a plurality of non - pivoting roller assemblies 38 and swiveling caster assemblies 39 by means of mounting pins 40 . in a preferred embodiment , two roller assemblies 38 are positioned on a forward section of the lower portion of platform 12 , while two caster assemblies are positioned on an aft section of the lower portion of platform 12 . these roller and caster assemblies 38 , 39 engage the surface upon which the upright bicycle 10 is positioned and maintain platform 12 in a generally horizontal orientation for increased user stability while permitting the platform 12 to easily be displaced over the surface . a user standing aft of upright frame 14 is positioned upon platform 12 so as to lean slightly forward against the sternal support 20 . this increases user stability and decreases the possibility of a rearward fall by the user . thus , in a preferred embodiment , the upper surface of platform 12 is angled upward from rear to front for increased upright bicycle stability . the upward tilt of platform 12 thus compensates for the forward leaning of the upright bicycle &# 39 ; s user for increased bicycle and user stability . also in a preferred embodiment , the forward roller assemblies 38 are positioned on the underside of platform 12 so as to be displaced slightly upward from the surface upon which the upright bicycle is positioned . the thus elevated forward roller assemblies are thus able to accommodate obstructions on and elevations in the surface upon which the upright bicycle moves . the upraised position of the forward roller assemblies permit it to more easily roll over such obstructions and elevations . the configuration of upright frame 14 will now be explained primarily in terms of the left hand portion of the apparatus shown in fig4 with the following discussion equally applicable to the right hand portion thereof . the upright frame 14 includes right and left lower gussets 42 which are pivotally coupled , in combination with a respective forward telescoping upright member 30 , to a forward portion of platform 12 via a connecting pin 32 . the other end of each lower gusset 42 is coupled by means of a respective rear bracket 52 to an intermediate portion of a lower element 30a of a respective rear telescoping upright meber 30 . similarly , upper gussets 44 are located on the right and left hand portions of the upright frame 14 and are coupled at one end to a lower gusset 42 by means of a gusset mounting bracket 45 , and at the other end to the axle 48 by means of an inner axle bracket 54 . finally , right and left forward gussets 46 couple the axle 48 to a respective forward telescoping upright member 30 by means of a forward bracket 50 and an outer axle bracket 56 . lower gusset 42 is inserted through an aperture within gusset mounting bracket 45 which is free to slide along the lower gusset . similarly , forward and rear brackets 50 , 52 are free to slide along the respective telescoping upright member 30 upon which they are positioned . by thus engaging the various upright members 30 and lower gussets 42 in a semi - rigid , sliding manner , the thus displaceable brackets provide for flexibility in the upright frame 14 permitting each of the telescoping upright members 30 to be displaced relative to one another in adjusting the height of the upright frame 14 as desired . thus , the unique arrangement of the various brackets which are free to slide along the various structural members upon which they are mounted provides for a certain , limited degree of displacement in adjusting the height of the upright frame 14 , while providing a rigid support structure once the height of the frame is fixed as desired . finally , left and right wheels 16 , 18 are rotationally mounted to the respective ends of axle 48 by means of conventional bearing assemblies ( not shown ). as described above , the upper portion 30b of each telescoping upright member 30 of the upright frame 14 is coupled by means of a connecting pin 62 to a respective right and left mounting rib 60 positioned on a lower portion of sternal support 20 . sternal support 20 in a preferred embodiment is comprised of a urethane foam . in addition , a horizontal support member 64 , or tray , may be mounted in a conventional manner to a forward portion of the sternal support 20 . a horizontal support member 64 thus mounted is positioned immediately forward of the user and may be utilized by a user for the convenient positioning of an object . for example , horizontal support member 64 may be used to write on , eat off of , support a book , or for virtually any imaginable use for which such a support element could be utilized . in addition , horizontal support member 64 may be comprised of a transparent material , such as a transparent plastic , so as not to restrict the visibility of a user , particularly when the upright bicycle is displaced in a forward direction . as stated above and as shown in fig1 the upright bicycle 10 includes right and left hand brakes 22 , 24 . the left hand brake 24 of fig1 is shown in greater detail in fig2 as viewed from right to left with respect to the rear of the upright bicycle 10 as shown in fig1 . the right hand brake 22 is symmetrically identical to the left hand brake and , therefore , the following detailed description of the structure and operation of the left hand brake 24 is equally applicable to the right hand brake 22 . as previously explained , a forward gusset 46 is coupled between the axle 48 and a forward telescoping upright member 30 by means of an outer axle bracket 56 and a forward bracket 50 positioned on respective ends of the forward gusset 46 . this is shown for the right and left hand portions of the upright frame 14 in fig1 . similarly , forward gusset 46 is shown in the lower portion of fig2 but its coupling to the axle via an axle mounting bracket is not shown therein for simplicity sake . the lower portion of a first fixed mounting bracket 80 is rigidly coupled to a respective forward gusset 46 by means of connecting pins 78 . an upper portion of the first fixed mounting bracket 80 is coupled to an aft portion of a second fixed mounting bracket 82 by means of connecting pins 86 . a forward portion of the second fixed mounting bracket 82 is pivotally coupled by means of pivot pin 88 to an intermediate portion of pivoting brake handle 90 . to the upper portion of the pivoting brake handle 90 is mounted a grip 92 which is grasped by a user in manually operating the hand brake . the lower portion of the pivoting brake handle 90 is coupled to a forward portion of a coupling bracket 94 by means of a cam block 104 . the cam block 104 is secured to the forward portion of coupling bracket 94 by means of connecting pins 102 , while an extension shaft 106 attached to and extending from facing surfaces of the lower portion of pivoting brake handle 90 is positioned within cam curve 108 . as explained , the first fixed mounting bracket 80 is pivotally coupled to coupling bracket 94 by means of pivot pin 84 . securely mounted to an aft portion of coupling bracket 94 is an l - shaped bracket 98 by means of connecting pin 96 . securely positioned on the upper surface of l - shaped bracket 98 is a brake pad 100 for engaging the inner surface of the inner rim 72 of the left wheel 16 . the left wheel 16 , as well as the right wheel 18 , includes a plurality of spokes 70 radiating outwardly from the center of the wheel and coupled to the inner rim 72 by means of a connecting pin 74 . the position of the various hand brake components when the hand brake is applied in engaging a respective wheel is shown in fig2 in dotted line form . when the upper portion of the pivoting brake handle 90 to which grip 92 is attached is moved from left to right as shown in fig2 the pivoting brake handle 90 pivots about pivot pin 88 . this causes the lower portion of pivoting brake handle 90 which is attached to cam block 104 by means of extension shaft 106 inserted therein , to be displaced leftward . the leftward displacement of the lower portion of pivoting brake handle 90 causes the forward portion of coupling bracket 94 , and cam block 104 mounted thereto , to be displaced downward by the action of the extension shaft 106 on the inner surface of the cam curve 108 located within cam block 104 . the downward displacement of cam block 104 causes coupling bracket 94 to pivot about pivot pin 84 . this results in an upward displacement of the aft portion of coupling bracket 94 to which l - shaped bracket 98 is securely mounted . the upward displacement of l - shaped bracket 98 causes the brake pad 100 to engage the inner surface of the wheel &# 39 ; s inner rim 72 in applying a retarding force on the rotation of the wheel 16 . brake pad 100 is preferably comprised of a high friction , rubber - like material for improved braking action . thus , the forward displacement of the upper portion of pivoting brake handle 90 results in the upward displacement of l - shaped bracket 98 and brake pad 100 coupled thereto . brake pad 100 then engages the inner surface of the wheel &# 39 ; s inner rim 72 for effective bicycle braking . with a pair of independently actuated , hand operated brakes , the left and right wheels 16 , 18 may be individually or simultaneously engaged by a respective brake mechanism . referring to fig3 there is shown an upper , rear side perspective view of the lower frame and platform portion of the upright bicycle of the present invention . two caster assemblies 39 are shown mounted to a lower , aft portion of platform 12 toward the respective lateral edges thereof . securely mounted to an aft portion of the upper surface of platform 12 are right and left foot retainers 120 , 122 . as shown in the figure , each foot retainer includes a flat portion 121 and an upraised portion 123 extending along the aft side portions and rear portion of the respective flat portions of each foot retainer . the right and left foot retainers 120 , 122 are adapted to receive and engage the feet of a bicycle user positioned upon platform 12 . in a preferred embodiment , each foot retainer is comprised of a polyurethane material , to the underside of which is affixed , such as by gluing , a metal plate ( not shown ). the metal plate may be secured to the upper surface of platform 12 by conventional means such as by bolts . the foot retainers 120 , 122 may be positioned as desired on the upper surface of platform 12 by merely placing a mounting aperture as desired thereon and inserting mounting bolts therethrough . the right and left foot retainers 120 , 122 are placed slightly aft of the rearward telescoping upright members 30 so as to allow the user to lean forward slightly against the aforementioned sternal support which is not shown in fig3 . mounted to respective right and left aft telescoping upright members 30 are right and left leg support assemblies 124 , 126 . the following description is directed to right leg support assembly 124 , but is equally applicable to the left leg support assembly 126 as shown in fig3 . each leg support assembly includes a frame mounting bracket 128 mounted on a respective telescoping upright member 30 by means of a connecting pin 132 . connecting pin 132 is also used to mount a first l - shaped bracket 130 to an aft surface of the frame mounting bracket 128 . the first l - shaped bracket 130 includes a generally horizontal slot 131 therein which permits the first l - shaped bracket 130 to be displaced toward or away from the other aft telescoping upright member 30 . a second l - shaped bracket 134 is utilized to mount a leg support 138 to the first l - shaped bracket 130 by means of connecting pins 136 , 137 . a respective leg support 138 may be pivotally displaced relative to the first l - shaped bracket 130 about an axis defined by connecting pin 136 . connecting pin 136 may then be tightened when the leg support 138 is positioned as desired so as to properly engage the lower leg of a user . each leg support 138 includes a recessed aft portion adapted to receive and engage the forward portion of the lower leg of a user such as the tibia immediately below the knee . thus , the leg supports 138 provide stable positioning for the infirm legs of a user which are retained in a stable position with respect to forward and lateral displacement thereof . finally , the entire right and left leg support assemblies 124 , 126 may be adjusted vertically along a respective telescoping upright member 30 by loosening connecting pin 132 , moving the entire assembly to the desired position along a respective telescoping upright member , and adjusting connecting pin 132 for securely coupling the frame mounting bracket 128 to the telescoping upright member 30 . the three aforementioned adjustments thus permit each leg support 138 to be adjusted vertically , forward and aft , and inward and outward relative to the center of platform 12 . shown in fig5 is a top plan view of another mounting arrangement for leg support 138 . in this embodiment , a third l - shaped bracket 139 is coupled to the second l - shaped bracket 134 by means of connecting pin 137 . by loosening connecting pin 137 , the combination of third l - shaped bracket 139 and leg support 138 is free to pivot about the axis of connecting pin 137 and to be secured in the desired orientation . the third l - shaped bracket 139 may be securely affixed to a forward portion of a leg support 138 by conventional means such as an epoxy cement . positioned immediately above right and left leg support assemblies 124 , 126 and mounted on a respective aft telescoping upright member 30 is a sacral support assembly 140 . sacral support assembly 140 includes right and left frame mounting brackets 144 , 146 positioned on respective telescoping upright members 30 . right frame mounting bracket 144 includes a generally horizontally oriented aperture into which a mounting pin 148 is inserted . by tightening mounting pin 148 , the right frame mounting bracket 144 may be securely attached to telescoping upright member 30 at the desired location thereon . an aft portion of right frame mounting bracket 144 includes a generally vertically oriented aperture 150 therein into which a belt clasp 152 may be inserted . attached to belt clasp 152 is one end of a flexible support belt 156 , the other end of which is securely engaged by belt hook 154 . belt hook 154 is adapted not only to securely engage one end of support belt 156 , but is also adapted to be mounted upon a telescoping upright member 30 . belt hook 154 is thus capable of being displaced along telescoping upright member 30 and of being securely positioned thereon at a desired location by means of the combination of clamping collar 142 and clamp screw 141 positioned therein . thus , clamping collar 142 is positioned immediately below and in contact with left frame mounting bracket 146 for the support thereof and clamp screw 141 is adjusted to firmly engage the telescoping upright member 30 for the secure positioning of the left - hand portion of the sacral support assembly 140 . coupled to left frame mounting bracket 146 is belt hook 154 which securely engages and retains one end of support belt 156 . attached to an intermediate portion of the front surface of support belt 156 is a support pad 158 . with belt clasp 152 secured to the other end of support belt 156 and inserted in aperture 150 of the right frame mounting bracket 144 , support belt 156 may be positioned aft of an upright bicycle user standing on a rear portion of platform 12 . the sacral support assembly 140 is intended to engage the lower aft portion of the torso of a user , i . e ., the buttocks area , to prevent the rearward displacement of that person while insuring his or her secure engagement with and support by the sternal support and leg supports . by means of the combinations of right frame mounting bracket 144 and connecting pin 148 and left frame mounting bracket 146 and clamping collar 142 with clamp screw 141 , the vertical position of the sacral support assembly 140 may be adjusted according to the size of the person using the upright bicycle of the present invention . upright frame 14 is designed to accommodate left and right wheels 16 , 18 of various sizes . in order to equip upright frame 14 with larger diameter side wheels , telescoping upright members 30 of a longer length are required and upper gussets 44 must also be lengthened accordingly . all other components of the upright frame 14 may remain unchanged . there has thus been shown an upright bicycle intended for use by a handicapped or infirm person which is capable of maintaining that person , regardless of the degree of infirmity , in a stable , generally upright position while affording that person the capability of self - propelled locomotion . the upright bicycle includes a lower stable platform upon which the person stands , a generally upright , pyramidal frame to which adjustable supports for the front , upper torso and rear , lower torso and also the legs of the user are provided . two large side wheels are mounted to the frame in close proximity to the hands and arms of the user . similarly , right and left hand - operated brakes are within the easy grasp of a user for engaging a respective wheel . while particular embodiments of the present invention have been shown and described , it will be obvious to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects . for example , while the present invention is described as including right and left leg support assemblies , these components may not be necessary , depending upon the degree of infirmity , to support a particular individual . thus , this aspect of the invention is not considered absolutely essential for its proper operation , but merely as an additional support feature . therefore , the aim of the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of the invention . the matter set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation . the actual scope of the invention is intended to be defined in the following claims when viewed in their proper perspective based on the prior art .

US-49392983-A

fragrances that provide a scent of freshness tend to be volatile and are therefore not very economical when used in typical applications such as washing or cleaning processes , so they have to be used in relatively large quantities to be able to produce adequate effects . the disclosed photolabile pro - fragrances provide a much longer - lasting sense of fragrance , in particular with a scent of freshness , when used in typical applications , thus allowing said fragrances to be used economically .

the following detailed description of the invention is merely exemplary in nature and is not intended to limit the invention or the application and uses of the invention . furthermore , there is no intention to be bound by any theory presented in the preceding background of the invention or the following detailed description of the invention . the object of the present invention was achieved by a compound of the general formula ( i ), r denotes a substituted hydrocarbon residue with 2 to 20 c atoms , having at least one carbonyl group or ester group , r1 , r2 each , independently of one another , denote hydrogen , a linear or branched , substituted or unsubstituted alkoxy group with 1 to 15 c atoms , a linear or branched , substituted or unsubstituted alkyl group or alkenyl group with 1 to 15 c atoms or a substituted or unsubstituted aryl residue , r3 , r4 , r5 , r6 and r7 each , independently of one another , denote hydrogen , an amino group , — no 2 , a linear or branched , substituted or unsubstituted alkoxy group with 1 to 15 c atoms , a linear or branched , substituted or unsubstituted alkyl group with 1 to 15 c atoms , a cycloalkyl residue , acyl residue , aryl residue , — oh , — nh 2 , halogen , nh - alkyl or — n ( alkyl ) 2 , and wherein at least one of the residues r3 , r4 , r5 , r6 , r7 denotes a quaternary ammonium residue of formula ( ii ), wherein a denotes a ch 2 or a ch 2 ch 2 o group with n = 1 to 20 and b denotes oxygen with m = 0 or 1 , wherein m = 0 if a is a ch 2 ch 2 o group , and r8 , r9 , r10 each , independently of one another , denote h or a substituted or unsubstituted , alkyl , cycloalkyl , alkenyl , aryl or acyl group - containing residue and wherein two of the residues r8 , r9 , r10 can in each case be joined together by ring closure . surprisingly , it has been found that the compounds according to the invention are particularly effective pro - fragrances , which attach particularly well to surfaces , in particular to textile surfaces . in particular the use of quaternary ammonium residues of formula ( ii ) in compounds of formula ( i ) has the effect that the compounds according to the invention are particularly effective pro - fragrances , and attach particularly well to surfaces , in particular to textile surfaces . the compounds according to the invention make possible the delayed release of scent ketones , in particular of damascone , or of scent esters , in particular of cinnamic acid esters and derivatives of cinnamic acid esters . the use of the compounds according to the invention in washing , cleaning or care agents led to an improved long - term scent effect when they were used , in particular in connection with textile treatment . for example , when compounds according to the invention were used in a laundry treatment agent , such as e . g . washing agents and fabric softeners , an improved long - term scent effect of the treated laundry was found . furthermore , corresponding products exhibit particularly good storage stability . the agents according to the invention also make it possible to reduce the total quantity of perfume that is contained in the agent , and yet to achieve odor advantages on the washed textiles , in particular with regard to the perception of freshness . the compound according to general formula ( i ) is suitable as a pro - fragrance for all conventional scent ketones and scent esters which , in their free form as a scent , comprise an alpha , beta - unsaturated carbonyl unit or mesomeric forms thereof . preferred scent ketones are selected in particular from buccoxime , iso - jasmone , methyl beta - naphthyl ketone , musk indanone , tonalide / musk plus , alpha - damascone , beta - damascone , delta - damascone , gamma - damascone , damascenone , damarose , methyl dihydrojasmonate , menthone , carvone , camphor , fenchone , alpha - ionone , beta - ionone , so - called gamma - methyl ionone , fleuramone , dihydrojasmone , cis - jasmone , iso - e - super ®, methyl cedrenyl ketone or methyl cedrylone , acetophenone , methylacetophenone , para - methoxyacetophenone , methyl beta - naphthyl ketone , benzylacetone , benzophenone , para - hydroxyphenylbutanone , celery ketone or livescone , 6 - isopropyldecahydro - 2 - naphthone , dimethyl octenone , frescomenthe , 4 -( 1 - ethoxyvinyl )- 3 , 3 , 5 , 5 - tetramethylcyclohexanone , methylheptenone , 2 -( 2 -( 4 - methyl - 3 - cyclohexen - 1 - yl ) propyl ) cyclopentanone , 1 -( p - menthen - 6 ( 2 ) yl )- 1 - propanone , 4 -( 4 - hydroxy - 3 - methoxyphenyl )- 2 - butanone , 2 - acetyl - 3 , 3 - dimethylnorbornane , 6 , 7 - dihydro - 1 , 1 , 2 , 3 , 3 - pentamethyl - 4 ( 5h ) indanone , 4 - damascol , dulcinyl or cassione , gelsone , hexylone , isocyclemone e , methyl cyclocitrone , methyl lavender ketone , orivone , para - tertiary butyl cyclohexanone , verdone , delphone , muscone , neobutenone , plicatone , veloutone , 2 , 4 , 4 , 7 - tetramethyloct - 6 - en - 3 - one , tetrameran or mixtures thereof . the ketones can preferably be selected from the damascones , carvone , gamma - methyl ionone , iso - e - super , 2 , 4 , 4 , 7 - tetramethyloct - 6 - en - 3 - one , benzylacetone , damascenone , methyl dihydrojasmonate , methyl cedrylone , hedione and mixtures thereof . most preferred are all the damascones and damascenone . the stored ketones can be released by the action of light comprising the wavelengths of 200 to 400 nm . preferred scent esters are selected from cinnamic acid esters and derivatives of cinnamic acid esters . particularly preferred are linaloyl cinnamate , 3 - phenylpropyl cinnamate , eugenol cinnamate , allyl cinnamate , benzyl cinnamate , butyl cinnamate , ethyl cinnamate , methyl cinnamate , menthyl cinnamate , heptyl cinnamate , cyclohexyl cinnamate , isoamyl cinnamate , isobutyl cinnamate , isopentyl cinnamate , isopropyl cinnamate , isoheptyl cinnamate , tetrahydrofurfuryl cinnamate and cinnamyl cinnamate . the stored esters can be released by the action of light comprising the wavelengths of 200 to 500 nm . according to a preferred embodiment of the invention , the substituent r2 in formula ( i ) denotes a linear or branched , substituted or unsubstituted alkyl group with 1 to 6 c atoms , preferably 1 to 3 c atoms , and is in particular a methyl residue . according to a preferred embodiment of the invention , in the quaternary ammonium residue of formula ( ii ), n = 1 to 6 , in particular 1 to 3 . it is further preferred if a denotes a ch 2 group , in particular a ch 2 group with n = 1 , 2 or 3 . it is particularly preferred if m = 1 . in particular , it is preferred if a denotes a ch 2 group with n = 1 , 2 or 3 and m = 1 . furthermore , a compound according to the invention of general formula ( i ) is preferred in which four of the five aryl substituents r3 , r4 , r5 , r6 and r7 denote hydrogen . it is additionally preferred that at least one of the substituents r4 and r5 each denotes a quaternary ammonium residue of formula ( ii ). a substitution in para - position ( r5 ) is particularly preferred since the electronic structure of the aromatic ring can be modified most effectively here , as a result of which the absorption maximum of compounds of general formula ( i ) can readily be adapted to a specific wavelength . in a preferred embodiment , the substituents r3 , r4 , r6 and r7 therefore each denote hydrogen and the residue r5 denotes a quaternary ammonium residue of formula ( ii ), wherein a denotes a ch 2 or a ch 2 ch 2 o group with n = 1 to 20 and b denotes oxygen with m = 0 or 1 , wherein m = 0 if a is a ch 2 ch 2 o group , and r8 , r9 , r10 each , independently of one another , denote h or a substituted or unsubstituted alkyl , cycloalkyl , alkenyl , aryl or acyl group - containing residue and wherein two of the residues r8 , r9 , r10 can in each case be joined together by ring closure . it is preferred if at least one of the residues r8 , r9 and r10 denotes a methyl group . if only one of the residues r8 , r9 or r10 denotes a methyl group , then it is particularly preferred if the other two residues are joined together by ring closure . if two of the residues r8 , r9 and r10 denote a methyl group , then it is particularly preferred if the third residue denotes an alkyl chain with 12 to 20 carbon atoms . according to a particularly preferred embodiment of the invention , compounds of formula ( i ) correspond to the following formulae ( iii ), ( iv ), ( v ), ( vi ), ( vii ), ( viii ), ( ix ) and ( x ): according to another particularly preferred embodiment of the invention , compounds of formula ( i ) correspond to the following formulae ( xi ), ( xii ), ( xiii ) and ( xiv ): the compounds according to the invention , in particular the compounds of formulae ( iii ) to ( xiv ), can be incorporated in a stable manner into the conventional washing or cleaning agent matrices , into cosmetics and existing scent compositions . compounds of formulae ( iii ) to ( x ) make possible a delayed release of the stored scent ketones , such as e . g . of damascones in the alpha , beta , gamma or delta form and of damascenones , in particular beta - damascenones . compounds of formulae ( xi ) to ( xiv ) make possible a delayed release of the stored scent esters . these ketones and esters impart a particularly long - lasting impression of freshness to conventional washing or cleaning agents and cosmetics . in particular the dried , washed textile benefits from the good long - term effect of a fresh scent . the slow release of the stored scent takes place after exposure to light ( electromagnetic radiation ) comprising the wavelengths of 200 to 400 nm , as illustrated in simplified form in the following reaction equations : with r according to r 8 , r 9 , r 10 from formula ( ii ). the present invention also provides a washing or cleaning agent , preferably a washing agent , fabric softener or washing auxiliary , containing at least one compound according to one of formulae ( i ) and / or ( iii ) to ( xiv ), wherein the said compound is contained preferably in quantities of between 0 . 0001 and 5 wt . %, advantageously between 0 . 001 and 4 wt . %, more advantageously between 0 . 01 and 3 wt . %, in particular between 0 . 1 and 2 wt . %, based in each case on the total agent . suitable cleaning agents are e . g . cleaning agents for hard surfaces , such as preferably dishwashing agents . they can also be cleaning agents such as e . g . household cleaners , all - purpose cleaners , window cleaners , floor cleaners etc . they can preferably be a product for cleaning toilet bowls and urinals , advantageously a flush cleaner for hanging in the toilet bowl , in particular a so - called toilet flusher . according to a preferred embodiment of the invention , the washing or cleaning agent according to the invention contains at least one surfactant , selected from anionic , cationic , nonionic , zwitterionic , amphoteric surfactants or mixtures thereof . according to another preferred embodiment of the invention , the agent according to the invention is present in solid or liquid form . the invention also provides a cosmetic agent containing at least one compound according to one of formulae ( i ) and / or ( iii ) to ( xiv ), which contains the said compound preferably in quantities of between 0 . 0001 and 5 wt . %, advantageously between 0 . 001 and 4 wt . %, more advantageously between 0 . 01 and 3 wt . %, in particular between 0 . 1 and 2 wt . %, based in each case on the total agent . the invention also provides a room scenting agent ( e . g . room air freshener , room deodorant , room spray etc . ), containing at least one compound according to one of formulae ( i ) and / or ( iii ) to ( xiv ), wherein the said compound is contained preferably in quantities of between 0 . 0001 and 50 wt . %, advantageously between 0 . 001 and 5 wt . %, more advantageously between 0 . 1 and 3 wt . %, in particular between 0 . 1 and 2 wt . %, based in each case on the total agent . according to another preferred embodiment of the invention , additional scents , in particular selected from the group comprising scents of natural or synthetic origin , preferably more volatile scents , higher boiling - point scents , solid scents and / or adherent scents , are contained in an agent according to the invention ( i . e . washing or cleaning agent , cosmetic agent or room scenting agent ). adherent scents that can be used with advantage within the framework of the present invention are , for example , essential oils , such as angelica oil , anise oil , arnica flower oil , basil oil , bay oil , bergamot oil , champaca flower oil , silver fir oil , silver fir cone oil , elemi oil , eucalyptus oil , fennel oil , fir needle oil , galbanum oil , geranium oil , gingergrass oil , guaiacwood oil , balsam gurjun oil , helichrysum oil , ho oil , ginger oil , iris oil , cajeput oil , calamus oil , chamomile oil , camphor oil , cananga oil , cardamom oil , cassia oil , pine needle oil , balsam copaiva oil , coriander oil , curled peppermint oil , caraway oil , cumin oil , lavender oil , lemon grass oil , lime oil , mandarin oil , melissa oil , ambrette seed oil , myrrh oil , clove oil , neroli oil , niaouli oil , olibanum oil , orange oil , oregano oil , palmarosa oil , patchouli oil , peru balsam oil , petitgrain oil , pepper oil , peppermint oil , pimento oil , pine oil , rose oil , rosemary oil , sandalwood oil , celery oil , spike lavender oil , star anise oil , turpentine oil , thuja oil , thyme oil , verbena oil , vetiver oil , juniper berry oil , wormwood oil , wintergreen oil , ylang - ylang oil , hyssop oil , cinnamon oil , cinnamon leaf oil , citronella oil , lemon oil , and cypress oil . however , higher boiling - point or solid scents of natural or synthetic origin can also be employed within the framework of the present invention as adherent scents or scent mixtures , i . e . scents . these compounds include the compounds mentioned below as well as mixtures thereof : ambrettolide , alpha - amylcinnamaldehyde , anethole , anisaldehyde , anisyl alcohol , anisole , anthranilic acid methyl ester , acetophenone , benzyl acetone , benzaldehyde , benzoic acid ethyl ester , benzophenone , benzyl alcohol , benzyl acetate , benzyl benzoate , benzyl formate , benzyl valerate , borneol , bornyl acetate , alpha - bromostyrene , n - decyl aldehyde , n - dodecyl aldehyde , eugenol , eugenol methyl ether , eucalyptol , farnesol , fenchone , fenchyl acetate , geranyl acetate , geranyl formate , heliotropin , heptyne carboxylic acid methyl ester , heptaldehyde , hydroquinone dimethyl ether , hydroxycinnamaldehyde , hydroxycinnamyl alcohol , indole , irone , isoeugenol , isoeugenol methyl ether , isosafrole , jasmone , camphor , carvacrol , carvone , p - cresol methyl ether , coumarin , p - methoxyacetophenone , methyl - n - amyl ketone , methylanthranilic acid methyl ester , p - methylacetophenone , methyl chavicol , p - methylquinoline , methyl beta - naphthyl ketone , methyl - n - nonyl acetaldehyde , methyl n - nonyl ketone , muscone , beta - naphthol ethyl ether , beta - naphthol methyl ether , nerol , nitrobenzene , n - nonyl aldehyde , nonyl alcohol , n - octyl aldehyde , p - oxyacetophenone , pentadecanolide , beta - phenylethyl alcohol , phenylacetaldehyde dimethyl acetal , phenylacetic acid , pulegone , safrole , salicylic acid isoamyl ester , salicylic acid methyl ester , salicylic acid hexyl ester , salicylic acid cyclohexyl ester , santalol , skatole , terpineol , thymene , thymol , gamma - undelactone , vanillin , veratrum aldehyde , cinnamaldehyde , cinnamyl alcohol , cinnamic acid , cinnamic acid ethyl ester , cinnamic acid benzyl ester . included among the more volatile scents are , in particular , the lower boiling - point scents of natural or synthetic origin , which can be used alone or in mixtures . examples of more volatile scents are alkyl isothiocyanates ( alkyl mustard oils ), butanedione , limonene , linalool , linalyl acetate and propionate , menthol , menthone , methyl n - heptenone , phellandrene , phenylacetaldehyde , terpinyl acetate , citral , citronellal . according to a further preferred embodiment , the agent according to the invention ( i . e . washing or cleaning agent , cosmetic agent or room scenting agent ) has at least one , preferably more than one , active component , in particular components having washing , care - providing or cleaning activity and / or cosmetic components , which are advantageously selected from the group comprising anionic surfactants , cationic surfactants , amphoteric surfactants , nonionic surfactants , alkalizing agents , anti - wrinkle agents , antibacterial substances , antioxidants , antiredeposition agents , antistatic agents , builder substances , bleaching agents , bleach activators , bleach stabilizers , bleach catalysts , ironing aids , co - builders , scents , shrinkage preventers , electrolytes , enzymes , color protectants , coloring agents , dyes , dye transfer inhibitors , fungicides , germicides , odor - complexing substances , adjuvants , hydrotropes , rinse aids , complexing agents , preservatives , corrosion inhibitors , water - miscible organic solvents , optical brighteners , perfume carriers , pearl luster pigments , ph adjusting agents , proofing and impregnating agents , polymers , swelling and anti - slip agents , foam inhibitors , sheet silicates , soil - repelling substances , silver protectants , silicone oils , soil - release active substances , uv - protection substances , viscosity regulators , thickening agents , vitamins and / or fabric - softening compounds . within the meaning of this invention , data for the agent according to the invention in wt . % refer , unless otherwise indicated , to the total weight of the agent according to the invention . the quantities of the individual ingredients in the agents according to the invention , i . e . washing or cleaning agent , cosmetic agent or room scenting agent , are guided in each case by the intended use of the respective agents and the person skilled in the art is , in principle , familiar with the orders of magnitude of the quantities of the ingredients to be employed or can take them from the relevant technical literature . depending on the intended use of the agents according to the invention , e . g . a higher or lower surfactant content will be selected . for example , the surfactant content of e . g . washing agents can usually be between 10 and 50 wt . %, preferably between 12 . 5 and 30 wt . % and in particular between 15 and 25 wt . %, while e . g . cleaning agents for automatic dishwashing can contain e . g . between 0 . 1 and 10 wt . %, preferably between 0 . 5 and 7 . 5 wt . % and in particular between 1 and 5 wt . % surfactants . the agents according to the invention ( i . e . washing or cleaning agent , cosmetic agent or room scenting agent ) can contain surfactants , in which case preferably anionic surfactants , nonionic surfactants and mixtures thereof , but also cationic surfactants , are suitable . suitable nonionic surfactants are in particular ethoxylation and / or propoxylation products of alkyl glycosides and / or linear or branched alcohols having in each case 12 to 18 c atoms in the alkyl portion and 3 to 20 , preferably 4 to 10 alkyl ether groups . furthermore , it is possible to use corresponding ethoxylation and / or propoxylation products of n - alkylamines , vicinal diols , fatty acid esters and fatty acid amides , which correspond to the above - mentioned long - chain alcohol derivatives with regard to the alkyl portion , and of alkylphenols having 5 to 12 c atoms in the alkyl residue . suitable anionic surfactants are in particular soaps , and those that contain sulfate or sulfonate groups with preferably alkali ions as cations . soaps that can be used are preferably the alkali salts of saturated or unsaturated fatty acids having 12 to 18 c atoms . these fatty acids can also be employed in incompletely neutralized form . included among the usable surfactants of the sulfate type are the salts of the sulfuric acid semiesters of fatty alcohols having 12 to 18 c atoms , and the sulfation products of the aforesaid nonionic surfactants having a low degree of ethoxylation . included among the usable surfactants of the sulfonate type are linear alkylbenzenesulfonates having 9 to 14 c atoms in the alkyl portion , alkanesulfonates having 12 to 18 c atoms , and olefin sulfonates having 12 to 18 c atoms that are produced upon reaction of corresponding monoolefins with sulfur trioxide , as well as alpha - sulfo fatty acid esters that are produced upon sulfonation of fatty acid methyl or ethyl esters . cationic surfactants are preferably selected from among the esterquats and / or the quaternary ammonium compounds ( qacs ) in accordance with the general formula ( r i )( r ii )( r iii )( r iv ) n + x − , in which r i to r iv denote identical or different c 1 - 22 alkyl residues , c 7 - 28 aralkyl residues or heterocyclic residues , such that two or , in the case of an aromatic bond such as in pyridine , even three residues , together with the nitrogen atom , form the heterocycle , e . g . a pyridinium or imidazolinium compound , and x denotes halide ions , sulfate ions , hydroxide ions or similar anions . qacs can be produced by the reaction of tertiary amines with alkylating agents , such as e . g . methyl chloride , benzyl chloride , dimethyl sulfate , dodecyl bromide , but also ethylene oxide . the alkylation of tertiary amines having a long alkyl residue and two methyl groups can be achieved particularly easily , and the quaternization of tertiary amines having two long residues and one methyl group can also be carried out using methyl chloride under mild conditions . amines that possess three long alkyl residues or hydroxy - substituted alkyl residues have low reactivity , and are quaternized e . g . using dimethyl sulfate . suitable qacs are , for example , benzalkonium chloride ( n - alkyl - n , n - dimethyl benzyl ammonium chloride ), benzalkon b ( m , p - dichlorobenzyl dimethyl c 1 - 2 - alkyl ammonium chloride ), benzoxonium chloride ( benzyl - dodecyl - bis ( 2 - hydroxyethyl ) ammonium chloride ), cetrimonium bromide ( n - hexadecyl - n , n - trimethylammonium bromide ), benzethonium chloride ( n , n - dimethyl - n -[ 2 -[ 2 -[ p -( 1 , 1 , 3 , 3 - tetramethylbutyl ) phenoxy ] ethoxy ] ethyl ] benzyl ammonium chloride ), dialkyldimethylammonium chlorides , such as di - n - decyldimethylammonium chloride , didecyldimethylammonium bromide , dioctyldimethylammonium chloride , 1 - cetylpyridinium chloride , and thiazoline iodide , as well as mixtures thereof . preferred qacs are the benzalkonium chlorides having c 8 to c 22 alkyl residues , in particular c 12 to c 14 alkylbenzyldimethylammonium chloride . preferred esterquats are methyl - n -( 2 - hydroxyethyl )- n , n - di ( tallow - acyl - oxyethyl ) ammonium methosulfate , bis ( palmitoyl ) ethyl hydroxyethyl methylammonium methosulfate or methyl - n , n - bis ( acyloxyethyl )- n -( 2 - hydroxyethyl ) ammonium methosulfate . commercially available examples are the methyl hydroxyalkyl dialkoyloxyalkylammonium methosulfates marketed by stepan with the trademark stepantex ® or the products from basf se known by the trade name dehyquart ® or the products from the manufacturer evonik industries ag known by the name rewoquat ®. surfactants are contained in the agents according to the invention ( i . e . washing or cleaning agent , cosmetic agent or room scenting agent ) in quantitative proportions of preferably 5 wt . % to 50 wt . %, in particular of 8 wt . % to 30 wt . %. in laundry post - treatment agents in particular , preferably up to 30 wt . %, in particular 5 wt . % to 15 wt . % surfactants , among these preferably at least a proportion of cationic surfactants , are employed . an agent according to the invention , in particular a washing or cleaning agent , preferably contains at least one water - soluble and / or water - insoluble , organic and / or inorganic builder . the water - soluble organic builder substances include polycarboxylic acids , in particular citric acid and sugar acids , monomeric and polymeric aminopolycarboxylic acids , in particular methylglycinediacetic acid , nitrilotriacetic acid and ethylenediaminetetraacetic acid as well as polyaspartic acid , polyphosphonic acids , in particular aminotris ( methylenephosphonic acid ), ethylenediaminetetrakis ( methylene - phosphonic acid ) and 1 - hydroxyethane - 1 , 1 - diphosphonic acid , polymeric hydroxy compounds , such as dextrin , and polymeric ( poly ) carboxylic acids , polymeric acrylic acids , methacrylic acids , maleic acids and copolymers of these , which can also contain small proportions of polymerizable substances without carboxylic acid functionality polymerized into them . suitable , although less preferred , compounds from this class are copolymers of acrylic acid or methacrylic acid with vinyl ethers , such as vinyl methyl ethers , vinyl esters , ethylene , propylene and styrene , in which the proportion of acid is at least 50 wt . %. all of the aforementioned acids are generally employed in the form of their water - soluble salts , in particular their alkali salts . organic builder substances can , if desired , be contained in quantities of up to 40 wt . %, in particular up to 25 wt . % and preferably of 1 wt . % to 8 wt . %. quantities close to the above upper limit are preferably employed in paste - like or liquid , in particular aqueous , agents according to the invention . laundry post - treatment agents , such as e . g . fabric softeners , can optionally also be free from organic builder . suitable as water - soluble inorganic builder materials are , in particular , alkali silicates and polyphosphates , preferably sodium triphosphate , e . g . zeolite a , p or x . inorganic builder substances are contained in the agents according to the invention , if desired , preferably in quantities of up to 60 wt . %, in particular of 5 wt . % to 40 wt . %. laundry post - treatment agents according to the invention , such as e . g . fabric softeners , are preferably free from inorganic builder . peroxygen compounds that are suitable are , in particular , organic peroxy acids or peroxy acid salts of organic acids , such as phthalimidoperoxycaproic acid , peroxybenzoic acid , or salts of diperoxydodecanedioic acid , hydrogen peroxide and inorganic salts that release hydrogen peroxide under application conditions , such as perborate , percarbonate and / or persilicate . the addition of small quantities of known bleaching - agent stabilizers , such as e . g . phosphonates , borates or metaborates , and metasilicates , as well as magnesium salts such as magnesium sulfate , may be useful . suitable enzymes usable in the agents are those from the class of the proteases , cutinases , amylases , pullulanases , hemicellulases , cellulases , lipases , oxidases , and peroxidases , as well as mixtures thereof . enzymatic active substances obtained from fungi or bacteria , such as bacillus subtilis , bacillus licheniformis , streptomyces griseus , humicola lanuginosa , humicola insolens , pseudomonas pseudoalcaligenes , or pseudomonas cepacia , are particularly suitable . the enzymes that are optionally used can be adsorbed onto carrier substances and / or embedded in encapsulating substances in order to protect them from premature inactivation . they are contained in the agents according to the present invention , if desired , preferably in quantities no greater than 5 wt %, in particular from 0 . 2 wt % to 2 wt %. the production of the compounds according to the invention is described in the examples section with reference to the production of a pro - fragrance containing delta - damascone by way of example . the other compounds of general formula ( i ) and in particular all compounds of formulae ( iii ) to ( xiv ) can also be obtained by the principle of this synthesis route . according to a preferred embodiment , the teaching according to the invention can be employed to reduce the proportion of perfume in washing or cleaning agents and cosmetic agents significantly . as a result , it is possible to offer perfumed products even for those particularly sensitive consumers who , because of specific incompatibilities and irritations , can use normally perfumed products only to a limited extent or not at all . a preferred solid , in particular powdered , washing agent according to the invention can also contain , in addition to the compound according to the invention , in particular components that are selected e . g . from the following : anionic surfactants , such as preferably alkylbenzene sulfonate , alkyl sulfate , e . g . in quantities of preferably 5 - 30 wt . % nonionic surfactants , such as preferably fatty alcohol polyglycol ether , alkyl polyglucoside , fatty acid glucamide , e . g . in quantities of preferably 0 . 5 - 15 wt . % builders , such as e . g . zeolite , polycarboxylate , sodium citrate , in quantities of e . g . 0 - 70 wt . %, advantageously 5 - 60 wt . %, preferably 10 - 55 wt . %, in particular 15 - 40 wt . %, alkalis , such as e . g . sodium carbonate , in quantities of e . g . 0 - 35 wt . % advantageously 1 - 30 wt . %, preferably 2 - 25 wt . %, in particular 5 - 20 wt . %, bleaching agents , such as e . g . sodium perborate , sodium percarbonate , in quantities of e . g . 0 - 30 wt . % advantageously 5 - 25 wt . %, preferably 10 - 20 wt . %, corrosion inhibitors , e . g . sodium silicate , in quantities of e . g . 0 - 10 wt . %, advantageously 1 - 6 wt . %, preferably 2 - 5 wt . %, in particular 3 - 4 wt . %, stabilizers , e . g . phosphonate , advantageously 0 - 1 wt . %, foam inhibitor , e . g . soap , silicone oils , paraffins , advantageously 0 - 4 wt . %, preferably 0 . 1 - 3 wt . %, in particular 0 . 2 - 1 wt . %, enzymes , e . g . proteases , amylases , cellulases , lipases , advantageously 0 - 2 wt . %, preferably 0 . 2 - 1 wt . %, in particular 0 . 3 - 0 . 8 wt . %, anti - grays , e . g . carboxymethyl cellulose , advantageously 0 - 1 wt . %, discoloration inhibitor , e . g . polyvinylpyrrolidone derivatives , preferably 0 - 2 wt . %, adjusting agents , e . g . sodium sulfate , advantageously 0 - 20 wt . %, optical brighteners , e . g . stilbene derivatives , biphenyl derivatives , advantageously 0 - 0 . 4 wt . %, in particular 0 . 1 - 0 . 3 wt . %, optionally further scents optionally water optionally soap optionally bleach activators optionally cellulose derivatives optionally soil repellents , in another preferred embodiment of the invention , the agent is present in liquid form , preferably in gel form . preferred liquid washing or cleaning agents contain water as the main solvent and optionally non - aqueous solvents . a preferred liquid , in particular gel , washing agent according to the invention can also contain , in addition to the compound according to the invention , in particular components that are selected e . g . from the following : anionic surfactants , such as preferably alkylbenzene sulfonate , alkyl sulfate , e . g . in quantities of preferably 5 - 40 wt . % nonionic surfactants , such as preferably fatty alcohol polyglycol ether , alkyl polyglucoside , fatty acid glucamide , e . g . in quantities of preferably 0 . 5 - 25 wt . % builders , such as e . g . polycarboxylate , sodium citrate , advantageously 0 - 15 wt . %, preferably 0 . 01 - 10 wt . %, in particular 0 . 1 - 5 wt . %, foam inhibitor , e . g . soap , silicone oils , paraffins , in quantities of e . g . 0 - 10 wt . %, advantageously 0 . 1 - 4 wt . %, preferably 0 . 2 - 2 wt . %, in particular 1 - 3 wt . %, enzymes , e . g . proteases , amylases , cellulases , lipases , in quantities of e . g . 0 - 3 wt . %, advantageously 0 . 1 - 2 wt . %, preferably 0 . 2 - 1 wt . %, in particular 0 . 3 - 0 . 8 wt . %, optical brighteners , e . g . stilbene derivative , biphenyl derivative , in quantities of e . g . 0 - 1 wt . %, advantageously 0 . 1 - 0 . 3 wt . %, in particular 0 . 1 - 0 . 4 wt . %, optionally further scents , optionally stabilizers , water , optionally soap , in quantities of e . g . 0 - 25 wt . %, advantageously 1 - 20 wt . %, preferably 2 - 15 wt . %, in particular 5 - 10 wt . %, optionally solvents ( preferably alcohols ), advantageously 0 - 25 wt . %, preferably 1 - 20 wt . %, in particular 2 - 15 wt . %, wt . % based in each case on the total agent . a preferred liquid fabric softener according to the invention can also contain , in addition to the compound according to the invention , in particular components that are selected from the following : cationic surfactants , such as in particular esterquats , e . g . in quantities of 2 - 30 wt . %, co - surfactants , such as e . g . glycerol monostearate , stearic acid , fatty alcohols , fatty alcohol ethoxylates , e . g . in quantities of 0 - 5 wt . %, preferably 0 . 1 - 4 wt . %, emulsifiers , such as e . g . fatty amine ethoxylates , e . g . in quantities of 0 - 4 wt . %, preferably 0 . 1 - 3 wt . %, optionally further scents dyes , preferably in the ppm range stabilizers , preferably in the ppm range solvents , such as e . g . water , in quantities of preferably 60 - 90 wt . %, wt . % based in each case on the total agent . the invention also provides a method for the long - lasting scenting of surfaces , wherein a compound according to one of formulae ( i ) and / or ( iii ) to ( xiv ) or a washing or cleaning agent according to the invention is applied onto the surface to be scented ( e . g . textile , dishes , floor ) and the said surface is then exposed to an electromagnetic radiation comprising the wavelengths of 200 to 400 nm . the invention also provides a method for long - lasting room scenting , wherein a room - scenting agent according to the invention is exposed to an electromagnetic radiation comprising the wavelengths of 200 to 400 nm . a microwave vial was initially charged with 0 . 35 ml ( 2 mmol ) of methoxypropiophenone and 1 . 32 g ( 6 mmol ) of [ bmim ][ br ], flooded with protective gas and sealed with a septum . the sample was allowed to react in the microwave and under the following conditions : after cooling the sample , 0 . 1m hcl ( ph = 1 ) was added to the reaction mixture and extraction was performed 3 times with etoac . the combined organic phases were washed with saturated nacl solution , dried over mgso 4 , filtered and the solvent was removed under vacuum . the desired product could be detected by gc / ms and 1 h - nmr spectroscopy . the yield was 0 . 27 g ( 90 %). δ ( ppm )= 7 . 91 ( d , 2h ); 6 . 90 ( d , 2h ); 5 . 29 ( s , 1h ); 2 . 95 ( q , 2h ), 1 . 22 ( t , 3h ). a round - bottomed flask was initially charged with 2 eq k 2 co 3 and 1 eq hydroxypropiophenone in 3 - pentanone . to this was added 1 eq 1 , 2 - dibromoethane and the mixture was stirred under reflux for 16 h . after cooling , the mixture was filtered , the solid was washed 2 × with 3 - pentanone and the combined phases were concentrated under reduced pressure . a round - bottomed flask was initially charged with the product obtained in step 2 and an excess of n - methylpyrrolidine in toluene , and the mixture was stirred at 60 ° c . for 16 h and worked up after cooling . other quaternary ammonium residues can be prepared in the same way as in step 3 . preparation of a compound of general formula ( i ) from compound ( a ) from step 3 and delta - damascene 8 . 50 g of diisopropylamine in 210 ml of thf were taken as the initial charge under nitrogen and the solution was cooled to − 78 ° c . this was followed by the addition of 14 . 1 g of compound ( a ) from step 3 and then the addition of 40 . 3 ml of a butyllithium solution ( 2 . 5 molar in hexane ; corresponding to 100 . 8 mmol ). the reaction solution was stirred for 1 hour at − 78 ° c . then , with stirring , 24 g of dried cerium chloride were added ( cerium iii chloride , dried ; corresponding to 98 mmol ; produced from : cerium iii chloride . 7h 2 o by drying for six hours at 150 ° c . in a high vacuum ). the reaction solution was then stirred for 30 minutes at − 78 ° c . next , 14 . 8 g of delta - damascone were added slowly , dropwise , using a dropping funnel and stirring of the reaction solution continued at − 78 ° c . the cooling was then removed and , at a temperature of approx . − 10 ° c ., the addition of a saturated ammonium chloride solution took place . for purification purposes , extraction was performed 3 times with 350 ml ether each time and the resulting light - yellow organic phase was then shaken out with water and later with saturated nacl solution . the organic phase was then dried over magnesium sulfate . the filtrate was freed of solvent under reduced pressure . the resulting crude product was finally distilled in a high vacuum . the desired target product was obtained in a quantity of 29 g . the reaction to form further compounds of general formula ( i ) with other scent ketones and with scent esters took place in the same way as for step 4 . the compound produced in this way displayed a very good scent effect when used in washing agents and fabric softeners in textile treatment . in particular , better persistence of the scent impression was found on the laundry that had been washed therewith and then dried , compared with washing agents and fabric softeners which contained an equivalent quantity of delta - damascone but were otherwise the same . the fresh scent impression of the textiles persisted for significantly longer , both after line drying and in particular after drying in an automatic dryer . the compounds to be compared were dissolved in 0 . 1 mmol in dichloromethane with 250 μl in each case applied onto cotton cloths measuring 5 × 5 cm . after evaporation of the solvent , they were immersed several times in a beaker with 500 ml of washing liquor ( made from commercially available washing agent without perfume substances in a conventional domestic concentration ) and finally rinsed with tap water . they were then irradiated freshly or after drying ( in the dark ) with uv light of 366 nm ( t = 5 min ). the odor intensity was evaluated by a panel of 6 trained persons . the odor intensity was scored on a scale of 1 to 6 , for which the following applies : the samples were then stored in the dark . the irradiation and subsequent evaluation of intensity were repeated after the specified time intervals ( 1 day , 3 , 7 and 14 days ). the tests and comparative tests that were performed clearly show that the compounds according to the invention of formula ( i ) with a quaternized ammonium group of formula ( ii ) bring about a clear increase in fragrance intensity after just one day compared with a compound of formula ( i ) without a quaternized ammonium group of formula ( ii ) or compared with the simple unmodified scent . the tests prove that the compounds according to the invention are particularly effective pro - fragrances and attach particularly well to surfaces . while at least one exemplary embodiment has been presented in the foregoing detailed description of the invention , it should be appreciated that a vast number of variations exist . it should also be appreciated that the exemplary embodiment or exemplary embodiments are only examples , and are not intended to limit the scope , applicability , or configuration of the invention in any way . rather , the foregoing detailed description will provide those skilled in the art with a convenient road map for implementing an exemplary embodiment of the invention , it being understood that various changes may be made in the function and arrangement of elements described in an exemplary embodiment without departing from the scope of the invention as set forth in the appended claims and their legal equivalents .

US-201414570053-A

the present invention relates to a portable bio - chemical decontaminant system and methods of using the same . specifically , the present invention provides a portable bio - chemical decontaminant system that is rapidly effective across a broad range of chemical and biological weapons agents . the disclosed portable bio - chemical decontaminant system electrochemically generates a decontaminant solution at the point of use obviating the need to transport corrosive or reactive chemicals , and dramatically simplifies the logistics of delivering an effective bio - chemical decontaminant system to wherever it may be needed . the portable bio - chemical decontaminant system electrochemically generates chlorine dioxide and hypobromite .

in the following detailed description , reference is made to the accompanying figures ( fig1 a - 20 ) which form a part hereof and illustrate specific exemplary embodiments by which the invention may be practiced . it should be understood that like reference numerals represent like elements throughout the figures ( fig1 a - 20 ). these embodiments are described in sufficient detail to enable those skilled in the art to practice the invention . it is to be understood that other embodiments may be utilized , and that structural changes , chemical changes , electrical changes , logical changes , and the addition or omission of steps may be made without departing from the spirit and scope of the present invention . the term “ comprising ” refers to various components , elements , structures or steps that may be conjointly employed , although additional components , elements , structures or steps may be utilized , if desired . accordingly , the term “ comprising ” may encompass the more restrictive terms “ consisting essentially of ” and “ consisting of ”. chlorine dioxide is generated from a halogen dioxide salt , e . g ., chlorite salts . the electrochemical generation of chlorine dioxide from aqueous sodium chlorite is represented in the reaction : naclo 2 + h 2 o + e -⇄ na + ( aq )+ clo 2 -( aq )+ h 2 o . the electrochemical generation of hypobromite is represented in the reaction : br -+ 2oh —& lt ;-& gt ; bro —+ h 2 o + 2e . this electrochemical method of in situ generation of chlorine dioxide and hypobromite offers several unique distinct advantages over classical generation methods , especially when generated by the disclosed portable decontaminant system . use of a single and stable precursor , for each chemical provided , eliminates the usual metering and mixing of several different chemicals and facilitates ease of packaging , storage and logistical support . simplicity of operation also minimizes training of personnel for optimum use . miniaturization of a portable bio - chemical decontaminant device allows for it to be easily transported and used by soldiers in the field , or by any others that need access to such a decontaminant system , e . g ., hospitals , firefighters , emergency responders , and the like . the highly reactive properties of aqueous chlorine dioxide , and the ability to be generated on site in a portable lightweight unit as needed , offers an attractive alternative approach to unique decontamination needs . in fig1 a - 1d , various embodiments of the portable decontaminant system 10 comprising a flow - through electrolysis cell 20 are illustrated . the system 10 generates chlorine dioxide from sodium chlorite and hypobromite , from a halide by flowing electrical current through an aqueous feed solution that passes through the flow - through electrolysis &# 39 ; s cell &# 39 ; s chamber . the flow - through electrolysis cell 20 comprises at least a pair of electrodes : an anode and a cathode . the portable decontaminant system 10 also comprises a cell chamber through which an aqueous feed solution passes , and includes passages adjacent to the anode and cathode . the passages include narrow surface layers adjacent to both the cathode and anode surface where the conversion reactions occur . different embodiments of the portable decontaminant system 10 are illustrated in fig1 a - 1d . the portable decontaminant system 10 comprises at least one flow - through electrolysis cell 20 which is illustrated in fig1 a . each of the other embodiments of the portable decontaminant system 10 depicted in fig1 b - 1d also comprise at least one flow - through electrolysis cell 20 . the portable decontaminant system 10 further comprises at least a main handle portion 200 , a nozzle 201 , a body portion 202 , a neck region 203 , and a trigger 204 . a trigger nozzle sprayer 201 , illustrated in fig1 a , can be used which can provide approximately 1 ml per spray . the pump nozzle sprayer 201 , illustrated in fig1 d , can be used which can provide approximately 300 ml / min . it should be appreciated that the trigger nozzle sprayer 201 can be any shape , size , and have a flow rate other than disclosed herein depending on the desired utility of the portable decontaminant system 10 . it should be appreciated that the portable decontaminant system 10 can be any shape or size other than those depicted in fig1 a - 1d . for instance , the portable decontaminant system 10 may be as large as a backpack that can be worn by a soldier on the field of battle , or the size of a typical fire extinguisher bottle kept in a school or hospital . as such , the present invention also contemplates the formation of a portable backpack decontamination system , e . g ., approximately 2 l and larger . this would allow the incorporation of a liquid pumping system with a spray nozzle to allow a soldier to reach underneath and on tops of contaminated vehicles . still referring to fig1 a - 1d , the nozzle sprayer 201 may be manually adjustable to provide a mist or a fine stream of effluent solution . the body portion 202 and neck region 203 may hold the aqueous fluid solution or , may comprise separate compartments that store the precursors used to form the effluent solution . in other words , there may be additional compartments separated from each other within the body portion 202 and neck region 203 . the flow - through electrolysis cell 20 is in fluid communication with the body portion 202 ; neck region 203 , main handle portion 200 , and nozzle sprayer 201 . in other words , the effluent solution will exit the portable decontaminant system 10 through nozzle sprayer 201 . referring now to fig2 , which is a blow - up image of fig1 a , a portable decontaminant system 10 with a trigger nozzle sprayer 201 is illustrated . the portable decontaminant system 10 comprises at least a main handle portion 200 , a nozzle sprayer 201 , a body portion 202 , a neck region 203 , and a trigger 204 . in this embodiment , a single flow - through electrolysis cell 20 is used . however , multiple flow - through electrolysis cells could be used , if desired . the portable decontaminant system 10 is a battery - operated pump sprayer in fig2 . it is operated by at least one double aa battery . in another embodiment , it is operated by 3 double aa batteries . it should be appreciated that any portable battery source may be used . the portable decontaminant system 10 allows for the effluent solution to be applied where and when needed . it should also be appreciated that the portable decontaminant systems 10 , illustrated in fig1 a - 1d , are reusable . in other words , once the systems 10 have been completely discharged , e . g ., substantially unable to discharge anymore effluent solution through nozzle 201 , the aqueous feed solution can be replenished . for instance , a pre - packaged powder or concentrate could be added with the addition of water . new batteries could also be used . as fig2 illustrates , the portable decontaminant system 10 can be dis - assembled by removing screws 207 . however , the portable decontaminant system 10 can also be assembled and disassembled by a number of other methods such as with no screws , or , by turning , twisting , or having a removable neck portion 203 from the body portion 202 or main handle portion 200 . in one embodiment of the present invention , as illustrated in fig3 , the portable decontaminant system 10 comprises a flow - through electrolysis cell 20 with an anode 21 and a confronting ( and preferably , co - extensive ) cathode 22 that are separated by a cell chamber 23 that has a shape defined by the confronting surfaces of the pair of electrodes 21 , 22 , and the shape of the portable decontaminant system 10 itself ( fig1 a - 1d ). the cell chamber 23 has a cell gap , which is the perpendicular distance between the two confronting electrodes 21 , 22 . typically , the cell gap will be substantially constant across the confronting surfaces of the electrodes . the cell gap is preferably greater than 0 . 5 mm and 5 mm or less , and more preferably 1 mm or greater and 3 mm or less . the flow - through electrolysis cell 20 can also comprise two or more anodes 21 , or two or more cathodes 22 ( not illustrated ). the anode 21 and cathode 22 plates are alternated so that an anode 21 is confronted by a cathode 22 on each face , with a cell chamber 23 therebetween . generally , the flow - through electrolysis cell 20 will have one or more inlet openings in fluid communication with each cell chamber 23 , and one or more outlet openings in fluid communication with the chambers 23 . the inlet opening is also in fluid communication with the source of aqueous feed solution , such that the aqueous feed solution can flow into the inlet , through the chamber , and from the outlet of the flow - through electrolysis cell 20 . the effluent can itself be a treated solution , where the aqueous feed solution contains microorganisms or some other oxidizable source material that can be oxidized in situ by the chlorine dioxide and hypobromite that is formed . fig3 illustrates merely one embodiment of a flow - through electrolysis cell 20 of the present invention . the flow - through electrolysis cell 20 comprises an anode 21 electrode and a cathode 22 electrode . the electrodes 21 , 22 are held a fixed distance away from one another by a pair of opposed non - conductive electrode holders 30 having electrode spacers 31 that space apart the confronting longitudinal edges of the anode 21 and cathode 22 to form a cell chamber 23 having a chamber gap . the chamber 23 has a cell inlet 25 through which the aqueous feed solution can pass into of the cell 20 , and an opposed cell outlet 26 from which the effluent solution can pass out of the flow - through electrolysis cell 20 . the assembly of the anode 21 and cathode 22 , and the opposed plate holders 30 are held tightly together between a non - conductive anode cover 33 ( shown partially cut away ) and cathode cover 34 , by a retaining structure ( not shown ) that can comprise non - conductive , water - proof adhesive , bolts , or other structures , thereby restricting exposure of the two electrodes 21 , 22 only to the aqueous feed solution that flows through the chamber 23 . anode lead 27 and cathode lead 28 extend laterally and sealably through channels made in the electrode holders 30 . in fig4 , the flow - through electrolysis cell 20 comprises an anode outlet 35 . the anode outlet 35 removes a portion of the electrolyzed feed solution flowing in the passage 24 adjacent the anode 21 as an anode effluent . the remainder of the cell &# 39 ; s effluent solution exits from the cell outlet 26 , and will be referred to as the cathode effluent and the cathode outlet , respectively . it should be appreciated that the flow - through electrolysis cell 20 can comprise a cathode outlet , alone or in combination with the anode outlet 35 , if desired . the electrodes 21 , 22 can have any shape that effectively conducts electricity through the aqueous feed solution between itself and the opposing electrode , and can include , but is not limited to , a planar electrode , an annular electrode , a spring - type electrode , and a porous electrode . the anode 21 and cathode 22 electrodes can be shaped and positioned to provide a substantially uniform gap between a cathode 22 and an anode 21 electrode pair , as shown in fig4 . on the other hand , the anode 21 and the cathode 22 can have different shapes , different dimensions , and can be positioned apart from one another non - uniformly . the important relationship between the anode 21 and the cathode 22 is for a sufficient flow of electrical current through the anode 21 at an appropriate voltage to promote the conversion of the salts within the cell passage adjacent the anode 21 and cathode 22 . the electrodes 21 , 22 are commonly metallic , conductive materials , though non - metallic conducting materials , such as carbon , can also be used . the materials of the anode 21 and the cathode 22 can be the same , but can advantageously be different . to minimize corrosion , chemical resistant metals are preferably used . preferred anode metals are titanium , stainless steel , platinum , palladium , iridium , ruthenium , as well as iron , nickel and chromium , and alloys and metal oxides thereof . preferred cathode metals are uncoated titanium , carbon , zinc , stainless steel , alloys and metal oxides thereof , and even more preferred is titanium . for example , more preferred electrode materials made of a valve metal such as titanium , tantalum , aluminum , zirconium , tungsten or alloys thereof , which are coated or layered with a group viii metal that is preferably selected from platinum , iridium , and ruthenium , and oxides and alloys thereof . one preferred anode is made of titanium core and coated with , or layered with , ruthenium , ruthenium oxide , iridium , iridium oxide , and mixtures thereof , having a thickness of at least 0 . 1 micron , preferably at least 0 . 3 micron . in other embodiments , a metal foil having a thickness of about 0 . 03 mm to about 0 . 3 mm can be used . foil electrodes should be made stable in the cell 20 so that they do not warp or flex in response to the flow of liquids through the passage that can interfere with proper electrolysis operation . the use of foil electrodes is particularly advantageous when the cost of the device must be minimized , or when the lifespan of the portable decontaminant system is expected or intended to be short , generally about one year or less . foil electrodes can be made of any of the metals described above , and are preferably attached as a laminate to a less expensive electrically - conductive base metal , such as tantalum , stainless steel , and others . a particularly preferred anode 21 or cathode 22 electrode of the present invention is a porous , or flow - through anode and / or cathode as illustrated in fig5 . the porous electrodes have a large surface area and large pore volume sufficient to pass there through a large volume of aqueous feed solution . the plurality of pores and flow channels in the porous electrodes provide a greatly increased surface area providing a plurality of passages , through which the aqueous feed solution can pass . porous media useful in the present invention are commercially available from astro met inc . in cincinnati , ohio , porvair inc . in henderson , n . c ., or mott metallurgical in farmington , conn ., among others . preferably , the porous electrodes 21 , 22 have a ratio of surface area ( in square centimeters ) to total volume ( in cubic centimeters ) of more than about 5 cm − 1 , more preferably of more than about 10 cm − 1 , even more preferably more than about 50 cm − 1 and most preferably of more than about 200 cm − 1 . preferably , the porous electrodes 21 , 22 have porosity of at least about 10 %, more preferably of about 30 % to about 98 %, and most preferably of about 40 % to about 70 %. the flow path of the aqueous feed solution through the porous electrodes 21 , 22 should be sufficient , in terms of the exposure time of the solution to the surface of the electrodes , to convert the salts . the flow path can be selected to pass the aqueous feed solution in parallel with the flow of electricity through the electrodes 21 , 22 ( in either the same direction or in the opposite direction to the flow of electricity ), or in a cross - direction with the flow of electricity . the porous electrodes 21 , 22 permit a larger portion of the aqueous feed solution to pass through the passages adjacent to the electrodes surface , thereby increasing the proportion of the salts conversion . fig5 illustrates a flow - through electrolysis cell comprising a porous electrode 21 . the porous electrode has a multiplicity of capillary - like flow passages 24 through which the aqueous feed solution can pass adjacent to the electrode surfaces within the porous electrode . in the flow - through electrolysis cell of fig5 , the aqueous feed solution flows in a parallel direction to the flow of electricity between the electrodes . a flow - through electrolysis cell 20 , and its various embodiments , that may be used in conjunction with the disclosed portable decontaminant system 10 are described in u . s . patent application ser . no . 10 / 674 , 669 . an electrical current supply provides a flow of electrical current between the electrodes 21 , 22 and across the passage of aqueous feed solution passing across the electrodes . in some embodiments , the preferred electrical current supply is a rectifier of household ( or industrial ) current that converts common 100 - 230 volt ac current to dc current . in other embodiments involving portable or small , personal use systems , such as the disclosed portable decontaminant systems in fig1 a - 1d , a preferred electrical current supply is a battery or set of batteries , preferably selected from an alkaline , lithium , silver oxide , manganese oxide , or carbon zinc battery . the batteries can have a nominal voltage potential of 1 . 5 volts , 3 volts , 4 . 5 volts , 6 volts , or any other voltage that meets the power requirements of the electrolysis device . most preferred are common - type batteries such as “ aa ” size , “ aaa ” size , “ c ” size , and “ d ” size batteries having a voltage potential of 1 . 5 v . it should be appreciated that smaller voltage batteries may be used , if desired . two or more batteries can be wired in series ( to add their voltage potentials ) or in parallel ( to add their current capacities ), or both ( to increase both the potential and the current ). re - chargeable batteries and mechanical wound - spring devices can also be employed . another alternative is a solar cell that can convert ( and store ) solar power into electrical power . solar - powered photovoltaic panels can be used advantageously when the power requirements of the flow - through electrolysis cell 20 draws currents below 2000 milliamps across voltage potentials between 1 . 5 and 9 volts . the electrical current supply can further comprise a circuit for periodically reversing the output polarity of the battery or batteries in order to maintain a high level of electrical efficacy over time . the polarity reversal minimizes or prevents the deposit of scale and the plating of any charged chemical species onto the electrode surfaces . the polarity reversal functions may be applied when using confronting anode 21 and cathode 22 electrodes . in one aspect , the present invention employs an electrical current passing through an aqueous feed solution between an anode and a cathode to convert the halogen dioxide salt precursor dissolved within the solution into a halogen dioxide . the aqueous feed solution is an electrolytic solution . the term ‘ electrolytic solution ’ is used in its broadest sense and means any chemical solution that can flow through the passage of the disclosed flow - through electrolysis cell 20 , and that contains sufficient electrolytes to allow a measurable flow of electricity through the aqueous feed solution . water , except for deionized water , is a preferred aqueous feed solution , and can include : sea water ; water from rivers , streams , ponds , lakes , wells , springs , cisterns , mineral water , city or tap water , rain water , and brine solutions , among others . electrolytic solutions can also include blood , plasma , urine , polar solvents , electrolytic cleaning solutions , beverages , among others . an electrolytic solution of the present invention is chemically compatible if it does not chemically explode , burn , rapidly evaporate , or if it does not rapidly corrode , dissolve , or otherwise render the portable decontaminant system unsafe or inoperative , in its intended use . the aqueous feed solution can naturally comprise a halogen dioxide salt precursor and halide salt , or , it can be added , if desired . in one embodiment , the halogen dioxide salt precursor is a sodium chlorite , i . e ., naclo 2 , and the resulting halogen dioxide is chlorine dioxide . halogen dioxide salts have the general structure a ( xo 2 ) y where x and is f , cl , br , or i and a is an alkali or alkali earth metal including li , na , k , ca , mg and y is 1 for alkali metals and 2 for alkali earth metals . it should be appreciated that although the present invention , in one aspect , relates to a halogen dioxide product such as chlorine dioxide , other halogen dioxide products are also contemplated such as iodine dioxide , bromine dioxide and fluorine dioxide . the aqueous feed solution may also comprise an alkali halide that is converted into a hypohalite . however , separate aqueous feed solutions can be used if it is desired to keep the hypohalite separate from the halogen dioxide . in one embodiment , the alkali halide is nabr and the resulting hypohalite is hypobromite . an alkali halide is a compound formed from elements of groups i and vii of the periodic table . a hypohalite is any salt of a hypophalous acid , having a general formula m ( ox ) n . hypobromite is any salt or ester of hypobromous acid . it should be appreciated that other halide salts are contemplated by the present invention such as hypochlorite , hypobromite , hypoiodite , and hypofluorite . moreover , additional salts can be used such as a persulphate which is a stable peroxygen chemical that is electrochemically generated from sulphate . when an aqueous solution flows through the chamber 23 of the flow - through electrolysis cell 20 of the portable decontaminant system 10 ( fig1 a - 1d ), and electrical current is passed between the anode 21 and the cathode 22 , chemical reactions occur that involve the water , as well as one or more of the other salts or ions contained in the aqueous feed solution . for example , at the anode 21 , within a narrow layer of the aqueous feed solution in the passage adjacent to the anode surface , the following reaction occurs : 6h 2 o o 2 ( g )+ 4h 3 o + + 4e − . the following chemical reactions occurring at the anode 21 and cathode 22 for the salt precursors : anode : clo2 − → clo 2 + e − and br -+ 2oh -& lt ;=& gt ; bro —+ h2o + 2e ; and , at the cathode : h 2 o + e − → ½h 2 + oh − and na + + oh − naoh . flow dynamics , which include the movement of molecules in a flowing aqueous solution by turbulence , predicts that the conversion of chlorite salts to chlorine dioxide will increase as the solution flow path nears the anode surface layer . this concept applies to both the anode and cathode , and for both reactions . consequently , the portable decontaminant system 10 preferably maximizes the flow of the aqueous feed solution through the surface layer adjacent the anode 21 , in order to maximize the conversion of chlorite to chlorine dioxide , and the surface layer adjacent the cathode 22 , in order to maximize the conversation of the hypohalite into hypobromite . referring now to fig6 , a cross - section of a portable decontaminant system 10 with a flow - through electrolysis cell 20 is illustrated . the flow - through electrolysis cell 20 comprises an anode electrode 21 and cathode electrode 22 . the anode 21 and cathode 22 are electrically connected to a power source 100 , e . g ., a battery . an aqueous feed solution 101 enters the flow - through electrolysis cell 20 from the top and exits the bottom as an effluent solution 102 . in one embodiment , naclo 2 enters as an aqueous feed solution 101 and exits as an effluent solution 102 , e . g ., clo 2 . concurrently , or , in a different flow - through electrolysis cell 20 , nabr enters as an aqueous feed solution 101 and exits as an effluent solution 102 , e . g ., bro − 1 . the electrochemically generated chlorine dioxide is an excellent oxidant against cwa &# 39 ; s such as hd ( mustard gas ) and vx , and also effective against a wide range of biological agents . the chlorine dioxide oxidizes hd to sulfoxide and sulfone , and vx is neutralized to ethyl methyl phosphonic acid . the electrochemically generated chlorine dioxide is a gas that is soluble in water and organics . it evaporates completely , minimizing any environmental impact , and is chemically effective over a broad ph range . it can also be generated as needed from a stable precursor with no special storage conditions , has a stable and long storage life , and no transportation restrictions . 200 ppm of chlorine dioxide can be used for sterilization . the electrochemically generated chlorine dioxide obtain greater than 600 ppm levels when formed with the disclosed portable decontamination systems 10 ( fig1 a - 1d ). fig7 illustrates the antimicrobial efficacy of electrochemically generated chlorine dioxide . the antimicrobial efficacy of electrochemically generated chlorine dioxide , with a lapse time period of one minute , results in a log kill greater than 6 for bacteria such as e . coli , p . aeruginosa , s . aureus , b . subtilis , and k . terrigena . it results in a log kill greater than 5 for bacteria such as s . choleraesuis . the antimicrobial efficacy of electrochemically generated chlorine dioxide , with a lapse time period of one minute , results in a log kill greater than 5 for viruses such as the rhinovirus , ms2 , and fr . it results in a log kill greater than 4 for viruses such as poliovirus and rotavirus . it results in a log kill greater than 6 for virus spores such as b . cereus . all assays measured were below the detection limit of the methodology . a vx reaction with electrochemically generated chlorine dioxide is illustrated in fig8 . the p — s bond cleavage by chlorine dioxide produces empa as the sole phosphorus product . empa generates additional chlorine dioxide by acidification of chlorite . it should be appreciated that not all of the naclo 2 is converted to clo 2 in the portable decontaminant system 10 ( fig1 a - 1d ). the additional chlorine dioxide generated in situ by empa accelerates the rate and increases the reactive capacity for vx , e . g ., chlorine dioxide is auto - generated . consequently , the capacity to neutralize vx is very high . the addition of empa to a chlorite solution is tested and the auto - generation of clo 2 occurs . in fig9 , vx ( 1 : 50 by volume ) is added to a 2m chlorite solution . each beaker displayed in fig9 represent 15 second intervals in sequence . the color darkens as higher chlorine dioxide concentrations are auto - generated . for example , chlorine dioxide is formed by acidifying chlorite . as vx reacts , it produces an acid that causes the ph to drop leading to production of chlorine dioxide . a hd reaction with electrochemically generated chlorine dioxide and hypobromite is illustrated in fig1 . the oxidation by electrochemically generated clo 2 / bro — produces approximately 81 % bis ( 2 - chloroethyl ) sulfoxide , approximately 4 % 2 - bromoethyl 2 - chloroethyl sulfoxide , approximately 12 % bis ( 2 - chloroethyl ) sulfone , and approximately 3 % of unidentified compounds . the poor solubility of hd in water limits performance ; but , the electrochemically generated chlorine dioxide gas readily partitions into hd from an aqueous solution , and there is no undesirable side - chain chlorination detected . chlorine dioxide is soluble in the hd and concentrates there when hd is in contact with solutions of chlorine dioxide . chlorination is an undesirable reaction with hd that chlorine dioxide does not cause . a surfactant may be used to enhance hd solubility . in fig1 , it is shown that clo 2 readily partitions into hd phase . in fig1 , hd is added ( 1 : 20 ) to an aqueous electrochemically generated chlorine dioxide solution without stirring or modifiers ( surfactants or solvents ). the electrochemically generated chlorine dioxide is concentrated into an hd droplet within 1 minute . consequently , the disclosed portable decontaminant system 10 ( fig1 a - 1d ) is ideal to generate electrochemically generated chlorine dioxide and hypobromite and to effectively neutralize hd . however , electrochemically generated chlorine dioxide has no effect on sarin ( gb ) or soman ( gd ). this is where the addition of an electrochemically generated nucleophile , such as hypobromite , is advantageous . the electrochemically generated hypobromite is an excellent nucleophile against bwa &# 39 ; s sarin and soman , e . g ., g - agents . the hypobromite is a catalyst for rapid gd hydrolysis and , it also neutralizes hd and vx . like electrochemically generated chlorine dioxide , electrochemically generated hypobromite can be generated from a stable precursor with no special storage conditions , has a stable and long storage life , and no transportation restrictions . in a gd reaction , electrochemically generated chlorine dioxide does not react with gd . a nucleophile , such as hypobromite , is electrochemically generated by the portable decontaminant system 10 ( fig1 a - 1d ), and catalyzes gd hydrolysis in alkaline solutions . a gd - acid is the sole product . in fig1 , a gd reaction is illustrated . gd is added by 1 : 50 loading by volume , e . g ., 50 fold excess of decontamination solution over the amount of agent , i . e ., if there is 1 ml of agent , then 50 ml of decontamination solution is used in the test . the buffer used is co 3 2 − . as can be seen , the combination of electrochemically - generated hypobromite and the buffer provides almost 100 % removal of gd under approximately 2 minutes . it is also noted that the higher the hypobromite concentration , the quicker decontaminants are removed . for instance , in fig1 , the disclosed portable decontaminant systems 10 comprising flow - through electrolysis cell 20 ( fig1 a - 1d ) produces hypobromite in situ from a stock solution of nabr . the generation of hypobromite requires less battery power when compared to electrochemically generating chlorine dioxide . for instance , the redox potentials for the chemical reactions are provided as follows relative to she : br -+ 2oh -& lt ;=& gt ; bro —+ h 2 o + 2e =− 0 . 76v vs . she , compared to chlorine dioxide with clo2 -& lt ;=& gt ; clo 2 ( aq )+ e =− 0 . 954v vs . she . the term “ she ” refers to the standard hydrogen electrode , and is a standard way of describing the potential , e . g ., voltage , required to make a reaction occur . the higher the concentration of hypobromite , the higher the efficacy and lower amount of time is required to remove the decontaminant . referring now to fig1 , the concentration of hypobromite should range from about 1 . 2 to about 1 . 5 . this can occur by either increasing the initial sodium bromide used in the portable decontaminant system 10 , or , by manipulating the geometry or creating a multi - pass system for the flow - through electrolysis cell 20 . fig1 illustrates a multi - pass system with multiple flow - through electrolysis cells 20 . in the multipass system the effluent from one electrolysis cell is fed into a second electrolysis cell to increase the conversion of salts . as a result , the combination of the nucleophile and oxidant electrochemically generated by the present invention is ideal for use . the aqueous feed solution comprises the halogen dioxide salt and alkali halide , which for simplicity will be exemplified herein after by the most preferred halite salt , sodium chlorite , i . e ., naclo 2 , and sodium bromide , i . e ., nabr as the alkali halide . sodium chlorite is not a salt ordinarily found in tap water , well water , and other water sources . consequently , the sodium chlorite salt is added to the aqueous feed solution at a desired concentration generally of at least 100 parts per million ( ppm ). the term ppm , as used herein , means that one ppm is substantially equivalent to 1 milligram of something per liter of water ( mg / l ). the nabr salt is added to the aqueous feed solution at a desired concentration generally of at least 100 ppm . the desired concentration of the sodium chlorite salt and sodium bromide is dependent on the desired decontaminant targeted . for instance , sanitation use requires a concentration of from about 500 to about 1000 ppm , disinfection use requires a concentration of from about 1000 to 5000 ppm , and sterilization use requires a concentration of from about 2000 to about 10 , 000 ppm . the term sanitation , as used herein , means that some object or mammal has been treated in order to be substantially free of live bacteria , other microorganisms , or some harmful chemical . the term disinfection , as used herein , means that some object or mammal has been treated in order to destroy live bacteria , other microorganisms , or some harmful chemical . the term sterilization , as used herein , means that some object or mammal has been treated to be substantially free of live bacteria , other microorganisms , or some harmful chemical . the precursor material from which the halogen dioxide is formed is referred to as a halogen dioxide salt . the more common and most preferred halogen dioxide salt is the corresponding halite salt of the general formula mxo 2 , wherein m is selected from alkali and alkali - metal earth metal , and is more commonly selected from sodium , potassium , magnesium and calcium , and is most preferably sodium ; and wherein x is halogen and is selected from cl , br , i and f , and is preferably cl . the halogen dioxide salt can comprise two or more salts in various mixtures . the aqueous feed solution also comprises the alkali halide , which for simplicity will be exemplified herein after by the most preferred halide , nabr . the sodium bromide is not ordinarily found in tap water , well water , and other water sources . consequently , an amount of the bromine halide is added to the aqueous feed solution at a desired concentration generally of at least 0 . 1 ( 10 , 000 ppm )- 2 ( 200 , 0000 ppm ) molar , and preferably 0 . 5 ( 50 , 000 ppm )- 1 . 5 ( 150 , 000 ppm ) molar . the desired concentration of the sodium bromide is dependent on the desired decontaminant targeted . the precursor material from which the hypohalite is formed is referred to as an alkali halide . the more common and most preferred hypohalite has the general formula m ( ox ) n , wherein m is selected from alkali and alkali earth metals , and is more commonly selected from alkali metals , and is most preferably na or k ; and wherein x is f , cl , br , i and is preferably cl , br . the alkali halide can comprise two or more alkali halides in various mixtures . the range of chlorine dioxide and hydrobromite conversion that is achievable in the flow - through electrolysis cells of the present invention generally ranges from greater than 0 . 01 % to less than 100 %. the level of conversion is dependent most significantly on the design of the portable decontaminant system 10 , as well as on the electrical current properties used in the portable decontaminant system 10 . the aqueous feed solution , as it exits the portable decontaminant system 10 from an outlet becomes an effluent solution that is discharged . the term ‘ effluent solution ’ means that the aqueous feed solution contains a higher level of decontaminant properties , e . g ., is a decontaminant biological and chemical solution , than it originally contained prior to undergoing electrolysis . the aqueous feed solution comprises one or more other salts in addition to the sodium chlorite . these salts can be used to enhance the sanitation , disinfection and sterilization and neutralization performance of the effluent that is discharged from the portable decontaminant system , or to provide other mixed oxidants in response to the passing of electrical current through the portable decontaminant system . as indicated above , the preferred other salt is an alkali halide , and is most preferably sodium bromide . the aqueous feed solution comprising the sodium chlorite can be provided in a variety of ways . a solid , preferably powdered , form of the sodium chlorite can be mixed into an aqueous solution to form a dissolved solution , which can be used as - is as the aqueous feed solution or , if in a concentrated solution can be subsequently diluted with water . preferably , a concentrated solution of about 0 . 5 to about 50 % sodium chlorite can be used . the aqueous feed solution comprising the source of halide ions can supplement the ordinary levels of halide ions in many water sources , such as tap water , to generate higher concentration levels of mixed oxidants in the effluent . the local source of halide ions can be a concentrated brine solution , a salt tablet in fluid contact with the reservoir of electrolytic solution , or mixtures thereof . a preferred localized source of halide ions is a solid form , such as a pill or tablet , of halide salt , such as sodium bromide . preferably , a concentrated solution of about 0 . 5 % to about 50 % sodium bromide can be used . as a result , the present invention can provide additional sources of halogen dioxide salt and / or halide salt , with a method for delivering the halogen dioxide salt and / or halide salt to the aqueous feed solution . this embodiment is used in situations when the aqueous feed solution does not contain a sufficient amount , or any , of the halogen dioxide salt and / or halide salt . the local source of halogen dioxide salt and / or halide salt can be released into a stream of the aqueous feed solution , which then passes through the portable decontaminant system . the local source of halogen dioxide salt and / or halide can also be released into a portion of a reservoir of the aqueous feed solution , which portion is then drawn into the portable decontaminant system . preferably , all the local source of halogen dioxide salt and / or halide salt passes through the portable decontaminant system , to maximize the conversion to halogen dioxide and hypohalite . the local source of halogen dioxide salt and / or halide salt can also supplement any residual levels of halogen dioxide salt and / or halide salt already in the aqueous feed solution , if any . for purposes of a simplified description , the halogen dioxide salt and halide salt will be collectively referred to herein as ‘ the two salts .’ the local source of the two salts can be delivered by a single salt chamber comprising the salts , in preferably a pill or tablet form , through which a portion of the aqueous feed solution passes , thereby dissolving a portion of the salts to form the aqueous feed solution . the salt chamber can comprise both salts , or , two separate salt chambers can be used to keep them separate . the salt chamber can comprise a salt void formed in the body of the device that holds the portable decontaminant system , which is positioned in fluid communication with the portion of aqueous feed solution that passes through the portable decontaminant system . any water source can be used to form the aqueous feed solution the ph of the aqueous feed solution comprising the halogen dioxide salt and halide salt is preferably 7 , and more preferably 12 . the aqueous feed solution is preferably maintained at a ph of 8 , and more preferably at a ph of 9 . 5 . most preferably , the ph of the feed solution is between about 8 and about 10 . the aqueous feed solution can be fed to the portable decontaminant system from a batch storage container . alternatively , the aqueous feed solution can be prepared continuously by admixing a concentrated aqueous solution of sodium bromide and sodium chlorite with a second water source , and passing continuously the admixture to the portable decontaminant system . optionally , a portion of the aqueous feed solution can comprise a recycled portion of the effluent from the portable decontaminant system . the aqueous feed solution can comprise a combination of any of the forgoing sources . the aqueous feed solution can flow continuously or periodically through the portable decontaminant system . the discharged effluent solution containing the electrochemically generated chlorine dioxide and hypobromite is removed from the flow - through electrolysis cell 20 and is used , for example , as an aqueous sanitation , disinfection or sterilization solution . the effluent solution can be used as - made by direct delivery to a site that is neutralized by the chlorine dioxide and hypobromite . oxidation is the main chemical reaction ; however , the hypobromite reacts with g - agents by nucleophilic displacement . the site can be a bwa which is destroyed when mixed or contacted with the effluent solution . the site can also be an article or object on which neutralizable material is affixed or positioned . the structure for passing the aqueous feed solution into the cell can be a pump or an arrangement where gravity or pressure forces aqueous feed solution from a storage container into the cell . the structure for delivering the aqueous effluent can be a pump as disclosed above , or can be a separate pump or gravity / pressure arrangement . the system 10 can also comprise a recirculation line through which a portion of the effluent solution is returned back to the inlet of the flow - through electrolysis cell 20 . as herein before described , re - circulating the effluent solution back to the cell 20 increases the total conversion of the halogen dioxide salt to the halogen dioxide product , and alkali halide into the nucleophile . the structure for returning the depleted effluent solution can be a collection tank with additional structures for recycling the depleted effluent solution back to the source . in one embodiment , a low powered portable flow - through electrolysis cell 20 is provided that can use the current and voltage delivered by conventional household batteries . the flow - through electrolysis cells 20 can come in various sizes , with anodes having a surface area of from about 0 . 1 cm 2 to about 60 cm 2 . one particular embodiment of the present invention comprises a spray nozzle having , in the spray effluent solution pathway leading to the spray nozzle , a flow - through electrolysis cell 20 with an anode having a surface area of from about 0 . 1 cm 2 to about 20 cm 2 , more preferably from about 2 cm 2 to about 8 cm 2 . the spray effluent solution can be pumped to the flow - through electrolysis cell 20 by a trigger - actuated pump or an electrically - driven motorized pump . such spray pump units will typically spray from about 100 to about 300 cc / min . of spray solution . in the aforementioned embodiment , the effluent solution can comprise the generation of about equal amounts of chlorine dioxide and hypobromite . typically , a mixed salt solution ( sodium chlorite and sodium bromide ) containing 0 . 5 - 2 molar of each of the two salts is used . this aqueous feed solution is passed through the flow - through electrolysis cell 20 and provides an effluent solution comprising about 1000 ppm of a mixture of chlorine dioxide and hypobromite which are in approximate equal amounts , e . g ., about 500 ppm of electrochemically generated chlorine dioxide and about 500 ppm of electrochemically generated hypobromite . the effluent solution can also be buffered if it is desired to have a specific ph . common buffers that can be used are those described in the “ crc handbook . of chemistry and physics published by the crc press in a preferred embodiment , carbonate and / or bicarbonate is used as the buffer for ph &# 39 ; s of about 9 to about 10 . 5 . in the absence of buffer , the electrolysis will lead to the formation of hydroxide ions that will raise the ph , and in some embodiments , this would be detrimental to efficacy or may lead to damage of surfaces undergoing decontamination . it should be appreciated that the ratio of electrochemically generated chlorine dioxide to electrochemically generated hypobromite can be in different ratios than disclosed above . for instance , the concentration of the salts in the aqueous feed solution can be manipulated to change the final effluent solution ratio of electrochemically generated chlorine dioxide to electrochemically generated hypobromite . the desired application will determine the final ratios . for the decontamination application , the hypobromite is being used as a nucleophile . chlorine dioxide is very effective , as illustrated above , against bwa &# 39 ; s and most of chemical weapons agents ( cwa ). however , it is not effective against one class of cwa nerve agent known as g - agents . this class includes sarin , soman and tabun . these agents are sensitive to nucleophiles and this is why the nucleophiles are preferably added to the aqueous feed solution . additional stable nucleophiles can also be used such as n - oxides and hydroxylamines as a way to provide g - agent neutralization . these are effective but need higher levels than hypobromite . generating hypohalites using the flow - through electrolysis cell 20 , such as hypobromite , is highly effective at g - agent neutralization . the nucleophiles can be selected from the group consisting of n - oxides , hydroxylamines , amines , and combinations thereof . for example , fig1 illustrates n - oxides that may be added to the aqueous feed solution in conjunction with nabr or in lieu , such as trimethylamine n - oxide ( tmano ), methylmorpholine n - oxide ( mmno ), pyridine n - oxide ( pno ), pyridylcarbinol n - oxide ( pcno ), 8 - hydroxyquinoline n - oxide ( hqno ), 4 - dimethylamine pyridine n - oxide ( dmapno ), methyoxy pyridine n - oxide hydrate ( mopnoh ), 4 -( 3 - phenylpropyl ) pyridine n - oxide ( pppno ), poly ( 4 - vinyl ) pyridine n - oxide ( pvpno ), and 6 - methoxyquinoline n - oxide ( moqno ). in one embodiment , at a buffered ph of 9 . 5 the n - oxide is preferably tmano . fig1 illustrates amines and oxides that may be added to the aqueous feed solution in conjunction with nabr or in lieu , such as diethyl hydroxylamine ( deha ), n , n - dibenzylhydroxylamine ( dbha ), alkyl dimethyl amine oxide ( ao ), isoniazid ( ia ), formic hydrazide ( fha ), n - hydroxyphthalimide ( hopa ), triethylphosphineoxide ( tepo ), octanoic hydrazide ( oha ), n - hydroxynaphthalimide sodium salt ( hona ), and triphenyl phosphineoxide ( tppo ). bacillius cereus spores , the surrogate for anthrax , is used in the aqueous sporocidal tests . the closest relatives of bacillius anthracis are the two species , bacillus thuringiensis ( an insect pathogen ) and bacillius cereus ( b . cereus ) ( a ubiquitous soil isolate and food borne human pathogen ). the distinguishing functional features of these species are primarily virulence genes carried on plasmids . the purpose of the aqueous sporocidal testing methodology is to determine the efficacy of chlorine and chlorine dioxide in killing vegetative cells and spores of b . cereus . first , a single cocktail with approximately equal population of five strains of b . cereus are used as illustrated in fig1 . second , the vegetative cells and spores are prepared . to grow the vegetative cells , the strains are grown in brain heart infusion ( bhi ) broth at approximately 30 ° c . for 24 h . the cultures are then transferred by loop inocula twice at 24 h intervals before inoculating bhi broth from which cells are used to prepare a five - strain mixture comprising approximately equal populations of each strain . these populations are achieved by centrifugation ( 6000 × g for 10 min at approximately 21 ° c .) of 24 hour cultures , and re - suspending in 30 ml of sterile de - ionized water , and combining predetermined volumes to yield a suspension comprising ca . 10 8 cfu / ml . this suspension ( 0 . 1 ml ) is added to 4 . 9 ml of chemical treatment solution ( and water control ) to yield the reaction mixture containing a population of 10 6 cfu / ml . to grow the spores , suspensions ( 0 . 1 ml ) of each strain is grown at approximately 30 ° c . for 24 h and are surface - plated on nutrient agar ( bbl / difco ) supplemented with manganese sulfate ( 50 μg / ml ). the plates are incubated at approximately 30 ° c . for approximately 72 hours , and then held at approximately 4 ° c . for approximately 40 h before spores are harvested . sterile de - ionized water ( approximately 5 ml ) is applied to the surface of each plate , followed by rubbing with a sterile bent glass rod to suspend cells and spores that are not sporulated . suspensions of each strain collected from 12 plates are course - filtered through sterile glass wool , pooled , and centrifuged ( 2600 × g for 20 min ). pellets are re - suspended in approximately 100 ml of sterile de - ionized water and undergo centrifugation ( 6000 × g for 10 min ). the washing procedure is continuously repeated until spores are substantially free of most cell debris originating from the original culture . suspensions ( ca . 50 ml of each strain ) are stored at approximately 1 - 2 ° c . until used . the number of spores ( cfu / ml ) in each stored suspension is measured . water ( approximately 4 ml ) in a glass test tube is adjusted to a temperature of approximately 80 ° c . in a water bath . the stock spore suspension is diluted approximately 10 - fold and approximately 1 ml is added to the hot water . after heating for approximately 10 min ., and approximately 1 ml is withdrawn and added to approximately 9 ml of sterile 0 . 1 % peptone with a temperature of approximately 21 ° c . serially - diluted suspensions are surface plated ( 0 . 1 ml ) on duplicate plates of brain heart infusion agar ( bhia ). plates are incubated at approximately 30 ° c . for 24 h before colonies are counted . populations of spores in stock suspensions are then calculated . the differences in populations among the five strains necessitated centrifugation ( 6000 × g for 10 min ) of some suspensions followed by re - suspending spores in different volumes of sterile water . a five - strain mixture of spores serves as an inoculum for chemical treatment solutions and water ( control ). preparing the inoculum comprising approximately equal populations of heat - shocked spores of each strain is done immediately before determining the efficacy of chlorine dioxide and chlorine treatments . next , the electrochemically generated treatment solutions are prepared using the disclosed portable decontaminant system . naocl ( sigma - aldrich ) is added to sterile 0 . 05 m potassium phosphate buffer ( ph 6 . 8 , 21 ° c .). the free chlorine content is determined using an amperometric titrator , e . g ., a hach colorimeter ( model dr / 820 , hach company , loveland , co .). the electrochemically generated chemical solution or water control ( 4 . 9 ml , 21 ° c .) are dispensed into 15 × 150 mm test tubes . vegetative cell suspension ( 0 . 1 ml ) or spore suspension ( 0 . 1 ml ) are added and mixed . after treatment for 5 min , 5 . 0 ml of 2 × dey - engley broth is added and mixed to achieve neutralization . all experiments are replicated three times . the treated suspensions then undergo microbiological analysis . the treated suspensions are surface plated in quadruplicate ( 0 . 25 g ml ) and duplicate ( 0 . 1 ml ) on bhia . suspensions serially diluted in peptone water are also surface plated ( 0 . 1 ml , in duplicate ) on bhia . plates are inoculated at approximately 30 ° c . for 24 h before colonies are counted . table 1 illustrates the results of these experiments . as table 1 illustrates , the 200 ppm clo 2 treatments result in viable spore counts that are below the limits of detection ( i . e ., provided complete kill , & gt ; 6 log reduction ) within 5 min . the efficacy of the e - clo 2 treatments ( electrochemically generated chlorine dioxide treatments ) after a 5 - min exposure is significantly greater than that achieved by treatment with 200 ppm hocl . consequently , the e - clo 2 treatments provide a complete kill in testing and are more effective than equivalent non - electrochemically generated chlorine solutions , and provide a significant and effective alternative to chlorine as a treatment to significantly reduce microbial pathogens . fig1 provides another way of illustrating the results achieved with a bacillus cereus cocktail of the five different strains . the e - clo 2 treatment is much more effective in killing the bacillus cereus spores ( i . e ., total kill ) as compared to the hypochlorite benchmark which only yielded 1 . 5 log kill . additionally , it is important to note that few other treatments would have provided total kill of the bacillus cereus spores since these are particularly difficult to kill . a series of carrier tests are conducted at p & amp ; g sharon woods technology center &# 39 ; s ( swtc ) microbiology laboratory , using e - clo 2 samples . the method is a quantified modification of the aoac use dilution test ( udt ), which is prescribed by the epa for hard surface cleaner fifra registrations . in this method , the challenge organisms in the presence of 5 % horse serum are inoculated and dried on stainless steel cylinders . the inoculated cylinders are exposed to various treatments at ambient temperatures . after approximately 1 minute contact time , the carriers are removed and neutralized . the numbers of surviving organisms are then enumerated and the log 10 reductions calculated versus the dry carrier controls , using standard plate counting techniques . the 40 ppm e - clo 2 killed microorganisms in carrier testing shows equivalency to 200 ppm hocl . the 1 minute exposure to 40 ppm e - clo 2 provides approximately greater than or equal to 5 log reduction against pseudomonas aeruginosa , a gram (−) bacterial species that is representative of naturally occurring microbial populations and an opportunistic human pathogen , and an approximately greater than or equal to 5 log reduction against escherichia coli , a gram (−) bacterial species commonly associated with food - borne illness . consequently , the e - clo 2 treatments provide a complete kill in testing and are more effective than equivalent non - electrochemically generated chlorine solutions , and provide a significant and effective alternative to chlorine as a treatment to significantly reduce microbial pathogens . fig1 demonstrates the antimicrobial efficacy of a 1 ppm e — clo 2 solution tested in various solutions of microorganisms with a decontaminant solution generated by the portable decontaminant system . the contact time is approximately one minute . in all tests , a total kill was achieved , i . e ., below the detection limit of the method . a series of carrier tests are conducted at the p & amp ; g swtc microbiology laboratory , using e - clo 2 samples . this method is a quantified modification of the aoac germicidal spray test ( gst ), which is also prescribed by the epa for hard surface cleaner fifra registrations . in this test , the challenge organisms are inoculated and dried onto glass carriers in the presence of 5 % horse serum . the inoculated carriers are then treated by spraying the product on the carriers and allowed to sit for approximately 10 min . after the 10 min contact time , the carriers are removed and neutralized . the numbers of surviving organisms are then enumerated and the log 10 reductions calculated versus the dry carrier controls , using standard plate counting techniques . the 200 ppm e - clo 2 killed microorganisms in carrier testing shows better efficacy than 200 ppm hocl . the 10 minute exposure to 200 ppm clo 2 provides an approximately greater than or equal to 5 log reduction against pseudomonas aeruginosa , and an approximately greater than or equal to 5 log reduction against salmonella choleraesuis . consequently , the e - clo 2 treatments provide a complete kill in testing and are more effective than equivalent non - electrochemically generated chlorine solutions , and provide a significant and effective alternative to chlorine as a treatment to significantly reduce microbial pathogens . fig2 demonstrates surface test results of testing the e - clo 2 at 100 ppm concentration on microbes which are deposited on hard substrates . the contact time is ten minutes . note that all tests showed complete kill of the microorganisms ( to below detection limit ). it should be appreciated that the combination of chlorine dioxide and hypobromite may also find consumer use applications , such as for household cleaning products , incorporated into air freshening , textiles , wovens , non - wovens , baby care products , health care products , and the like . for example , a household cleaning product could incorporate electrochemically generated chlorine dioxide and hypobromite at lower concentrations . the electrochemically generated chlorine dioxide will range from about 1 ppm to about 200 ppm , and preferably from about 10 ppm to about 100 ppm . the electrochemically generated hypobromite will range from about 20 ppm to about 2000 ppm , and preferably from about 100 ppm to about 1000 ppm . the disclosed portable decontaminant system 10 ( fig1 a - 1d ), electrochemically generates an oxidant and nucleophile . in a preferred embodiment , the oxidant is chlorine dioxide and the nucleophile is hypobromite . the electrochemically generated chemicals rapidly neutralizes all bwa &# 39 ; s and cwa &# 39 ; s . the portable decontaminant system is simple , safe , and easy for an individual to use , such as a soldier on a battlefield . the system is also very stable over years of storage and can be readily transported without restrictions . there are minimal or no effects on surface materials . the electrochemical generation of active species resolves the conflict between the required high activity and the need for storage stability and transportability . the reactive species are produced on demand from stable precursors . the disclosed portable decontamination unit is portable , and , scalable . the dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited . instead , unless otherwise specified , each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value . for example , a dimension disclosed as “ 40 mm ” is intended to mean “ about 40 mm ”. all documents cited in the detailed description of the invention are , in relevant part , incorporated herein by reference ; the citation of any document is not to be construed as an admission that it is prior art with respect to the present invention . to the extent that any meaning or definition of a term in this &# 39 ; written document conflicts with any meaning or definition of the term in a document incorporated by reference , the meaning or definition assigned to the term in this written document shall govern . while particular embodiments of the present invention have been illustrated and described , it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention . it is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention .

US-98103707-A

the present disclosure relates to surgical fasteners and more particularly to surgical fasteners coated with wound treatment materials . according to an aspect of the present disclosure , a surgical fastener for use in combination with a surgical fastener applying apparatus is provided . the surgical fastener includes a pair of legs ; a crown interconnecting the pair of legs ; and a wound treatment material coating at least a portion of the legs and crown .

embodiments of the presently disclosed surgical fasteners will now be described in detail with reference to the drawing figures wherein like reference numerals identify similar or identical elements . as used herein and as is traditional , the term “ distal ” refers to that portion which is farthest from the user while the term “ proximal ” refers to that portion which is closest to the user . with reference to fig1 and 2 , a surgical fastener , in the form of a surgical staple , is generally shown as 100 . surgical staples of the present disclosure typically include any metallic staple used to join together tissue parts and / or adjacent tissues . surgical staples 100 may be made of metal , such as , for example , stainless steel or titanium , or any other material known by one having skill in the art . for example , surgical staples 100 may also be fabricated from bio - absorbable material or the like . bio - absorbable materials used for surgical staples 100 include , and are not limited to , those fabricated from homopolymers , copolymers or blends obtained from one or more monomers selected from the group consisting of glycolide , glycolic acid , lactide , lactic acid , p - dioxanone , a - caprolactone and trimethylene carbonate . other bio - absorbable materials include and are not limited to , for example , polyglycolic acid ( pga ) and polylactic acid ( pla ). with continued reference to fig1 and 2 , surgical staple 100 includes a pair of legs 102 , 104 which are interconnected to one another by a crown or backspan 106 extending between first ends 102 a , 104 a , respectively , thereof . as seen in fig1 and 2 , crown 106 is substantially perpendicular to legs 102 , 104 . however , it is envisioned that crown 106 may take on any shape and / or form as needed and / or desired and may have any orientation relative to legs 102 , 104 . for example , crown 106 may include two sections which extend angularly from legs 102 , 104 and are connected at an apex ( not shown ). as seen in fig1 and 2 , respective distal ends 102 b , 104 b of legs 102 , 104 are sharpened to facilitate penetration of legs 102 , 104 into tissue or the like . in accordance with the present disclosure , surgical staple 100 is coated with a wound treatment material “ w ”. it is envisioned that wound treatment material “ w ” may be applied to the entirety of surgical staple 100 ( as seen in fig1 and 2 ), or may be applied to any specific area of surgical staple 100 that is to come into contact with tissue of the like . for example , wound treatment material “ w ” may be applied solely to legs 102 , 104 ( see fig3 ); solely to one of legs 102 , 104 ( not shown ); solely to crown 106 ( not shown ); or any portion thereof . it is further envisioned that wound treatment material “ w ” may be impregnated into legs 102 , 104 and crown 106 of surgical staple 100 , as seen in fig4 . in one embodiment , surgical staples 100 may be fabricated from a bio - absorbable material which is desirably impregnated with wound treatment material “ w ”. accordingly , in use , the wound treatment material component of surgical staples 100 may function to retard any bleeding which may occur from the tissue , in the manner of a sealant , and to secure the approximated tissue together , in the manner of an adhesive . the bio - absorbability of surgical staples 100 allows for the at least a portion of surgical staples 100 to be absorbed into the body after a predetermined amount of time . for example , surgical staples 100 may remain in place in the body for approximately 2 - 3 weeks in order for the anastomosis to sufficiently heal prior to surgical staples 100 being absorbed into the body . as mentioned above and as shown in fig3 , it is envisioned that surgical staples 100 may be impregnated with a wound treatment material “ w ” which is a pre - cured adhesive or sealant . the pre - cured sealant or adhesive will react with the moisture and / or heat of the body tissue to thereby activate the sealing and / or adhesive properties of the sealant or adhesive . it is envisioned that the pre - cured sealant or adhesive may be a hydro - gel or the like . it is contemplated that the wound treatment material “ w ” is any material for joining , healing , sealing or otherwise treating tissue . in a preferred embodiment , the wound treatment material is a bio - compatible sealant , including , and not limited , to sealants which cure upon tissue contact , sealants which cure upon exposure to ultraviolet ( uv ) light , sealants which are two - part systems which are kept isolated from one another and are combined or any combinations thereof . any known suitable adhesive may be used . in one embodiment , it is contemplated that such sealants and / or adhesives are curable . for example , sealants may have a cure time of from about 10 to 15 seconds may be used . in preferred embodiments , the sealant and / or adhesive is a bioabsorbable and / or bio - resorbable material . in another embodiment , it is contemplated that a sealant and / or adhesive having a cure time of about 30 seconds may be used . it is further envisioned that wound treatment material “ w ” may be a pre - cured adhesive or sealant . in certain preferred embodiments , the wound treatment material “ w ” comprises a sealant . such a sealant is desirably a peg - based material . examples of classes of materials useful as the sealant and / or adhesive include acrylate or methacrylate functional hydrogels in the presence of a biocompatible photoinitiator , alkyl - cyanoacrylates , isocyanate functional macromers with or without amine functional macromers , succinimidyl ester functional macromers with amine or sulfhydryl functional macromers , epoxy functional macromers with amine functional macromers , mixtures of proteins or polypeptides in the presence of aldehyde crosslinkers , genipin , or water - soluble carbodiimides , anionic polysaccharides in the presence of polyvalent cations , etc . some specific materials which may be utilized include isocyanate terminated hydrophilic urethane prepolymers derived from organic polyisocyanates and oxyethylene - based diols or polyols , including those disclosed in u . s . pat . nos . 6 , 702 , 731 and 6 , 296 , 607 and u . s . published patent application no . 2004 / 0068078 ; alpha - cyanoacrylate based adhesives including those disclosed in u . s . pat . no . 6 , 565 , 840 ; alkyl ester based cyanoacrylate adhesives including those disclosed in u . s . pat . no . 6 , 620 , 846 ; adhesives based on biocompatible cross - linked polymers formed from water soluble precursors having electrophilic and nucleophilic groups capable of reacting and cross - linking in situ , including those disclosed in u . s . pat . no . 6 , 566 , 406 ; two part adhesive systems including those based upon polyalkylene oxide backbones substituted with one or more isocyanate groups in combination with bioabsorbable diamine compounds , or polyalkylene oxide backbones substituted with one or more amine groups in combination with bioabsorbable diisoycanate compounds as disclosed in u . s . published patent application no . 2003 / 0032734 , the contents of which are incorporated by reference herein ; and isocyanate terminated hydrophilic urethane prepolymers derived from aromatic diisocyanates and polyols as disclosed in u . s . published patent application no . 2004 / 0115229 , the contents of which are incorporated by reference herein . it is envisioned and within the scope of the present disclosure that wound treatment material “ w ” may include one or a combination of adhesives , hemostats , sealants , or any other tissue or wound - treating material . surgical biocompatible wound treatment materials “ w ”, which may be used in accordance with the present disclosure , include adhesives whose function is to attach or hold organs , tissues or structures , sealants to prevent fluid leakage , and hemostats to halt or prevent bleeding . examples of adhesives which can be employed include protein derived , aldehyde - based adhesive materials , for example , the commercially available albumin / glutaraldehyde materials sold under the trade designation bioglue ™ by cryolife , inc ., and cyanoacrylate - based materials sold under the trade designations indermil ™ and derma bond ™ by tyco healthcare group , lp and ethicon endosurgery , inc ., respectively . examples of sealants , which can be employed , include fibrin sealants and collagen - based and synthetic polymer - based tissue sealants . examples of commercially available sealants are synthetic polyethylene glycol - based , hydrogel materials sold under the trade designation coseal ™ by cohesion technologies and baxter international , inc . examples of hemostat materials , which can be employed , include fibrin - based , collagen - based , oxidized regenerated cellulose - based and gelatin - based topical hemostats , as well as aluminum alum ( i . e ., ammonium alum or aluminum ammonium sulfate ). examples of commercially available hemostat materials are fibrinogen - thrombin combination materials sold under the trade designations costasis ™ by tyco healthcare group , lp , and tisseel ™ sold by baxter international , inc . hemostats herein include astringents , e . g ., aluminum sulfates , and coagulants . a further example of a hemostat includes “ quick clot ™”, commercially available from z - medica , inc ., newington , conn . the medicament may include one or more medically and / or surgically useful substances such as drugs , enzymes , growth factors , peptides , proteins , dyes , pigments , diagnostic agents or hemostasis agents , monoclonal antibodies , or any other pharmaceutical used in the prevention of stenosis . the medicament may be disposed on structure 100 or impregnated into structure 100 . wound treatment material “ w ” may include visco - elastic film forming materials , cross - linking reactive agents , and energy curable adhesives . it is envisioned that wound treatment material “ w ”, and in particular , adhesive may be cured with the application of water and / or glycerin ( 1 , 2 , 3 ,- pranatetriol , also known as glycerol or glycerine ) thereto . in this manner , the water and / or glycerin cure the adhesive and hydrate the wound . it is further contemplated that wound treatment material “ w ” may include , for example , compositions and / or compounds which accelerate or beneficially modify the healing process when particles of the composition and / or compound are applied to or exposed to a surgical repair site . for example , the wound treatment material “ w ” may be a therapeutic agent which will be deposited at the repair site . the therapeutic agent can be chosen for its antimicrobial properties , capability for promoting repair or reconstruction and / or new tissue growth . for example , the wound treatment material “ w ” may comprise “ silvasorb ™”, commercially available from acrymed , inc , portland , oregon . antimicrobial agents such as broad spectrum antibiotic ( gentamycin sulfate , erythromycin or derivatized glycopeptides ) which are slowly released into the tissue can be applied in this manner to aid in combating clinical and sub - clinical infections in a tissue repair site . to promote repair and / or tissue growth , wound treatment material “ w ” may include one or several growth promoting factors , e . g ., fibroblast growth factor , bone growth factor , epidermal growth factor , platelet derived growth factor , macrophage derived growth factor , alveolar derived growth factor , monocyte derived growth factor , magainin , and so forth . some therapeutic indications are : glycerol with tissue or kidney plasminogen activator to cause thrombosis , superoxide dimutase to scavenge tissue damaging free radicals , tumor necrosis factor for cancer therapy or colony stimulating factor and interferon , interleukin - 2 or other lymphokine to enhance the immune system . it is further envisioned and within the of the present disclosure for wound treatment material “ w ” to include any microbial agent , analgesic , growth factor , and anti - inflammatory agent known by one having skill in the art or any combination thereof . those skilled in the art will recognize that the successful surface treatment of surgical staple 100 , prior to the application of wound treatment material “ w ”, may include pre - cleaning surgical staple 100 and controlling the moisture at the surface of surgical staple 100 in order to ensure complete and / or proper coating of surgical staple 100 . multi - step cleaning and drying operations can therefore be used to provide a clean surface and to control moisture . once the surface of surgical staple 100 is treated , as described above , a solution containing wound treatment material “ w ” is applied to the treated surgical staple 100 . it is contemplated and within the scope of the present disclosure for any of the surgical staples 100 disclosed herein to be used in connection with linear - type surgical staplers , non - linear - type surgical stapler , annular - type surgical staples , endoscopic - type surgical staplers , skin - type surgical staplers and the like . it is further contemplated and within the scope of the present disclosure for any of the surgical staples 100 disclosed herein to have equal length legs , un - equal length legs , a relatively short crown as compared to the length of the legs , a relatively long crown as compared to the length of the legs , a symmetrical transverse cross - sectional profile in at least one of the legs and the crown , and an asymmetrical transverse cross - sectional profile in at least one of the legs and the crown . for example , each leg and / or the crown may have a cross - sectional profile which is polygonal , such as , triangular , rectangular , hexagonal any combination thereof or the like . moreover , each leg and / or the crown may have a cross - sectional profile which is circular , ovular or the like . it is further envisioned that the crown may be either linear of non - linear . it is still further contemplated and within the scope of the present disclosure for any of the surgical staples 100 disclosed herein to include legs which do not lie in the same plane as one another . in other words , one leg and the crown of the surgical staple 100 define a first plane , and the other leg of the surgical staple 100 lies in a second plane which is non - coplanar , or transverse to the first plane . as seen in fig5 , a surgical fastener , in the form of a two - part fastener , is generally shown as 200 . the physical structure of an exemplary surgical fastener 200 is shown and described in u . s . pat . no . 4 , 534 , 352 , the entire content of which is incorporated herein by reference . generally , surgical fastener 200 includes a retainer member 210 and fastener member 202 , which has two prongs or legs 204 that are driven through tissue ( not shown ) to engage apertures 212 in retainer member 210 . prongs 204 each include a barb 206 attached to a shank 208 . in accordance with the present disclosure , surgical fastener 200 , including retainer member 210 and fastener member 202 may be constructed from any of the materials disclosed hereinabove either identically ( constructed from the same materials ) or uniquely ( i . e ., constructed from different materials ) from one another . it should be understood that various changes in form , detail and application of the support structures of the present disclosure may be made without departing from the spirit and scope of the present disclosure .

US-201313857452-A

the transfer device of an agricultural harvester , in particular a self - propelled forage harvester , is controlled to avoid crop loss and improve operating efficiency . the harvested crop is transferred from the agricultural harvester to a transport receptacle via an upper discharge chute . apparatus controls the pivoting and vertical movement of the transfer device while the crop stream is spewed in a manner to avoid crop loss and improve the filling capacity during the transfer . the angle between the pivotable transfer device and the longitudinal direction of the agricultural harvester is calculated from the quantity of the correcting value to predetermine the direction of travel of the agricultural harvester . during travel , the apparatus is effective even during a curved path of travel .

generally , harvesting crop is performed with an agricultural harvester 1 along predetermined crop rows or swaths . to avoid crop loss , the rows or swaths are sown or deposited in a uniform pattern . irregularities in the rows or swaths are largely leveled out by the front harvesting attachment when the crop is picked up . changes in direction of travel when the crop is picked up are therefore only minor . from the quantity that predetermines the direction of travel , the transport receptacle &# 39 ; s 3 location can be derived . the transfer device can then be controlled accordingly without response . the self - propelled forage harvester 1 shown in fig1 - 4 has articulated frame steering about an articulation joint 2 , and a transport receptacle 3 is mounted therebehind . the harvested crop is picked up from the harvesting area by a front harvesting attachment and fed by feed units 6 to a subsequent processing unit . the processed crop is then transferred via a transfer device 4 having an upper discharge chute which is adjustable in height , to the transport receptacle 3 . discharge flaps 5 predetermine the direction of ejection of the crop stream . in a forage harvester 1 with articulated frame steering 2 in which the transport receptacle 3 is mounted directly on a trailing frame , the upper discharge chute 4 angle can be controlled in such a way that the crop is transferred , for example , in the direction of the center of the transport receptacle 3 . articulated frame steering is used on self - propelled pick - up loaders ( i . e . a sugar beet pick - up loader and self - propelled forage harvester ). a full transport receptacle 3 is emptied by a tipping device or floor conveyor to a further transport receptacle . the type of control embodying the present invention is used when the crop is transferred to the trailing transport receptacle 3 . the transport receptacle 3 can be transported in various ways behind a forage harvester 1 . in one example , the transport receptacle 3 has its own running gear and is hitched to the forage harvester 1 via a ring hitch . it can be a transfer receptacle or an ordinary transport . it is possible to automatically control the upper discharge chute 4 on forage harvesters 1 independently of a transport receptacle detector . a response on the degree of filling or the relative position of the transport receptacle 3 to the forage harvester 1 can be dispensed with . in the above examples of transfer of the crop to the transport receptacle 3 , the transport receptacle 3 follows the track of the forage harvester 1 with a time lag and minor deviation . the transfer device is oriented approximately in the direction of a longitudinal axis 10 of the harvesting machine . the apparatus for controlling the transfer device consists of an electronic analyzer or computer 20 with sensors 24 , 25 for detection of the relative angular position of the quantity that predetermines the direction of travel of the agricultural harvester 1 and of at least the relative angular position of the transfer device 4 to the longitudinal axis 10 of the harvester . the computer 20 is further coupled to an electronic bus system 29 , so that further harvester parameters such as the ground speed and the position of other guide elements on the transfer device are available when determining the direction of transfer . the computer 20 determines the quantity that predetermines the direction of travel of the forage harvester 1 and then , taking other parameters into account , calculates a nominal chute angle . from the control difference between actual chute angle and nominal chute angle is then derived a correcting variable for adjustment of the direction of transfer . during adjustment , utilizing adjusting means 32 , 33 known in the art such as for example an electrohydraulic adjusting device , the speed of adjustment is then selected as a function of the correcting variable . the calculation of the nominal transfer quantity is derived from simple tests . the angle of the transfer device relative to the longitudinal axis 10 of the combined harvester and transport receptacle which is necessary for directional transfer , hereinafter referred to as the chute angle , can be determined empirically and stored in memory of the computer 20 in the form of a data field or with the aid of a characteristic curve that can be determined therefrom . also there is the possibility of performing control of the transfer device with the aid of definitions by theoretical calculations . a side view of the self - propelled forage harvester 1 with articulated frame steering 2 and semitrailer coupling 7 , i . e . a fifth wheel , is shown in fig2 . distance “ a ” is the distance between the vertical axis of rotation of the upper discharge chute 4 and the pivot point of the articulated frame steering 2 . distance “ b ” is the distance between the pivot point of the articulated frame steering 2 and the semitrailer coupling 7 . a top view of the self - propelled forage harvester 1 with articulated frame steering 2 , semitrailer coupling 7 and a mounted front harvesting attachment 8 is shown in fig3 . the forage harvester 1 is traveling straight ahead , and the quantity which predetermines the direction of travel of the agricultural harvester , here the angle of articulation , is therefore equal to zero . the transfer device , here an upper discharge chute 4 , is oriented in such a way that the crop is spewed past the semitrailer coupling 7 . pivoting of the transfer device about its vertical axis can be performed by a planetary gear 9 . the planetary gear 9 is driven in a forage harvester 1 by a hydraulic motor . the latter is driven by an electrohydraulic valve control system in the direction predetermined by the apparatus for controlling the transfer device . the relative position of the transfer device to the longitudinal axis 10 of the coupled harvester and transport is determined by sensors 24 , 25 such as an incremental transducer with detection of the direction of rotation and fed to the computer 20 . a top view of the self - propelled forage harvester 1 with turned articulated frame steering 2 is shown in fig4 . the angle a denotes an angle of articulation . this angle is the nominal quantity for control of the direction of transfer of the upper discharge chute 4 . an angle reference α is the actual angle of the transfer device to the longitudinal axis 10 of the coupled harvester and transport . in this figure , the direction of transfer is controlled in such a way that the crop is conveyed beyond the semitrailer coupling 7 . if the apparatus is used on a forage harvester 1 with articulated frame steering 2 hitched to a semitrailer 11 , the upper discharge chute 4 angle can be controlled in such a way that the crop stream is transferred in the direction of the center of the semitrailer coupling 7 , when the transport receptacle 3 is located over the semitrailer coupling 7 . whether a transport receptacle 3 or a semitrailer 11 is hitched to the forage harvester 1 , the nominal chute angle can be calculated from the geometrical dimensions of the forage harvester 1 and the actual angle of articulation β . at what point the crop stream actually arrives in the transport receptacle 3 depends on the degree of filling and on the position of other crop stream guiding elements , such as chute height or chute flap . a geometric schematic derived from the calculation quantities of fig2 and 4 used to calculate the upper discharge chute 4 angle is shown in fig5 . the forage harvester &# 39 ; s 1 geometrical dimensions “ a ” and “ b ” are known distances . the angle β is determined by the sensing means 24 , 25 in the articulated frame steering 2 . from the known quantities , angle α of the transfer device can then be calculated according to the following equation : α = arctan   ( b × sin   β a + b   cos   β ) from the calculations derived from this equation , the transfer device can be controlled to direct the crop stream past the semitrailer coupling 7 . further , the last mentioned equation can be used to control the transfer device when the transport receptacle 3 is mounted directly on the articulated control arm . distance “ b ” is a remote location with respect to the articulated frame steering 2 where the crop stream is to be directed . distance “ b ” is fed to the electronic analyzer 20 as a standard value by a simple presetting device ( i . e . a potentiometer ). a change as a function of the transfer distance of the transfer device is another possibility . the direction of transfer is controlled by this presetting device in such a way that the crop stream is transferred in the direction or via this point . a side view of a self - propelled forage harvester 1 with articulated frame steering 2 and hitched semitrailer 11 is shown in fig6 . the forage harvester 1 can also be fitted with a semitrailer coupling 7 at the rear . the semitrailer 11 is hitched and towed behind the forage harvester 1 during filling . these semitrailers 11 can be quickly exchanged for an empty semitrailer 11 from the forage harvester 1 by the semitrailer coupling 7 . further , there is also the possibility of integrating a transport receptacle 3 on the chassis of the forage harvester 1 . the full transport receptacle 3 is then transferred to a transport receptacle by means of a floor conveyor or tipping device . with this configuration , there is also the possibility of determining the angle between the longitudinal axis 10 of the transport receptacle 3 and the semitrailer coupling 7 . from this sensed value , extended control of the transfer device 4 can then be carried out . the direction of transfer can then also deviate from the alignment with the semitrailer coupling 7 . furthermore , by this means it is possible to align the transfer device 4 with points located behind the fifth wheel coupling 7 . by means of a measured transfer distance , there is then also the possibility of varying the transfer target distance and obtaining reliable transfer . a top view of the forage harvester 1 towing a semitrailer 11 momentarily traveling along a bend is shown in fig7 . here the upper discharge chute 4 is oriented in such a way that the direction of transfer , hence crop stream , is aligned with the semitrailer coupling 7 . fig8 shows the possibility of a self - propelled transport receptacle or a transport receptacle 14 towed directly behind the forage harvester 1 by a tractor 13 or the like . the direction of travel of the forage harvester 1 is generally predetermined by the steering angle of a stub axle - steered steering axle . the direction of travel can be further predetermined by a rotation about a vertical axis of frame portions , with each associated with at least one rigid axle . the stub axle - steered self - propelled forage harvester 1 and independent trailing tractor 13 with hitched transport receptacle 14 is shown in fig8 . the path traveled is a curved track 15 with a constant radius of curvature . the forage harvester &# 39 ; s 1 steering angle “ γ ” and wheelbase “ d ” can be used to calculate the radius of curvature “ r ”. the assumption is that the distance “ c ” compared with the transfer target distance “ e ” is minimal and with the aid of trigonometry and the set of short sides of a right - angled triangle , the chute angle α can be calculated with reference to the following equation : a = arcsin   ( e 2 × r ) if there is no direct coupling to the transport receptacle 3 , control of the chute angle β can be performed with the aid of the quantity which predetermines the direction of travel and a transfer target distance . this transfer target distance can be a prefixed distance or a quantity that can be preset by the harvester operator . further , the transfer target distance can be calculated from the elements which determine the transfer distance of the transfer device . the transfer distance can be derived from the settings of the transfer device by converting , for example , the chute height , the chute flap position and the transfer target height to the transport receptacle 3 , to a transfer target distance . a block diagram of the apparatus for controlling a transfer device is shown in fig9 . the apparatus consists of the electronic analyzer 20 , other sensors and actuators . control of the transfer device is activated or deactivated by a button 21 . the status of the apparatus is indicated by an optical or acoustic indicator 31 . the standard transfer target distance “ e ” can be selected by a scaled potentiometer 22 . if the transfer target distance “ e ” is to be derived from the instantaneous settings 24 , 25 , 26 of the transfer device and a standard target height , this can be done by actuation of the button 23 . the chute angle α and the discharge flap angle are detected by the sensing means 24 or 25 , preferably as potentiometer values . the height of the transfer device is derived from determination of the chute height angle 26 . further buttons 27 or 28 are provided for manual control of the transfer device and presetting an offset . the quantity which predetermines the direction of travel of the forage harvester 1 is determined by a sensing device 30 . the electronic analyzer 20 is further connected to the bus system 29 of the forage harvester 1 . under this system , machine - specific settings ( i . e . wheelbase ), necessary geometrical data , transfer ratings ( i . e . transfer target height ) and variable values ( i . e . ground speed ) are transmitted . to adjust the direction of transfer , the electronic analyzer 20 is connected to adjusting elements 32 , 33 . these adjusting elements 32 , 33 can be a hydraulic pump and motor combination or , as designed here , two electrohydraulic valves for an ordinary left / right hydraulic motor control system . in one embodiment the transfer target distance can be programmed into the computer 20 . the transfer device is , for example , set manually so that the crop stream is transferred to the center of the transport receptacle 3 . this transfer distance is then programmed as a further transfer target distance . in case of further automatic control of the direction of transfer , a manually performed change of transfer distance , for example , the chute flap position , is then not further taken into consideration . the transfer device is pivoted for example by means of a hydraulic motor . it is another embodiment that the pivot speed of the transfer device can be performed with variable speed . the inertia of the transfer device means that the pivot device runs on after switching off the pivot drive in case of automatic pivoting can result in overshooting the desired position . this problem can be solved in two possible ways . first , the drive can be switched off before reaching the nominal position . second , the pivot speed can be adjusted towards zero as far as the nominal position . the variation in pivot speed needs separate control with proportional valves . a simple solution to the problem is achieved by multi - stage pivot speed control . at its simplest , this is done by two - stage valve switching . the pivot speed can be derived from the quantity of the correcting variable at which the transfer device is automatically pivoted . on falling below a given correcting variable , the pivot drive is then switched to a reduced pivot speed . the nominal direction of transfer can thus be controlled with sufficient precision . in another embodiment , the apparatus detects the track covered by the forage harvester 1 . as mentioned above , the transport receptacle 3 follows the forage harvester 1 at a distance when transferring crops . if a new direction of travel is selected by the machine operator , that is to say , the harvester carries on traveling with an altered radius of curvature , there is also a change in the relative direction of the transfer device to the transport receptacle 3 . if the transport receptacles 3 directly coupled to the forage harvester 1 , the transfer device can be adjusted without delay to the new direction of transfer . if there is no direct coupling , the transfer device must be controlled with reference to a given standard . as the transport receptacle 3 follows behind , it must first still remain on the old , past track of the forage harvester 1 until the track with the new radius of curvature begins . the direction of transfer must therefore be controlled in such a way that the crop stream enters the transport receptacle 3 located on the past track . the transfer device 4 is advantageously controlled with reference to the track covered . for a new radius of curvature or a new quantity which predetermines the direction of travel of the forage harvester 1 , the apparatus predetermines a new nominal chute angle α . but the latter is not set immediately by the apparatus , rather as a function of a track covered . the correlation is , for example , a linear relationship . the track covered can easily be derived from detection of the ground speed . in another embodiment , the pivot speed of the transfer device 4 is controlled as a function of the ground speed of the harvester 1 . the result is also track - dependent or delayed changes in direction of transfer . track - dependent control has the advantage that , when the machine stops and at the same time the quantity which predetermines the direction of travel of the forage harvester 1 changes , the direction of transfer is not altered automatically . the track covered is stored in memory of the computer 20 in conjunction with the quantity which predetermines the direction of travel in another embodiment of the apparatus . from the stored values , the course of the track covered can be determined . by using a ring memory only , a small number of values are kept on standby for calculation of the track covered . these memory contents are updated with a new data pair in a given time cycle or advantageously only after traveling a given track distance . with additional data such as a programmed transfer target distance and height , the direction of transfer is controlled in such a way that the crop stream enters the transport receptacle 3 located on the past track . from the individual stored pairs of values , the course of the track covered is calculated from the instantaneous position . the individual pairs of values contain a track distance and each one associated quantity which predetermines the direction of travel of the forage harvester 1 . from the two values , the forage harvester &# 39 ; s 1 change in position can be determined , starting from a coordinate system oriented by the instantaneous direction of travel . calculation of the course of the track covered is not very accurate . changes in the quantity which predetermines the direction of travel of the forage harvester 1 , between the storage of adjacent pairs of values , are not detected . furthermore , the track is subject to slippage . if the direction of transfer is not exactly aligned , this is compensated first by the width of the transport receptacle 3 and a subsequent correction of the course of travel of the transport receptacle . it is further provided that control of the transfer device is possible at any time by manual control of the direction of transfer without deactivating automatic control of the transfer device as a result . the manually entered offset is maintained until the next manual change or until deactivation of the apparatus . an ordinary button connected to the control system of the apparatus is provided for activation or deactivation of the apparatus . this button can be , for example , a foot switch on the floor of the operator &# 39 ; s cab of a forage harvester 1 . activation / deactivation of the apparatus is indicated each time by an acoustic signal or a visual display . the invention is not limited to the control of the direction of transfer for the transfer of crops from the forage harvesters 1 to the following transport receptacles 3 . it is obvious for those with ordinary skill in the art to apply the quantity which predetermines the direction of travel of the forage harvester 1 to other control functions of the transfer device . it is conceivable to apply the quantity which predetermines the direction of travel of the forage harvester 1 to control of the transfer distance of the device or within certain limits to control of the transfer device when the forage harvester 1 turns with transfer of the crops to a parallel - traveling transport receptacle 3 . furthermore , it is conceivable to use the transfer device to produce an adjustment of the guide flap on the upper discharge chute 4 or the chute angle α of a self - propelled forage harvester 1 , in order to produce a kind of oscillating distributing movement . while specific embodiments have been shown and described , this has been by way of illustration and not limitation , and the invention should not be limited except as required by the scope of the appended claims .

US-42042999-A

a sealable cabinet that permits a human or animal to experience a dry bath for carbon dioxide or other gases , with said cabinet fitted with gas , water , and power connections , and a controller to optimize the temperature , gas concentrations , and water vapor content of the interior , plus a switchable means for selecting between a sauna environment and said carbon dioxide bath , with a business method that enables a provider of services involving such equipment to achieve a profitable interface with patients and customers .

in the preferred embodiment , the present invention is a rigid cabinet with a door that opens sufficiently to enable the user to enter the cabinet . a seat or platform is provided within the cabinet to help position the user . sources of carbon dioxide gas and water vapor , and sensors , are provided to an electronic controller circuit that optimizes the gas balance inside the cabinet and controls overall operation . a heating system is provided , and a temperature sensor is connected to the electronic controller to permit optimization of temperature . a timer is integrated into the controller to enable control of the time the user is exposed to the dry carbonic bath . ducting and a fan circulate the interior gases inside the cabinet , ensuring mixing . the controller circuit has inputs for temperature , gas concentration , humidity , and a time reference , and uses known logic and simple software to optimize the dry carbonic bath process . a safety system monitors co2 concentration , temperature , and time , and faults to an off condition with all valves closed and an audible and light alarm when a failure is detected . the preferred business method enables a practitioner to purchase the present invention and offer its benefits to users , who will pay for time in the cabinet . however , there are equally preferential methods by which operation of the cabinet is dependent upon acceptance of a near field communication ( nfc ) portable rf device , or a credit card entered by either the practitioner ( thus providing metered operation ) or the user . the enclosure can be rigid ( metal , plastic , wood ) or flexible , and in the latter case it can be fabric or plastic supported by an internal or external frame . the cabinet can be attached to free - standing external water and co2 sources , or such sources can be carried upon a shelf on the rear of the cabinet , so when fitted with wheels the complete system can be rolled from one location to another . in a hospital or large therapy facility , each cabinet can be part of a group , all of which are attached to central supplies of water , gas , and power . the cabinet can be sized to seat only one user , or can be sized to seat more than one user . the cabinet door can be hinged at the bottom , at one side , or at both sides with a central seam , to facilitate entry and exit . the front door can be fitted with a movement rate controller or damper , to prevent human injury if it inadvertently swings closed upon a portion of the user &# 39 ; s body . the front door of the cabinet can be removable and replaced with a flexible fabric or plastic curtain that is sealed around the edge of the door , thus increasing the internal volume of the cabinet and permitting it to be used with an obese user . the seating surface can be height - adjustable , or an optional cushion provided to elevate the user &# 39 ; s head to match the aperture at the top of the cabinet . the seating surface , including the backrest , can be fabricated of webbing , thus increasing the area of the user &# 39 ; s body that is exposed to the internal gases of the cabinet . the configuration of the basic cabinet will permit the user to sit upon a chair ; a horizontally - elongated cabinet can permit the user to lie on a platform set at a sufficient slant to ensure that the user &# 39 ; s head remains higher than the rest of the body , and a vertically - elongated cabinet can permit the user to stand within it . the collar around the user &# 39 ; s neck can be of gas - impervious plastic or fabric , designed to provide a seal between the cabinet &# 39 ; s aperture and the neck of the user . the co2 management system can inject gas into the known approximate volume of the cabinet to achieve the required concentration when the system is activated , or a gas concentration detection method can be used to permit active management of concentration with feedback to the controller , which then activates a valve . it is superior to enable active management , since the volume of the user is not predictable and a large user will have a higher concentration of co2 , and a small one will have a lower concentration . an aromatic or therapeutic additive can be combined with the circulating gas . the circulating air passage provided by the ducting and fan ( s ) or blower ( s ) can be achieved outside of the cabinet , as opposed to integrated with the chair . this requires an external duct connecting the bottom of the chamber to the top , with a fan or blower serial to the duct , thus achieving the desired flow rate and homogeneity of the gas - air mixture . the safety circuit can activate an exhaust fan or blower to remove the gas mixture from the cabinet . it is not mandatory to individually and manually control all operating parameters . the human - machine interface can include simplified settings buttons , each of which establish a known combination of operating parameters including time , humidity , gas concentration , and temperature . setting “ a ” might be a substantially different combination than setting “ b ”, “ c ” “ d ”, etc . the system can be owned or leased by the practitioner or user , who then is responsible for servicing the system ( replacing gas tank , etc .). alternatively , credit card processing equipment with communication can be integrated into the system , so individual treatments or groups of treatments can be purchased by either the practitioner or a user , thus enabling another party to actually own the system . the patient ( in a medical setting ) or client ( in other settings ) ( collectively , the “ user ”) is briefed and given a location in which to disrobe , and to don a gas - permeable disposable garment . while changing , the system is powered , seat height is adjusted , and settings are entered for the session . the door is opened , the air dam or collar , which creates a seal between the user &# 39 ; s neck and the upper aperture of the cabinet , is fitted around the neck , and the user sits inside . at the end of the session the system is turned off , the user exits and is offered a shower . the patient / client dresses and leaves . fig1 depicts a side view and partial top view of the system , in which the cabinet or cabinet 1 is fitted with a hinged or removable door 2 and a perforated internal seat and seatback 3 under which is a combined gas management system and blower 4 into which co2 and water vapor flow from an external source via port 5 and excessive internal pressure can be vented via outlet 6 , while the blower 4 causes airflow 7 within the cabinet , atop which is an large opening 8 with an air dam 9 to prevent gas leakage around the neck of the user , and an aperture 10 for the head of the user . fig2 depicts a block diagram of the control circuitry , in which a gas concentration and flow sensing circuit 11 , a temperature sensors circuit 12 , and a humidity and dew point detector 13 output their sensed values to a central processor or microcontroller 14 , which regulates gas valves for co2 and other gases 15 , heater 16 , and humidifier 17 , plus a settable timer 18 to control the period of system operation and a safety system 19 to reduce hazard , which monitors operating conditions and can exercise independent control over the co2 gas valve 15 , heater , 16 , and humidifier 17 , all to regulate the overall conditions in the cabinet system 20 by controlling gas 21 , moisture content of the air from a water source 22 , and power 23 . fig3 depicts the human - machine interface , a control panel 24 that provides visual indications of various parameters 25 and control via a manual entry device such as a keypad 26 , whereupon the desired time , temperature , and concentrations of water vapor and co2 can be set . fig4 provides an image of the complete system in operation , where cabinet 1 has an upper opening 9 for the user &# 39 ; s head , and is fitted with door 2 on which appears the human - machine interface 24 . fig5 expands the control and sensor connections and shows data flow .

US-95331510-A

this invention protects the use of nicotine , analogues thereof precursors thereof or its derivates for treatment of inflammatory , infectious , candidal or degenerative , depression , obesity , bone disease and the like , which can be improved by means of intensification of the actions of α - msh , given the fact that this hormone are extraordinary properties : e . g ., it has an antipyretic potency 20 , 000 times as great as acetaminophen , its antimicrobian potency , is comparable to gentamycine , it is the best anticandidiasic known ; it inhibits apoptosis of various stem cells , and significantly modulates the immune reactions , and therefore the use of agents that affect its release may have significant therapeutic potential . this patent protects the use of nicotine , analogues thereof , precursors thereof or its derivates for the purpose of increasing and / or reducing the bioavailability of α - msh in blood and / or central or peripheral tissues to accentuate or diminish the effect of the α - msh by means of changes in its concentration or its effect on the corresponding receptors of any cell , tissue or organ in the body , administrated for therapeutic and / or prophylactic purposes in the short medium and / or long term .

this invention protects the use of substances that promote , facilitate or intensify the releasing and the action or activity of α - msh hormone ( melanocyte stimulating hormone ), as nicotine , analogues thereof , precursors thereof or derivatives through its indirect effect mainly on the melanotrophs located in the pars intermedia of the hypophysis in close relationship with lactotrophs . there are different susceptible pathological conditions the which can be improved by administration of α - msh , because the stem cells that respond to said stimulus participate in several mainly functions in the organism , among them we have as an example , ( but not imitated ): proliferatives retinopathies where the eye fibroblasts , as any organism fibroblast , in presence of hypoxia reacts secreting collagen ( dr . humberto montoya de lira , 2000 ), initial stages of retrolental fybroplasia , the proliferative diabetic retinopathy , the post traumatic proliferative retinopathy ; primary , secondary , local and distant ; the proliferative retinopathy caused by hypoxia : primary , secondary , local and distant , infectious syndrome where secondary alterations of liver , kidney and lung may be prevented ; in conditions where α - msh is a protective factor against the degenerative osteoarthrosis , against eclampsya , against parkinson disease , against alzheimer , against arthritis from different etiology , against the rejection of transplanted tissues , improves depression , diminish in a 95 % the tissue deterioration in experimental models of ischemia / reperfusion in kidney , lung , intestine , protects vessels from deterioration caused by bacterians lps ( lipopolysaccharides ), protects liver from deterioration induced by lps , it has also been reported that diminishes liver cirrhosis ; at the same time α - msh is considered a protective factor in degenerative osteoarthrosis it seems to protect cartilage . also antidepressive effect has been described for α - msh , which can have an important therapeutic role in obesity control . the α - msh is a three decapeptide with a potent anti inflammatory action , with prominent actions reducing the inflammatory mediators for example , reduces the level of tumor necrosis factor , including cytokines . alpha - msh hormone is a compound of 13 amino acid derivated from propiomelanocortin , it expresses in several regions of the central nervous system and in peripheral cells , including melanocytes , fagocytes , macrophages , condrocytes , keratocytes , glial cells and keratinocytes among other stem cells , for up to date there have not been identified all the stem cells that respond to α - msh . the anti - inflammatory effects are mainly through the antagonism of proinflammatory mediators including α - tumor necrosis factor , interleukina 6 and nitric oxide ( no ) but its powerful actions are very constant in all tissues and inclusive they superimpose . the α - msh neuropeptide is an endogenic modulator of inflammation . the idea that α - msh is important in the host responses begins from the inicial observation from the antipyretic properties of the molecule . the α - msh potency for reducing the fever as resulted of endogenous pyrogens is dramatic : 20 000 ( twenty thousand ) times as great as acetaminophen ( airagui , lorena 2000 ) when the relation molecule to molecule is compared . alpha - msh also inhibits fever caused by endotoxin , il - 6 and alpha - tnf ( α - tnf ), so it has an inhibitor effect on il - 1 , and on the increase induced by α - tnf in the circulating proteins from acute stage and neutrophyles . so α - msh also inhibits the tissue trauma in systemic inflammation models as acute respiratory syndrome and peritonytis caused by cecal ligation and punction as well as in isquemic acute renal defect . mortality , by combination of acute renal insufficiency and acute respiratory insufficiency reaches an 80 %. the severe trauma , burns , haemorrhages , sepsis , shock , or severe local tissular trauma , can iniciate a systemic inflammatory response provoking the multiple organic failure and death . there are pathogenic and epidemiological connection between renal and lung trauma . a great part of risk increase due to acute renal failure after heart surgery comes from extra renal complications such as respiratory failure severe tissular trauma happened after a prolongated ischemia in the inferior torso or during a complicated surgery of aorthic abdominal aneurism or during an acute respiratory failure syndrome . in animal models , secondary pulmonary trauma ( or distant ) can be started by severe local ischemia in liver , in the gastrointestinal tract , in inferior member , kiney or chemical pancreatytis . for example , renal traumatism by ischemia / reperfussion , can increase lung vascular permeability , as well as produce intersticial edema , alveolar haemorrhage and damage of reological properties of eritrocytes . due to lung has the biggest microcapilar trauma in the organism , responds to circulating proinflammatory signs with activation of lung macrophages , secretion of proinflammatory cytokines , attraction of neutrophyls and macrophages , finally resulting a lung trauma . there are many similarities in the activation of local pathways of tissular trauma , after pulmonary trauma and acute renal and secondary pulmonary traumatism . the renal ischemia / reperfussion causes apoptosis and necrosis in rectum proximal tubules and inflammatory infiltration of leukocytes . earlier in the reperfussion period , there is an activation of activated kinases by stress ( for example , kinase protein p - 38 activated by mitogens [ mapk ]) and by transcription kb factor of nuclear factors ( nf - κb ) and protein activator ( ap - 1 ) and induction of proinflammatory cytokines ( α - tnf and adhesion molecules ( intercellular adhesión molecule - 1 [ icam - 1 ]). the selective inhibition of α - tnf and / or of icam - 1 diminishes acute renal trauma . parallely , proinflamatory traces nf - kb , p - 38 and ap - 1 are activated after acute pulmonary trauma , and the inhibition of nf - κb and p - 38 reducing distant pulmonary trauma or secondary . although , there is no agent has shown to inhibit both local trauma and distant pulmonary trauma . for example the inhibitor of p - 38 cni - 1493 partialy reduces distant pulmonary trauma but does not have effect in subyacent renal trauma by ischemia / reperfussion . alpha - msh hormone ( α - stimulant of melanocytes ) is an anti inflammatory citokyne that inhibits chronic or acute systemic inflammation . alpha - msh inhibits renal trauma by ischemia / reperfussion , by cysplatin administration , or after a transplant by marginal donor ; but not after administration of mercury . ( mercury poisons melanocytes ). mechanism of action of α - msh is extense , and the actions documented by us are : the inhibition of inflammatory traces , cytoxics , and apopotics pathways activated by renal ischemia . it has been demostrated that α - msh inhibits activation of α - tnf and icam - 1 four hours after the reperfussion . although , the earlier molecular mechanisms activated by α - msh are not elucidated . in models of ischemia / reperfussion disease and other similars , α - msh inhibits the production of many cytokines , chemokines , and the inducible synthase of nitric oxide ; this suggests that α - msh acts in one or several early common steps in inicial pathway of inflammation . recent studies have demonstrated that α - msh suppresses the stimulation of nf - κb in brain inflammation and in cell culture exposed to lps ( lipopolysacharides ). alpha - msh also inhibits p38 mapk in melanoma cells b16 and in ap - ligand - dna in dermic fibroblasts , but not in macrophages . by means , it has been determined that α - msh diminishes pulmonary trauma caused by renal trauma from ischemia / reperfussion . in animal models , it has been demostrated that serum creatinine increases , in an important form , at 4 , 8 and 24 hours after renal ischemia / reperfussion in comparison with witness and control animal . at the same time , animals that received α - msh had important lower levels of creatinine than animals that only had vehicles as well as less cylinders and necrosis evaluated by quantitative citology at 4 hours . effects of α - msh in leukocytes accumulation : preliminary studies have shown that renal ischemia causes leukocytic infiltration in kidney and lung and α - msh inhibits locally leukocytes accumulation after acute inflammation and in renal ischemia . the stain with stearate of chloroacetate shows an increase in leukocyte accumulation in lung four hours after renal ischemia / reperfussin compared with witness animals . treatment with α - msh before releasing of patch ( clamp ) diminishes leukocyte infiltration . these changes were evaluated by counting positive stearase cells in lung and kidney . there were elevated infiltrating leukocytes in lung and kidney in very early stages after renal trauma by ischemia / reperfussion , and said accumulation was inhibited by α - msh effects of α - msh on α - tnf and icam - 1 . renal ischemia increases α - tnf and icam - 1 and the inhibition of both pathways diminish , in a dramatic form , the renal damage . it has been found that renal ischemia causes phosphorylation ( by means , activation ) from iκbα cytosolic in kidney as well as in lung during 15 - 30 minutes after reperfussion . administration of α - msh just before releasing of patch ( clamp ) inhibits phosphorylation of iκbα as in kidney as in lung . phosphorylation of iκbα causes its own destruction ; it allows that the dimers of nf - κb containing p65 traslocated to the nucleus . as it was to hope , phosphorylation of iκbα lets appear p65 in the nucleus rapidly in kidney as well as in lung , which could be inhibited by administration of α - msh . the activity ligand nf - κb increased rapidly in lung as well as in kidney at the end of the ischemia period , the treatment with α - msh inhibited the ligand nf - κb activity in kidney and lung . renal ischemia / reperfussion also causes a rapid phosphorylation ( and of course activation ) from p38 of kidney and lung without changes in the total p38 . phosphorylation of p38 was inhibited with α - msh treatment . it has been found inflammatory cells infiltrating , intensely and rapidly , the lung after renal ischemia ; and it has been proved that α - msh has a dramatic effect in pulmonary trauma , because it inhibites pulmonary infiltration in 4 and 8 h after renal ischemia , with similar effects on kidney . effect of α - msh is more dramatic at 8 hours than in 4 , may be because can inhibit most early responses of stress / inflamatories , some or all of them can contribute to the ability of α - msh for diminishing the progress of damage . it has been found that renal ischemia / reperfussion increases levels of mrna ( messenger ) for α - tnf - and icam - 1 after cysplatin inhibition . alpha - tnf is important in pathogenesis of distant organ damage ; because antibodies against α - tnf reduce pulmonary damage after liver ischemia and agents that diminish distant pulmonary damage also diminish α - tnf located in pulmonary tissue . this evidence suggests the importance of inflamation and α - tnf particularly in distant pulmonary trauma induced by ischemia or damage to extra pulmonary organs . some of α - msh effects are probably mediated by direct effect on leukocytes , because the neutrophyls and macrophages express receptors for α - msh . alpha - msh inhibits the migration of neutrophyls in vitro and the production of nitric oxide in culture of macrophages . although α - msh inhibits damage by renal ischemia / reperfussion until in absence of leukocytes infiltration , which suggests that α - msh can also act by different ways from leukocytes . administration of α - msh just before reperfussion has a great protective effect in lung as well as in kidney . alpha - msh reduces , in a dramatic form , the activation of distant or secondary pulmonary damage caused by lung transplant , pancreatytis , liver ischemia , haemorrhages or secondary reactions to bacterian lipopolysacharides . the events that cause distant renal damage after renal ischemia / reperfussion are unknown . pretreatment for distant ischemia that inhibits terminal - kinase c - jun n and activation of p38 , prevent renal damage after ischemia / reperfussion , but unfortunately , it is not a viable therapeutic alternative , is much more practical the administration of α - msh . there are more evidences every time that suggest the activation of nf - κb proceeds and may cause secretion of α - tnf after myocardial ischemia and kidney ischemia . the combined acute lung and kidney failure comes with an extremely high morbility and mortality , whose subyacent mechanisms are unknown but administration of α - msh improves overlife in 90 %. alpha - msh reverts liver cirrhosis , gets better diseases such as alzheimer , prevents parkinson ; among many others . the severe tissular trauma presented in the burnt , in the polytraumatized patients , in the ischemia prolongated of the inferior torso or complicated surgery by abdominal aneurism aorthic , frecuently provoke the subsequent events that cause the multiple organic failures . actually therapeutic steps available are very elementals and are limited to replace the function of the lost organ , controlling ventilation and dialysis ; preventing barotrauma , and optimizing cardiovascular function with resucitation of the adequate volumen and inotropic support . treatment with medication is not desirable . recently , c - protein activated showed some utility to diminish death by sepsis . additional strategies to prevent and / or treat multiple organic failures will be extremely useful . in this moment we do not know any medicine that reduces pulmonary damage nor renal damage . it has been demostrated that administration of α - msh just before reperfussion inhibits acute renal damage as well as pulmonary damage . the ability of α - msh to inhibit the damage in both organs , the extension of protection that reaches or gets , and the wide action mechanism distinguishes α - msh from other agents used to prevent , limit , protect or delay damage by ischemia / reperfussion . this suggests that α - msh can have an important therapeutic effect on adequate patients . ( deng , hu , yuen , star , am j respir crit care med vol 169 pp 749 - 756 , 2004 .). alpha - msh can have an important therapeutic role for treatment of vasculitis , sepsis , chronic and acute inflammatory diseases from different ethiology . ( endocrinology 144 : 360 - 370 , 2003 ). in intermittent hemodialysis , it can characteristically appreciate elevation of α - tnf , il - 6 and no ; so that α - msh is liberated in these patients to counteract the proinflammatoriy effects of these cytokines ( lorena airagui , leticia garofalo , maria grazia cutuli . nephrol dial trans 2000 ( 15 ): 1212 - 1216 ). alpha - msh modulates α - tnf local and circulating in experimental models of brain inflammation ( nilum rajora , giovanni boccoli , dennos burns . the journal of neuroscience mar . 15 , 1997 ; 17 ( 6 ): 2181 - 2186 .) in this research , the secretion of α - tnf in central nervous system was induced by a local injection of bacterian lps . the plasma concentration of α - tnf had an important elevation after central application of lps , indicating that the host peripheral response was increased by induction of cns sign . the inhibition of α - tnf synthesis by α - msh was confirmed using inhibition of mrna . although some inflammatory cytokines contribuye to central nervous system inflammation ( cns ), α - tnf is specially important because it is identified as an important agent in physiopathogenic of cns diseases as multiple sclerosis , hiv infection of cns , alzheimer disease , meningitis , severe cranium encephalic traumatism consequently to the ischemia / reperfussion and / or trauma . the increase of α - msh levels , by endogenic or exogenic administration , has an important therapeutic or prophylactic effect for dimishing the diseases with α - tnf increased , as above mentioned . effect of α - msh in central nervous system ( cns ) degeneration . almost every one of degenerative diseases of cns is associated with chronic inflammation . an important stage in this process is the activation of brain fagocytic mononuclear cells named microglia . it has been reported the nicotine neuroprotector effects due to its action over selective nicotinic antagonist receptors : α7 ; in illneseses as parkinson , alzheimer , depression , obesity , ageing etc . ( cholinergic modulation of microglial activation of α - 7 nicotic receptors . r douglas shytle , takashi mori , kira townsed , journal of neurochemistry , 2004 , 89 , 337 - 443 .) it is congruent that beneficial effects of α - msh include whole organism as : skin , mucous , eyes , intestine , muscle , joints , etc , because they have common methabolic pathways stimulated by said hormone . the invention mainly consists in administration of nicotine , analogues , thereof precursors , thereof or its derivates to adequate patients , in pharmacophores and effective dosis , by the suitable pathway in each case ; in therapeutic form and or prophylactic , through its effect on hypothalamus ( main action but not the unique ), the α - msh releasing induced by melanotrophs from pars intermedia of the hypophysis , because this secretion ( α - msh ) is tonic . by means the hypothalamus has a suppressor effect more than secretor , to difference to others hypothalamic effect on hypophysis . it seems to be one of the few hypophysary hormone released in tonic form ( constant ) and the hypothalamus inhibits this releasing through the dopamine secretion ( hypothalamic ) ( another hypophysary hormone released in tonic form is the prolactine from mamotrophs ). the nicotine precursors thereof analogues , or derivates , administrated by adequate form in effective dosis and adequate pharmacophore , provoke an effect on hypothalamus diminishing of dopamine secretion , and the melanotrophs of the pars intermedia of the hypophysis releasing α - msh tonically , ( to more hypothalamic inhibition less tonic α - msh release and viceverse ), as it happens during all its life , as resulted of several factors , said secretion is diminished and / or inclusive interrupted ; said factors can be environmental , emocional , differents acute or chronic diseases , infectious diseases , surgeries , different therapeutic actions , pesticides , hormone , chemical agents , different xenobiotics types , etc ., inciding the α - msh secretion in all cases , in one or another sense . the action of nicotine suggested in this patent and maybe not only the unique effect of nicotine , analogues thereof , precursos thereof , or derivates , said action is to provoke the α - msh releasing mainly from melanotrophs located in the pars intermidia of the hypophysis in close contact with mamotrophs , although it is not the unique pathway , the which maybe documented in complete form , more scientific , because up to now it is the only way in which we can document in the more complete and scientific form , without rulling out other action sites the skin ( keratinocytes ), pilose follicle , etc . macrophages etc , may be depending of the nicotine dosis used as well as the administration pathway . this invention claims pharmaceutical compositions with active substances and pharmaceutical vehicles that induce releasing of endogenic α - msh in humans , coming from stem cells , this compositions can have prophylactics and / or therapeutic purpose in inflammatory chronic and / or acute , degenerative and infectious diseases . the releasing of α - msh provokes the “ photosynthesis ” in human ( patient ) and animal , due to release of α - msh increase the synthesis of melanin promote the releasing of oxygen and hydrogen in the tissue from water ( wo2006 / 132521 ), increasing importantly the energy available into eucarionte cell energizing the main reactions during the life . this energy , the which is stimeted in a third part , used or required , of the whole , it is not additional moreover is the mailny , the which must happen at the first time , in order to provoke another ones , and its diminishing provoke that the other two third parts will also be reduced , promotinging disease . this explains why the photosynthesis stimulating the induction of endogenic α - msh release , ( by administration of nicotine , its derivates or its analogues ), provoke a dramatic positive response in all tissues . it is difficult to understand how nicotine , its derivates or analogues provoke so many good effects in all tissues . nasa defines life as a self sustentable chemical system that eventually is in darwinian evolution . melanin may be precursor of life because it is stable in water , and could have been stood in it during thousand of years and more , to be in water , with electromagnetic radiations originated from sun , generated energy in almost constant form , it was only accross the time for provoking the other chemical reactions done by the first living organisms , because they disposed of elemental energy for doing sustentable the beginings of chemical system that after was completed with carbon sources as glucose 6 phosphate , but it was afterwads . we could say that melanin is to animal kingdom as chlorophyle is to vegetal kingdom . about the use nicotine in this patent we have some examples female patient 27 years old she is in the ninth month of pregnant without diabetes or hypertension or neuropathy antecedents . no surgery antecedents begins with a intense pain in the right renal region in 72 hours of evolution , she can not sleep , requires the administration of analgesics every three hours . twenty four hours later amikacina im every 12 hours was administered . she could not be in a free attitude due the intense pain , apart from the natural upsets in the ninth pregnat month . it was decided to administrate nicotine in watery vehicle by sublingual pathway in a concentration of 3 mg / ml . at the beginning 15 drops were administrated and 30 minutes later 10 drops more . patient slept and after three days she could sleep all night , pain diminished significantly that she did not awake . general physical state improves in the dramatic form , the analgesic was limited to a half aspirine every 12 hours and the antibiotics course continued for 8 days more . nicotine was administrated during 4 weeks in dosis of 5 drops by sublingual pathway every three hours . male patient just born , ( his mother is patient from example 1 ) born by cesarean who had in the first hours hypothermia and vomit , few hours after appeared petequias in the back , in blood analysis it was found plateletopenia and increase of sedimentation velocity analysis , considering that it was a sepsis amikacina iv was administered initially ; agree to mother treatment , it was began the administration of nicotine by sublingual pathway in a dosis of 1 drop every 12 or 24 hours ; in concentration of 3 mg / ml . patient slept deep and long , curiously the heart increased its rate from 110 per minute to 130 and the periferal oxygen was not diminished of 930 %. twenty four hours later the baby had increased 80 grams weight . now the kid is growing well and without consequences . male patient 25 years old with post traumatic bleeding ( hyphema ). she was reviewed at 14 th of its disease , and the hyphema of 900 % did not improve with the first treatment , the patient came to us because his doctor suggested him a surgery to evacuate blood for avoiding loose his eye . we explained to patient the treatment to stimulate α - msh could be an alternative form in order to protect the tissue from apoptosis as a potent anti - inflammatory agent , when the nicotine induces the α - msh release . we indicated a dosis of 2 drops sublingual pathway every hour , for the hyphema was of 90 % the vision was poor and the intraocular pressure was 40 mmhg despite last treatment . all medicine was suspended and began the new treatment . three weeks later vision was 20 / 40 . the recovery was dramatic and complete in a 90 % after four weeks . it will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof . it is understood , therefore , that this invention is not limited to the particular embodiments disclosed , but it is intended to cover modifications within the spirit and scope of the present invention as defined by the appended claims .

US-41899309-A

use as agricultural fungicides of n - acyl - n - hydroxyalkanoic acid compounds of the formula ## str1 ## and salts thereof , wherein each of the symbols has an assigned meaning .

it has been found that fungi , particularly mildews , are controlled by n - acyl - n - hydroxyalkanoic acid compounds of the formula ## str2 ## wherein r 1 is hydrogen or phenyl , r 2 is hydrogen or methyl and r 3 is hydrogen , methyl or ethyl , and salts thereof . preferably r 3 represents hydrogen and the compound is a salt . a salt of the compound of formula ( i ) may contain the monovalent anion in which the carboxyl group is ionized or the divalent anion in which the n - hydroxy group also is ionized . polyvalent metal ions generally form salts with , or chelates derived from , the divalent anion , while monovalent metal ions can form mono - or divalent salts . weak bases in general form only monovalent salts . typical metal salts include salts of lithium , sodium , potassium , magnesium , calcium , zinc , copper , lead , manganese or iron . typical non - metal salts include ammonium and substituted ammonium salts , for example those in which the cation has the formula . sup .⊕ nr 4 r 5 r 6 r 7 in which each of r 4 , r 5 , r 6 and r 7 independently represents a hydrogen atom or an optionally substituted alkyl , cycloalkyl or aryl group having up to 12 carbon atoms . optional substituents include for example halogen atoms and alkyl , alkoxy , haloalkyl , haloalkoxy , hydroxy , cyano , nitro , amino , carboxy , alkoxycarbonyl , phenyl and phenoxy groups , any alkyl moiety present preferably having up to 4 carbon atoms . further suitable substituted ammonium salts include those in which the nitrogen atom forms a part of a saturated or unsaturated ring , which may also contain one or more additional hetero - atoms , especially nitrogen , oxygen and / or sulphur atoms . typical salts of this type are pyridinium , pyrrolidinium , piperidinium and morpholinium salts . suitable salts thus include the salts of nitrogen bases , generally . further suitable salts include those with polymeric substances containing basic groups , such as ion exchange resins . such salts can be especially useful in applications where insoluble materials are required . especially preferred for use in the method of the invention are the salts . it will be appreciated that the compounds of formula ( i ) contain an asymmetric carbon atom at the 2 position and hence will exist in two optically isomeric forms , which will not necessarily have equal fungicidal activity . individual optical isomers , as well as deliberate and incidental mixtures of these isomers , such as racemic mixtures , are included within the scope of this invention . the invention also provides a method for combating fungus at a locus , which comprises treating the locus , which may for example be plants subject to or subjected to fungal attack , seeds of such plants or the medium in which such plants are growing or are to be grown , with a fungicidally effective amount of a n - acyl n - hydroxyalkanoic acid compound as defined above . the present invention is of wide applicability in the protection of crop plants against fungal attack . many organisms of the class oomycetes are controled , for example phytophthora infestans , bremia latucae , and peronospora destructor . typical crops which can be protected include tobacco , potato , tomato , lettuce and cocoa . the present invention is of particular value in the protection of vines against fungal disease , such as downy mildew , plasmopara viticola , because of the ability of the active compounds to provide a protective effect in those parts of the vine plant remote from the site of application . thus , if the upper surfaces of leaves of a vine are sprayed , the plant becomes more resistant to fungal attack not only on the leaf undersurfaces ( translaminar protection ) but also on the plant surfaces emerging after the treatment . the active material can also be effective when applied to the stem or roots of the plant ( s ) to be protected . the duration of such protection is normally dependent on the individual compound selected , and also a variety of external factors , such as climate , whose impact is normally mitigated by the use of a suitable formulation . a composition according to the invention preferably contains from 0 . 5 to 95 % by weight of active ingredient , plus an inert carrier and / or a surfactant . a carrier in a composition according to the invention is any inert material with which the active ingredient is formulated to facilitate application to the locus to be treated , which may for example be a plant , seed or soil , or to facilitate storage , transport or handling . a carrier may be a solid or a liquid , including a material which is normally gaseous but which has been compressed to form a liquid , and any of the carriers normally used in formulating fungicidal compositions may be used . suitable solid carriers include natural silicas such as diatomaceous earths ; magnesium silicates , for example talcs ; magnesium aluminium silicates , for example attapulgites and vermiculites ; aluminium silicates , for example kaolinites , montmorillonites and micas ; calcium carbonate ; calcium sulphate ; synthetic hydrated silicon oxides and synthetic calcium or aluminium silicates ; elements , for example carbon and sulphur ; natural and synthetic resins , for example coumarone resins , polyvinyl chloride , and styrene polymers and copolymers ; solid polychlorophenols ; bitumen ; waxes , for example beeswax , paraffin wax , and chlorinated mineral waxes ; and solid fertilisers , for example superphosphates . suitable liquid carriers include water ; alcohols , for example isopropanol and glycols ; ketones , for example acetone , methyl ethyl ketone , methyl isobutyl ketone and cyclohexanone ; ethers ; aromatic or araliphatic hydrocarbons , for example benzene , toluene and xylene ; petroleum fractions , for example kerosine and light mineral oils ; chlorinated hydrocarbons , for example carbon tetrachloride , perchloroethylene and trichloroethane . mixtures of different liquids are often suitable . fungicidal compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application . the presence of small amounts of a carrier which is a surface - active agent facilitates this process of dilution . thus preferably at least one carrier in a composition according to the invention is a surface - active agent . for example , a composition may contain at least two carriers , at least one of which is a surface - active agent . of particular interest in enhancing the duration of the protectant activity of the compounds of this invention is the use of a carrier which will provide a slow release of the fungicidal compound into the environment of the plant which is to be protected . such slow - release formulations could , for example , be inserted in the soil adjacent to the roots of a vine plant , or could include an adhesive component enabling them to be applied directly to the stem of a vine plant . a surface - active agent may be an emulsifying agent , a dispersing agent or a wetting agent ; it may be nonionic or ionic . examples of suitable surface - active agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids ; the condensation products of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and / or propylene oxide ; fatty acid esters of glycerol , sorbitan , sucrose or pentaerythritol ; condensates of these with ethylene oxide and / or propylene oxide ; condensation products of fatty alcohol or alkyl phenols , for example p - octylphenol or p - octylcresol , with ethylene oxide and / or propylene oxide ; sulphates or sulphonates of these condensation products ; alkali or alkaline earth metal salts , preferably sodium salts , of sulphuric or sulphonic acid esters containing at least 10 carbon atoms in the molecule , for example sodium lauryl sulphate , sodium secondary alkyl sulphates , sodium salts of sulphonated castor oil , and sodium alkylaryl sulphonates such as sodium dodecylbenzene sulphonate ; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide . the compositions of the invention may for example be formulated as wettable powders , dusts , granules , solutions , emulsifiable concentrates , emulsions , suspension concentrates and aerosols . wettable powders usually contain 25 , 50 or 75 % w of active ingredient and usually contain , in addition to solid inert carrier , 3 - 10 % w of a dispersing agent and , where necessary , 0 - 10 % w of stabiliser ( s ) and / or other additives such as penetrants or stickers . dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant , and may be diluted in the field with further solid carrier to give a composition usually containing 1 / 2 - 10 % w of active ingredient . granules are usually prepared to have a size between 10 and 100 bs mesh ( 1 . 676 - 0 . 152 mm ), and may be manufactured by agglomeration or impregnation techniques . generally , granules will contain 1 / 2 - 25 % w active ingredient and 0 - 10 % w of additives such as stabilisers , slow release modifiers and binding agents . emulsifiable concentrates usually contain , in addition to a solvent and , when necessary , co - solvent , 10 - 50 % w / v active ingredient , 2 - 20 % w / v emulsifiers and 0 - 20 % w / v of other additives such as stabilisers , penetrants and corrosion inhibitors . suspension concentrates are usually compounded so as to obtain a stable , non - sedimenting flowable product and usually contain 10 - 75 % w active ingredient , 0 . 5 - 15 % w of dispersing agents , 0 . 1 - 10 % w of suspending agents such as protective colloids and thixotropic agents , 0 - 10 % w of other additives such as defoamers , corrosion inhibitors , stabilisers , penetrants and stickers , and water or an organic liquid in which the active ingredient is substantially insoluble ; certain organic solids or inorganic salts may be present dissolved in the formulation to assist in preventing sedimentation or as antifreeze agents for water . the compositions may also contain other ingredients , for example other compounds possessing pesticidal , especially insecticidal , acaricidal , herbicidal or fungicidal , properties . aqueous dispersions and emulsions , for example compositions obtained by diluting a wettable powder or a concentrate according to the invention with water , also lie within the scope of the present invention . the said emulsions may be of the water - in - oil or of the oil - in - water type , and may have a thick ` mayonnaise `- like consistency . the compounds used in this invention can be synthesized by known procedures , for example via the corresponding nitrone as described in u . s . pat . no . 3 , 154 , 578 , or by suitable modifications of such procedures . however , an improved synthetic route has been discovered . accordingly , in another embodiment , the invention also provides a process for the preparation of a compound of the general formula i given above or a salt or an ester thereof , in which each of r 1 and r 2 have the meaning already given herein , which comprises reacting an ester of an acid of the general formula : ## str3 ## in which l represents a suitable leaving group , with hydroxylamine , to yield an ester of the acid of the general formula ## str4 ## optionally converting the resulting ester into the corresponding free acid or a salt thereof ; and acylating the resulting compound with a suitable acylating agent ; and if desired converting a resulting ester of the acid i into any required salt or ester or the free acid , by methods analogous to known methods . any leaving group which will be displaced by the hydroxylamine can be used . suitable moieties include halogen , especially chlorine or bromine , atoms , and organic sulphonic acid groups of the formula qso 2 o -- where q is a hydrocarbon group , for example an alkyl , aryl or alkaryl group ; typical groups of this type are the mesylate and tosylate groups . the reaction with hydroxylamine is perferably carried out in the presence of an acid acceptor , for example an amine , e . g . a trialkylamine . the molar ratio of the reactants is not crucial . it may be convenient to use approximately stoichiometric quantities , and preferably at least one mole of hydroxylamine is used per mole of starting ester . an excess of hydroxylamine may be used as an acid acceptor . the reaction may for example be carried out at a temperature in the range of from 0 ° to 100 ° c ., especially 15 ° to 70 ° c . if desired , the hydroxylamine may be prepared in situ , for example by reaction of a hydroxylamine salt , such as hydroxylamine hydrochloride , with a base , for example an alkali metal hydroxide or alkoxide or an amine . if desired , the ester iii may be converted by known methods into the corresponding free acid or salt , which is then acylated . preferably however it is the ester which is acylated . any suitable acylating agent may be used for reaction with the compound iii , for example an anhydride , ester or acid halide derived from the acid r 1 cooh . mixed anhydrides are often useful . when r 1 represents a hydrogen atom , prefered acylating agents are the mixed anhydride of formic acid and acetic acid , which may be added as such , or formed in situ from a mixture of formic acid with acetic anhydride . preferably at least one mole , for example from 1 to 5 moles , of acylating agent is used per mole of compound iii . the reaction may for example be carried out at a temperature in the range of from 0 ° to 100 ° c ., especially 15 ° to 70 ° c . in some cases , when using an ester iii but requiring a salt or acid as the final product , it is possible to convert the ester group in the ester iii into the free acid or a salt thereof in the same reaction vessel as the acylation , if the acylation step is carried out under conditions to which the ester group is not stable , for example under strongly acidic conditions . an especially preferred method of preparing a free acid i or a salt thereof , involves the use of an ester in which the ester group is readily removed in the last step of the process . such esters include for example the benzyl or , especially , the tertiary butyl ester , which groups are readily removed by hydrolysis or solvolysis either after the acylation step or simultaneously with the acylation step . the starting ester of the acid ii may be prepared in any suitable manner , for example by transesterification of any other ester of the acid ii , or by esterification of the free acid or its acid halide . a preferred method of preparing the tertiary butyl ester comprises reaction of the free acid ii with 2 - methyl propane under acidic conditions . suitable acid catalysts for use in this embodiment include , for example , mineral acids such as sulphuric acid , organic acids such as p - toluene sulphonic acid , and acidic ion exchange resins . if it is desired to prepare a single optical isomer of the required compound , this may be done by using as starting material the appropriate chiral ester , and by conducting the various reaction steps under carefully controlled reaction conditions to avoid racemisation . the use of organic sulphonic acid leaving groups l is especially useful when working with chiral materials . the following examples illustrate the invention . in each case , the identities of the products and intermediates were confirmed by appropriate chemical and spectral analyses . 1 . 0 mole of z - benzaldoxime and 1 . 1 moles of alpha - bromopropionic acid were added to sodium ethoxide solution , prepared from 2 moles of sodium metal in 4 l of ethanol . the solution was heated for three hours at 65 °- 70 ° c . with stirring , cooled , and the resulting crystals of the sodium salt of n - benzylidene alanine n - oxide were filtered off . this product was dissolved in water and acidified with 2 n hydrochloric acid . the resulting acid nitrone crystals obtained were washed with ether and dried to yield the free acid , m . p . : 168 °- 170 ° c . 40 g of the acid nitrone was treated with 400 ml of formic acid and 80 ml of acetic anhydride and the resulting mixture was stirred at room temperature for 1 hour , then stirred a further 3 / 4 hour , at 40 °- 45 ° c . the solvents were evaporated . the resultant oil was dissolved in water , washed with benzene and the aqueous layer neutralized by the addition of concentrated ethanolic sodium hydroxide solution . ethanol was added slowly , and the resulting sodium salt of n - formyl - n - hydroxy alanine was filtered off . m . p . : 193 °- 195 ° c . the free acid was conveniently obtained by passing the sodium salt down a dowex - 50 ion exchange column and eluting with water ; the acid had a melting point of 77 °- 79 ° c . in a parr hydrogenation flask was placed 0 . 33 mole of alpha - bromopropionic acid , 2 moles of isobutylene and 1 . 7 ml of concentrated sulphuric acid . the reaction mixture was shaken for 48 hours , then poured into a vigorously stirred solution of 20 % sodium hydroxide , extracted with ether and dried to yield the crude tert .- butyl ester of alpha - bromopropionic acid . hydroxylamine was generated in methanol by the addition of 0 . 1 mole of sodium methoxide or hydroxide to 0 . 1 mole of hydroxylamine hydrochloride , followed by filtering off the sodium chloride , and was added to 0 . 1 mole of the above ester and 0 . 1 mole of triethylamine , in methanol , and the reaction mixture refluxed for 24 hours . after cooling , ether was added and the insoluble triethylamine hydrobromide filtered off . evaporation of the solvents yielded a semi - solid product which was treated with petroleum ether ( 80 - 100 ) to yield n - hydroxyalanine tert . butyl ester , m . p . : 69 °- 70 ° c . 5 g of the ester was stirred at room temperature for 1 hour , with 40 ml of formic acid and 10 ml of acetic anhydride , then for a further 1 hour at 40 °- 45 ° c . the solvents were removed at low temperature , the residue dissolved in water and washed with benzene . the aqueous layer was treated with an equivalent of concentrated aqueous sodium hydroxide solution and ethanol slowly added to yield the sodium salt of n - formyl - n - hydroxyalanine , m . p . : 186 °- 187 ° c . ( c ) following such procedures , the further species of n - formyl - n - hydroxyamino acid derivatives of formula i listed in table i were prepared . to a solution of 1 mole of n - hydroxy - n - formyl alanine in water was added , with stirring , 1 mole of lead acetate in water . the precipitate obtained was dried under high vacuum for several days to yield the lead salt , m . p . : 180 ° c . ( dec ). following a similar procedure the following salts of the same acid with other polyvalent ions were obtained : equimolar amounts of n - formyl - n - hydroxy alanine and strychnine were dissolved in a mixture of acetone and ethanol and stirred at a temperature of 4 ° c . for 24 hours . at the end of this time , the resulting precipitate was filtered off and treated with aqueous sodium hydroxide solution . the resulting precipitate was filtered off and the filtrate was freeze dried . the solid was then recrystalized from aqueous ethanol , to give the (+) isomer of the sodium salt of n - formyl - n - hydroxy alanine , which had a specific optical rotation in aqueous solution of + 26 . 3 °. the above procedure was then repeated but using brucine instead of strychnine . the (-) isomer of the sodium salt of n - formyl - n - hydroxy alanine had a specific optical rotation of - 25 . 2 °. 0 . 35 mole of the s optical isomer of 2 - mesyloxypropionic acid was dissolved in 25 ml of pyridine and 500 ml of t - butanol , and 65 g of phosphoryl chloride was added , with stirring , at - 5 ° c . after a further 30 minutes stirring at - 5 ° c ., and a further 2 hours at 20 ° c ., the mixture was poured into ice - water , and methylene chloride was added . the organic layer was washed successively with dilute hydrochloric acid , sodium bicarbonate , and water , and then evaporated to give a solid which was recrystalised from light petroleum ether to give ( s ) t - butyl 2 - mesyloxypropionate . 0 . 05 mole of this ester was then dissolved in 25 ml of n - methylpyrrolidone and 0 . 051 mole hydroxylammonium chloride and 0 . 1 mole of triethylamine were added . the mixture was stirred overnight at 50 ° c ., after which time it was poured into water , diethyl ether was added , the organic layer was evaporated down and the resulting product was purified by chromatography over silica using diethyl ether and methylene chloride as eluants . ( r ) t - butyl 2 - hydroxyaminopropionate , having an optical rotation in chloroform solution of + 22 . 6 °, was obtained . this material could then be reacted with formic acid and acetic anhydride as described in ( b ) above , to give the required product . the test is a direct antisporulant one using a foliar spray . the lower surfaces of leaves of whole vine plants are inoculated by spraying with an aqueous suspension containing 10 5 zoosporangia / ml 2 days prior to treatment with the test compound . the inoculated plants are kept for 24 hours in a high humidity compartment , and then 24 hours at glasshouse ambient temperature and humidity . the plants are then dried and infected leaves detached and sprayed on the lower surfaces with a solution of active material in 1 : 1 water / acetone containing 0 . 04 % triton x - 155 . the spraying is carried out with a moving track sprayer which delivers 620 l / ha , and the concentration of active material is calculated to give an application rate of 1 kg / ha . after drying , the petioles of the sprayed leaves are dipped in water and the leaves returned to high humidity for a further 96 hours incubation , followed by assessment . assessment is based on the percentage of the leaf area covered by sporulation compared with that on control leaves . the test is a translaminar protectant one using a foliar spray . the upper surfaces of leaves of whole vine plants are sprayed at a dosage of 1 kilogram of active material per hectare using a track sprayer as described under ( a ). the lower surfaces of the leaves are then inoculated , up to 6 hours after treatment , with the test compound , by spraying with an aqueous suspension containing 10 5 zoosporangia / ml . the inoculated plants are kept for 24 hours in a high humidity compartment , 5 days at glasshouse ambient temperature and humidity and then returned for a further 24 hours to high humidity . assessment is based on the percentage of the leaf area covered by sporulation compared with that on control leaves . the test is a direct eradicant one using a foliar spray . the under - surface of the detached vine leaves are inoculated by pipetting ten large drops of an aqueous suspension containing 5 × 10 5 conidia / ml on to them . the inoculated leaves are kept uncovered overnight during which time the fungus has penetrated the leaf and a visible necrotic lesion may be apparent where the drop was made . the infected regions are sprayed directly with a dosage of 1 kg of active material per hectare using a track sprayer as described under ( a ). when the spray has dried the leaves are covered with petri dish lids and the disease allowed to develop under these humid conditions . the extent of the necrotic lesion beyond the original drop together with the degree of sporulation is compared with that on control leaves . the test measures the direct protectant activity of compounds applied as a foliar spray . tomato plants , cultivar outdoor girl , 10 - 15 cms high , in monopots are used . the whole plant is sprayed at a dosage of 1 kilogram of active material per hectare using a track sprayer as described in ( a ). the plant is then inoculated up to 6 hours after treatment with the test compound , by spraying with an aqueous suspension containing 5 × 10 3 zoosporangia / ml . the inoculated plants are kept in high humidity for 3 days . assessment is based on comparison between the levels of disease on the treated and control plants the test is a direct anti - sporulant one using a foliar spray . the upper surfaces of leaves of whole apple seedlings are inoculated by spraying with an aqueous suspension containing 10 5 conidial / ml 2 days prior to treatment with the test compound . the inoculated plants are immediately dried and kept at glasshouse ambient temperatures and humidity prior to treatment . the plants are sprayed at a dosage of 1 kilogram of active material per hectare using a track sprayer as described under ( a ). after drying the plants are returned to a compartment at ambient temperature and humidity for up to 9 days , followed by assessment . assessment is based on the percentage of the leaf area covered by sporulation compared with that on leaves of control plants . the test is a direct eradicant one using a foliar spray . the leaves of rice seedlings ( about 30 seedlings per pot ) are sprayed with an aqueous suspension containing 10 5 spores / ml 20 - 24 hours prior to treatment with the test compound . the inoculated plants are kept overnight in high humidity and then allowed to dry before spraying at a dosage of 1 kg of active material per hectare using a track sprayer as described in ( a ). after treatment the plants are kept at 25 °- 30 ° c . and high humidity . assessments are made 4 - 5 days after treatment and are based on the density of necrotic lesions and the degree of withering when compared with control plants . the extent of disease control in all the above tests is expressed as a rating compared with a diluent sprayed control according to the criteria : a representative selection of n - acyl - n - hydroxy amino acid derivatives were evaluated using the above procedures , with the results set out in table i , the compounds being identified by reference to the substituents in the formula given therein . table i__________________________________________________________________________ ## str5 ## compound fungicidal activityr . sup . 1 r . sup . 2 r . sup . 3 x p . v . a . p . v . t . b . c . p . i . p . p . o . p . l . __________________________________________________________________________h ch . sub . 3 h h 2 2 0 0 --. sup . ( a ) 1h ch . sub . 3 c . sub . 2 h . sub . 5 h 2 2 -- -- -- -- h ch . sub . 3 na h 2 0 2 0 -- 0h ch . sub . 3 na na 2 0 0 0 -- 0h ch . sub . 3 li h 2 0 0 0 2 0h ch . sub . 3 k h 2 1 0 0 0 0 . bhorizbrace . h ch . sub . 3 mg 2 0 0 0 0 0h ch . sub . 3 ca 2 0 0 0 0 0h ch . sub . 3 cu 2 2 0 0 -- 1h ch . sub . 3 pb 2 0 0 0 -- 0h ch . sub . 3 fe 2 0 0 0 0 0h ch . sub . 3 mn 2 0 0 0 -- 0 . bhorizbrace . h ch . sub . 3 zn 2 0 0 0 -- 0h ch . sub . 3 nh . sub . 4 . sup .⊕ h 2 2 -- -- -- 0h ch . sub . 3 . sup .⊕ nh . sub . 3 . ( ch . sub . 2 ). sub . 2 oh h 2 0 -- -- -- 0h c . sub . 3 . sup .⊕ nh . sub . 2 . [( ch . sub . 2 ). sub . 2 oh ]. sub . 2 h 2 0 -- -- -- 0h ch . sub . 3 . sup .⊕ nh . [( ch . sub . 2 ). sub . 2 oh ]. sub . 3 h 2 1 -- -- -- 0 h ch . sub . 3 ## str6 ## h 2 1 -- -- -- 0 h ch . sub . 3 . sup .⊕ nh . sub . 3 . ( ch . sub . 2 ). sub . 4 ch . sub . 3 h 2 0 -- -- -- 0h ch . sub . 3 . sup .⊕ nh . sub . 3 . ( ch . sub . 2 ). sub . 9 . ch . sub . 3 h 2 0 -- -- -- 2 h ch . sub . 3 ## str7 ## h 2 1 -- -- -- 1 h ch . sub . 3 . sup .⊕ nh . sub . 2 ( c . sub . 2 h . sub . 5 ). sub . 2 h 2 1 -- -- -- 0h ch . sub . 3 . sup .⊕ nh ( c . sub . 2 h . sub . 5 ). sub . 3 h 2 2 -- -- -- 0h ch . sub . 3 . sup .⊕ n [ ch . sub . 3 . ( ch . sub . 2 ). sub . 3 ]. sub . 4 h 2 0 -- -- -- 2 h ch . sub . 3 ## str8 ## h 2 0 0 0 -- 0 h ch . sub . 3 ## str9 ## h 2 1 0 0 -- 0 h ch . sub . 3 amberlite * h 2 0 0 0 0 -- cg400h ch . sub . 3 amberlite * h 2 2 0 0 -- 0 ira193h ch . sub . 3 amberlyst * h 2 1 0 0 -- 1 a26h ch . sub . 3 amberlyst * h 2 1 0 0 -- 0 a21h ch . sub . 3 dowex * h 2 0 0 0 -- 0 1 - x8h ch . sub . 3 zerolit * h 2 1 0 0 -- 0 fx1pc . sub . 6 h . sub . 5 h h h 1 2 0 1 -- -- h h c . sub . 2 h . sub . 5 h 2 0 1 0 -- -- h h na h 2 2 0 2 0 -- __________________________________________________________________________ *- ion exchange resins , trade marks . . sup . ( a ) not tested with respect to this organism . the protective fungicidal activity of selected compounds was evaluated by the following procedure . test compounds were applied to the leaves of intact vine plants ( cv . cabernet - sauvignon ) growing in 5 &# 34 ; diam ., pots in the glasshouse . the spray was composed of acetone and water ( in 1 : 1 proportion ), and a surfactant ( tween 20 trade mark ) at 0 . 04 % w / v . eight days after treatment the plants were inoculated with a suspension of spores of plasmopara viticola ( 10 3 zoosporangia / ml .). after a further eight days readings were made on the degree of sporulation on the abaxial surfaces of sprayed leaves . from these readings , the reduction in sporulation attributable to the chemical treatment was calculated , and expressed as a percentage , by comparison with plants ( controls ) sprayed with the acetone / water / surfactant diluent . the results of these tests are given in table ii . table ii______________________________________compound dose ppm % sporulation reduction______________________________________n - formyl - n - hydroxy alanine 500 100n - acetyl - n - hydroxy alanine 1000 72 . 6n - formyl - n - hydroxy 2 - amino - butanoic acid , sodium salt 1000 50 . 8______________________________________

US-33935082-A

a method for synchronized positioning of a web for manufacturing products . the method includes feeding the web into a production apparatus at a first speed ; processing in the production apparatus , with the web being fed forward at a second speed ; and detection of each synchronization mark for positioning the respective motif in a predetermined position on each product . the method includes the following steps : generation of a reading of the actual value of a virtual master function upon the detection , which includes a cyclic clock where the number of cycles per product includes an integer ; comparison between the actual value and the expected value of the virtual master function ; and stretching of the web in response to any deviation between the actual value and the expected value , with the aim of minimizing the deviation .

fig1 is a schematic and simplified view of an arrangement 1 for manufacturing absorbent products , that is arranged in accordance with a preferred embodiment of the present invention . more specifically , the arrangement 1 is arranged for manufacturing absorbent products that start out as a first essentially continuous web of material 2 , which is fed forward in a known way from a roll ( not shown ) or the like , in a direction that is indicated by an arrow in fig1 . according to the preferred embodiment , the first web of material 2 consists of a backing layer for a disposable diaper , that is a material of the type that is non - permeable to liquid or that has at least a high resistance to the penetration of liquid , but which , however , is breathable . for this purpose , the first web of material 2 consists suitably of a thin and waterproof plastic film of , for example , polyethylene , polypropylene or polyester . alternatively , a laminate of non - woven material and plastic film or other suitable and previously - known layers of material can be utilized as a liquid - tight backing layer . the first web of material 2 can be fed forward by means of two rollers 3 , 4 which are arranged to give the first web of material 2 , that will become the backing layer , a certain given feed speed v 1 . fig1 also shows that the first web of material 2 is processed in such a way that it comprises a printed motif 5 . this motif 5 is suitably pre - printed on the first web of material 2 . in addition , the motif 5 is applied in such a way that it recurs at a certain predetermined distance in such a way that one and the same motif is provided on each individual product that is manufactured from the first web of material 2 . in addition , the motif 5 is indicated by broken lines in fig1 to indicate that it is printed on the underside of the first web of material 2 . in the finished product , the final position of the printed motif 5 will thus be in a predetermined position on the back of the product . the motif 5 is printed at certain given regular intervals and is intended to be synchronized , which means that the final position of the motif 5 is intended to be in the same position on each individually manufactured product of the type in question . for this purpose , the first web of material 2 is provided with a number of reference marks or synchronization marks 6 , suitably in the form of relatively short lines that are suitably pre - printed onto the first web of material 2 . in the embodiment shown in fig1 , the synchronization marks 6 are printed on the underside of the first web of material 2 . the invention is not , however , restricted to this , but it is possible to print the synchronization marks 6 on both sides of the first web of material 2 . in fig1 , the synchronization marks 6 are also indicated by broken lines , in order to indicate that they are printed on the underside of the first web of material 2 . as will be described in detail below , the object of each synchronization mark 6 is to constitute a detectable reference element , by means of which various work elements and process steps that are carried out by means of the arrangement 1 are synchronized correctly in relation to each printed motif 5 . in this way , the motif 5 can be positioned in the correct position on the finished product . in the embodiment that is shown in fig1 , a processed element in the first web of material 2 is utilized , in the form of a printed motif 5 . it should , however , be noted that the principle behind the invention is not limited to only the case when a printed motif is utilized . in other words , the invention can also be used for other positioned elements in the form of patterns , embossing , applications and ornamentation that constitute processing of the first web of material 2 . similarly , the principle behind the invention can be used for elements that consist of embossed patterns , folds , notches , holes and similar elements that are intended to be positioned in a predetermined , that is “ synchronized ”, way on a finished product . as shown in fig1 , the first web of material 2 can be divided into a certain nominal division length l n , that is a length that is defined between two transverse positions 7 , 8 that delimit a particular product . according to the embodiment that is shown in fig1 , the nominal division length l n consists in particular of a product length that corresponds to the front edge and back edge of a finished product . these positions 7 , 8 are indicated by broken lines in fig1 . however , these lines are not printed on the first web of material 2 . each printed motif 5 is placed in a position that is in a given and predetermined relationship to the respective synchronization mark 6 . this means that each synchronization mark 6 is printed at a regularly recurring distance l s that corresponds to the periodicity of the printed motif 5 . as shown in fig1 in a schematic and simplified way , the first web of material 2 is fed through a processing apparatus 9 where a number of work elements and process steps are carried out in a way that is already known . these work elements can comprise , for example , the application of various types of absorbent material , wadding material and the like , and any other material and components such as , for example , elastic , adhesive tape and the like . the work elements that are carried out in the processing apparatus 9 can also comprise folding , cutting , ultrasound welding and other processing steps . the manufacture of absorbent products by means of a series of such work elements is already known , and for this reason will not be described here in detail . as an example , however , reference can be made to the said patent document wo 00 / 59429 mentioned in the introduction , that describes an example of a previously - known manufacturing process for absorbent products . still with reference to fig1 , it can be noted that the first web of material 2 has passed a detecting device 10 just before it is fed into the processing apparatus 9 . in a way that will be described in detail below , the detecting device 10 is arranged to detect the presence of each synchronization mark 6 . the feeding of the first web of material 2 is carried out by means of a feeding device that preferably consists of a suction conveyor 11 which is a known feeding device that can be controlled to feed forward the first web of material 2 at a given feed speed v 2 . in addition , the first web of material 2 is fed past a gluing station 12 at which adhesive is applied in order to enable a subsequent outer layer to be glued on , in the way that will be described below . the detecting device 10 consists preferably of a suitable device for optical inspection , according to the embodiment in the form of a video camera that is arranged in association with the first web of material 2 . the detecting device 10 is arranged in such a way that it continually inspects and records images along the underside of the first web of material 2 as shown schematically in fig1 . for this purpose , the detecting device 10 comprises a set of light - sensitive elements , by means of which it records the light transmission from the first web of material 2 while this is moved in relation to the detecting device 10 . in addition , the detecting device 10 is connected to a computer - based control unit 13 . information from the detecting device 10 is transmitted in this way to the control unit 13 , which in turn is provided with software for image processing that is arranged to detect each synchronization mark 6 that passes over the detecting device 10 . in addition , the control unit 13 is connected , in a way that will be described in detail below , to a speed - control device 14 for controlling the speed v 1 at which the first web of material 2 is fed forward . the control unit 13 is also connected to the suction conveyor 11 for controlling the speed v 2 of this . according to an alternative embodiment , the detecting device 10 can be , for example , a ccd camera (“ charged coupled device ”), i . e . with a set of light - sensitive sensors arranged in one or more rows . by means of this arrangement , the position of each synchronization mark 6 can be detected . according to yet another alternative embodiment , the detecting device can be based on , for example , laser technology , that is with a laser light source that is utilized in conjunction with a light - sensitive detector to detect the position of each synchronization mark 6 . according to yet another variant , the synchronization mark can consist of an electronically detectable sensor , for example of the transponder type , that is applied on the first web of material 2 and with the abovementioned regular intervals l s . such a synchronization mark can then be read by a detecting device that comprises a radio transmitter and radio receiver for this purpose in a known way . according to yet another alternative embodiment , the said synchronization marks can be printed with magnetic ink that can then be detected by a sensor that detects magnetism . when the first web of material 2 has been fed past the detecting device 10 , it meets a second web of material 15 , according to the embodiment in the form of an essentially liquid - permeable layer that is intended to form an outer layer of the finished product . for this reason , the second web of material 15 consists suitably of a non - woven material with a soft and smooth surface , such as , for example , a spun bond material of polypropylene fibre . other examples of materials that are suitable for constituting the outer layer are perforated plastic films , such as , for example , a perforated polyester film . the second web of material 15 is thus joined to the first web of material 2 ( together with any additional layers of material and other components that are added in association with the processing apparatus 9 as described above ) for example by means of the adhesive that was previously applied at the gluing station 12 . in this way , a complete web of material 16 is created , intended to define a number of manufactured products , which is fed forward in a direction that is indicated by an arrow in fig1 and taken up and fed forward by means of additional driving units , for example in the form of two rotating feeding rollers 17 , 18 arranged respectively over and under the complete web of material 16 . in this way , the complete web of material 16 can be fed forward . after the assembly with the second web of material 15 , a complete continuous web of material 16 is thus created , consisting of a number of finished absorbent products that are still joined together . this web of material 16 is finally fed past a cutting station 19 , suitably of the “ cross - cutter ” type , where cutting is carried out at positions that essentially correspond to the imaginary boundary lines 7 , 8 for each finished product . in this way , a number of finished products are created in the form of absorbent products 20 . with reference again to the detecting device 10 , it can be noted in particular that it is arranged to detect the position of each synchronization mark 6 . information regarding a detected position for a given synchronization mark 6 is then used for various process steps that , for example , are carried out in the processing apparatus 9 in order to ensure that the printed motif 5 is always positioned in a correct position on each finished product 20 . for this purpose , the control unit 13 is arranged with a virtual data - based reference function or master function , which will now be described with reference initially to fig2 a . the virtual master function is a cyclic clock that preferably turns one revolution per product 20 . as described in detail below , the master function is not limited to only to this periodicity . an event - controlled reading off of this clock can be interpreted as the relative position of the event in question in relation to a fixed point on the product in question , that is in relation to a type of virtual zero point or reference for the product . fig2 a shows the virtual master function in the form of a ramp - like curve 21 that recurs at regular intervals . the detecting device 10 is utilized first to detect a particular synchronization mark 6 along the first web of material 2 . when a synchronization mark 6 is found , the control unit 13 is used to detect in what position along the virtual master function 21 the synchronization mark 6 is located . information about the actual position of the virtual master function 21 is thus recorded by means of the control unit 13 . thereafter , the control unit 13 compares the actual position of the virtual master function ( actual value ) with an expected position ( desired value ). the speed v 1 of the first web of material 2 is then changed in relation to the speed v 2 of the suction conveyor 11 in response to any deviation between the actual position and the expected position . the slower the speed v 1 in comparison with v 2 , the more the material in the first web of material 2 will be stretched . this is then utilized to obtain a correct synchronization of the first web of material 2 . fig2 a shows the said master function or reference function in the form of a ramp - like curve 21 that recurs at regular intervals and that symbolizes a periodic clock that is utilized for detecting each synchronization mark 6 . for this reason , the curve 21 is drawn in an xy - coordinate system where the x - axis corresponds to the time t , and where a period in the curve 21 corresponds to the time t that it takes for a nominal division length l n of the material in question to pass the detecting device 10 . in addition , the y - axis corresponds to a length l for the first web of material 2 , with a maximal value l n of the curve 21 corresponding to the length of each product . the curve 21 indicates in a schematic way a rise from a zero value that indicates one end of a product to a maximal value l n that indicates the other end of the product and that , according to the described embodiment , corresponds to the length of the product . a value of the position of the virtual master function that has been read off ( when a synchronization mark 6 has just been detected ) is thus compared periodically with an expected position along the virtual master function . the expected value , that is the desired value , is indicated in fig2 by the reference numeral 22 and corresponds to the printed motif 5 being positioned correctly in its intended place on the finished product . the precise position for this desired value 22 is determined by a number of factors , such as , for example , the equipment comprised in the arrangement 1 , the dimensions of the comprised material , the process speed , etc . the curve 21 with its desired value 22 thus consists of predefined data that is stored in the control unit 13 . for this reason , the reference function or master function that is illustrated by the curve 21 can be said to be “ virtual ”, as it is generated and stored in the form of software in the control unit 13 . fig2 b shows an alternative embodiment , in which the virtual master function 21 is arranged in such a way that two periods in the curve 21 correspond to the time t that it takes for a nominal division length l n of the material in question to pass the detecting device 10 . fig2 c shows yet another embodiment in which the virtual master function 21 is arranged in such a way that a period in the curve 21 corresponds to twice the time t that it takes for a nominal division length l n of the material in question to pass the detecting device 10 . taken as a whole , as illustrated by fig2 a , 2 b and 2 c , a basic principle is that the master function 21 consists of a cyclic clock where the number of cycles t per product 20 , or alternatively the number of products 20 per cycle t , consists of integers . in all the embodiments that are shown in fig2 a , 2 b and 2 c , the principle is used that detection of a given synchronization mark 6 is carried out using the detecting device 10 . this results in the recording of a position along the curve 21 that corresponds to this detected synchronization mark 6 . this position then constitutes an actual value that is indicated schematically by the reference numeral 23 in fig2 a , 2 b , 2 c . as the length of the period t for the curve 21 can be said to have a given relationship to the product length of each product , the actual value 23 will consist of a numerical value corresponding to a certain proportion of the total product length . in addition , the control unit 13 is arranged to compare the desired value 22 and the actual value 23 ( that is the actual position ) that was recorded during the detection of a particular synchronization mark 6 . according to the examples that are shown in fig2 a , 2 b and 2 c , there is a difference between the desired value 22 and the actual value 23 . this difference can be expressed as a difference between the proportion of the whole product length that corresponds to the desired value 22 minus the proportion of the product length that corresponds to the actual value 23 . if there is a relatively large difference between the desired value 22 and the actual value 23 ( as shown in , for example , fig2 a ), the printed motif 5 would be positioned on the first web of material 2 displaced somewhat in relation to its intended position , that is the motif 5 would not then be correctly synchronized . for this reason , it is an underlying principle that the position of the printed motif 5 on the finished product 20 is adjusted by stretching the first web of material 2 if there is such a deviation between the desired value 22 and the measured value 23 . for this reason , the synchronization marks 6 are pre - printed on the first web of material 2 in such a way that they recur at regular intervals l s that are somewhat shorter than the intended product length l n . this means that the distance l s between two consecutive synchronization marks 6 is shorter than the product length l n , which in turn corresponds to the intended final length of the finished product 20 . the fact that the distance l s between two synchronization marks 6 is shorter than the product length l n makes it possible to stretch the first web of material 2 to a certain extent , in order in this way to position the printed motif 5 so that , in its final position , it is in the correct position on the finished product 20 . according to the embodiment shown , the abovementioned stretching of the first web of material 2 is achieved by a control of the speed of the first speed - control device 14 , which in turn controls the feed speed v 1 for the first web of material 2 . more specifically , the control unit 13 is arranged to control the speed - control device 14 in such a way that the first web of material 2 is given a speed v 1 that is somewhat lower than the speed v 2 of the suction conveyor 11 . this leads in turn to a stretching of the material in the first web of material 2 when it runs through the process apparatus 9 . in this way , the position of the printed motif 5 on the finished product and thereby also the position of the respective synchronization mark 6 , is adjusted in such a way that the deviation between the desired value 22 and the actual value 23 relating to the position of the synchronization mark 6 is eliminated . according to the embodiment , the distance l s between two consecutive synchronization marks 6 is of the order of 2 % shorter than the product length l n . this makes it possible to utilize the natural elasticity of the first web of material 2 for stretching it in accordance with the abovementioned principles . the invention is , however , not limited to any specific ratio between the product length l n and the distance between synchronization marks l s , but instead this ratio can vary , depending upon the comprised material and which type of process apparatus is utilized . nor is the invention limited to the nominal division lengths having to be connected to the product length , but instead other divisions of the first web of material 2 are possible within the framework of the invention . to sum up , the disclosure is based on a detection of synchronization marks 6 , the position of which is detected and utilized for synchronizing a printed motif 5 in the correct intended position on a finished product . the synchronization is carried out using a virtual reference function or “ master ” function that is stored in the control unit 13 and that is arranged to provide references in order to make it possible to stretch the first web of material 2 if a deviation is recorded between an actual position and the expected position of each synchronization mark 6 . in this way , a simple and accurate process is obtained for synchronizing the printed motif 5 . the invention is not limited to what is described above , various embodiments being possible within the framework of the patent claims . for example , the invention is particularly suitable for use in association with a manufacturing process for making absorbent products such as diapers , incontinence pads , sanitary towels and panty liners , but is not limited only to this type of product , being able , in principle , to be utilized in other manufacturing processes that are based on an essentially continuous web of material being divided into a certain product length and where a printed motif or other similar process is synchronized in the correct position . the invention is particularly suitable for use with the applications where the first web of material 2 consists of a material intended to form a backing layer in a diaper . such a material then consists suitably of a plastic film that is non - permeable to liquid , which is suitable for the abovementioned stretching procedure and is also suitable for printing with high quality colour motifs . the invention can , however , be used with other material than just the backing layer for diapers , for example other elastic and stretchable webs of material , for example non - woven material , that is fibrous materials with fibres such as for example polyolefins , that is polymer material such as polyethylene and polypropylene , or alternatively polyester , nylon or the like . the invention can also be utilized when the first web of material consists of some other type of synthetic or textile material . the invention can also be used for different types of laminates comprising varying numbers of layers of material . regarding the printed motif 5 , this can be provided by being pre - printed onto the first web of material 2 . alternatively , the actual manufacturing process that is obtained with the process apparatus 9 can comprise a process for printing the motif . in addition , it can be noted , with reference to fig2 , that a period length t in the reference function 21 can correspond to a product length , as described above . alternatively , a period length t can correspond to two or more product lengths , or a certain proportion of a product length . this means that the synchronization marks can be positioned in a corresponding way , for example in every other position in comparison with what is shown in fig1 . with reference to fig2 , it can be pointed out that the invention is not limited to a virtual master function where a period corresponds clearly to a product length . alternatively , the invention can be arranged in such a way that a given product length corresponds to two or more synchronization marks and thus also two or more periods in the virtual master function .

US-29755506-A

a thermoelectric device comprising an elongated panel of two foam layers , and having an inserted thermoelectric string is incorporated into a seat cushion , planting pot , and battery thermal manager . several enhancements to the string and the panel improve its durability , visual appeal , and tactile appeal over the prior art .

in a prior patent application ser . no . 14 / 025 , 495 filed jul . 12 , 2013 , the inventors described how an array of foam pillars underneath a thermoelectric panel could allow for airflow across heat exchangers made from braided or stranded wire . the pillars , attached to the insulating foam layer , permit independent vertical movement thereby distributing pressure evenly . the inventors shown in application ser . no . 14 / 025 , 495 filed jul . 12 , 2013 that this construction could retain the pressure distribution characteristics of whatever cushioning was underneath , which is a significant feature for a generalized heating / cooling layer that may be applied to a variety of surfaces . in this application , we show methods for manufacturing the pillars and optimizing their shape , protecting the wire and thermoelectric elements from cyclic stress , smoothing the surface , and constructing an entire heated and cooled cushion using a small number of parts with low manufacturing costs . fig1 ( a )- 1 ( d ) show the internals of a completed form - factor cushion . fig1 a shows the two layers 101 and 106 of foam arranged as described in application ser . no . 14 / 025 , 495 and having the thermoelectric string 103 inserted into the top layer , and pillars 106 in the bottom layer . the heat exchangers 107 made from stranded wire are exposed in the airflow layer as shown in the underside view of fig1 c . the red button 108 in the center of fig1 c is a pushbutton switch that acts as an occupancy switch to turn on the heating or cooling when a user is sitting or lying down on the cushion . without limitation , an occupancy sensor could replace the switch . such a sensor inputting to control electronics could perform the same function . fig1 b shows the electronics enclosure 102 at the back of the cushion separated from the panel . this enclosure contains or may contain the fans 109 , airflow ducting 105 , control electronics , wiring 104 , power connectors , switches , knobs , and batteries . the fans 109 pull air 105 from the front of the cushion shown by the arrows in fig1 a . as shown in fig1 c , the fans push the air 105 upward but diagonally away from the user assuming the user is in the sitting position as shown in the close up view in fig1 c . fig2 ( a )- 2 ( b ) show two views of a manufactured , dual - layer foam stack with one layer 112 and 106 patterned with pillars . first , the optimum type of foam for the continuous layer 111 is selected for comfort and feel , as this layer will become the foam surface of the cushion . next , the optimum type of foam for the pillared layer 112 and 106 is selected to allow airflow when under pressure of the user . to begin the manufacture , two continuous layers of each type of foam are bonded together . then , the pillars are formed . fig2 ( a )- 2 ( b ) show the pillars formed using a router machine , which routs out the channels between the pillars . without limitation , the pillars can also be formed using a hot wire cut machine , wherein the hot wire traverses a u shaped path to construct a channel . without limitation , many hot wires could be employed simultaneously to increase throughput . also without limitation , the patterned pillars 106 and 112 in fig2 ( a )- 2 ( b ) could be formed in a mold as the foam is produced . the continuous layer 111 could be formed in place on top of the pillared layer 112 and 106 , or be bonded afterwards . analysis and simulations performed by the inventors indicate that square pillars 106 like the ones in fig2 ( a )- 2 ( b ) are not the optimal shape for airflow . staggered round pillars 106 allow more uniform airflow 105 , as indicated in the computer - aided analysis illustrated in fig3 a and 3 b . fig4 ( a )- 4 ( b ) show how a round pillar may be approximated using a hot wire cut machine . fig4 a shows how 4 hot - wire cut directions along the dotted lines can form octagonal pillars 106 with remaining foam base material 112 . fig4 b shows how 3 hot - wire cut directions along the dotted lines can form hexagonal pillars 106 . without limitation , the hot wire cut operation could be replaced with an abrasive wire saw or vibrating operation . fig5 ( a )- 5 ( e ) show many different design enhancements to the base thermoelectric string to protect the wires from breakage after repeated bending cycles when in the cushion after numerous sitting cycles . the objective of these enhancements is to limit the bend radius of the wire during the bending cycles . it has been known for a long time in the industry that putting a lower bound on the bend radius of a wire can increase its bend cycle life by several orders of magnitude . fig5 a shows a closed - cell foam plug in the shape of a cylinder 201 . without limitation , the plug may have a y shape cut in the side for placement of the thermoelectric junction . or , the plug may have a hole in the center and the junction inserted into the hole from above . the y cut or the hole allows a path for the two links 202 and the one loop 204 of the thermoelectric junction to exit the foam plug . the hardness of the foam is selected to result in a gradual but not severe bending of the wire under compression from directly above . the attachment of the wire to the junction is protected inside the foam plug by preventing acute bending at this location . without limitation , the material used for this purpose could be closed cell foam , open cell foam , styrofoam , rubber , plastic , or gel . fig5 b shows another method for protecting the thermoelectric string . here , a length of latex tubing 205 is cut partway down to form two flaps . the flaps protect the two links leaving the junction , and the tubular portion protects the loop &# 39 ; s attachment to the junction . without limitation , this material used for this purpose could be silicone , polyurethane , plastic , teflon , gel , or any other similar material . fig5 c shows another method for protecting the thermoelectric string . here , lengths of fiberglass tape 206 are attached to the outside of the junction and extend along the loop and along the link to beyond the 90 degree angle at the surface . the tape adhered to the wire and junction forces a mild bend radius at all points where the tape is present . without limitation , the material used could be foam tape , rubber tape , electrical tape , woven plastic tape , plastic tape , teflon tape , gel tape , or any other similar material with adhesive or without such as liquid plastics that solidify after placement . fig5 d shows another method for protecting the thermoelectric string . here , a latex nipple 207 , similar to those used in baby bottles , is used to limit the bend radius and protection the wire - to - board attachments . a foam plug 208 is used to maintain electrical insulation between the links . the loop wire is routed through a hole at the narrow end of the nipple . the links are routed over the wide end of the nipple . without limitation , this nipple shape could be made of silicone , polyurethane , rubber , plastic , teflon , gel , or any other similar material . fig5 e shows a length of stranded wire 209 that is combined with cloth fibers to improve the tensile strength of the links and reduce the bending stress on the wires . when the cushion has the weight of a person &# 39 ; s torso , the compression lengthens the surface of the foam , which in turn puts tensile stress on the links . now , we generalize the design of the thermoelectric ribbon further in a way that durability is achieved and is predictable . the physical process of metal wires flexing and then breaking is rooted in the repeated weakening of each bend . if the wire &# 39 ; s strength is weakened even slightly on each cycle of stress , then breakage is likely to occur after the 3 , 000 to 100 , 000 stress cycles required for the durability of a consumer product . the slight weakening of a metal wire on each flex can be predicted by looking at its deformation . if the wire &# 39 ; s original shape returns after the flex , then the deformation is elastic . if the wire &# 39 ; s shape changes after the flex , then the deformation is plastic . plastic deformation of a wire changes its physical properties and weakens the wire . repeated plastic deformation of a wire is certain to lead to breakage . repeated elastic deformation of a wire will last much longer . plastic or elastic deformation is observable on a thermoelectric ribbon inserted into a panel on the first cycle of a durability test . hence , the nature of the deformation on the first cycle of a thermoelectric panel is predictive of its durability . further , a thermoelectric panel can be designed to only incur elastic deformation or to avoid plastic deformation , or both , as verified in the first cycle or a small number of cycles of a durability test . fig6 ( a )- 6 ( d ) show two designs of the thermoelectric ribbon , as it would appear in a panel . the panel is not shown for illustrative purposes . fig6 a is the traditional design with vertical junctions 210 inside the panel , horizontal links 202 along the surface of the panel , and curled heat exchangers underneath the junctions positioned in an airflow layer . after applying compression to this ribbon with an equivalent displacement of the standard durability test , the wires in the ribbon become plastically deformed as shown in fig6 b . fig6 c shows the end view of the angled design , wherein the plane containing the lines of the junctions 210 intersects at a 45 - degree angle the plane of the links 202 along the surface . fig6 d shows the string after a stress cycle that compressed the ribbon to a very narrow vertical clearance . the resting shape of the ribbon in fig6 d after compression stress has returned to that of fig6 c , indicating the absence of plastic deformation . without limitation , all designs of a thermoelectric ribbon that avoid plastic deformation in a cycle of stress are covered by this invention . the angled design of fig6 c can be inserted into the foam panel of the cushion 101 in fig1 a such that the junction 210 in fig6 c is positioned either above the pillar 106 in fig1 a or between the pillars . placing the junction above the pillar allows the junction to be cushioned by the pillar in severe compression . placing the junction between the pillar allows the wires to bend more freely in the soft foam and hence less susceptible to plastic deformation . both placement locations have advantages depending on the stress conditions and the spring constants of the two foam layers . fig6 e through 6 f show how shaping the woven strands in link 202 can make the system more durable in a stress test . one failure mode of an office cushion occurs when the links 202 are forced to lengthen in order to accommodate the depression made in the foam when a person sits on it . with the fishnet - woven braid in fig6 a , the outer strands of the weave do not have sufficient slack to accommodate the necessary lengthening , which results in tensile stress on the wire strands where they join the junction . fig6 f through 6 h show steps in shaping the links wires to achieve more slack and hence lengthening capability under stress . first , in fig6 f , the terminated ends of the link 202 are pushed inwards towards each other , which creates a bulge on wires surrounding an empty cavity . next , in fig6 g , the bulging section is folded into a z shape , which shortens the length from termination to termination of the link . then , the fold is flattened to achieve the final shape in fig6 h . note how in fig6 h the fold lessens as the ends of the link are pulled away from each other . this slack in the link allows for further lengthening under stress of a person sitting on a cushion with these links 202 on the surface . as previously mentioned , maintaining a radius of curvature of the wires is critical to prevent the wires from breaking under repeated sitting cycles of the thermoelectric panel in a cushion . furthermore , it is desirable to make the foam surface as smooth as possible for tactile and visual appeal . fig7 ( a )- 7 ( c ) show a low - cost method for protecting the wire as it turns along the surface and additionally for smoothing the surface . a flap 301 is cut in the foam as shown in fig7 a using a u - shaped blade inserted at an angle to the surface . the flap 301 of foam is lifted up and the thermoelectric junction is inserted through to the airflow layer . then the flap 301 is returned to it original position as shown in fig7 b . now , the presence of foam both above and below the wire 202 at the point where it turns 90 degrees along the surface limits the curvature under pressure stress or rolling stress . this method of using the flap also reduces the “ egg - crating ” irregularity of the surface , which naturally results from the wire 202 being routed into and out of the surface foam . the surface of fig7 b is still irregular because of the profile height and rigidity of the wires 202 are elevated from the foam surface . this irregularity is easily seen and felt through many different types of covers . a thick cover can reduce this irregularity , but thick covers also degrade the thermal performance of the panel . hence , a better solution is needed to smooth the surface without introducing thermal resistance . fig7 c shows such a method for smoothing the surface . a material 302 with the similar profile height and rigidity as the wire 202 is placed around the wire . in fig7 c , the material is a canvas cloth . without limitation , any material that matches the height of the woven wire could be used . the material may be stretchy to match the hammock deformation of the underlying cushion when in use . the material may be made from , without limitation , a solid polyurethane sheet , tape , spandex cloth , closed cell foam sheet , or other suitable material . in all of the embodiments of the thermoelectric panel in this and previous patent applications , the link wires along the surface are most effective when in close proximity to the skin of the person being heated or cooled , i . e . when the cover over the wires is thin . however , a human hand can feel these wires through a smooth thin cover and this tactile feel is undesirable . and , some covers will stretch over the wires during use and remain permanently stretched with an apparent bagginess pattern to the cover over time . designs of covers that address these issues are covered in fig8 ( a )- 8 ( b ). fig8 a shows an embossed bed cover 401 and a stitched textile pattern 402 , which could be used as a cover over a thermoelectric panel . this cover is made from a thin material , like a bed sheet fabric , but the embossing or stitching creates peaks and valleys in the surface contour . a human hand moving along a thermoelectric panel with this cover will not be able to distinguish the embossed or stitched peaks and valleys with the feel of the wires underneath , especially and without limitation , if the spacing and size of the embossed or stitched features is comparable with the spacing and size of the wires . these covers also visually create a pattern that is visually indistinguishable from any pattern of bagginess from the cover stretching over the wires that might occur over time . and , because the embossed fabric 401 flattens under the weight of a person and the area of the stitching in 402 is very small , the net thickness during use is very thin . hence , these patterned fabrics address the issues with the wires under the cover , optimizing the visual appearance , the tactile feel , and the thermal performance . fig8 b shows several embossed patterns for leather . again , the embossed features flatten out under the weight of a person , allowing for good thermal conduction in the contact area . another application for a thermoelectric string , panel , and possibly airflow layer is for controlling the temperature of soil for plants . fig9 a shows that the productivity of plants is a strong function of the soil temperature . plants typically categorized as “ cool season ” plants have productivity profile 501 , “ temperature season ” plants have productivity profile 502 , and “ warm season ” plants have profile 503 . these three profiles have optimal soil temperatures of approximately 65 f , 75 f , and 85 f respectively . fig9 b shows a list of plants in these three categories . it is desirable to grow warm season plants in the winter and cool season plants in the summer , and to be able to grow mixed combinations of plants in a single environment . controlling soil temperature enables optimization of plant productivity and flexibility in the thermal environment of the plants . fig1 a shows a plant pot containing soil wherein the temperature of the soil is controlled by a thermoelectric string and panel . an insulating top layer 504 is needed to prevent heat transfer through the topsoil , and this layer could be made of decorative pumice stone or other material with good insulating properties . the pot consists of an inner wall 505 and an outer wall 506 . between these two walls is a thermoelectric panel . the apparatus of fig1 a does not contain an airflow layer , as natural convection removes heat from wall 506 when the soil is being cooled . by reversing the electrical current in the thermoelectric panel , the soil is warmed instead of cooled . the temperature probe in fig1 b shows that the soil near the side 506 is 67 . 4 f ; fig1 c shows that the temperature of the soil in the center of the pot is 70 . 0 f and the ambient temperature is 79 . 6 f . these temperature readings were taken in steady state conditions and show that the soil is cooled by about 10 degrees f . from ambient by the thermoelectric panel , meeting the requirement to cover optimum temperature range of + or − 10 f shown in fig9 ( a ). fig1 d shows that this result was accomplished by applying 6 . 3 volts and 2 . 11 amps to the thermoelectric panel , which included a thermoelectric string of 85 junctions . yet another application of a thermoelectric string , panel , and possibly an airflow layer is thermal management of batteries . battery temperature needs to be controlled for three reasons : efficiency , lifetime , and safety . fig1 shows how the a thermoelectric string 202 and 210 is in thermal contact with a battery 602 on one side and possibly an airflow layer on the other side that contains moving air 105 . alternatively , a cold plate that is in thermal contact with the loop wires could replace the airflow layer . an insulated container 601 is added if the temperature outside the battery is adversely affecting its temperature in the regions beyond the thermoelectric panel . many applications for thermoelectric panel are challenged in having the airflow layer covering one whole side of the panel . in seating and bedding , for example , forming an airflow layer underneath the panel and under the weight of the user presents design and form - factor challenges in some cases . in these cases , it is helpful to have a heat spreader that can move the excess heat to another location that is more convenient for the airflow layer or other heat exchanger . fig1 a illustrates a thin plate 701 with a moving fluid inside that moves heat very effectively from the flat area to the sides . fig1 b shows an actual product from thermavant technologies , inc . that spreads heat using this method . in fig1 c , this heat spreader 701 is mounted underneath , and in thermal contact with , the thermoelectric panel 111 . because of the spreader 701 essentially conducts heat very effectively , the airflow 105 , or other heat exchanger , may be moved to another location . in fig1 c , this new location is at the end of the spreader 701 . without limitation , the inventions described herein can be applied to seats , seat backs , seat tops , bed tops , wheelchair cushions , hospital beds , animal beds , and office chairs .

US-201414530360-A

a method of extending eyelashes is described herein . specifically , an adhesive - based method of extending eyelashes is disclosed . the method can comprise wearing a ring on a first hand and manipulating forceps with a second hand . the ring can comprise a bowl , while the bowl can comprise eyelash adhesive . in addition , the method can comprise attaching a first side of an eye patch to a surface , attaching a tape on a second side of the eye patch , and supporting a plurality of loose extension lashes on the tape . the extension lashes on the tape can be removed with forceps . a portion of the eyelash extension can be dipped into the eyelash adhesive within the ring . lastly , the method can comprise attaching the eyelash extension to a natural lash on a user

described herein is a system and method for securing extension lashes during an eyelash extension procedure . the following description is presented to enable any person skilled in the art to make and use the invention as claimed and is provided in the context of the particular examples discussed below , variations of which will be readily apparent to those skilled in the art . in the interest of clarity , not all features of an actual implementation are described in this specification . it will be appreciated that in the development of any such actual implementation ( as in any development project ), design decisions must be made to achieve the designers &# 39 ; specific goals ( e . g ., compliance with system - and business - related constraints ), and that these goals will vary from one implementation to another . it will also be appreciated that such development effort might be complex and time - consuming , but would nevertheless be a routine undertaking for those of ordinary skill in the field of the appropriate art having the benefit of this disclosure . accordingly , the claims appended hereto are not intended to be limited by the disclosed embodiments , but are to be accorded their widest scope consistent with the principles and features disclosed herein . fig1 illustrates a first hand 100 wearing a ring 101 , and a second hand 102 holding forceps 103 . ring 101 can be a circular band that can be worn around a finger . ring 101 can be made of any materials such as plastic , metal and / or glass that can be designed in various color , shape , and / or sizes . forceps 103 can be any tool , such as tweezers , which can be used for manipulating natural lashes and lash extensions . furthermore , ring 101 can comprise a container 104 , and a lid 105 . container 104 can be used for storing glue 106 . glue 106 can be made of a sticky and / or liquid adhesive material for adhering a prosthetic lash to a natural lash . in one embodiment , container 104 can be a concave portion at the top surface of ring 101 . in such embodiment , ring 101 and container 104 can be molded as a single device . in another embodiment , container 104 can be a small receptacle attached to ring 101 through weld , solder , glue or other method known in the art . lid 105 can cover or seal container 104 . fig2 illustrates a plurality of extension lashes 200 attached on a piece of an eye patch 201 . extension lashes 200 can be designed with various length , thickness , color , and / or curl . extension lashes 200 can be divided into two parts , a base 200 a , and a tip 200 b . base 200 a can be the thicker part of extension lashes 200 , while tip 200 c can be thinner end of extension lashes 200 . base 200 a can be the portion of extension lashes 200 that can be adhered onto a natural lash . as a non - limiting example , extension lashes 200 can have a length that is between 1 to 30 millimeters . as another non - limiting example , extension lashes 200 can have a thickness that is between 0 . 01 to 0 . 25 . as another non - limiting example , extension lashes 200 can have various curls , which can range between straight , curled , and extra - curled . eye patch 201 can be worn around near the eye area . in a preferred embodiment , eyepatch 201 can be an under eye patch curved in a shape that is compatible to be placed under the eye area . eye patch 201 can comprise tape 202 . tape 202 can be any strip of material capable holding eyelashes in an orderly manner and maintaining a fixed position during extension lash 200 removal from tape and installation onto user . in one embodiment , eye patch 201 can comprise adhesive on one or both sides . in such embodiment , a first side of eyepatch 201 that attaches on the eye area can comprise of gel and / or a mask that is capable of adhering to the skin , while a second side of eye patch 201 can comprise an adhesive that can hold extension lashes 200 . in another embodiment , eyepatch 201 can support tape 202 on a top surface of eyepatch 201 , while a bottom surface of eyepatch 201 can affix to the user &# 39 ; s skin . tape 202 can be double - sided . one side of tape 202 can connect to eyepatch 201 , while the other side of tape 202 can hold extension lashes 200 . fig3 illustrates a human face comprising eyes 300 . eyes 300 can comprise eyelids 301 , and a plurality of eyelashes 302 . eyes 300 can have different types , as eyes 300 vary in shapes and sizes such as , but not limited to , almond - shaped , oval - shaped , round - shaped , small and / or big eyes . eyelids 301 can be divided into zones , in which extension lashes 200 can be attached in order to create different looks . fig4 a illustrates how eyelids 301 can be divided into three zones . in such embodiment , eyelids 301 can comprise an inner zone 401 , middle zone 402 , and outer zone 403 . inner zone 401 can be an area of eyelid 301 that can be near the tear ducts of eye 300 . middle zone 402 can be the center portion of eyelid 301 located just above the pupil . outer zone 403 can be the portion of eyelid 301 farther from the tear ducts . fig4 b illustrates how eyelids 301 can be divided into four zones . in such embodiment , inner zone 401 can be divided into two sections . as such , inner zone 401 can comprise first inner zone 401 a , and a second inner zone 401 b . first inner zone 401 a can be a portion closest to the tear ducts . second inner zone 401 b can be the portion connecting first inner zone 401 a and mid - zone 402 . fig5 a illustrates how to make extension lashes 200 appear natural when applied onto eyelashes 302 . in such embodiment , extension lashes 200 can be attached on inner zone 401 . length extension lashes 200 with a length one - millimeter longer than the inner zone lashes can be applied to middle zone 402 . extension lashes 200 on outer zone 403 can be one - millimeter longer than middle zone 402 . in one embodiment , inner zone 401 can comprise eight - millimeter extension lashes 200 , middle zone 402 can have nine - millimeter extension lashes 200 , and outer zone 403 can comprise ten - millimeter extension lashes . fig5 b illustrates application of extension lashes 200 onto eyelashes 302 to achieve a cute or doll - eyed look . in such embodiment , extension lashes 200 can be attached on inner zone 401 . length extension lashes 200 , having a length that is two - millimeters longer than the inner zone lashes , can be applied to middle zone 402 . extension lashes 200 on outer zone 403 can be one millimeter shorter than the middle zone 402 . as a non - limiting example , inner zone 401 can comprise eight - millimeter extension lashes 200 , middle zone 402 can have ten - millimeter extension lashes 200 , and outer zone 403 can comprise nine - millimeter extension lashes . fig5 c illustrates application of extension lashes 200 on to eyelashes 302 to achieve sexy look . in such embodiment , extension lashes 200 can be attached on inner zone 401 . length extension lashes 200 having a length two - millimeter longer than the inner zone lashes can be applied to middle zone 402 . outer zone 403 extension lashes 200 can be two or three - millimeters longer than middle zone 402 . as a non - limiting example , inner zone 401 can comprise eight - millimeter extension lashes 200 , middle zone 402 can have ten - millimeter extension lashes 200 , and outer zone 403 can comprise twelve or thirteen - millimeter extension lashes . such applications of extension lashes 200 on eyes 300 can create a seductive look and make eyes 300 appear almond in shape . fig5 d illustrates application of extension lashes 200 onto eyelashes 302 to achieve a gorgeous look . in such embodiment , extension lashes 200 can be attached on first inner zone 401 a . length extension lashes 200 having a length one - millimeter longer than first inner zone lashes can be applied to second inner zone 401 b . length extension lashes 200 having a length one - millimeter longer than first inner zone lashes can be applied to second inner zone 401 b . length extension lashes 200 having a length one - millimeter longer than second inner zone lashes can be applied to middle zone 402 . outer zone 403 extension lashes 200 can be the same length as lashes of the middle zone 402 . as a non - limiting example , first inner zone 401 a can comprise eight - millimeter extension lashes 200 , second inner zone 401 b can comprise nine - millimeter lashes , middle zone 402 can have ten - millimeter extension lashes 200 , and outer zone 403 can comprise ten - millimeter extension lashes . in such embodiment , eyes 300 can look more dramatic , attractive , and fuller . for purposes of this disclosure , different thickness and curls of extension lashes 200 can be applied in different zones to achieve various looks for the user . to make eyes 300 appear larger and wider , thin and / or thick extension lashes 200 can be applied onto eyelashes 302 . additionally , extension lashes 200 can vary from curled to extra - curled to open up eyes 300 and make them appear larger . to make eyes 300 appear smaller , a thicker and / or extra - thick extension lashes 200 can be applied onto eyelashes 302 . selecting and applying more extension lashes 200 can make eyes 300 appear smaller and full . fig6 illustrates how extension lashes 200 can be applied onto eyelash 302 . eye patch 201 can be placed on a portion of human face or at the back of first hand 100 . second hand 102 holding forceps 103 can be used to pick extension lashes 200 from eye patch 201 , or from tape 202 in an embodiment where tape 202 holds extension lashes 200 . extension lashes 200 can be picked using forceps 103 near the base 200 b . as such , extension lashes 200 can be easily grasped , and directed into a desired area . concurrently , first hand 100 wearing ring 101 can be moved towards second hand 102 in order to dip base 200 a into container 104 . as such , base 200 a can be coated with glue 106 . further , base 200 a can be attached near the bottom of single natural eyelash 302 . extension lashes 200 can be attached one at a time and / or per row on every individual natural eyelash 302 . in one embodiment , first hand 100 can hold forceps 103 b and second hand 102 can hold first forceps 103 a . first hand 100 can separate lashes on eye by using first forceps 103 . as first hand 100 adjusts space between lashes accordingly to clear space , second hand 102 can manipulate lash extension . second hand 102 can use second forceps 600 to pick up lash off from strip , dip lash in adhesive / glue and apply lash to space created between lashes from first hand 100 using first forceps 103 . in one embodiment , strip can be on the first hand 100 with ring 101 . eye patch 201 can be placed on a portion of user &# 39 ; s face ( such as on under - eye covering ) or at the back of first hand 100 . second hand 102 , using forceps 103 a can pick an extension lash 200 from eye patch 201 or from tape 202 . concurrently , first hand 100 wearing ring 101 can be moved towards second hand 102 in order to dip base 200 a into container 104 , coating base 200 a with glue 106 . base 200 a can then be attached near to natural eyelash 302 . various changes in the details of the illustrated operational methods are possible without departing from the scope of the following claims . some embodiments may combine the activities described herein as being separate steps . similarly , one or more of the described steps may be omitted , depending upon the specific operational environment the method is being implemented in . it is to be understood that the above description is intended to be illustrative , and not restrictive . for example , the above - described embodiments may be used in combination with each other . many other embodiments will be apparent to those of skill in the art upon reviewing the above description . the scope of the invention should , therefore , be determined with reference to the appended claims , along with the full scope of equivalents to which such claims are entitled . in the appended claims , the terms “ including ” and “ in which ” are used as the plain - english equivalents of the respective terms “ comprising ” and “ wherein .”

US-201514936676-A

a method minimizing artifacts in dual or multiple energy images includes : obtaining first and second offset images from a detector after obtaining first and second exposure image data sets from the detector . other embodiments include : changing the dosage of the exposures , changing the gain of the detector , changing the pixel acquisition resolution of the detector , and leaving the detector unscrubbed between the first and second read times .

fig1 illustrates an imaging system 100 used in accordance with a preferred embodiment of the present invention . the imaging system 100 includes a plurality of subsystems . for the purposes of illustration only , the imaging system 100 is described as dual mode x - ray system . it will be recognized that the present invention may be applied to other modalities as well , such as , for example , gamma rays . in addition , it will be recognized that the present invention may be applied to multiple image systems such as , for example , tomosynthesis systems . tomosynthesis is performed by acquiring multiple images ( typically 5 to 50 images ) with a digital detector to reconstruct tomography images . tomosynthesis may be performed using many different tube motions including linear , circular , elliptical , hypocycloidal , and others . the imaging system 100 includes subsystems , such as an x - ray detector 110 , an x - ray detector scan area 115 , an x - ray source 120 , a scintillator 125 . the imaging system 100 also includes an image acquisition unit 140 with read - out electronics 145 . a patient 130 or target object is positioned in the imaging system 100 . an x - ray source 120 is positioned above the patient 130 . the x - ray detector 110 is positioned below the patient 130 . the scintillator 125 is positioned between the patient 130 and the x - ray detector 110 . x - rays are transmitted from the x - ray source 120 through the patient 130 to the scintillator 125 . the scintillator 125 emits light in response to the x - rays transmitted from the x - ray source 120 through the patient 130 . the emitted light is transmitted to the x - ray detector 110 and the x - ray detector scan area 115 . fig2 illustrates an example of a solid state x - ray detector scan area 115 within the x - ray detector 110 . the x - ray detector scan area 115 is comprised of cells 210 corresponding to pixels in an x - ray image . the cells 210 may be arranged in columns 220 and rows 230 . the cells 210 are controlled by scan lines along row 230 and read out by data lines along column 220 . one or more cells 210 are uniquely mapped to one or more pixels in an x - ray image . the pixels are activated to produce the desired digital x - ray image of the patient 130 . fig3 is an example of a lower - level view of the solid state x - ray detector scan area 115 within the x - ray detector 110 . each cell 210 comprises a photodiode 320 and a field effect transistor ( fet ) 330 . data lines 340 connect the cells 210 to the read - out electronics 145 of the image acquisition module 140 . through the read - out electronics 145 , the image acquisition unit 140 acquires an x - ray image from the x - ray detector scan area 115 . the image acquisition module 140 may acquire an x - ray image from the x - ray detector scan area 115 by receiving a signal from the data lines 340 from the cells 210 in the x - ray detector scan area 115 . the signal from the data lines 340 may be generated by charge stored in the photodiodes 320 . the charge stored in the photodiodes 320 may result from absorption of light by the photodiodes 320 . the light is emitted by the scintillator 125 directly above the photodiodes 320 in response to absorption of x - ray energy by the scintillator 125 . the fets 330 allow the charge stored in the photodiodes 320 to travel as a signal through the data lines 340 . the fets 330 may be actuated by the fet controller ( not shown ) in the image acquisition module 140 . the signal received by the image acquisition module 140 may include an offset produced by the charge retention characteristics and photoconductive effects of the fets 330 . operation of system 100 can be described generally with reference to the flow chart of fig4 and the acquisition sequence time line of fig5 . referring first to fig5 , line 510 denotes the exposure control signal that controls exposure sequence and timing wherein the x - ray source 120 is turned on when exposure signal 510 is high and off when the signal 510 is low . line 515 denotes an acquisition control signal that controls the sequence and timing with which data is read from the detector 110 . the various steps of fig4 , described below , are indicated in their respective time steps of fig5 . in step 402 of fig4 , the detector 110 is “ scrubbed ” one or more times . that is , a detector read is performed without exposure and without sending image data . in step 404 of fig4 , the detector 110 is exposed to a first exposure from an energy source 120 . in a preferred embodiment , the first exposure is a lower dose exposure , which will produce a darker image . a darker image may have less photoconductive effect than a brighter image . in step 406 , a first set of image data is obtained from the first exposure . the first set of image data is obtained following a first delay . preferably , the first delay is the minimum delay to reduce the photoconductive effects of the darker image . typically , photoconductive effects are less in a darker image than a brighter image . thus , the delay time for a darker image is less than the delay time for a brighter image . the first set of image data may be obtained from the detector 110 during a first read time . preferably , the first read time is less than the second read time because the first image data set comprises a darker image data set with a smaller dynamic range than the image resulting from the second , higher dose exposure . the darker image with a smaller dynamic range may use fewer conversion levels to convert the data for each line 340 of the detector 110 . in step 408 the detector 110 gain is decreased . for example , the gain of the individual fets 330 may be increased . by decreasing the gain of detector 110 , the pixels generated in response to the second ( higher ) exposure and the first ( lower ) exposure are normalized . also in step 408 , the pixel acquisition resolution is increased from that used in step 406 for acquiring the first set of image data . the reduced pixel acquisition resolution used for acquiring the first set of image data may be accomplished , for example , by pixel binning . that is , by acquiring data from fewer than all of the cells 210 in detector 110 . for example if detector 110 is a 2048 × 2048 pixel element detector ( 2048 × 2048 cells ), then the reduced pixel acquisition image may be read using only the output from 1024 × 1024 of the cells . this can be accomplished by “ binning ” the pixels during the read process . for example , 2 × 2 binning involves combining each group of 4 pixels ( 2 in column direction , 2 in row direction ) into a single pixel . this reduces the image size to 1024 × 1024 cells . the advantage is that 1024 × 1024 pixels can be read out and transferred faster ( 50 % for 2 × 2 ) which reduces the amount of time between any two xray pulses . the cost is image resolution . the time interval is weighed against the resolution to optimize the overall process . in step 408 , the resolution is increased so that the higher resolution image ( e . g ., the 2048 × 2048 cell image ) is used in the second ( higher ) exposure of step 410 . in step 410 , the detector 110 is exposed to a second exposure from the energy source 120 . preferably , the second exposure is a higher dose exposure . typically , a higher dose exposure will produce a brighter image . in step 412 , a second set of image data is obtained from the second exposure . the second set of image data is obtained following a second delay . the second set of image data is obtained from the detector 110 during a second read time . the second read time may be longer than the first read time . the brighter image caused by the higher ( second ) exposure has a larger dynamic range than the darker image caused by the lower ( first ) exposure . the larger dynamic range may use more conversion levels than the darker image . in step 414 , the detector 110 is again scrubbed one or more times . notable is the lack of scrubs between the exposures in steps 404 and 410 . in a typical radiographic sequence , many scrubs ( typically four or more ) are issued between x - ray exposures . this serves to maintain the electrical stability of the amorphous silicon substrate and to reduce the image lag . in the present invention , the management of offset and lag allows the scrubs to be performed after the second image data set is obtained , thereby reducing the critical time between exposures . in step 416 , the detector 110 obtains a first offset image . an offset image is a “ dark ” scan in which the fets on detector 110 are activated and data are recorded . the time between frames for both the first offset image of step 416 and the first image data set of step 406 are consistent , allowing the effect of charge retention in the fets to be determined . that is , the time from the end of 402 to the beginning of 406 is the same as the time from the end of 414 to the beginning of 416 . by subtracting the “ dark ” scan from the actual “ exposed ” scan of the desired object , the charge retention effects on the first image data set of step 406 may be eliminated . in step 418 , the detector 110 obtains a second offset image . as with the first offset image , the time between frames for both the second offset image of step 418 and the second image data set of step 410 are consistent , allowing the effect of charge retention in the fets to be determined . by subtracting the “ dark ” scan from the actual “ exposed ” scan of the desired object , the charge retention effects on the second image data set of step 406 may be eliminated . the embodiment shown in fig4 is preferably used in a system 100 employing automatic exposure control ( aec ). a system with aec utilizes an x - ray sensitive ion chamber coupled with integrating electronics and a feedback control signal to control the xray source 120 . the setup of the aec includes setting the desired xray level ( typically by the operator ), which is translated into an integrated voltage threshold through a calibrated transfer function . during operation , the integrator circuit is reset , xrays are enabled , and the xray level integrated until its threshold is reached , at which time , the controlling signal terminates the xray . during this operation the actual exposure time is not known apriori . the digital detector and its offset are sensitive to the time between frames . thus , in the embodiment of fig4 , the consistency of the timing between the xray acquisition and the offset acquisition is maintained . where the system is under manual control , rather than under the control of the aec , the detector timing is known and is set to be the same for all xray images in an image sequence . since the timing is the same for all xray frames , only a single offset is needed and is acquired at the same timing as the xray . accordingly , in an embodiment where system 100 employs manual control , only one offset acquisition is required , and this offset acquisition is preferably performed before the first exposure . with reference to fig4 , therefore , in the embodiment where system 100 employs manual control , steps 416 and 418 are omitted and a step of obtaining an offset image is performed prior to step 404 ( e . g ., between steps 402 and 404 ). in step 420 , the detector is again scrubbed . in step 422 , it is determined whether more frames are to be obtained . if no more frames are to be obtained , the method ends . if more frames are to be obtained , the method proceeds to step 424 where the gain of detector 110 is increased . by increasing the gain of detector 110 , the pixels generated in response to the second ( higher ) exposure and the first ( lower ) exposure are normalized . also in step 420 , the pixel acquisition resolution is decreased from that used in step 412 for acquiring the second set of image data . as previously discussed , the reducing the pixel acquisition resolution may be accomplished , for example , by pixel binning . that is , by acquiring data from fewer than all of the cells 210 in detector 110 . in step 420 , the resolution is decreased so that the lower resolution image ( e . g ., the 1024 × 1024 cell image ) is used in the first ( lower ) exposure of step 410 . the method of fig4 continues until all frames have been obtained . steps 406 and 412 act to reduce the detector read time by reducing the dynamic range for the readout . in step 406 , the dose per frame is reduced from that used in step 412 . as noted , reducing the dose per frame reduces the photoconductive effects on the fets , thus allowing the critical time to be reduced . where fast , multiple frames are to be acquired , as in tomosynthesis , the dynamic range may be reduced for the entire sequence . that is , with fast , multiple frames , x - ray source 120 may be configured such that the dose per frame is reduced as compared to a general - purpose radiographic exposure by a factor in the range of two to ten . that is , the dose per frame may be reduced from a general purpose radio graphic exposure of 1 . 0 micro roentgen to a range of between about 0 . 1 micro roentgen to 0 . 5 micro roentgen . this reduced dynamic range translates into a reduced number of conversion levels . each conversion level “ costs ” a fixed amount of time per line . accordingly , this reduced number of conversion levels can decrease the conversion time a few ( 2 - 10 ) microseconds per line . when used on a detector with 2048 lines , this can amount to 10 - 20 milliseconds . steps 408 and 424 act to reduce the detector read time by decreasing the pixel acquisition resolution . where fast , multiple frames are to be acquired , as in tomosynthesis , the pixel acquisition resolution may be reduced for the entire sequence . that is , with fast , multiple frames , detector 110 may be configured to provide a low pixel acquisition resolution ( e . g ., 1024 × 1024 ) for the entire sequence . alternatively , the “ low ” pixel acquisition resolution ( e . g ., 1024 × 1024 ) can be used in step 412 for obtaining the second image data set , and an even lower pixel acquisition resolution can be used in step 406 for obtaining the first image data set . a further reduction in the critical time can be obtained by operating with a longer charge integration time ( i . e ., fet “ on ” time ). this will reduce the amount of first - frame lag as we allow more time constants for more of the charge to be transduced . in general , this will increase the detector read time , as the time needed per scan line read will be increased . the common method to reduce lag is to scrub the detector . a scrub takes an entire detector read interval to complete . thus a longer fet on time ( several micro seconds per scan line ) is much shorter time ( several milliseconds ) than an additional detector read . thus , a method has been described which reduces the time between x - ray acquisitions times to minimize patient motion and minimize potential for detector artifacts . also , the method minimizes total exam time and allows a fast read of the detector without sacrificing image quality issues . a system incorporating this method has also been described . while the invention has been described with reference to a preferred embodiment , it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention . in addition , many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof . therefore , it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention , but that the invention will include all embodiments falling within the scope of the appended claims . moreover , the use of the terms first , second , etc . do not denote any order or importance , but rather the terms first , second , etc . are used to distinguish one element from another .

US-68399202-A

the present invention is directed to an optoelectronic unit for directing the eye gaze of the patient during examination or documentation of the fundus of the eye . the solution according to the invention for internal eye gaze guidance in fundus cameras provides a spatial light modulator for generating the fixation mark comprising imaging optics by which the displayed fixation mark is imaged on the eye fundus by a semitransparent mirror arranged in an observation beam path and via a swivel mirror arranged in a documentation beam path . the spatial light modulator is connected by a control unit to an actuating element for positioning the fixation mark . the device , which is preferably provided for fundus cameras , can facilitate the diagnosis of diseases of the eye fundus in that the documented recordings can be exactly reproduced and therefore exactly compared . in particular , the tracking and presentation of the course of diseases can be improved in this way .

in the unit , according to the invention , for internal eye gaze guidance in fundus cameras , a spatial light modulator is provided for generating the fixation mark . the spatial light modulator has imaging optics by which the fixation mark is imaged on the fundus via a semitransparent mirror arranged in an observation beam path and a swivel mirror arranged in a documentation beam path . the spatial light modulator is connected by a control unit to an actuating element for positioning the fixation mark . fig1 shows the basic construction of a fundus camera with the internal fixation device according to the invention . a spatial light modulator in the form of high - resolution , graphics - capable lcds 1 are provided for generating the fixation mark 2 and have imaging optics 3 by which the fixation mark 2 is imaged on the eye fundus 8 by a semitransparent , preferably dichroic , mirror 5 arranged in an observation beam path 4 , a swivel mirror 7 arranged in a documentation beam path 6 , and diverse optical elements . the spatial light modulator 1 is connected by a control unit 9 to an actuating element 10 for positioning the fixation mark 2 . displays other than high - resolution , graphics - capable lcds ( liquid crystal displays ), e . g ., lcos ( liquid crystal on silicon ), led ( light emitting diode ), o - led ( organic light emitting diode ), or dmd ( digital micromirror device ), can also be used as a spatial light modulator . the dichroic mirror 5 arranged in the observation beam path 4 has the advantage that the light yield is as large as possible and stress on the patient is minimized as far as possible . fig2 shows the transmission behavior of a dichroic mirror 5 to be used . the infrared light for observation which is emitted by the light source 12 arranged in the illumination beam path is focused on the fundus 8 by different optical components , reflected by the fundus 8 , and imaged on the ccd rangefinder camera 13 by the swivel mirror 7 and the dichroic mirror 5 . the infrared illumination light is imaged in its entirety on the ccd rangefinder camera 13 corresponding to the transmission behavior of the dichroic mirror 5 , while the fixation mark which is projected on the fundus 8 and lies in the visible spectral range is reflected . the visible light for the image recording which is emitted by the strobe light source 16 arranged in the illumination beam path 11 is focused on the fundus 8 via different optical components , reflected by the fundus 8 and imaged on the ccd documentation camera 17 when the swivel mirror 7 is not located in the documentation beam path 6 . since a pc is preferably used as control unit 9 , the keyboard 14 , a mouse , a trackball , a joystick , or the like , is used as an actuating element 10 for positioning the fixation mark 2 and is connected to the pc by a parallel , serial , usb or firewire interface . it is also advantageous to use an additional monitor 15 for displaying the fundus image that is imaged in the observation beam path 4 . in order to examine and / or document certain fundus areas again at a later time , it is particularly advantageous to store data of the corresponding fixation mark such as , e . g ., shape , color , intensity , coordinates , and the like , along with the corresponding fundus image . by activating this stored fixation mark , it is ensured that the patient gazes at a later time in the same direction so that the same fundus area is examined and / or documented . changes are immediately visible by overlaying the images that were recorded at different times . in the method according to the invention for internal eye gaze guidance in fundus cameras , a fixation mark 2 which is generated by a spatial light modulator in the form of high - resolution , graphics - capable lcds 1 is imaged on the eye fundus 8 by imaging optics 3 , a semitransparent mirror 5 arranged in an observation beam path 4 , and a swivel mirror 7 arranged in a documentation beam path 6 and is accordingly visible to the patient . the positioning of the fixation mark 2 is carried out by means of an actuating element 10 which is connected by a control unit 9 to the spatial light modulator 1 . the coordinates of the pixels of the spatial light modulator 1 presenting the fixation mark 2 and , therefore , the position of the image of the displayed fixation mark 2 focused on the fundus 8 are changed by moving the actuating element 10 . since a pc is preferably used as control unit 9 , a mouse , a trackball , a joystick , or the like connected to the pc by a parallel , serial , usb or firewire interface is an obvious choice as an actuating element 10 . further , the pc serving as control unit 9 advantageously has a keyboard 14 for operation and a monitor 15 for displaying the fundus image that is imaged in the observation beam path 4 . when using a semitransparent mirror 5 in the observation beam path 4 , the position or the movement of the fixation mark 1 which is positioned by means of the actuating element 10 and focused on the fundus 8 is displayed together with the image of the fundus on a monitor 15 connected to the control unit 9 . in contrast , when a dichroic mirror 5 is used in the observation beam path 4 , the position or movement of the fixation mark 1 which is positioned by means of the actuating element 10 and focused on the fundus 8 is displayed in the form of a cursor corresponding to the fixation mark synchronously and , in a second plane , is superimposed on the image of the fundus and displayed on the monitor 15 connected to the control unit 9 . the use of a dichroic mirror 5 has the advantage that the light yield is as large as possible and stress on the patient is minimized as far as possible . fig2 shows the transmission behavior of a dichroic mirror 5 to be used . the infrared light for observation which is emitted by the light source 12 arranged in the illumination beam path 11 is focused on the fundus 8 by different optical components , reflected by the fundus 8 , and imaged on the ccd rangefinder camera 13 by the swivel mirror 7 and the dichroic mirror 5 . the infrared illumination light is imaged in its entirety on the ccd rangefinder camera 13 corresponding to the transmission behavior of the dichroic mirror 5 , while the fixation mark which is reflected by the fundus 8 lies in the visible spectral range and is accordingly reflected by the dichroic mirror 5 and not shown in the viewing image . the swivel mirror 7 is swiveled out of the documentation beam path 6 when the fundus 8 is photographed . the visible light which is emitted by the strobe light 16 arranged in the illumination beam path 11 is focused on the fundus 8 via different optical components , reflected by the fundus 8 and imaged on the ccd documentation camera 17 . the internal fixation mark 1 is not shown on the recording . in order to examine and / or document certain fundus areas again at a later time , it is particularly advantageous to store data of the corresponding fixation mark such as , e . g ., shape , color , intensity , coordinates , and the like , along with the corresponding fundus image . by activating this stored fixation mark , it is ensured that the patient gazes at a later time in the same direction so that the same fundus area is examined and / or documented . changes are immediately visible by overlaying the images that were recorded at different times . in order to correctly assess the course of diseases , it is necessary to obtain images or image sections of exactly the same fundus area and to overlay them . the position of the fixation mark is entered simply and directly either by entering the corresponding coordinates by the keyboard or in that the fixation point is determined interactively by the examiner by clicking the mouse while observing the fundus of the patient . for repeat recordings , the coordinates of the fixation point can be read out of the stored data from the earlier recording and then entered manually or transferred directly from this recording by pressing a button . since the patient &# 39 ; s eye to be examined should be fixated in its eye gaze direction by the generated fixation mark , the accuracy of the gaze direction is substantially determined by the size of the fixation mark and / or by the detail of its structures . the accuracy of the gaze direction is , in turn , very important for the reproducibility of the recordings . the fixation mark can be formed as an individual point or , for patients with defective vision , over a larger surface so that it can be more easily perceived by this group of patients . in addition , it is possible to vary the color of the displayed fixation mark . in order to direct the gaze of small children , it is even possible to generate colored , child - appropriate fixation marks in which certain details of the fixation mark can be designated as the target point so that an exact and reproducible guidance of eye gaze can be ensured for obtaining “ coincident ” images . the solution according to the invention possesses an almost unlimited possibility for generating any desired shape of fixation mark . any graphic shape that can be displayed on a pc monitor can also be used as a fixation mark in practice . for example , the often used “ sighting rings ” can be generated for patients suffering from macular degeneration , the generated internal fixation mark is realized by the high - resolution , graphics - capable display with a sufficiently large number of image points in that every desired point of the display or groups of points can be activated in a software - controlled manner . a substantial advantage of the method of guiding eye gaze according to the invention consists in that the reproducibility of digital recordings is appreciably improved by this method because the fixation mark can be generated again in a pixel - exact manner , that is , in the micrometer range . accordingly , one or more recordings of the eye fundus that have been taken at different times can be made to coincide exactly . therefore , by manipulating the images in a corresponding manner , it is easily possible for changes over time , i . e ., the course of the disease , to be made visible in an appreciably clearer manner . the diagnosis and description of the course of a disease is substantially facilitated by corresponding image processing procedures such as differential image display or false color display . further , it is advantageous that the unit according to the invention and the method according to the invention for internal gaze guidance in fundus cameras can also be used for patients with defective vision because it is easily possible to generate fixation marks of different sizes . for such persons , the fixation mark is enlarged by means of clicking a mouse until it is visible for the patient . in this case , either the coordinates of all of the “ partial points ” taking part in the fixation mark can be stored , or the necessary data and details required for reproducing the shape and size of the specific fixation point can be stored in addition to the coordinates of the central “ partial point ”. while the foregoing description and drawings represent the present invention , it will be obvious to those skilled in the art that various changes may be made therein without departing from the true spirit and scope of the present invention .

US-79219206-A

a pitting machine comprises a punching head that performs a curvilinear oscillatory movement in synchronization with the translation movement of fruits to be pitted , in particular for use in industries that process food such as pitted dried or dehydrated plums and which are currently performing manual operations or using rudimentary equipment .

said traction means are constituted by a main axis 3 mounted on bearings 2 . said main axis 3 supports gears 4 on each of the ends thereof , each of said gears pull a pair of closed loop parallel chains 5 which connect said main axis 3 to rear axis 6 , intermediate axis 7 and return axis 8 . main axis 3 has a crown or gear 9 controlled or driven by a gear or pinion 10 which is mounted on a central axis 12 by means of a chain 11 . said central axis 12 is mounted on bearings 13 and is arranged under the pitting area 23 . said central axis 12 is controlled or driven through a gear 14 by means of chain 15 of a driving pinion 16 which is directly coupled to the overstress clutch of a reducing motor 18 . traction means are in turn associated to a closed loop conveyor belt 17 housing fruit 25 containers 19 . said containers 19 are displaced from the loading area consisting of a loading bin 20 , passing along the fruit 25 selection means constituted by rejecting brushes 21 , which allow entering of one fruit 25 into each container 19 of the conveyor belt 17 , passing then through fruit orientation means 22 and up to the pitting area 23 where there are separation means 30 and a plurality of punches 24 possessing an oscillatory movement which is almost perpendicular to conveyor belt 17 . said punches 24 pierce moving fruits 25 and remove pits 26 . conveyor belt 17 continues advancing towards the front of the machine and commences its return at the unloading area 28 , where pitted fruits 25 fall under gravity . unloading area 28 comprises an unloading bin 27 complemented by a sector 29 comprising a cam 31 which confers vertical vibration onto conveyor belt 17 in order for it to expel those fruits 25 not expelled at the unloading bin 27 itself . selection means are conformed by rejecting brushes 21 which are driven through said intermediate axis 7 , which is actuated by effect of the same conveyor belt 17 which rests its chains 5 on gears 32 . said intermediate axis 7 bears another gear 33 mounted over it and which through chain 34 confers rotation to smaller gears 35 in turn mounted on the rejecting brushes axes 21 . on the other hand , there are also included vibration means at the loading area which favour entering of each of the fruits 25 into containers 19 . said vibration means are comprised of a motor 36 associated to a pulley 37 that through belt 38 rotates vibration axis 39 through pulley 40 . vibration axis 39 rests on bearings 41 and possesses in the central part thereof an eccentric counterweight 42 that upon rotation generates an orbital vibration which is transmitted to vibration axis 39 and this in turn to bearings 41 which are associated to tracks 43 where conveyor belt 17 is supported . said tracks 43 also rest on regulators 44 which purpose is to limit and regulate vibration of tracks 43 and thus obtain the maximum yield in terms of fruits 25 entering into each of the containers 19 . on the other side , separation means 30 are placed above said fruit 25 containers 19 and under said punching head 61 . said separation means 30 are constituted by a plurality of parallel flat rods 66 spaced one from each other by a distance smaller than the diameter of each container 19 and larger than the diameter of each punch 24 . separation means 30 allow separation of fruits 25 from punches 24 after pitting . as can be seen on fig3 , orientation means are constituted by a tablet 45 laterally associated to said chains 5 by means of screws 47 . said tablet 45 houses rubber supports 46 and is associated to bearings 48 by means of special screws 49 which are adjusted on said screw 47 head . these bearings 48 support prune buckets 50 rigidly connected to an axis 51 and the latter , in turn , is rigidly connected to pushing die 52 on one end and axially slidable on the other . this kind of connection allows axial opposite movement between pushing dies 52 of both ends of said axis 51 . axial movement of each prune bucket 50 / axis 51 assembly is enabled through rolls 53 and bolts 54 . upon the translation movement of conveyor belt 17 , roll 53 rests on cam tracks 55 and thus compresses or reduces the space between prune buckets 50 , and by means of a spring 56 it is able to alternatively open and close , and in this manner there is attained , first , orientation of fruit 25 and then holding thereof upon pitting and further , the discharge thereof after pitting is accomplished . optionally and as a complement a tablet cover 57 may be included , which cover is screwed on bearings 48 . as previously mentioned , one of the ends of punching header 61 bears spring - free punches 24 , which carry out an orbital type movement and during their trajectory should pierce fruits 25 within full translation movement . in order to attain such a synchronism , as can be seen on fig4 , the inventive machine has the following combination of mechanical means : at least two eccentrics 59 mounted on a central axis 12 arranged under the pitting area 23 , said at least two eccentrics 59 being located externally to said chassis 1 , and each of them being articulately connected to at least one crankshaft 58 and to one end of horizontal connecting rod 64 , said crankshaft 58 being in turn connected to one end of a vertical connecting rod 60 and the other end of said vertical connecting rod 60 being articulately connected to one of the sides of the end of said punching head 61 which includes punches 24 , each of the sides of the other end of said punching head 61 being articulated to one of the ends of an oscillating post 62 placed externally to said chassis 1 , and the other end of said oscillating post 62 being articulated to a pivot axis 63 rigidly mounted on said chassis 1 ; both oscillating posts 62 also comprising at some point between their ends a projection 65 on which the other end of said horizontal connecting rod 64 articulates . this combination of means , and more particularly the location of pivot axis 63 allows punches 24 to perform a curvilinear oscillating movement which is not perpendicular to the machine direction but does not affect pitting efficiency . in fact , said oscillating movement draws a large radius curve , which renders said movement substantially rectilinear . it may also be appreciated on said fig4 an orbital diagram illustrating the trajectory of the end of a punch 24 .

US-14767805-A

an optical alignment system using at least one ccd array for positioning an instrument in a chosen relationship to an object is disclosed . means for &# 34 ; electronically &# 34 ; aligning the optical components and providing a macro view of the object on a crt without additional illumination are also disclosed . alignment may be achieved manually , if the operator observes the position of symbols on a crt that move in response to movement of the instrument by the operator using a joystick , or automatically using information provided by the array .

referring to fig1 an ophthalmic instrument shown generally at 1 , has a base 2 with a frame 3 to provide a steadying rest for the head of a patient . the test mechanism ( not shown ) of instrument 1 is contained within housing 4 movably mounted on base 2 . member 5 represents a portion of the instrument to be positioned in a predetermined relationship to the patient &# 39 ; s eye . to accomplish this relationship , the operator uses joystick 6 to move housing 4 three dimensionally on base 2 , while watching the resulting movement of symbols ( not shown ) relative to reticle 7 on screen 8 . when the operator has achieved alignment by moving housing 4 until the symbols are contained within or superimposed on reticle 7 , he presses button 9 on joystick 6 to initiate the desired test . referring to fig2 eye 10 is flooded with light on one side of its axis 12 by light from source 14 and on the other side of its axis with light from source 16 . sources 14 and 16 may conveniently be leds emitting light in the infrared region . the advantage of infrared illumination resides in the insensitivity of the human eye to the infrared region . this avoids any discomfort , when high levels of radiation are required . center ray 18 from source 14 is reflected from cornea vertex 20 along path 22 and sequentially through pinhole occluder 24 , and lens 26 to ccd array 28 . similarly , center ray 30 of source 16 is reflected from cornea vertex 20 along path 32 and sequentially through pinhole occluder 34 and lens 36 to ccd array 38 . a small bundle of rays closely adjacent to center rays 18 and 30 will remain substantially parallel thereto and pass along with the respective center ray through the respective pinhole occluder . a portion of the remaining light from each of sources 14 and 16 is reflected toward lens 40 to produce an image of eye 10 on video image detector 44 . in the case of a non - contact tonometer , lens 40 is located behind air - pulse discharge tube 42 . the alignment system components may be conveniently mounted on plate 46 which has a plurality of mounting members 48 for holding sources 14 and 16 ; pinhole occluders 24 and 34 ; lenses 26 and 36 ; ccd arrays 28 and 38 ; objective lens 40 and video image detector 44 . one advantage of the present invention which may be realized is that mounting members 48 do not require precise machining to close tolerances in order to provide exact angles and dimensions , since normal variations may be corrected electronically rather than optically . electronic correction is achieved by positioning the instrument , containing the alignment system of the present invention , in the chosen relationship to the object such as a replica of a human eye . if the spot produced by occluders 24 and 34 is relatively close , e . g . & lt ; 0 . 1 mm , to the center of the respective arrays , the xy location of the spot is conveniently stored in a device such as an eerom . however , gross errors may be compensated for by moving the ccd to a new position in a plane normal to the respective paths 22 and 32 . the reference locations ( the locations of the respective spots on the ccd arrays ) are thereafter considered to be the &# 34 ; center &# 34 ; of the respective ccd array . referring now to fig3 another embodiment of the present invention is illustrated . light from sources 14 and 16 is reflected back from corneal surface 120 in the same general direction from which it came along paths 122 and 132 , respectively to ccd arrays 28 and 38 . in other respects , this embodiment operates in substantially the same manner as the embodiment of fig2 . fig4 illustrates still another embodiment . light from sources 14 and 16 is reflected by the respective sides of cornea 120 along paths 222 and 232 toward objective 20 . beam splitter 250 diverts a portion of the light toward occluder 224 having two pinholes 252 and 254 . light passing through pinholes 252 and 254 is imaged by lens 226 on ccd array 228 . in this embodiment , sources 14 and 16 are alternately strobed in order for ccd array 228 to identify which of sources 14 and 16 produced the spot being observed . referring again to fig2 signals identifying the xy location of the spots on ccd arrays 28 and 38 are delivered to ccd evaluating electronics 56 by leads 58 and 60 . electronics 56 compares the reported xy position of the spot to the stored reference location for each ccd array . an output from electronics 56 representing the location of the spot relative to the reference location is provided to display electronics 62 which in turn drives crt 66 through leads 64 to provide symbols on crt 66 . the signal from video image detector 44 is similarly provided to display electronics 62 through lead 68 in order to provide a macro image of the eye on crt 66 . the location of the spot on a ccd array can be identified conveniently using a raster sweep of the ccd pixel signals . the signal and location values of the first pixel are stored until a higher signal value is encountered during the sweep . each time a higher signal value is encountered , the new pixel signal and location values are stored replacing the values previously stored until the sweep is complete . the location values stored at the end of the sweep identify the center of the spot on the respective ccd array . if a minimum signal threshold is set , artifacts , such as glare spots that can result from illumination for the macro view , are ignored by the system . when an optical system of the type illustrated by fig4 is used , the timing of the raster sweep of ccd array 228 is synchronized with the strobe of sources 14 and 16 in order that even raster sweeps relate to one source and odd raster sweeps to the other . a preferred optical system according to fig2 is diagrammatically presented in fig5 and has the following values : ______________________________________ele - index ofment radius thickness spacing refraction______________________________________14 s1 = 55 . 020 s2 = 60 . 024 d1 = 0 . 5 t1 = 0 . 5 s3 = 0 . 5r1 = 30 . 48926 t2 = 3 . 00 n1 = 1 . 5168r2 = - 30 . 489 s4 = 60 . 02816 s5 = 55 . 020 s6 = 60 . 034 d2 = 0 . 5 t3 = 0 . 5 s7 = 0 . 5r3 = 30 . 48936 t4 = 3 . 00 n2 = 1 . 5168r4 = - 30 . 489 . s8 = 60 . 03820 s9 = 12 . 3042 s10 = 87 . 7r5 = 50 . 81340 t5 = 5 . 00 n3 = 1 . 5168r6 = - 50 . 813 s11 = 100 . 044______________________________________ wherein , radii , r1 to r6 , thicknesses , t1 to t5 , spacings , s1 to s11 , pinhole diameters , d1 and d2 , are in mm ; radii having their center of curvature on the eye 10 side of the lens are indicated by a minus (-) sign ; and indexes of refraction , n1 to n3 , are absolute values . the pinhole - lens combinations can be replaced by small diameter lenses if desired . the model texas instruments tc211 ccd array is suitable for practicing this invention . the amount of instrument movement necessary to obtain distance ( s9 ) of object 10 from component 42 of the instrument being aligned can easily be calculated using the location value related to movement in a direction parallel to the plane containing the optical elements of the alignment system obtained from each ccd array . for example , if α = 45 ° and α &# 39 ;= 42 ° and x and x &# 39 ; are the relative locations in the directions indicated by the arrows labeled x and x &# 39 ; in fig5 δs9 =( x - x )-( x &# 39 ;- x &# 39 ;), where x and x &# 39 ; are the reference locations for the respective ccd array . the amount of movement can be presented two dimensionally , for example on the crt , by using one symbol for the horizonal ( x ) axis and another for the vertical ( y ) axis . the space between the symbols can be used to represent δs9 . when δs9 = 0 , the two symbols are superimposed . a simpler and more user - friendly procedure is the use of a cursor which moves above the screen center , if the instrument is too far from the object and below the screen center , if the instrument is too close . the cursor type of presentation is preferred because it has several advantages . one advantage is the ease with which the user can recognize whether the instrument is too close or too far away . another advantage is that the x and y positions can be displayed by means that do not require superimposition of symbols to indicate correct positioning . for example , a narrow vertical line can be used to represent the relative horizonal position and a narrow horizonal line to indicate the relative vertical position , while the cursor indicates the relative distance from the object . prior art alignment systems did not permit a choice of display formats . referring now to fig6 signals from timing generator 350 drive x / y counters 352 , the raster sweep of ccd array 354 and timing of a / d converter 358 . each pixel signal is amplified by amplifier 356 , sent to a / d converter 358 , whose output is evaluated by peak detector 360 . the outputs of x / y counters 352 are stored by latches 362 , each time peak detector 360 signals a new high for the pixel signals from ccd array 354 . obviously , each array requires an amplifier , a / d converter , peak detector and output latches . the outputs of latches 362 are evaluated at the end of each raster sweep by alignment and calibration electronics 364 which updates operator display 366 . if an automatic alignment system is desired , motor controllers 368 and motors 370 , 372 and 374 can be added as shown in fig7 . the value of δz is determined as explained previously for the determination of δs9 , ## equ1 ## these δ values are provided to motor controllers 368 by alignment and calibration electronics 364 to position the system until all three δ &# 39 ; s = 0 .

US-22848288-A

an hnrnp a2 * protein , including an amino acid sequence represented by seq id no : 1 . the protein is a complete protein , a protein fragment , a protein analog or a protein derivative .

for further illustrating the invention , experiments detailing heterogeneous nuclear ribonucleoprotein a2 * ( hnrnp a2 *), a nucleic acid encoding the protein and uses thereof are described below . it should be noted that the following examples are intended to describe and not to limit the invention . research ideas of the invention are illustrated by experiments to reveal the hnrnp a2 * protein purification and analyze principle of g - quadruplex unfolding by hnrnp a2 *, etc . nuclear matrix proteins responsible for maintaining chromosome territories were isolated from rat liver ( ma h , siegel a j , berezney r ( 1999 ) association of chromosome territories with the nuclear matrix . disruption of human chromosome territories correlates with the release of a subset of nuclear matrix proteins . j cell biol 146 : 531 - 542 ). the nuclear matrix proteins were used for affinity purification of biotin - labeled telomeric dna oligonucleotides ( ttaggg ) 3 conjugated to streptavidin - coated agarose beads . the purification was performed in the presence of yeast trna and sonicated salmon sperm dna . binding proteins were eluted from beads with a 2 m nacl solution . the affinity purified proteins were resolved on 12 % sodium dodecyl sulfate polyacrylamide gel electrophoresis ( sds / page ). a band corresponding to a 28 - kda protein was excised from gel and subjected to tryptic digestion , followed by malditof mass spectrometric analysis . data obtained were submitted to the ms - fit web site ( http :// prospector . ucsf . edu / prospector / mshome . htm ) 9 segment data were returned , which indicates they matched with the segments of the hnrnpa2 protein . dnase - treated mrna from rat liver was reverse - transcribed into cdna using a poly - t primer . an oligonucleotide complementary to a sequence of an exon 7 of hnrnp a2 was annealed to cdna of hnrnp a2 , and an annealed part was cleaved by an endonuclease xhoi . cdna obtained from the reverse - transcription of mrna of hnrnp a2 * was then amplified by rt - pcr with primers 5 ′- tagctagcatggagagagaa aaggaa - 3 ′ ( seq id no : 23 ) and 5 ′- aagagctctcaatatcggctccttcca - 3 ′ ( seq id no : 24 ) using exon removal method ( wang f , zhao y , hao y h , tan z ( 2008 ) identification of low - abundance alternatively spliced mrna variants by exon exclusive reverse transcriptase polymerase chain reaction . anal biochem 383 : 307 - 310 ). the amplicon was cloned into the nhei / saci site of pet - 28b , and an obtained plasmid is transformed into the e . coli strain bl21 ( de3 ) ( provided by beijing bioteke biotechnology co . ltd ). transformed cells were cultured in an lb medium at 37 ° c . for 4 hrs . 1 mm of isopropyl - β - d - thiogalactoside was used to induce protein expression of hnrnp a2 * with a his 6 tag . after 2 hrs induction , e . coli cells were harvested and lysed by sonication in one pellet volume of a buffer a [ 50 mm nah 2 po 4 ( ph 8 . 0 ), 300 mm nacl , 40 mm imidazole , 1 mm dithiothreitol ( dtt ), and 1 mm phenylmethylsulfonyl fluoride ] at 4 ° c . a resulting cell lysate was centrifuged in the presence of a 20000 × g at 4 ° c . for 20 min , and an obtained supernatant was loaded on an affinity histrap hp column . after washing with the buffer a for 10 - column volume , the his - hnrnp a2 * was eluted from the column with a buffer b [ 50 mm nah 2 po 4 ( ph 8 . 0 ), 300 mm nacl , and 40 mm imidazole ]. the rtr sequence was performed with reverse transcription polymerase chain reaction ( rt - pcr ) amplification and cloned into a pmd19 - t plasmid . restriction enzyme cleavage sites existing in the rtr sequence were cleaved by restriction endonucleases crf 131 , rsa i , fspb i , and bamh i . the plasmid was linearized . the linearized plasmid was performed with transcription with a t7 transcription kit , and a transcript product was labeled with [ γ - 32 p ] atp in the presence of a t4 polynucleotide kinase . 80 nm oligonucleotides having 5 ′ ends labeled with [ γ - 32 p ] atp ( 32 p - labeled oligonucleotides ) were incubated with 400 nm recombinant hnrnp a2 * at 4 ° c . for 30 min in a binding buffer [ 10 mm tris ( hydroxymethyl ) metyl aminomethane ( tris ) ( ph 8 . 0 ), 1 mm ethylenediaminetetraacetic acid ( edta ), and 150 mm kcl ] and resolved on a 8 % ( wt / vol ) native page gel . the gel was then visualized by phosphoimaging using a typhoon phosphorimager . 50 nm 32 p - labeled oligonucleotides were incubated with 1 . 5 μm hnrnp a2 * or pot1 at 4 ° c . for 15 min in the binding buffer [ 10 mm tris ( ph 8 . 0 ), 1 mm edta , and 150 mm kcl ], then incubated at 4 ° c . for 1 mm after being added with 0 . 5 u of t4 polymerase and 1 μl 10 × endonuclease buffer [ 330 mm tris - acetate ( ph 7 . 8 ), 100 mm mg ( ch 3 co 2 ) 2 , and 5 mm dtt ] for carrying out cleavage . the reaction was stopped by phenol - chloroform extraction , followed by ethanol precipitation . the products were resolved on a 19 % ( wt / vol ) polyacrylamide gel containing 7 m urea . hela cells or rat rrl - 3a cells extract was prepared as described ( kim n w , piatyszek m a , prowse k r , harley c b , west m d , et al . ( 1994 ) specific association of human telomerase activity with immortal cells and cancer . science 266 : 2011 - 2015 ). the cell extract was performed with affinity purification using ( ttaggg ) 3 having the 5 ′ end labeled with a biotin conjugated to a streptavidin - agarose to remove guanine - rich telomeric dna sequence binding protein . the analysis of catalytic activity of telomerase was carried out with telomeric repeat amplification protocol ( trap ) using either ts ( 5 ′- aatccgtcgagcagagtt - 3 ′) ( seq id no : 25 ) or tsg4 ( 5 ′- gggctagggctagggctagggagtt - 3 ′) ( seq id no : 26 ) as substrates . the telomerase substrates were incubated in the presence of different concentrations of hnrnp a2 * or pot1 the telomerase extract from 5 , 000 cells in 50 μl volume . after being added with 0 . 25 mm dntp , extension reaction was carried out at 30 ° c . ( ts ) or 37 ° c . ( tsg4 ) for 10 min and stopped by heating the sample to 75 ° c . for 5 min . phenol - chloroform extraction and ethanol precipitation were conducted in the presence of internal reference standard sequences ( 5 ′- aatccgtcgagcagagttaaa aggccgagaagcgat - 3 ′ ( seq id no : 27 ) and 5 ′- atcgcttctcggcctttt - 3 ′ ( seq id no : 28 ) were used for ts substrate , and 5 ′- gggctagggctagggctaggg agttaagcggccgagaagcgag - 3 ′ ( seq id no : 29 ) and 5 ′- ctcgcttctcggc cgctt - 3 ′ ( seq id no : 30 ) were used for tsg4 substrate ). obtained products were amplified by pcr ( 33 cycles : 94 ° c . for 30 s ; 59 ° c . for 30 s ), in which ts and 5 ′- gcgcg gcttacccttacccttaccctaacc - 3 ′ ( seq id no : 31 ) were used as primers to amplify the ts substrate , and tsg4 and 5 ′- gtgcccttacccttacccttaccctaa - 3 ′ ( seq id no : 32 ) were used as primers to amplify the tsg4 substrate . the pcr products were resolved on a 12 % native polyacrylamide gel , stained with ethidium bromide , and visualized on a chemilmager 5500 . telomerase activity was represented by a multiple of that of the control group of hnrnp a2 * or pot1 based on the equation ( tp / tpo ( iso / is ) where tpo and iso represent a total amount of a telomerase catalytic product and a total amount of an internal reference product , respectively , and tp and is represent total amounts of the product obtained in the presence of hnrnp a2 * and pot1 , respectively . a modified version of trap assay as described ( xue y , kan z y , wang q , yao y , liu j , et al . ( 2007 ) human telomeric dna forms parallel - stranded intramolecular g - quadruplex in k + solution under molecular crowding condition . j am chem soc 129 : 11185 - 11191 ) was conducted using tsnt as the internal reference to analyze telomerase processivity . mts substrate was incubated in a 50 μl volume containing a telomerase extract from 5 , 000 cells , 0 . 25 mm dntp , and 0 . 5 μm hnrnp a2 * or pot1 in the presence or absence of 40 % peg - 200 for 10 min , and the reaction was stopped by heating the sample to 75 ° c . for 5 min . thereafter , phenol - chloroform extraction and ethanol precipitation were conducted after added with internal reference sequences ( 5 ′- agcatccgtcgagcagagttaaaaggccgagaagcgat - 3 ′ ( seq id no : 33 ) and 5 ′- atcgcttctcggcctttt - 3 ′) ( seq id no : 28 ). obtained oligonucleotides were amplified by pcr ( 2 cycles : 94 ° c . for 30 s , 55 ° c . for 60 s , and 72 ° c . for 90 s ; and 29 cycles : 94 ° c . for 30 s , 63 ° c . for 30 s , and 72 ° c . for 30 s ) in the presence of 10 pmol rp , 0 . 02 pmol rpc3 g , and 1 u taq dna polymerase . the pcr products were resolved on the 12 % native polyacrylamide gel , stained with ethidium bromide , and visualized on a chemilmager 5500 . subcellular fractions were acquired as described ( luderus m e , van steensel b , chong l , sibon o c , cremers f f , et al . ( 1996 ) structure , subnuclear distribution , and nuclear matrix association of the mammalian telomeric complex . j cell biol 135 : 867 - 881 ) with minor modification . briefly , hnrnp a2 * transfected brl - 3a cells was washed twice by a cold earle &# 39 ; s solution and suspended in a 10 times volume of rsb solution [ 0 . 1 m nacl , 1 . 5 mm magnesium chloride , 10 mm tris - hcl ( ph 7 . 4 ), and 0 . 1 % digitonin ] at 4 ° c . for 10 min . the cells were lysed by passing through a 19 . 5 - gauge needle five times . the cell lysate was centrifuged at 23000 × g for 30 min in a rsb solution containing 10 % glycerine . a supernatant from the centrifuge was collected as a cytoplasmic extract . nuclei collected from a precipitation was incubated in the rsb solution at 37 ° c . for 20 mm and lysed with an lis solution [ 10 mm lis , 100 mm lithium acetate ( liac ), 1 mm edta , 0 . 1 % digitonin , 0 . 05 mm spermine , 0 . 125 mm spermidine , 0 . 25 mm pmsf , and 20 mm hepes - koh ( ph 7 . 4 )] at the room temperature for 20 min with 2 × 10 6 cells per milliliter the lis solution . lis - treated nuclei were then centrifuged at 20000 × g for 20 min , and a supernatant and a pellet were collected as a nucleoplasmic and nuclear matrix fraction , respectively . proteins of the three cell ingredients were resolved on the 10 % sds / page and transferred to a nitrocellulose membrane . ha - hnrnp a2 * and hnrnpa2 / b1 were detected by mouse anti - ha monoclonal antibody and goat anti - hnrnp a2 / b1 polyclonal antibody , respectively . organs were taken immediately after male rats were killed for analyzing telomerase activity and extracting rna . for telomerase activity assay , tissues to be tested were added with the lysate with 0 . 5 milligram tissues per millimeter telomerase extract lysate , homogenized with a sterile duall tissue grinder , and incubated for 30 min on ice . cell lysate was centrifuged at 12000 × g for 30 min at 4 ° c . the resulting supernatants were frozen in liquid nitrogen , and stored at − 80 ° c . until use . protein concentration of the supernatants was determined using bradford assay . total protein ( 200 ng ) was used in each trap assay . an amount of rna was detected by rt - pcr . 0 . 05 μg of total rna was conducted with reverse transcription with mmlv reverse transcriptase and pcr amplification . brl - 3a rat and hela cells were cultured at 37 ° c . under 5 % co 2 in dmem medium supplemented with 10 % fbs , penicillin ( 100 units / ml ), and streptomycin ( 0 . 1 mg / ml ). hnrnp a2 * cdna was amplified by pcr with hm6 forward primer 5 ′- gatggt accatggagagagaaaaggaacagttc - 3 ′ ( seq id no : 34 ) and hm6 antisense primer 5 ′- gacgaattcattctcaatatcggctccttccac - 3 ′ ( seq id no : 35 ), and the amplified fragment was inserted into the kpni / ecori sites of the phm6 expression vector . the ha - hnrnp a2 * segment was then amplified by the t7 promoter forward primer 5 ′- taatacgagtcactataggga - 3 ′ ( seq id no : 36 ) and the hm6 antisense primer and was cloned into the pgem - t vector . ha - hnrnp a2 * could then be subcloned into the noti - ecori sites of pqcxin retroviral vector ( for brl - 3a cells ) or ecorv - kpni sites of pmscv - ithyl - 1 retroviral vector ( for hela cells ). the recombinant pgem - t ha - hnrnp a2 * vector was transfected into ecopack 2 - 293 cells and pmscvithyl - 1 ha - hnrnp a2 * was transfected together with pgagpol and pmd . g - vsvg - env into 293t cells to produce retrovirus . medium containing the virus was collected 48 h after the transfection . rat brl - 3a at about 70 % confluence were exposed to a mixture of a virus - containing medium and a fresh culture medium with a ratio of 1 : 1 for 12 h . the culture medium for brl - 3a cells was then replaced by a fresh medium containing 800 μg / ml g418 , and the culture medium for hela cells was then replaced by a fresh medium containing 300 μg / ml g418 . brl - 3a cells were cultivated in the new medium for two weeks , and the hela cells were cultivated in the concentration of 100 μg / ml g418 . the brl - 3a cells were cloned cells whereas the hela cells were non - cloned cells . brl - 3a cells growing on coverslips with were fixed for 8 min at the room temperature in a pbs ( ph 7 . 4 ) containing 2 % paraformaldehyde and permeabilized in a pbs buffer containing 0 . 5 % triton x - 100 in pbs . the brl - 3a cells on the coverslips were then blocked with 10 % serum from the same species as the secondary antibody . primary antibodies used included goat or rabbit polyclonal anti - tert , rabbit polyclonal anti - coilin , mouse monoclonal anti - ha , rabbit polyclonal anti - hrap1 . secondary antibodies included cy3 - conjugated donkey anti - goat , fluorescein - conjugated goat or donkey anti - mouse , and dylight649 - conjugated donkey anti - rabbit at the dilutions recommended by the manufacturers . the incubation time was 1 h for the primary antibody and 45 min for the secondary antibody at the room temperature , followed by pbs washes ( four times ; 5 min each ). coverslips were mounted with vectashield mounting medium containing 0 . 5 μg / ml dapi . images were acquired with a zeiss 510 meta confocal microscope using a 100 × oil objective . recombinant human pot1 protein was prepared as described ( kelleher c , kurth i , lingner j ( 2005 ) human protection of telomeres 1 ( pot1 ) is a negative regulator of telomerase activity in vitro . mol cell biol 25 : 808 - 818 .). the plasmid pet - 14 - pot1 ( gift from joachim lingner , swiss institute for experimental cancer research , lausanne , switzerland ) was transformed into the e . coli strain bl21 ( de3 ). the cells were grown in a tb medium supplemented with 1 % glucose and 0 . 05 mg / ml carbenicillin at 37 ° c . for 5 h . pot1 expression was induced with 5 μm isopropyl thiogalactoside for an additional 2 h at 25 ° c . cells were harvested and suspended in one pellet volume of a buffer c [ 20 mm nah 2 po 4 ( ph 8 . 0 ), 200 mm nacl , 0 . 2 % tween - 20 , 10 mm imidazole , 20 % glycerol , and 5 mm β - mercaptoethanol ] containing 1 mg / ml of lysozyme . cells were allowed to stand at 4 ° c . for 20 min and sonicated . a lysate was centrifuged at 20 , 000 × g for 20 min at 4 ° c ., and a supernatant was loaded on the affinity histrap hp column after washing with the buffer a for 10 - column volume , the his - pot1 was eluted from the column with the buffer c containing 400 mm imidazole . purified proteins were dialyzed against a buffer d [ 20 mm nah 2 po 4 ( ph 8 . 0 ), 50 mm nacl , 0 . 2 % tween - 20 , 20 % glycerol , and 5 mm β - mercaptoethanol ] and stored at − 70 ° c . oligonucleotide ggg ( ttaggg ) 3 ( seq id no : 37 ) labeled with a fluorescein ( fam ) ( donor ) at the 5 ′ end and a tetramethylrhodamine ( tmr ) ( acceptor ) at the 3 ′ end was mixed with 200 nm hnrnp a2 * or 1 μm cdna ccc ( taaccc ) 3 ( seq id no : 38 ) in a tris - edta ( il ) buffer ( ph 8 . 0 ) containing 150 mm kcl . the kinetics of g - quadruplex opening upon addition of hnrnp a2 * or cdna was immediately monitored at 25 ° c . by recording the donor fluorescence at 515 nm using a slit of 5 nm and an excitation wavelength of 480 nm . pcr amplification of hnrnp a2 * in rat , mouse , and human cells pcr was conducted in 25 μl volume with cdna transcribed using a poly ( t ) primer from 0 . 2 μg of rna of rat brl - 3a cells , hela cells , and mouse liver , respectively . amplification was carried out with an initial denaturation at 94 ° c . for 2 min , followed by 32 cycles for human and mouse samples ( 29 cycles for rat samples ) of 94 ° c . for 30 s , 62 ° c . for 30 s , and 72 ° c . for 30 s . telomerase pull - down was conducted as described ( eversole a , maizels n ( 2000 ) in vitro properties of the conserved mammalian protein hnrnp d suggest a role in telomere maintenance . mol cell biol 20 : 5425 - 5432 .) with minor modifications . brl - 3a cells ( lx 10 6 ) were lysed in 100 μl of a chaps buffer [ 0 . 5 % chaps , 10 mm tris ( ph 8 . 0 ), 1 mm mgcl2 , and 0 . 1 mm pmsf ]. a total of 30 μg of recombinant his - tagged hnrnp a2 * was immobilized to a nickel resin . the beads were blocked with 1 % bsa at 4 ° c ., followed by two washes with a cold chaps buffer , and 100 μl of cell lysate and 100 μl of the chaps buffer were added and incubated at 4 ° c . for 2 h . after three times washing with the cold chaps buffer , the beads were used to detect telomerase activity using the trap method . untreated beads or cell extract pretreated with 200 μg / ml rnase a for 30 min were used as controls . the average length of telomeric restriction fragment ( trf ) was measured as described ( zhao y , sfeir a j , zou y , buseman c m , chow t t , et al . ( 2009 ) telomere extension occurs at most chromosome ends and is uncoupled from fill - in in human cancer cells . cell 138 : 463 - 475 .). a short interfering ( si ) rna duplex targeting rat tert sequence ( gccagcatg ttaggaagaa ) ( seq id no : 39 ) was provided by ribobio co ., ltd ( guangzhou , china ). nontargeting sirna was used as a control . cells growing on a coverslip of a e - well cell culture plate were incubated with 50 nm sirna in 2 ml of medium containing lipofectamine 2000 . cells were then examined for the expression of tert protein using immunofluorescence microscope . a primary antibody pert ( d - 16 ) utilized was provided by santa cruz co ., ltd . an fitc - labeled donkey anti - goat secondary antibody was provided by protein tech group , inc . identification of hnrnp a2 *, a single - stranded telomeric dna - binding protein from the nuclear matrix . the nuclear matrix was prepared , and the single - stranded telomeric dna - binding protein was isolated by affinity purification and then resolved on the sds / page ( fig1 a , left ). binding activities of the telomere - binding proteins was identified by southwestern blot using the 32 p - labeled ( ttaggg ) 3 probe ( fig1 a , right ). the most abundant protein , with a molecular mass of 28 kda , was excised from the gel and analyzed by maldi - tof mass spectrometry ( table 1 ). nine of the tryptic peptides from this protein mapped to hnrnp a2 , with eight peptides being found within the n - terminal half and one near the c terminus ( fig1 b ). because the peptides span a region of hnrnp a2 greater than 28 kda , it was speculated that the newly isolated telomere - binding protein is a splice variant of hnrnp a2 ( 36 kd ) lacking these exons . to test this , a newly developed “ exon - exclusive rt - pcr ” ( wang f , zhao y , hao y h , tan z ( 2008 ) identification of low - abundance alternatively spliced mrna variants by exon exclusive reverse transcriptase polymerase chain reaction . anal biochem 383 : 307 - 310 ) was used to specifically amplify the variant ( fig1 c ). sequence analysis of the pcr product confirmed it is an hnrnp a2 isoform lacking exons 7 - 9 ( fig1 d ). hnrnp a2 * is a conserved protein that is expressed in rat , mouse , and human cells ( fig1 e ). the cdna encoding hnrnp a2 * was cloned and expressed in escherichia coli , producing a recombinant protein with the expected molecular mass ( fig2 a ). the exons 7 - 9 coded the glycine - rich domain ( grd ) and provided additional dna / rna binding sites in addition to two rna recognition sites ( rrm ). the emsa result revealed that the deletion of exons 7 - 9 of hnrnp a2 * leads the high binding specificity to the telomeric dna and that hnrnp a2 * binds the ssdna telomeric repeat ( ttaggg ) 3 with high specificity but has very low or no binding affinity for ( taaggg ) 3 , ( ttgggg ) 3 , ( tta gag ) 3 , or double - stranded ( ttaggg ) 3 ( fig2 c ). this is in contrast to hnrnp which has a broad dna - binding specificity with the consensus sequence n ( a , c , t )( c , t )( a , g ) g ( c , g , t )( a , t ) nnn . results of additional emsa experiments using different sizes of telomeric dna revealed a minimal binding site ( mbs ) of 5 ′- tagggttagg - 3 ′ ( seq id no : 13 ) for hnrnp a2 * ( fig2 d ), and this sequence resembles the mbs of human pot1 except that it is 1 nt longer at the 3 ′ end . the binding specificity of hnrnp a2 * was further verified by constructing 10 mutant variants of the mbs , each carrying a single mutation to cytosine at each nucleotide . all the mutations within the mbs abolished the bindings except the mutations of thymines in the vicinity of ggg ( fig2 e ). these results further demonstrated the exquisite binding specificity of hnrnp a2 *. mutations outside of the mbs did not affect binding . hnrnp a2 * actively unfolds g - quadruplex , preferentially binds to the mbs at the 3 ′ end of telomeric dna , and exposes a five - nucleotide 3 ′ tail . the interaction between hnrnp a2 * and telomeric g - quadruplex was analyzed using fluorescence resonance energy transfer ( fret ). 5 ′-( gggtta ) 3 ggg - 3 ′ was labeled with fluorescein ( fam ) at the 5 ′ end ( the fret donor ) and tetramethylrhodamine ( tamra ) at the 3 ′ end ( the fret receptor ) ( fig3 a ). when this oligomer forms g - quadruplex , the two fluorophores are closely juxtaposed and fret occurs between the two fluorophores , suppressing the donor fluorescence . when g - quadruplex was incubated with hnrnp a2 *, donor fluorescence increased rapidly , suggesting that hnrnp a2 * promotes g - quadruplex unwinding , which separates the two from each other and weakens the energy transfer from the fret donor to the fret receptor . it was noted that the rate of fluorescence increase and g - quadruplex unwinding in the presence of hnrnp a2 * was much faster than the slow spontaneous unwinding of g - quadruplex in the presence of excess complementary 5 ′- ccc ( attccc ) 3 - 3 ′, which suggests that hnrnp a2 * actively unfolds g - quadruplex , whereas the fret was not altered by hnrnp a2 * when an irrelevant linear and hairpin dna substrate was used ( fig6 a - 6b ). the 3 ′- terminal sequence of most native telomeres is ttag - 3 ′. to compare the binding ability of hnrnp a2 * and pot1 to the 3 ′ end , linear telomeric dna was digested by t4 dna polymerase in the presence of hnrnp a2 * or pot1 . the results show that both hnrnp a2 * and pot1 bind to their respective mbs at the very 3 ′ end when more than one mbs was available , and thus the exposed tail of hnrnp a2 * is gttag - 3 ′ ( fig3 b ), and pot1 protected the entire dna substrate from cleavage ( fig6 c ) importantly , the same 3 ′- end preference and specificity for each protein was observed when the dna substrate was telomeric g - quadruplex ( fig3 c ). these results do not reflect secondary structure in the dna substrate , because they were completely susceptible to digestion by t4 dna polymerase in the absence of protein ( fig6 d ). hnrnp a2 * enhances the catalytic activity and processivity of telomerase in vitro . the exposed tail 5 ′- gttag - 3 ′ of hnrnp a2 * is complementary to and forms watson - crick base pairs with 5 ′- cuaac - 3 ′ in the rna template of vertebrate telomerase . it is , thus , conceivable that the binding of hnrnp a2 * and the tail of the telomere could enhance the telomerase activity . this possibility had been tested in vitro using a conventional trap , and hnrnp a2 * significantly enhanced the activity of human or rat telomerase ( rtr ) ( fig3 d , 7a ). because the trap assay uses a nontelomeric ts substrate , telomerase must synthesize several telomeric repeats before hnrnp a2 * binds and / or g - quadruplex can form . the results suggest that hnrnp a2 * may stimulate telomere extension by inhibiting formation of g - quadruplex and leaving an appropriate 3 ′- terminal sequence available for telomerase binding . in contrast , pot1 does not stimulate telomerase in a trap assay . this result is consistent with a previous study , which reported that pot1 did not stimulate telomerase activity , by a direct , non - pcr - based method using a nontelomeric primer . these data support the proposal that “ pot1 may modulate telomerase activity by regulating the access of telomerase to the primer but not during extension ”. the ability of hnrnp a2 * to unwind telomeric g - quadruplex was also examined by a modified trap assay using tsg4 as a substrate in which a thymidine next to the g - tract was mutated into cytosine so that it forms g - quadruplex but is still recognized by hnrnp a2 * ( fig2 e ). such mutation enables the tsg4 substrate to differ from the extended sequence region , so that pcr amplification can be realized . it was founded from experiments that hnrnp a2 * stimulates the telomerase activity to the tsg4 to a greater extent ( fig3 e , 7b ) compared with the nontelomeric ts substrate ( fig3 d , 7a ), which indicates that hnrnp a2 * promotes telomerase function by unfolding g - quadruplex during telomerase extension . in the contrary , pot1 does not stimulate telomerase activity with either dna substrate ( fig3 e ). although human telomerase can processively add multiple telomeric repeats to a single primer , processive dna synthesis by telomerase is inhibited by g - quadruplex , because it interferes with telomerase translocation . since hnrnp a2 * is capable of effectively unfolding the g - quadruplex , the impact of hnrnp a2 * on telomerase processivity was examined using a modified trap assay . in a dilute solution , telomerase showed a relatively high processivity ( fig3 f , 7c , first lane ). it has been reported previously that in the presence of peg 200 , a crowding agent widely used to mimic the molecularly crowded intracellular environment , the thermal stability of telomere g - quadruplex increases and the processivity of human telomerase decreases . extension was realized in the presence of peg200 , and the processivity was significantly decreased ( second lane ), results of which was similar to the previous reports . hnrnp a2 * stimulated telomerase processivity in the presence of peg 200 ( third lane ), but pot1 did not ( fourth lane ). because both hnrnp a2 * and pot1 can disrupt g - quadruplex , this difference may reflect the fact that hnrnp a2 * exposes a free 3 ′ end when it binds to telomeric dna , but pot1 does not . hnrnp a2 * localizes to the nuclear matrix and associates with telomerase at telomeres and in cajal bodies in vivo . the protein region encoded by exons 7 - 9 in hnrnp a2 , which is missing from hnrnp a2 *, is entirely hydrophilic . as a result , hnrnp a2 * is more hydrophobic than hnrnp a2 . hnrnp a2 localizes predominantly to the nucleoplasm , whereas hnrnp a2 * localizes exclusively to the nuclear matrix proved by western blot . this suggests that hnrnp a2 and hnrnp a2 * have distinct cellular functions . some proteins from the hnrnp family interact directly with telomerase , as well as with telomeric dna , in vitro . it was founded that hnrnp a2 * could pull - down telomerase activity from cell lysate ( fig9 a ) as did hnrnp a2 , demonstrating that hnrnp a2 * can physically interact with telomerase ( fig4 a ). in addition , hnrnp a2 * directly binds the rna component of rtr in vitro ( fig4 b ). this binding is dependent on the size / sequence and possibly the secondary structure of rtr . hnrnp a2 can also interact with the rat telomerase , but the working principle of hnrnp a2 is different from that of hnrnp a2 , because hnrnp a2 binds to the 0 - 269 fragment of rtr ( fig9 b ), whereas hnrnp a2 * does not ( fig4 b ). to examine whether hnrnp a2 * interacts with telomeres and telomerase in vivo , ha - tagged hnrnp a2 * was expressed in rat cells and immunofluorescence experiments were performed to localize the expressions . consistent to experiment results in vitro , it was showed that a fraction of hnrnp a2 * colocalized with rap1 and with tert ( fig1 a , top and middle images ). fluorescence reduction of tert by sirna ( fig1 b ) and selective staining of ha - hnrnp a2 *- expressing cells ( fig1 c ) respectively corroborated that the antibody has specificity to the ha - hnrnp a2 * and tert . interestingly , it was also founded that hnrnp a2 * can also colocalize with cajal bodies ( fig1 a , bottom images ). because cajal bodies are involved in the processing and positioning of telomerase at telomeres , it was hypothesized that hnrnp a2 * may play a role in these processes . these interactions were further explored using three - color immunofluorescence . when hnrnp a2 *, tert , and telomere were detected at the same time , most hnrnp a2 */ telomere foci was often positive for telomerase ( fig4 c top images , fig1 a ). out of the 39 hnrnp a2 */ rap1 foci observed , 37 were also positive for telomerase ( hnrnp a2 */ rap1 / tert foci ). the hnrnp a2 */ tert / cajal bodies forci also revealed a close relation between hnrnp a2 * and the telomerase . out of the 21 hnrnp a2 */ cajal bodies foci observed , 20 were found existing in the form of hnrnp a2 */ cajal bodies / tert complexes ( fig4 c bottom images , fig1 b ). about half of the tert at telomeres or in cajal bodies was associated with hnrnp a2 *. the prevalent colocalization of hnrnp a2 * with telomerase at telomeres and in cajal bodies strongly suggests that hnrnp a2 * is a close partner of telomerase . it is possible that hnrnp a2 * is assembled into the telomerase holoenzyme at cajal bodies and delivered to telomeres . the finding that the binding of hnrnp a2 * with rtr ( fig4 b ) involves the 3 ′ region of rtr ( 269 - 419 nt ), which contains the cajal body box ( cab ) motif responsible for its mobilization to the cajal body , supports this hypothesis . hnrnp a2 * expression correlates with telomerase activity , and overexpression of hnrnp a2 * increases telomere length in vivo . correlations between the expression of hnrnp a2 * in vivo and the telomerase activity was also studied in the invention in order to corroborate the relation between hnrnp a2 * and the telomerase . amounts of hnrnp a2 , hnrnp a2 *, and tert from rat tissues were determined by rt - pcr , and telomerase activity was quantified by trap ( fig5 a , 12a ). although telomerase activity did not correlate well with expression of tert mrna . for example , tert mrna is highly expressed in liver cells whereas the telomerase activity detected by trap is very low . but the telomerase activity well correlates with the expression of hnrnp a2 *. this correlation implies an important role of hnrnp a2 * for telomerase activity in vivo . on the contrary , this correlation is not presented between hnrnp a2 * and the telomerase . because hnrnp a2 * is expressed at a low level in human and rat cells , and because the abundance of hnrnp a2 * correlates with higher telomerase activity in rat tissues ( fig5 a , 12a ), it was predicted that overexpression of hnrnp a2 * might correlate with increased telomere length . in fact , when hnrnp a2 * was overexpressed in cultured hela and rat cells by retrovirus - mediated transfection , telomere length increased relative to control cells carrying empty vector ( fig5 b , 12b ). interestingly , the longer telomeres in the rat cells regressed over time , and in this context , subsequent telomere shortening correlated with a gradual decrease in hnrnp a2 * expression ( fig1 b bottom part ). the dependence of the telomere length on the hnrnp a2 * expression level further corroborates that hnrnp a2 * is a positive factor for the telomerase to regulate the telomere extension . while particular embodiments of the invention have been shown and described , it will be obvious to those skilled in the art that changes and modifications may be made without departing from the invention in its broader aspects , and therefore , the aim in the appended claims is to cover all such changes and modifications as fall within the true spirit and scope of the invention .

US-201514683152-A

the present invention relates to pharmaceutical compositions of gabapentin tannate , processes for production of those compositions and methods of use of those compositions . the present invention provides a novel process for preparation of the tannate salt of gabapentin in liquid or semi - solid dosage form for human and veterinary pharmaceutical use . tannate salts of active pharmaceutical ingredients are used in sustained release applications and to improve certain organoleptic properties such as taste . the process may utilize either natural or synthetic tannic acid .

the present invention involves a novel method of synthesizing the tannate salt of the active pharmaceutical ingredient ( api ) gabapentin and subsequently processing the gabapentin tannate into liquid and semisolid pharmaceutical dosage forms . gabapentin is a neuroleptic agent indicated as adjunctive therapy in the treatment of central nervous system conditions in mammalian subjects such as partial seizures , with and without secondary generalization , epilepsy , faintness attacks , hypokinesis , pain associated with shingles and cranial traumas . gabapentin is a white to off - white crystalline solid and is a polymorphic substance . it is freely soluble in water and across a wide range of ph and is characterized by a marked bitter taste . chemically , gabapentin is l -( amino methyl ) cyclohexaneacetic acid with the empirical formula c 9 h 17 no 2 and a mw of 171 . 24 . typically , gabapentin is administered in multiple doses for optimal pharmacological action . the literature describes many ways of preparing gabapentin from a variety of starting materials . u . s . pat . no . 4 , 024 , 175 describes at least three methods of preparing gabapentin from cyclohexyl - 1 , 1 - diacetic acid . each of these methods results in the formation of gabapentin hydrochloride salt , which may be converted to 1 -( aminomethyl )- 1 - cyclohexaneacetic acid by treatment with a basic ion exchanger and then crystallized from a solvent such as ethanol / ether . there is no mention or suggestion of preparing gabapentin tannate in the prior art . further , there is no suggestion of liquid or semi - solid pharmaceutical dosage forms containing gabapentin tannate . the formation of a tannate salt of gabapentin is unexpected because of the close proximity of a carboxylic acid group to the amine group . the negative charge on the carboxylic acid group was expected to shield and possibly neutralize the positive charge on the proximal nitrogen . since tannate salts are thought to normally form through an ionic interaction with a positively charged amine functional group , the close proximity of the carboxylic acid group was expected to prevent the formation of the tannate salt . gabapentin is structurally related to the neurotransmitter γ - aminobutyric acid ( gaba ) but unlike gaba , is able to cross the blood - brain barrier . although its exact mechanism of action remains unclear , gabapentin was recently shown to be a selective agonist at the gb1a - gb 2 heterodimer and post - synaptic gaba b receptor , a newly identified receptor subtype . the pharmacokinetics of gabapentin have been well characterized in adults . peak plasma gabapentin concentrations occur 2 - 3 hours post - dose . the absolute bioavailability of gabapentin is approximately 60 % after administration of 300 mg and is dose - dependent . while steady - state plasma gabapentin concentrations increased with increasing doses , the increase is not proportional to dose possibly due to saturation of the active transport across the gut via the l - amino acid transporter . gabapentin does not bind to plasma proteins and is not metabolized . gabapentin is eliminated via glomerular filtration , and dosage adjustment is necessary in patients with renal impairment . in subjects with normal renal function , gabapentin elimination half - life averages between 5 and 7 h . dosing recommendations are 900 - 1800 mg / day for anticonvulsant activity and panic disorders may require dosages in the range of between about 3000 to 3600 mg / day of gabapentin . the bioavailability and high dosage requirements for pharmacological action stipulate multiple dosings of gabapentin . naturally occurring tannic acid comprises a mixture of compounds . they are considered to be secondary metabolites , with a molecular weight of 500 - 5000 da , that have no specific metabolic function . they are complex phenol - rich polymers found in many foods . as with many natural polymers , a rigorous chemical definition of tannins is difficult . in general two classes are distinguished — the hydrolyzable and the condensed tannins . hydrolyzable tannins or tannic acids are referenced in the various pharmacopeias and are composed of gallic acid or its condensation product ellagic acid esterified to the hydroxyl groups of glucose . hydrolyzable tannins are molecules with a polyol ( generally d - glucose ) as a central core , with the hydroxyl groups of the carbohydrate partially or totally esterified with phenolic groups . they derive their name from their propensity to be hydrolyzed by mild acids or mild bases to yield carbohydrates and phenolic acids . synthetic tannic acid may comprise a purified form of any of the components of naturally occurring tannic acid . the present invention may utilize tannic acid of either a natural or synthetic source . the term “ tannic acid ” herein refers to either natural or synthetic tannic acid as described above . tannic acid elicits a characteristic astringent taste . a ph independent decrease in measures of amiloride - sensitive sodium channels in the tongue , which are regarded as conveying salty taste , has been observed when tannic acid was applied to the lingual surface . physiologically , it has been demonstrated that there is a ph independent inhibition of chorda tymphani responses to bitter and salty stimuli in the presence of tannic acid . the above mechanism of action has been used to explain experimental results which showed a taste suppression of 100 % by tannic acid , of compounds like quinine hcl , papaverine hcl ( bitter tasting compounds ), nacl ( salty ) and tartaric acid ( sour ). these properties explain why tannate salts of the active ingredients also possess better organoleptic properties , such as taste . the formation of the tannate salt is by the reaction of the amine groups ( in the 1 °, 2 °, 3 °, 4 ° or amphoteric configuration ) or of other basic functional groups with the carboxylic and hydroxyl groups present in tannic acid . for example , the amine groups of the api could react covalently with the hydroxyl groups of tannic acid by an oxime formation or by the ionization of the tannic acid and the protonation of the nitrogen atom in the amine group to form an ionic bond , to generate the tannate salt . in the present invention the active ingredient gabapentin is present in zwitter - ionic form . the protonated nitrogen reacts with tannic acid to form the tannate salt . the formation of a tannate salt of gabapentin is unexpected because of the close proximity of a carboxylic acid group to the amine group . the negative charge on the carboxylic acid group was expected to shield and possibly neutralize the positive charge on the proximal nitrogen . since tannate salts are thought to normally form through an ionic interaction with a positively charged amine functional group , the close proximity of the carboxylic acid group was expected to prevent the formation of the tannate salt . the ratio of the gabapentin to tannic acid has a marked effect on the yield of the reaction to form the tannate salt . typically , tannic acid needs to be present in a concentration of at least one half to five - fold that of the api by weight . the dispersing or anti - clumping agents used are naturally occurring gums or other polymers used as thickening agents . the amount and ratio of dispersing or anti - clumping agent and tannic acid , required for the completion of the reaction , is determined by the concentration of the gabapentin . the dispersing or anti - clumping agent serves as an adherent or a solid support for the tannic acid molecules to facilitate the reaction between the gabapentin and tannic acid . in addition it also prevents the clumping and aggregation of the tannate salt formed , which aids in the uniform distribution of the precipitate in the mixture . the synthetic process can be used as a conversion method for generating tannate salts of gabapentin and is a novel way of directly incorporating them into suitable liquid dosage forms . in the dispersion method , the gabapentin tannate salt obtained from the conversion process can be transferred directly to a suitable liquid medium , which comprises co - solvents , preservatives , sweetening / flavoring , ph adjusting , coloring , thickening and anti - caking agents . the resulting mixture can be processed into suspensions and other suitable liquid dosage forms . by starting with a commonly available form of the gabapentin , which is converted to a tannate salt , the invention provides an efficient and reproducible method to manufacture products containing gabapentin tannate salts as active ingredients . the complex thus obtained can be further incorporated into liquid or semi - solid dosage forms for pharmaceutical use . the compositions of the present invention may be prepared for oral administration in the form of elixirs , syrups and the preferred forms of suspensions formulated so that ideally each 5 ml ( approximately 1 teaspoon ) of suspension would contain approximately 0 . 1 to 3600 mg of gabapentin in the tannate salt form , at a ph range of 2 . 0 - 11 . 0 . suspensions of the compositions of the present invention may be prepared , such that each 5 ml ( one teaspoon ) contains 900 mg of gabapentin tannate , preferably by reacting the aqueous solution or the powder form of the drug with a tannic acid mixture in liquid or powder form , without the use of volatile solvents . the tannate salt prepared can then be directly incorporated into suitable pharmaceutically effective dosage forms without further purification and isolation . the suspension formulations may additionally contain one or more of the following : sodium benzoate , coloring , natural and artificial flavors , xanthan gum , magnesium aluminum silicate , methyl paraben , purified water , saccharin , sodium hydroxide , tannic acid and sucrose or sorbitol . example 1 , which is illustrative of a typical suspension formulation of the present invention , is prepared as follows : the conversion process used in this example to synthesize the tannate salt of gabapentin is done using the following procedure at room temperature : about 150 ml of purified water is placed in a suitable vessel and gabapentin is added to the water and stirred to form a solution . 500 ml of purified water is placed in a suitable container and mixed . while mixing the water , the magnesium aluminum silicate is added in small portions . subsequently , tannic acid is added and mixing is continued to form a dispersion . while mixing the tannic acid dispersion , the solution of gabapentin is added slowly to obtain the gabapentin tannate salt . the saccharin sodium , sucrose , xanthan gum and a part of the mas are dispersed in purified water , using a suitable mixer . the coloring agent and the artificial strawberry flavor are then added and mixing is continued to generate the suspending medium . the gabapentin tannate as prepared is transferred to the suspending medium and mixing is continued to disperse the tannate salt . the sodium benzoate and methylparaben are then dispersed in the glycerin and added to the suspending medium containing the active and mixed to get a uniform dispersion . finally , purified water is added to make up to the suspension to the required volume and mixed to obtain an elegant product . tannic acid may also be used for ph adjustment . monobasic sodium phosphate , usp , and dibasic sodium phosphate , usp , anhydrous may also be included in the formula for ph adjustment . the conversion process used in this example to synthesize the tannate salt of gabapentin is done using the following procedure at room temperature : 500 ml of purified water is placed in a suitable container and mixed . while mixing the water , the magnesium aluminum silicate is added in small portions . subsequently , tannic acid is added and mixing is continued to form a dispersion . while mixing the tannic acid dispersion , gabapentin powder is added slowly to obtain gabapentin tannate salt . the saccharin sodium , sucrose , kaolin and a part of the mas are dispersed in purified water in a stainless steel mixing tank , using a suitable mixer . the coloring agent and the artificial grape flavor are then added and mixing is continued to generate the suspending medium . the gabapentin tannate prepared as described is transferred to the suspending medium and mixing is continued to disperse the tannate salt . the pectin is dispersed in glycerin in a mixing tank using a mixer . the benzoic acid and methylparaben are then dispersed in the glycerin mixture in the tank . the glycerin mixture is added to the suspending medium containing the active ingredients and mixed to get a uniform dispersion . finally , purified water is added to make up the suspension to the required volume and mixed to obtain an elegant product . the dosage administered will be dependent on the age , health and weight of the recipient , kinds of concurrent treatment , if any , frequency of treatment and desired effect . it should be understood that the above examples are only illustrative of the invention disclosed herein . given the present disclosure , it is anticipated that numerous variations will occur to those skilled in the art without departing from the spirit and scope of the present invention . for example , while compositions of gabapentin tannate for oral administration have been described , it should be appreciated that like compositions could also be prepared for nasal and intravenous administration if desired . a latitude of modification , substitution and change is intended and in some instances , some features of the invention may be employed without a corresponding use of other features . accordingly , it is intended that the spirit and scope of the invention disclosed herein should be limited only by the following claims .

US-80626004-A

a toothpick assembly which includes a pointed lower end to piercingly connect to a piece of garnish , such as an olive or a cherry , and a buoyant float about the toothpick and adjacent the upper end of the toothpick to float a piece of garnish in a beverage which can be retrieved by grasping the upper end of the toothpick .

in fig1 there is shown a glass 10 having ice cubes such as 12 and beverage indicated at 14 at its upper surface or what could be termed the upper float line . within the glass , there is a toothpick assembly generally indicated by the numeral 16 which is seen to include a toothpick or elongate length segment 18 having a lower pointed end as at 20 and an upper end zone as at 22 . on the length of the toothpick assembly , there is a float means 24 . the float 24 is shown in fig2 and 3 . in a preferred embodiment , it is symmetrical with respect to a vertical center line extending between the bottom end of the float 26 and its upper surface 28 . the side surface of the float is designated by the numeral 30 . there is a central through bore 32 between the lower end and the upper surface to jacket a toothpick along its elongate length , slidably , so that the float 24 can be adjusted to a position adjacent the upper end 22 as seen in fig1 . in an alternative embodiment , the toothpick assembly is integrally formed with the float 24 , thereby making a single non - adjustable piece . both can either be molded of the same material or of two different materials with the float 24 being fixedly secured to the toothpick assembly . in use , a garnish is pierced by the tapered and pointed lower end and , as indicated in fig1 and 3 , dropped into the glass . it will float in the attitude shown in fig1 where it can be easily removed by lifting it from the glass using the upper end to clasp it and retrieve the garnish . the overall length of the toothpick is between about 21 / 2 inches and 41 / 2 inches and its cross - sectional diameter between the end zones is between 1 / 16 of an inch and 1 / 8 of an inch . in the embodiment shown in fig4 a somewhat elongate toothpick is shown at 40 for a somewhat taller glass indicated by the numeral 10 &# 39 ;. in this case , garnish as indicated which may be in the form of a cherry 42 and a piece of pineapple for example , as indicated at 44 . in the embodiment shown in fig5 the elongate toothpick length 50 is provided extending upwardly from the float 51 with handle means which can be clasped to lift the toothpick assembly with garnish on it from a glass with a beverage in it , the handle means being designated by the numeral 53 ; and , prior to use , it is adapted to cradle a piece of garnish such as the pineapple slice indicated at 54 . finally , in the embodiment shown in fig6 the upper end 60 of the elongate toothpick length 62 may be provided with a decorative portion such as a parasol 63 while the lower end , as indicated , is used to pierce a piece of garnish . in a preferred embodiment , the upper surface of the float means is between about 1 / 2 of an inch and 3 / 4 of an inch in diameter with the side wall tapering symmetrically to the lower end as indicated preferably in a curved decorative design . while the float may be of any desired material , it is only required that it have sufficient buoyancy so that its upper surface is at about the level of the drink when it is served ; and , therefore , the end opposite to the pointed lower tip will extend out of the water so that it can be grasped , the assembly floating in a generally upright position with garnish on the lower end so that access can be had to it conveniently by a user . while this invention has been shown and described in what is considered to be a practical and preferred embodiment , it is recognized that departures may be made within the spirit and scope of this invention which should therefore not be limited except as set forth in the claims and within the doctrine of equivalence .

US-11657793-A

this invention relates to cholesterol synthesis and to the accumulation and regulation of cholesterol levels in body tissue . more specifically , the invention provides that the compound 26 - aminocholesterol , ## str1 ## and analogs and derivatives thereof , exhibit biological activity as a potent inhibitor of cholesterol synthesis and / or cholesterol accumulation in body tissue . the compounds strongly inhibit of the enzyme hmgcoa reductase and low density lipoprotein accumulation by non - hepatic cells . surprisingly , it has been discovered that 26 - aminocholesterol is selective for fibroblast cells , and has little or no effect on hepato cells . therapeutic compounds according to the invention include substituted or unsubstituted sterols of the formula : ## str2 ## wherein the carbon atoms at positions 5 and 6 of the sterol are one of saturated and unsaturated , r 1 is one of a 3 - hydroxyl group and a 3 - keto group , r 2 is one of a hydroxyl group and a keto group , and wherein at least one of r 3 , r 4 and r 5 is an amino group and the others are each selected from the group consisting of hydrogen and an amino group .

the compound 26 - aminocholesterol , ## str3 ## has been found to influence de novo cholesterol synthesis and low - density lipoprotein ( ldl ) binding in human serum fibroblasts , while having no impact on human hepatocytes . thus , it appears that the compound is either selective for the synthesis and accumulation of cholesterol in fibroblast cells , or is selectively ignored or avoided by liver cells , perhaps through rapid metabolic decomposition in the liver . these findings also suggests that the biosynthetic pathways for cholesterol production in serum and in the liver may be different , and may employ different mechanisms of action . 25 ( r ), 26 - aminocholesterol was prepared by lithium aluminum hydride ( lah ) reduction of 25 ( r ), 26 - azidocholesterol 3 - acetate synthesized from 26 - tosylcholesterol 3 - acetate . see , tschesche et al ., chem ber ., 112 : 2680 - 2691 ( 1979 ); and seo , et al ., j . chem . soc . perkin trans . i , 411 - 414 ( 1986 ). the 26 - azidocholesterol 3 - acetate starting material was obtained by dissolving 397 mg ( 0 . 663 mmoles ) of 26 - tosyl - cholesterol 3 acetate in 25 ml of anhydrous dimethyl formamide ( dmf ) in a 100 ml three - neck flask fitted with a stir bar and a nitrogen bubbler . then , 56 mg ( 0 . 853 mmoles ) of sodium azide and 1 ml of water was added , and the solution was heated to between 90 ° and 100 ° c . after two hours , the solution was cooled to room temperature an poured into a 500 ml separatory funnel containing 200 ml of water . the aqueous solution was extracted three times with diethyl ether and the pooled extracts were washed with saturated sodium chloride solution and dried . rotoevaporation yields 254 mg of 26 - azidocholesterol 3 - acetate as a white powder ( 81 . 6 % yield ) that was subsequently recrystallized in ethanol to yield 126 mg of white waxy crystals . the melting point of this intermediate product was 90 °- 90 . 5 ° c . nmr analysis revealed the following , in ppm : 0 . 701 ( 3 , s , c - 18 methyl ), 0 . 941 ( 3 , d , c - 27 methyl , j = 6 . 6 hz ), 0 . 970 ( 3 , d , c - 21 methyl , j = 6 . 6 hz ), 1 . 042 ( 3 , s , c - 19 methyl ), 2 . 058 ( 3 , s , methyl of acetate on c - 3 ), 3 . 1765 ( 3 , multiplet abx , j = 38 . 17 hz , j = 11 . 89 hz , j = 5 . 97 hz ), 4 . 626 ( 1 , m , c - 3 ), 5 . 398 ( 1 , d , c - 6 , j = 4 . 50 hz ). ir analysis , ( 1 / cm ) provided : 2950 ( c -- h ), 2100 ( n -- n ), 1725 ( c ═ o ), 1250 ( n -- n ) and 1050 ( c -- o ). the 26 - azidocholesterol 3 - acetate ( 100 mg , 0 . 213 mmoles ) was dissolved in 20ml of anhydrous diethyl ether in a 50 ml three - neck flask fitted with a stir bar and a nitrogen bubbler . lah ( 20 mg , 0 . 527 mmoles ) supplied by aldrich ( 95 %) was added directly to the flask and the exothermic reaction was refluxed for one hour . the reaction mixture was quenched with water and was poured into a 100 ml separatory funnel . the aqueous layer was removed and the ethereal layer was washed with saturated sodium chloride solution and dried . rotoevaporation resulted in 70 mg of 26 - aminocholesterol as a crude white powder ( 81 . 9 % yield ). this was purified via flash chromatography ( 93 : 7 : 1 chloroform : ethanol : 29 % ammonium hydroxide , using 230 - 400 mesh silica gel supplied by merck ) to afford 48 mg of the desired final product , 26 - aminocholesterol . the melting point of the product was 149 °- 152 ° c . ( 148 °- 151 ° c ., see , tschesche , supra ). nmr analysis revealed the following , in ppm : 0 . 669 ( 3 , s , c - 18 methyl ), 0 . 875 ( 3 , d , c - 27 methyl , j = 6 . 6 hz ), 0 . 906 ( 3 , d , c - 21 methyl , j = 6 . 6 hz ), 0 . 999 ( 3 , s , c - 19 methyl ), 2 . 528 ( 3 , 2 , m , c - 26 ), 3 . 499 ( 1 , m , c - 3 ), and 5 . 342 ( 1 , d c - 6 proton , j = 5 . 1 hz ). ir analysis , ( 1 / cm ) provided : 3600 ( n -- h ), 2950 ( c -- h ), and 1050 ( c -- o ). melting points were determined in open capillary tubes on a thomas - hoover capillary melting point apparatus and uncorrected . nmr spectra ( cdcl 3 ) were run on a nicolet qe - 300 spectrometer . ir spectra were obtained on a matteson polaris ftir instrument . all reagent grade chemicals , except as otherwise noted , were obtained from aldrich chemical company . normal ldlr (+) human fibroblasts ( gm3440 ) were obtained from the national institute of general medical sciences human genetic cell repository . stock fibroblast monolayers were maintained in t - 75 disposable nunc flasks , in a medium comprising 10 ml of mem ( eagle &# 39 ; s minimum essential medium with earl &# 39 ; s salts , ph 7 . 4 ) supplemented with 10 % ( v / v ) fetal bovine serum ( fbs ), 2 % ( v / v ) non - essential and essential amino acids , 1 % ( v / v ) mem vitamins , 1 % l - glutamine ( 292 ug / ml ), 1 % penicillin ( 100 u / ml )- streptomycin ( 100 ug / ml ). the fibroblast stock was maintained at 37 ° c . in a humidified atmosphere of 5 % co 2 and 95 % air . hepg2 cells were obtained from dr . barbara knowles of the wistar institute , pennsylvania . the hepg2 stock monolayers were maintained under the same conditions as the fibroblast monolayers , in a medium comprising mem supplemented with 10 % heat - inactivated fbs , and 1 % ( v / v ) each of penicillin - streptomycin solution , non - essential and essential amino acids , and l - glutamine . the medium was routinely changed every 3 - 4 days and the cells were massaged ( 1 : 3 ) every 7 days . the ingredients for these media were supplied primarily by gibco chemical co . for experiments using fibroblasts , confluent stock cultures ( 5 - 18 passages ) were washed once with dulbecco &# 39 ; s pbs ( phosphate buffered saline ) prior to the addition of 3 ml aliquots of experimental mem containing 25 % ( v / v ) d 2 o , 9 % ( v / v ) dilapidated fbs , 1 % fbs ( v / v ), 1 % mem vitamins and l - glutamine , and 2 % of essential and non - essential amino acids and 20 mm hepes buffer . for experiments using hepg2 cells , confluent stock monolayers were washed once with dulbecco &# 39 ; s pbs , dissociated with 0 . 05 - 0 . 02 % trypsin - edta followed by treatment with deoxyribonuclease i ( 0 . 1 %), and were seeded ( 3 . 0 × 10 6 ) under identical conditions . the experimental mem contained 25 % ( v / v ) d 2 o , 9 % ( v / v ) delipidated fbs , and 1 % ( v / v ) each of heat - inactivated fbs , penicillin - streptomycin , essential and non - essential amino acids , l - glutamine and 20 mm hepes . the fibroblast and hepatoblastoma cells were cultured in media containing 25 % d 2 o and 1 % fbs in order to determine de novo cholesterol synthesis under conditions that permit receptor mediated cholesterol transport , according to the method of easterman & amp ; javitt et al ., j . lipid res ., 26 : 950 - 954 ( 1985 ). dish cultures of each cell type were prepared , and 26 - aminocholesterol , dissolved in n , n - dimethylformamide ( dmf , 9 ul per dish , 0 . 3 % v / v ) was added to each culture . the cells were then grown to confluence ( 96 hours , day 5 ). no effect on cell growth was observed at the maximum concentrations tested . duplicate or triplicate dishes containing 9 ul of dmf , but without 26 - aminocholesterol , were used as controls . the effect of 26 - aminocholesterol on ldl receptor binding , de novo cholesterol synthesis , and distribution of total and esterified cholesterol were determined at this stage of growth . ldl ( d , 1 . 019 - 1 . 03 ) was isolated by sequential preparative ultracentrifugation of normal human plasma , using solid kbr for density adjustment , according to the methods of havel et al ., j . clin . invest ., 34 : 1345 - 1353 ( 1955 ) and radding & amp ; steinberg , j clin . invest ., 39 : 1560 - 1569 ( 1960 ). the isolated ldl was then iodinated with 125 ina by the monochloride procedure of mcfarlane , nature , 102 : 53 ( 1958 ), as modified for lipoproteins according to bilheimer et al ., biochim . biophys . acta . 260 : 212 - 221 ( 1972 ). to remove free iodine , the ldl preparation was subjected to column chromatography on a sephadex g - 25m disposable mini - column ( pharmacia pd - 10 ) and was dialized against 0 . 15 m nacl and 0 . 3 nm edta , ph 7 . 4 . the specific activity of all ldl preparations ranged between 160 - 300 cpm / mg of ldl proteins . 125 i - ldl was stored at 4 ° c . and was sterilized by filtration through a 0 . 45 um membrane just prior to incubation with the treated fibroblast and hepatoblastoma cell cultures and control cultures . for binding studies , a fixed concentration of 10 ug / ml of 125 i - ldl was added directly to the monolayers of the confluent culture medium ( at or near the 96th hour ) and incubation was continued for a further 4 hours at 37 ° c . for fibroblasts and 4 ° c . for hepg2 cells . after this incubation , the culture dishes were placed on ice , the medium was removed , and the cell monolayers were washed as described in goldstein & amp ; brown , j . biol . chem ., 249 : 5153 - 5162 ( 1974 ). the monolayers were then scraped off the dishes with a teflon policeman and were solubilized with 1 ml of 0 . 1 n naoh . cell - associated radioactivity was measured in a packard auto gamma scintillation spectrometer model 5160 , and cell protein was measured by the method of lowry et al ., j . biol . chem ., 193 : 265 - 275 ( 1951 ), using bovine serum albumin as a standard . total 125 i - ldl binding was expressed as the mass of 125 i - ldl ( mg ) per mg of cell protein . after 96 hours of incubation , medium was removed from the cell cultures , and the cells were washed with dulbecco &# 39 ; s pbs and were harvested with 0 . 05 % trypsin - 0 . 02 % edta . the protease was deactivated with an equivolume aliquot of soybean trypsin inhibitor , and the resulting cell suspension was centrifuged for 5 minutes at 500xg . an internal standard of 5b - cholestan - 3b - ol was added to the pellets prior to extraction with an 8 : 4 : 3 chloroform : methanol : water folch mixture , as described in folch et al ., j . biol . chem ., 266 : 497 - 509 ( 1957 ). an aliquot of the extract was blown to dryness under nitrogen and silylated with 2 : 1 : 1 mstfa ( a sylated reagent supplied by pierce co . ): toluene :- pyridine . free cholesterol was determined by gas - liquid chromatography ( glc ) on a perkin - elmer capillary gas - liquid chromatography model 8320 fitted with a 20 m de - 1 methylsilicon glass column ( supelco ). the remaining extract was dried and saponified with 2 % ethanolic koh at 80 ° c . for one hour . the 26 - aminocholesterol was then re - extracted and total cholesterol was measured by glc after silylation . cholesterol ester was calculated as the difference between the total and free cholesterol determinations . newly synthesized cholesterol was determined by glc - ms isotope mass ratios , using a hewlett - packard gc - ms spectrometer model 5890 fitted with db - 1 methyl silicon 0 . 18 i . d . 20 m glass column ( supelco ), according to the method of j . lipid . res ., 26 : 950 - 954 , supra . for purposes of comparison , 125 i - ldl and cholesterol assays were also conducted in cultures prepared according to the above methods , but incubated with 26 - hydroxycholesterol in one set of experiments and with the sterol 26 - thiacholesterol in another set of experiments . these sterols were obtained according to known methods , similar to those described above for 26 - aminocholesterol . the results of the ldl binding and cholesterol experiments are shown in the following tables , with table 1 showing the effect of the tested sterols on ldl binding and cholesterol synthesis in fibroblast cells , and table 2 showing the results for hepg2 cells . table 1__________________________________________________________________________ldl binding and cholesterol in human fibroblastseffect of 26 - nh . sub . 2 , 26 - sh and 26 - oh cholesterol on totalcell cholesterol , percent esterified cholesterol , denovo cholesterol synthesis , and . sup . 125 i - ldl binding toldlr (+) human fibroblasts ( n = 3 ) 26 - nh . sub . 2 26 - aminocholesterol 26 - oh 26 - hydroxycholesterol 26 - sh 26 - thiacholesterol total cholesterol ug cholesterol . sup . 125 i - ldl binding per mg cell ug ldl protein persterol protein % ester % de novo mg cell protein__________________________________________________________________________none 32 . 1 +/- 1 . 2 28 . 5 19 . 0 49 . 7 +/- 0 . 926 - 0h0 . 625 um 24 . 7 +/- 2 . 8 28 . 7 3 . 9 22 . 0 +/- 2 . 426 - nh . sub . 20 . 156 um 27 . 9 +/- 5 . 3 26 . 4 16 . 7 29 . 6 +/- 1 . 10 . 312 um 31 . 5 +/- 6 . 1 18 . 6 10 . 0 22 . 6 +/- 5 . 40 . 625 um 20 . 3 +/- 6 . 4 6 . 4 2 . 7 13 . 3 +/- 1 . 626 - sh 5 . 0 um 26 . 0 +/- 1 . 7 13 . 6 27 . 8 37 . 9 +/- 1 . 810 . 0 um 31 . 3 + /- 4 . 5 31 . 1 21 . 9 25 . 7 +/- 0 . 720 . 0 um 26 . 1 +/- 1 . 0 33 . 1 13 . 6 35 . 7 +/- 4 . 8__________________________________________________________________________ table 2__________________________________________________________________________ldl binding and cholesterolin human hepg2 hepatocyteseffect of 26 - nh . sub . 2 , 26 - sh and 26 - oh cholesterolon total cell cholesterol , de novo cholest - erol synthesis , and . sup . 125 i - ldl binding to hepg2cells ( n = 3 ) 26 - nh . sub . 2 26 - aminocholesterol 26 - oh 26 - hydroxycholesterol 26 - sh 26 - thiacholesterol total cholesterol ug cholesterol i - ldl binding per mg cell ug ldl protein persterol protein % de novo mg cell protein__________________________________________________________________________none 28 . 7 +/- 0 . 2 55 . 8 36 . 0 +/- 0 . 926 - oh0 . 625 um 24 . 7 +/- 2 . 8 57 . 1 53 . 6 +/- 1 . 326 - nh . sub . 20 . 156 um 30 . 6 +/- 3 . 7 38 . 3 40 . 9 +/- 3 . 10 . 312 um 25 . 0 +/- 0 . 6 45 . 1 43 . 9 +/- 4 . 00 . 625 um 28 . 8 +/- 1 . 8 42 . 0 52 . 4 +/- 8 . 826 - sh 5 . 0 um 25 . 5 +/- 4 . 3 49 . 7 37 . 8 +/- 3 . 410 . 0 um 27 . 4 +/- 4 . 0 47 . 9 45 . 8 +/- 3 . 920 . 0 um 23 . 2 +/- 1 . 2 41 . 9 35 . 7 +/- 4 . 8__________________________________________________________________________ these data reveal that 26 - hydroxycholesterol and 26 - aminocholesterol act as potent inhibitors of cholesterol synthesis , since they result in significant reductions in ldl - binding and de novo cholesterol synthesis in human fibroblasts . however , these compounds do not exhibit the same biological activity in hepg2 cells . therefore , 26 - aminocholesterol ( and 26 - hydroxycholesterol ) appear to be selective inhibitors of serum cholesterol . they inhibit cholesterol synthesis in plasma , but do not provide a similar reduction in hepatic ldl - binding and de novo synthesis . the experiments also reveal that 26 - aminocholesterol is significantly more potent , and not all reactive substitutions of 26 - hydroxycholesterol are effective regulators of cholesterol production . for example , 26 - thiacholesterol , which substitutes an sh - group for the nh 2 of 26 - aminocholesterol , has no impact on either fibroblast or hepg2 ldl - binding and de novo synthesis . other compounds that are within the scope of the invention include substituted or unsubstituted sterols having an amino group (-- nh 2 ) on any of the terminal carbons of the aliphatic side chain at position 17 of the sterol . thus , compounds according to the invention include the following substituted or unsubstituted sterols which are either saturated or unsaturated at carbons 5 and 6 ( as shown by the dotted line ). ## str4 ## wherein r 1 is one of a 3 - hydroxy and 3 - keto group ; r 2 is one of hydrogen , a hydroxyl group and a keto group ; and r 3 , r 4 , and r 5 are each selected from the group consisting of hydrogen and an amino group , wherein at least one of them is an amino group . the most preferred compounds are 3 - hydroxy sterols with an amino group at one or more of positions 25 , 26 and 27 of the sterol . of these , the most preferred is 26 - aminocholesterol , wherein r 2 = nh 2 at position 26 ) and r 1 = r 3 = methyl ( ch 3 ) at positions 25 and 27 . additional examples of compounds according to the invention and formula ii are : these compounds are amine - substitutions of known oxysterols that repress hmg - coa reductase . the finding that amino (-- nh 2 ) substitution of the side chain unexpectedly enhances cholesterol inhibition in comparison to naturally occurring oxygenated or hydroxy (-- oh ) compounds suggests that the addition of one or more polar groups at or near the terminal end of the aliphatic side chain of a sterol will produce potent cholesterol inhibitors , since nh 2 is more polar than oh in this context . this is supported by the fact that thio (-- sh ) substitution of the side chain results in a reduction in cholesterol inhibition in comparison to both -- oh and -- nh 2 , apparently because the thio group (-- sh ) is less polar than both the hydroxy and amino groups . another theory is that the receptor cite for the cholesterol inhibitor compound has a higher affinity for proton acceptors , such as nh 2 ( a base ) than with oh , or with sh ( an acid ). thus , contemplated equivalents of the invention would be biososteric substitutions of the compound of formula ii , wherein each -- nh 2 group is replaced by a group that is as or more polar or more basic than a hydroxy group . the compounds of formula ii are either known and are available , or can be synthesized by a chemist according to known methods . for example , substitution at a terminal carbon of the sterol can be achieved by lithium aluminum hydride ( lah ) reduction according to the procedure set forth above for the preparation of 26 - aminocholesterol . starting materials and intermediates are readily available or can be readily obtained , and the variations in this method that would be suitable for each substituted compound are well within the skill of an ordinary synthetic chemist . thus , the following scheme is representative of the manner in which compounds according to the invention can be obtained : ## str5 ## although it is believed that the inventive compounds , and 26 - aminocholesterol in particular , achieve reduced ldl - binding and cholesterol synthesis by acting as a downregulator of ldl receptors and consequently as an inhibitor of the rate - limiting enzyme hmg coa reductase , the precise mechanism of action is not well understood , nor has the relationship between sterol structure and enzyme inhibition been fully investigated . in theory , the bioisosteric substitution of an amino group at a terminal aliphatic carbon ( as in formula ii ), and preferably the c - 26 position of a sterol with a five carbon side chain , provides a marked increase in capacity to interact with specific configurations on a cytostolic oxysterol carrier protein that is believed to participate in the biosynthetic pathway for cholesterol production . it is also believed that observed reductions in cholesterol esterification are the result of decreased cholesterol synthesis , rather than interference with the process of esterification itself , a process which appears to be substrate driven . without relying on any particular theory , the potent inhibition of cholesterol synthesis observed in the present experiments suggests that the mechanisms of oxysterol metabolism cholesterol production may be different for fibroblast and hepatoblast cells , and that hmg coa reductase may play a less significant role in hepatic cholesterol production . this reasoning is consistent with findings that hepg2 cells synthesize approteins and bile acids , and therefore hepatocytes contain sterol intermediates in bile acid synthesis that are not normally known to be present in fibroblasts . fibroblasts and hepatocytes perform different metabolic functions , and therefore it is not unreasonable for different synthetic mechanisms and / or differing sensitivities to certain sterols to be observed . the experiments also suggest that different synthetic mechanisms may be implicated in cell replication and turnover , which occurs frequently in the in vivo fibroblast population , as opposed to the production of cholesterol for metabolic functions in non - replicating cells , such as hepatocytes in vivo . this hypothesis is based on the fact that the present experiments measure cholesterol in cells that have reached confluent growth , meaning that the tested cultures have undergone a period of rapid cell replication , for which cholesterol is needed . further support can be found in experiments which show that 26 - aminocholesterol and other oxygenated sterols tend to downregulate dna synthesis and cell growth through a mechanism that appears to be independent of hmg coa reductase activity . whatever the mechanism of action , it has been observed that 26 - aminocholesterol downregulates ldl binding and is specific for tissue cells . for administration to a patient , 26 - aminocholesterol and other compounds of the invention can be provided as a pure compound , or as mono and di - esterified derivatives and other pharmaceutically acceptable derivatives thereof , such as mono and di - ethers . the esters can be formed using naturally occurring fatty acids , or other organic or inorganic esters can be formed using known pharmaceutically acceptable substituents can be used , such as sulfates , carbonates and glucuronides . esterification and / or etherification can be at the 3 - and / or 26 - position . aryl and / or alkyl ethers , such as methyl , ethyl or cycloalheles ( e . g ., cyclopentyl ethers ) are also contemplated . furthermore , acid salts and other pharmaceutically acceptable substitutions can be used . the compounds of the present invention , ( e . g ., 26 - aminocholesterol ) are administered in amounts ranging from about 1 mg / kg to 25 mg / kg , preferably 1 to 5 mg / kg , one to three times per day . the precise dose in each instance will depend on the needs of the patient , and will be readily apparent to skilled practitioners and clinicians . pharmaceutical preparations including the compound can be administered as a solid or liquid , or as an injectable preparation , in combination with suitable pharmaceutical carriers . suitable pharmaceutical preparations include tablets , capsules , oral liquid and parenteral injectables and other equivalent means of administration . in a preferred embodiment , the compound is administered as a conventional solid tablet or capsule formulation using conventional diluents and excipients , such as lactose . parenteral injections can be prepared using conventional solvents used with lipid - soluble materials , or a water - soluble salt of the sterol can be prepared . these and other aspects and variations of the invention will be apparent to the skilled artisan . moreover , the foregoing experiments , examples , and proposed theories of drug action are illustrative , and do not serve to limit the scope of the invention as claimed .

US-24644488-A

a two - piece bath squirting toy comprising two separable pieces of flexible material , with each piece forming a section of a toy or an animal such that when the pieces are combined , they form a complete toy or animal . each piece includes a portion of a liquid fluid reservoir inside of the squirting toy , with an interior wall of the portion of each piece directly contacting fluid within the liquid fluid reservoir .

for purposes of description herein , the terms “ upper ,” “ lower ,” “ right ,” “ left ,” “ rear ,” “ front ,” “ vertical ,” “ horizontal ,” and derivatives thereof shall relate to the invention as orientated in fig1 . however , it is to be understood that the invention may assume various alternative orientations , except where expressly specified to the contrary . it is also to be understood that the specific devices and processes illustrated in the attached drawings , and described in the following specification are simply exemplary embodiments of the inventive concepts defined in the appended claims . hence , specific dimensions and other physical characteristics relating to the embodiments disclosed herein are not to be considered as limiting , unless the claims expressly state otherwise . the reference number 10 ( fig1 - 2 ) generally designates a two - piece bath squirting toy embodying the present invention . in the illustrated example , the two - piece bath squirting toy 10 comprises a first section 12 including a first connection member 14 and a second section 16 including a second connection member 18 . the first section 12 and the second section 16 of the two - piece bath squirting toy 10 are removably connected together by the first connection member 14 and the second connection member 18 . the first connection member 14 and the second connection member 18 allow the first section 12 and the second section 16 to be separated to allow both an exterior 20 and an interior 22 of the two - piece bath squirting toy 10 to be cleaned . in the illustrated example , the two - piece bath squirting toy 10 forms a toy to be used in a bath 100 ( see fig7 ). the two - piece bath squirting toy 10 includes at least one opening 24 for allowing water or other fluid to enter and exit the two - piece bath squirting toy 10 . the two - piece bath squirting toy 10 is formed of elastic material as is well known to those skilled in the art . the elastic material allows the two - piece bath squirting toy 10 to be squeezed to expel air and / or water from the interior 22 of the two - piece bath squirting toy 10 through the at least one opening 24 . once the two - piece bath squirting toy 10 is released from its squeezed state , the elasticity of the two - piece bath squirting toy 10 will reform the two - piece bath squirting toy 10 into its original shape , thereby creating a partial vacuum within the two - piece bath squirting toy 10 . the partial vacuum will suck air and / or water into the interior 22 of the two - piece bath squirting toy 10 . if filled with water , the two - piece bath squirting toy 10 can be squeezed to expel the water within the two - piece bath squirting toy 10 through the at least one opening 24 , with the at least one opening 24 acting as a nozzle . the first section 12 and / or the second section 16 of the two - piece bath squirting toy 10 can be formed and / or coated with a viral and / or bacterial resistant or repellant material to prevent viruses and bacteria from forming or staying on the first section 12 and / or the second section 16 ( as is well known to those skilled in the art ). the illustrated two - piece bath squirting toy 10 is formed of the first section 12 and the second section 16 to allow the two - piece bath squirting toy 10 to be separated into two parts to allow both an exterior 20 and an interior 22 of the two - piece bath squirting toy 10 to be cleaned . as illustrated in fig1 and 2 , the first section 12 and the second section 16 of the two - piece bath squirting toy 10 are removably connected together by the first connection member 14 and the second connection member 18 . in the illustrated example , the first connection member 14 includes a first press fit section 26 forming a ledge 26 ′ and the second connection member includes a second press fit section 28 forming a groove 28 ′. the ledge 26 ′ is pressed into the groove 28 ′ to connect the first connection member 14 to the second connection member 16 . although the first connection member 14 and the second connection member 18 are illustrated as being press fit sections , it is contemplated that the first connection member 14 and the second connection member 18 can include any elements for removably connecting the first section 12 to the second section 16 . for example , the first connection member 14 and the second connection member 18 can comprise mating threaded sections , snaps , or buttons ( see , for example , fig4 and 5 ). furthermore , while the two - piece bath squirting toy 10 is illustrated in fig1 and 2 as being in the form of a cat , it is contemplated that the two - piece bath squirting toy 10 can form any exterior shape . for example , the two - piece bath squirting toy 10 can form any animal ( e . g ., a fish ( as shown in fig6 ), a vehicle or any person ( real or fictional )). fig3 illustrates a generic two - piece bath squirting toy 10 a having a first connection member 14 a including a first press fit section 26 a forming a ledge 26 a ′ and a second connection member 18 a including a second press fit section a 28 forming a groove 28 a ′. the first press fit section 26 a forming the ledge 26 a ′ and the second press fit section a 28 forming the groove 28 a ′ in fig3 is the same connection scheme as shown in fig1 - 2 . fig3 is used to illustrated that the connection as shown in fig1 - 2 can be used on a toy having any exterior and interior shape . the first connection member 14 a can be formed out of the material used to directly form the first section 12 a of the generic two - piece bath squirting toy 10 a ( e . g ., molded in a unitary piece as shown in fig1 and 2 ) or can be a member fit into or connected ( e . g ., by interference fit or adhesion ) to the first section 12 a . fig4 and 5 illustrate another embodiment of a generic two - piece bath squirting toy 10 b , with the connection scheme employing a external threaded member 27 on one of the sections and an internal threaded member 29 on the other of the sections . in fig4 , the first connection member 14 b is formed out of the first section 12 b . the second connection member 18 b can be formed out of the material used to directly form the second section 16 b of the generic two - piece bath squirting toy 10 b ( e . g ., molded in a unitary piece ). fig5 illustrates the first connection member 14 b being formed out of a first separate member 52 that is fit into or connected to the first section 12 b and the second connection member 18 b being formed out of separate member 50 that is fit into or connected to the second section 16 b . in the illustrated example , it is also contemplated that only one of the first connection member 14 , 14 a or 14 b and the second connection member 18 , 18 a or 18 b can be a separate piece and that the other of the first connection member 14 , 14 a or 14 b and the second connection member 18 , 18 a or 18 b can be molded with their respective section . furthermore , the connection members can be reversed on the sections of the toy 10 , 10 a or 10 b ( e . g ., the second connection member 14 could include the first press fit section 26 forming the ledge 26 ′ and the first connection member 12 could includes the second press fit section 28 forming the groove 28 ′). fig6 illustrates two two - piece bath squirting toys 10 and 10 c , with a first one of the two - piece bath squirting toys 10 being in the form of a cat and a second one of the two - piece bath squirting toys 10 being in the form of a fish . the sections of the two two - piece bath squirting toys 10 and 10 c can be mixed such that the first section 12 of the first one of the two - piece bath squirting toys 10 is connected to the second section 14 c of the second one of the two - piece bath squirting toys 10 c and the first section 12 c of the second one of the two - piece bath squirting toys 10 c is connected to the second section 14 of the first one of the two - piece bath squirting toys 10 . fig8 illustrated a method 500 of using any of two - piece bath squirting toys described above . the method 500 includes a first step 502 of placing the two - piece bath squirting toy in a tub , a second step 504 of filling the two - piece bath squirting toy with water and a third step 506 of squirting water out of the two - piece bath squirting toy . fig8 a illustrates a first method 600 of the second step 504 of filling the two - piece bath squirting toy with water . the first method 600 includes a first step 552 of separating the first section of the two - piece bath squirting toy from the second section of the two - piece bath squirting toy , a second step 554 of filling one of the sections of the two - piece bath squirting toy with water and a third step 556 of connecting the sections of the two - piece bath squirting toy to enclose the interior 22 of the two - piece bath squirting toy . a second method of the second step 504 of filing the two - piece bath squirting toy with water includes squeezing the two - piece bath squirting toy under water as described above . fig9 illustrates a method 600 of cleaning the two - piece bath squirting toy . the method 600 includes separating the first section of the two - piece bath squirting toy from the second section of the two - piece bath squirting toy at step 602 and cleaning the sections of the two - piece bath squirting toy at step 604 . the separated sections of the two - piece bath squirting toy can be cleaned by hand or in a dishwasher ( or in other similar manners ). the separability of the sections of the two - piece bath squirting toy allow the two - piece bath squirting toy to be easily cleaned since the interior 22 of the two - piece bath squirting toy can be easily accessed once the sections of the two - piece bath squirting toy are separated . the foregoing detailed description is considered that of a preferred embodiment only , and the particular shape and nature of at least some of the components in this embodiment are at least partially based on manufacturing advantages and considerations as well as on those pertaining to assembly and operation . modifications of this embodiment may well occur to those skilled in the art and to those who make or use the invention after learning the nature of this preferred embodiment , and the invention lends itself advantageously to such modification and alternative embodiments . therefore , it is to be understood that variations and modifications can be made on the aforementioned structure without departing from the concepts of the present invention , and further it is to be understood that such concepts are intended to be covered by the following claims unless these claims by their language expressly state otherwise .

US-201113079894-A

introduced are methods and systems for an adjustable bed device configured to : gather biological signals associated with multiple users , such as heart rate , breathing rate , or temperature ; analyze the gathered human biological signals ; and heat or cool a bed based on the analysis .

examples of a method , apparatus , and computer program for automating the control of home appliances and improving the sleep environment are disclosed below . in the following description , for the purposes of explanation , numerous specific details are set forth in order to provide a thorough understanding of the embodiments of the invention . one skilled in the art will recognize that the embodiments of the invention may be practiced without these specific details or with an equivalent arrangement . in other instances , well - known structures and devices are shown in block diagram form in order to avoid unnecessarily obscuring the embodiments of the invention . brief definitions of terms , abbreviations , and phrases used throughout this application are given below . in this specification , the term “ biological signal ” and “ bio signal ” are synonyms , and are used interchangeably . reference in this specification to “ sleep phase ” means light sleep , deep sleep , or rem sleep . light sleep comprises stage one and stage two , non - rem sleep . reference in this specification to “ one embodiment ” or “ an embodiment ” means that a particular feature , structure , or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure . the appearances of the phrase “ in one embodiment ” in various places in the specification are not necessarily all referring to the same embodiment , nor are separate or alternative embodiments mutually exclusive of other embodiments . moreover , various features are described that may be exhibited by some embodiments and not by others . similarly , various requirements are described that may be requirements for some embodiments but not others . unless the context clearly requires otherwise , throughout the description and the claims , the words “ comprise ,” “ comprising ,” and the like are to be construed in an inclusive sense , as opposed to an exclusive or exhaustive sense ; that is to say , in the sense of “ including , but not limited to .” as used herein , the terms “ connected ,” “ coupled ,” or any variant thereof , means any connection or coupling , either direct or indirect , between two or more elements . the coupling or connection between the elements can be physical , logical , or a combination thereof . for example , two devices may be coupled directly , or via one or more intermediary channels or devices . as another example , devices may be coupled in such a way that information can be passed there between , while not sharing any physical connection with one another . additionally , the words “ herein ,” “ above ,” “ below ,” and words of similar import , when used in this application , shall refer to this application as a whole and not to any particular portions of this application . where the context permits , words in the detailed description using the singular or plural number may also include the plural or singular number respectively . the word “ or ,” in reference to a list of two or more items , covers all of the following interpretations of the word : any of the items in the list , all of the items in the list , and any combination of the items in the list . if the specification states a component or feature “ may ,” “ can ,” “ could ,” or “ might ” be included or have a characteristic , that particular component or feature is not required to be included or have the characteristic . the term “ module ” refers broadly to software , hardware , or firmware components ( or any combination thereof ). modules are typically functional components that can generate useful data or another output using specified input ( s ). a module may or may not be self - contained . an application program ( also called an “ application ”) may include one or more modules , or a module may include one or more application programs . the term “ on top of ” means that the two objects , where the first object is “ on top of ” the second object , can be rotated so that the first object is above the second object relative to the ground . the 2 objects can be in direct or indirect contact , or may not be in contact at all . the terminology used in the detailed description is intended to be interpreted in its broadest reasonable manner , even though it is being used in conjunction with certain examples . the terms used in this specification generally have their ordinary meanings in the art , within the context of the disclosure , and in the specific context where each term is used . for convenience , certain terms may be highlighted , for example using capitalization , italics , and / or quotation marks . the use of highlighting has no influence on the scope and meaning of a term ; the scope and meaning of a term is the same , in the same context , whether or not it is highlighted . it will be appreciated that the same element can be described in more than one way . consequently , alternative language and synonyms may be used for any one or more of the terms discussed herein , but special significance is not to be placed upon whether or not a term is elaborated or discussed herein . a recital of one or more synonyms does not exclude the use of other synonyms . the use of examples anywhere in this specification , including examples of any terms discussed herein , is illustrative only and is not intended to further limit the scope and meaning of the disclosure or of any exemplified term . likewise , the disclosure is not limited to various embodiments given in this specification . fig1 is a diagram of a bed device , according to one embodiment . any number of user sensors 140 , 150 monitor the bio signals associated with a user , such as the heart rate , the breathing rate , the temperature , motion , or presence , associated with said user . any number of environment sensors 160 , 170 monitor environment properties , such as temperature , sound , light , or humidity . the user sensors 140 , 150 and the environment sensors 160 , 170 communicate their measurements to the processor 100 . the environment sensors 160 , 170 , measure the properties of the environment that the environment sensors 160 , 170 are associated with . in one embodiment , the environment sensors 160 , 170 are placed next to the bed . the processor 100 determines , based on the bio signals associated with said user , historical bio signals associated with said user , user - specified preferences , exercise data associated with said user , or the environment properties received , a control signal , and a time to send said control signal to a bed device 120 . according to one embodiment , the processor 100 is connected to a database 180 , which stores the biological signals associated with a user . additionally , the database 180 can store average biological signals associated with the user , history of biological signals associated with a user , etc . the database 180 can be associated with a user , or the database 180 can be associated with the bed device . fig2 illustrates an example of the bed device of fig1 , according to one embodiment . a sensor strip 210 , associated with a mattress 200 of the bed device 120 , monitors bio signals associated with a user sleeping on the mattress 200 . the sensor strip 210 can be built into the mattress 200 , or can be part of a bed pad device . alternatively , the sensor strip 210 can be a part of any other piece of furniture , such as a rocking chair , a couch , an armchair etc . the sensor strip 210 comprises a temperature sensor , or a piezo sensor . the environment sensor 220 measures environment properties such as temperature , sound , light or humidity . according to one embodiment , the environment sensor 220 is associated with the environment surrounding the mattress 200 . the sensor strip 210 and the environment sensor 220 communicate the measured environment properties to the processor 230 . in some embodiments , the processor 230 can be similar to the processor 100 of fig1 a processor 230 can be connected to the sensor strip 210 , or the environment sensor 220 by a computer bus , such as an i2c bus . also , the processor 230 can be connected to the sensor strip 210 , or the environment sensor 220 by a communication network . by way of example , the communication network connecting the processor 230 to the sensor strip 210 , or the environment sensor 220 includes one or more networks such as a data network , a wireless network , a telephony network , or any combination thereof . the data network may be any local area network ( lan ), metropolitan area network ( man ), wide area network ( wan ), a public data network ( e . g ., the internet ), short range wireless network , or any other suitable packet - switched network , such as a commercially owned , proprietary packet - switched network , e . g ., a proprietary cable or fiber - optic network , and the like , or any combination thereof . in addition , the wireless network may be , for example , a cellular network and may employ various technologies including enhanced data rates for global evolution ( edge ), general packet radio service ( gprs ), global system for mobile communications ( gsm ), internet protocol multimedia subsystem ( ims ), universal mobile telecommunications system ( umts ), etc ., as well as any other suitable wireless medium , e . g ., worldwide interoperability for microwave access ( wimax ), long term evolution ( lte ) networks , code division multiple access ( cdma ), wideband code division multiple access ( wcdma ), wireless fidelity ( wifi ), wireless lan ( wlan ), bluetooth ®, internet protocol ( ip ) data casting , satellite , mobile ad - hoc network ( manet ), and the like , or any combination thereof . the processor 230 is any type of microcontroller , or any processor in a mobile terminal , fixed terminal , or portable terminal including a mobile handset , station , unit , device , multimedia computer , multimedia tablet , internet node , cloud computer , communicator , desktop computer , laptop computer , notebook computer , netbook computer , tablet computer , personal communication system ( pcs ) device , personal navigation device , personal digital assistants ( pdas ), audio / video player , digital camera / camcorder , positioning device , television receiver , radio broadcast receiver , electronic book device , game device , the accessories and peripherals of these devices , or any combination thereof . fig3 illustrates an example of layers comprising the bed pad device of fig1 , according to one embodiment . in some embodiments , the bed pad device 120 is a pad that can be placed on top of the mattress . bed pad device 120 comprises a number of layers . a top layer 350 comprises fabric . a layer 340 comprises batting , and a sensor strip 330 . a layer 320 comprises coils for cooling or heating the bed device . a layer 310 comprises waterproof material . according to another embodiment , the layer 320 comprises a material that can be heated or cooled in the 10 ° c . to 50 ° c . range without changing the materials properties such as the state of matter . an example of such materials can be air , water , argon , a synthetic material such as carbon nanotubes , etc . according to one embodiment , the layer 320 is connected to an external thermal regulator which heats or cools the material , based on the signal received from the processor 230 . according to another embodiment , the layer 320 comprising the material is integrated into the mattress , the bed sheets , the bed cover , the bed frame , etc . the layer 320 comprising the material can also be integrated with any piece of furniture . fig4 a illustrates a user sensor 420 , 440 , 450 , 470 placed on a sensor strip 400 , according to one embodiment . in some embodiments , the user sensors 420 , 440 , 450 , 470 can be similar to or part of the sensor strip 210 of fig2 . sensors 470 and 440 comprise a piezo sensor , which can measure a bio signal associated with a user , such as the heart rate and the breathing rate . sensors 450 and 420 comprise a temperature sensor . according to one embodiment , sensors 450 , and 470 measure the bio signals associated with one user , while sensors 420 , 440 measure the bio signals associated with another user . analog - to - digital converter 410 converts the analog sensor signals into digital signals to be communicated to a processor . computer bus 430 and 460 , such as the i2c bus , communicates the digitized bio signals to a processor . fig4 b is the sensor strip 400 , according to one embodiment . the sensor strip 400 comprises several layers , such as a fabric layer 471 , a foam layer 473 , 475 , a piezo sensor 470 , 440 , a polycarbonate stiffener 485 , a stiffener foam 487 , and a temperature sensor 450 , 420 . region 477 of the fabric layer 471 is the tail region of the sensor strip 400 . wire leads 489 associated with piezo sensor 470 , 440 , and temperature sensor 450 , 420 are placed on top of the tail region 477 . the fabric layer 471 includes two short edges and two long edges . the length of the short edge varies from 40 - 70 mm . the fabric layer 471 has at least one coated surface . the foam layer 473 , 475 also has two short edges and two long edges . one of the long edges includes multiple protrusions 491 , and multiple gaps 493 , between the multiple protrusions 491 . fig4 c is a flowchart of a process to manufacture the body of the sensor strip 400 , according to one embodiment . in step 472 , the fabric layer 471 is laid out with the coated surface pointing up . in step 474 , a first foam layer is applied to the fabric layer 471 . in one embodiment , the first foam layer 473 is centered on the fabric layer 471 , with a margin of 10 mm from the first short edge and a margin of 5 mm from the long edges . the margin to the second short edge of the fabric layer 471 is greater than the margin to the first short edge . in one embodiment , the margin to the second short edge is at least twice as big than the margin to the first short edge . the margin to the second short edge of the fabric layer 471 is considered a tail part of the sensor strip 400 , comprising the tail region 477 of the fabric layer 471 . in step 476 , two temperature sensors 450 , 420 are placed on the first foam layer 473 . in one embodiment , the temperature sensors are placed 17 mm from a long edge of the fabric layer 471 . in step 478 , two piezo sensors 470 , 440 are placed on the first foam layer 473 . in one embodiment , the piezo sensors are centered on the fabric layer 471 . in step 480 , a second foam layer 475 is applied on top of the piezo sensors . in one embodiment , the second foam layer 475 is centered on the fabric layer 471 , with a margin of 10 mm from the short edges , and 5 mm from the long edges . further , the second foam layer 475 is placed as a mirror image of the first foam layer 473 , and is interlaced with the first foam layer 473 . in step 482 , a second fabric layer is applied on top of the second foam layer 475 . in step 484 , the whole assembly , comprising all the layers , is laminated . fig4 d is a flowchart of a process to manufacture the tail part of the sensor strip 400 , according to one embodiment . in step 486 , first polycarbonate stiffener layer 485 is placed on top of the tail region 477 of the fabric layer 471 . in one embodiment , the dimensions of the polycarbonate stiffener layer 485 are 40 - 70 mm by 5 - 25 mm . the 40 - 70 mm edge matches the length of the 40 - 70 mm edge of the sensor strip 400 . in step 488 , the first stiffener foam layer 487 is applied on top of the polycarbonate stiffener layer 485 . in step 490 , the wire leads 489 of the piezo sensors 470 , 440 , and the wire leads 489 of the temperature sensors 450 , 420 are placed on top of the first stiffener foam layer 487 , and past the tail region 477 of the fabric layer 471 . in step 492 , the second stiffener foam layer is applied on top of the wire leads 489 . the dimensions of the second stiffener foam layer are identical to the first stiffener foam layer 487 . in step 494 , the second polycarbonate stiffener layer is applied on top of the second stiffener foam layer . the dimensions of the second polycarbonate stiffener layer are identical to the dimensions of the first polycarbonate stiffener layer 485 . in step 496 , the whole tail part assembly is laminated . fig5 a and 5b show different configurations of the sensor strip , to fit different size mattresses , according to one embodiment . fig5 c and 5d show how such different configurations of the sensor strip can be achieved . specifically , sensor strip 400 comprises a computer bus 510 , 530 , and a sensor striplet 505 . the computer bus 510 , 530 can be bent at predetermined locations 540 , 550 , 560 , 570 . bending the computer bus 515 at location 540 produces the maximum total length of the computer bus 530 . computer bus 530 combined with a sensor striplet 505 , fits a king size mattress 520 . bending the computer bus 515 at location 570 produces the smallest total length of the computer bus , 510 . computer bus 510 combined with a sensor striplet 505 , fits a twin size mattress 500 . bending the computer bus 515 at location 560 , enables the sensor strip 400 to fit a full - size bed . bending the computer bus 515 at location 550 enables the sensor strip 400 to fit a queen - size bed . in some embodiments , twin mattress 500 , or king mattress 520 can be similar to the mattress 200 of fig2 . fig6 a illustrates the division of the heating coil 600 into zones and subzones , according to one embodiment . specifically , the heating coil 600 is divided into two zones 660 and 610 , each corresponding to one user of the bed . each zone 660 and 610 can be heated or cooled independently of the other zone in response to the user &# 39 ; s needs . to achieve independent heating of the two zones 660 and 610 , the power supply associated with the heating coil 600 is divided into two zones , each power supply zone corresponding to a single user zone 660 , 610 . further , each zone 660 and 610 is further subdivided into subzones . zone 660 is divided into subzones 670 , 680 , 690 , and 695 . zone 610 is divided into subzones 620 , 630 , 640 , and 650 . the distribution of coils in each subzone is configured so that the subzone is uniformly heated . however , the subzones may differ among themselves in the density of coils . for example , the data associated with said user subzone 670 has lower density of coils than subzone 680 . this will result in subzone 670 having lower temperature than subzone 680 , when the coils are heated . similarly , when the coils are used for cooling , subzones 670 will have higher temperature than subzone 680 . according to one embodiment , subzones 680 and 630 with highest coil density correspond to the user &# 39 ; s lower back ; and subzones 695 and 650 with highest coil density correspond to user &# 39 ; s feet . according to one embodiment , even if the users switch sides of the bed , the system will correctly identify which user is sleeping in which zone by identifying the user based on any of the following signals alone , or in combination : heart rate , breathing rate , body motion , or body temperature associated with said user . in another embodiment , the power supply associated with the heating coil 600 is divided into a plurality of zones , each power supply zone corresponding to a subzone 620 , 630 , 640 , 650 , 670 , 680 , 690 , 695 . the user can control the temperature of each subzone 620 , 630 , 640 , 650 , 670 , 680 , 690 , 695 independently . further , each user can independently specify the temperature preferences for each of the subzones . even if the users switch sides of the bed , the system will correctly identify the user , and the preferences associated with the user by identifying the user based on any of the following signals alone , or in combination : heart rate , breathing rate , body motion , or body temperature associated with said user . fig6 b and 6c illustrate the independent control of the different subzones in each zone 610 , 660 , according to one embodiment . set of uniform coils 611 , connected to power management box 601 , uniformly heats or cools the bed . another set of coils , targeting specific areas of the body such as the neck , the back , the legs , or the feet , is layered on top of the uniform coils 611 . subzone 615 heats or cools the neck . subzone 625 heats or cools the back . subzone 635 heats or cools the legs , and subzone 645 heats or cools the feet . power is distributed to the coils via duty cycling of the power supply 605 . contiguous sets of coils can be heated or cooled at different levels by assigning the power supply duty cycle to each set of coils . the user can control the temperature of each subzone independently . fig7 is a flowchart of the process for deciding when to heat or cool the bed device , according to one embodiment . at block 700 , the process obtains a biological signal associated with a user , such as presence in bed , motion , breathing rate , heart rate , or a temperature . the process obtains said biological signal from a sensor associated with a user . further , at block 710 , the process obtains environment property , such as the amount of ambient light and the bed temperature . the process obtains environment property from and environment sensor associated with the bed device . if the user is in bed , the bed temperature is low , and the ambient light is low , the process sends a control signal to the bed device . the control signal comprises an instruction to heat the bed device to the average nightly temperature associated with said user . according to another embodiment , the control signal comprises an instruction to heat the bed device to a user - specified temperature . similarly , if the user is in bed , the bed temperature is high , and the ambient light is low , the process sends a control signal to the bed device to cool the bed device to the average nightly temperature associated with said user . according to another embodiment , the control signal comprises an instruction to cool the bed device to a user - specified temperature . in another embodiment , in addition to obtaining the biological signal associated with said user , and the environment property , the process obtains a history of biological signals associated with said user . the history of biological signals can be stored in a database associated with the bed device , or in a database associated with a user . the history of biological signals comprises the average bedtime the user went to sleep for each day of the week ; that is , the history of biological signals comprises the average bedtime associated with said user on monday , the average bedtime associated with said user on tuesday , etc . for a given day of the week , the process determines the average bedtime associated with said user for that day of the week , and sends the control signal to the bed device , allowing enough time for the bed to reach the desired temperature , before the average bedtime associated with said user . the control signal comprises an instruction to heat , or cool the bed to a desired temperature . the desired temperature may be automatically determined , such as by averaging the historical nightly temperature associated with a user , or the desired temperature may be specified by the user . the technology disclosed here categorizes the sleep phase associated with a user as light sleep , deep sleep , or rem sleep . light sleep comprises stage one and stage two sleep . the technology performs the categorization based on the breathing rate associated with said user , heart rate associated with said user , motion associated with said user , and body temperature associated with said user . generally , when said user is awake the breathing is erratic . when the user is sleeping , the breathing becomes regular . the transition between being awake and sleeping is quick , and lasts less than 1 minute . fig8 is a flowchart of the process for recommending a bed time to the user , according to one embodiment . at block 800 , the process obtains a history of sleep phase information associated with said user . the history of sleep phase information comprises an amount of time the user spent in each of the sleep phases , light sleep , deep sleep , or rem sleep . the history of sleep phase information can be stored in a database associated with the user . based on this information , the process determines how much light sleep , deep sleep , and rem sleep , the user needs on average every day . in another embodiment , the history of sleep phase information comprises the average bedtime associated with said user for each day of the week ( e . g . the average bedtime associated with said user on monday , the average bedtime associated with said user on tuesday , etc .). at block 810 , the process obtains user - specified wake - up time , such as the alarm setting associated with said user . at block 820 , the process obtains exercise information associated with said user , such as the distance the user ran that day , the amount of time the user exercised in the gym , or the amount of calories the user burned that day . according to one embodiment , the process obtains said exercise information from a user phone , a wearable device , a fitbit bracelet , or a database storing said exercise information . based on all this information , at block 830 , the process recommends a bedtime to the user . for example , if the user has not been getting enough deep and rem sleep in the last few days , the process recommends an earlier bedtime to the user . also , if the user has exercised more than the average daily exercise , the process recommends an earlier bedtime to the user . fig9 is a flowchart of the process for activating a user &# 39 ; s alarm , according to one embodiment . at block 900 , the process obtains the compound bio signal associated with said user . the compound bio signal associated with said user comprises the heart rate associated with said user , and the breathing rate associated with said user . according to one embodiment , the process obtains the compound bio signal from a sensor associated with said user . at block 910 , the process extracts the heart rate signal from the compound bio signal . for example , the process extracts the heart rate signal associated with said user by performing low - pass filtering on the compound bio signal . also , at block 920 , the process extracts the breathing rate signal from the compound bio signal . for example , the process extracts the breathing rate by performing bandpass filtering on the compound bio signal . the breathing rate signal includes breath duration , pauses between breaths , as well as breaths per minute . at block 930 , the process obtains user &# 39 ; s wake - up time , such as the alarm setting associated with said user . based on the heart rate signal and the breathing rate signal , the process determines the sleep phase associated with said user , and if the user is in light sleep , and current time is at most one hour before the alarm time , at block 940 , the process activates an alarm . waking up the user during the deep sleep or rem sleep is detrimental to the user &# 39 ; s health because the user will feel disoriented , groggy , and will suffer from impaired memory . consequently , at block 950 , the process activates an alarm , when the user is in light sleep and when the current time is at most one hour before the user specified wake - up time . fig1 is a flowchart of the process for turning off an appliance , according to one embodiment . at block 1000 , the process obtains the compound bio signal associated with said user . the compound bio signal comprises the heart rate associated with said user , and the breathing rate associated with said user . according to one embodiment , the process obtains the compound bio signal from a sensor associated with said user . at block 1010 , the process extracts the heart rate signal from the compound bio signal by , for example , performing low - pass filtering on the compound bio signal . also , at block 1020 , the process extracts the breathing rate signal from the compound bio signal by , for example , performing bandpass filtering on the compound bio signal . at block 1030 , the process obtains an environment property , comprising temperature , humidity , light , sound from an environment sensor associated with said sensor strip . based on the environment property and the sleep state associated with said user , at block 1040 , the process determines whether the user is sleeping . if the user is sleeping , the process , at block 1050 , turns an appliance off . for example , if the user is asleep and the environment temperature is above the average nightly temperature , the process turns off the thermostat . further , if the user is asleep and the lights are on , the process turns off the lights . similarly , if the user is asleep and the tv is on , the process turns off the tv . fig1 is a diagram of a system capable of automating the control of the home appliances , according to one embodiment . any number of user sensors 1140 , 1150 monitor biological signals associated with said user , such as temperature , motion , presence , heart rate , or breathing rate . any number of environment sensors 1160 , 1170 monitor environment properties , such as temperature , sound , light , or humidity . according to one embodiment , the environment sensors 1160 , 1170 are placed next to a bed . the user sensors 1140 , 1150 and the environment sensors 1160 , 1170 communicate their measurements to the processor 1100 . the processor 1100 determines , based on the current biological signals associated with said user , historical biological signals associated with said user , user - specified preferences , exercise data associated with said user , and the environment properties received , a control signal , and a time to send said control signal to an appliance 1120 , 1130 . the processor 1100 is any type of microcontroller , or any processor in a mobile terminal , fixed terminal , or portable terminal including a mobile handset , station , unit , device , multimedia computer , multimedia tablet , internet node , cloud computer , communicator , desktop computer , laptop computer , notebook computer , netbook computer , tablet computer , personal communication system ( pcs ) device , personal navigation device , personal digital assistants ( pdas ), audio / video player , digital camera / camcorder , positioning device , television receiver , radio broadcast receiver , electronic book device , game device , the accessories and peripherals of these devices , or any combination thereof . the processor 1100 can be connected to the user sensor 1140 , 1150 , or the environment sensor 1160 , 1170 by a computer bus , such as an i2c bus . also , the processor 1100 can be connected to the user sensor 1140 , 1150 , or environment sensor 1160 , 1170 by a communication network 1110 . by way of example , the communication network 1110 connecting the processor 1100 to the user sensor 1140 , 1150 , or the environment sensor 1160 , 1170 includes one or more networks such as a data network , a wireless network , a telephony network , or any combination thereof . the data network may be any local area network ( lan ), metropolitan area network ( man ), wide area network ( wan ), a public data network ( e . g ., the internet ), short range wireless network , or any other suitable packet - switched network , such as a commercially owned , proprietary packet - switched network , e . g ., a proprietary cable or fiber - optic network , and the like , or any combination thereof . in addition , the wireless network may be , for example , a cellular network and may employ various technologies including enhanced data rates for global evolution ( edge ), general packet radio service ( gprs ), global system for mobile communications ( gsm ), internet protocol multimedia subsystem ( ims ), universal mobile telecommunications system ( umts ), etc ., as well as any other suitable wireless medium , e . g ., worldwide interoperability for microwave access ( wimax ), long term evolution ( lte ) networks , code division multiple access ( cdma ), wideband code division multiple access ( wcdma ), wireless fidelity ( wifi ), wireless lan ( wlan ), bluetooth ®, internet protocol ( ip ) data casting , satellite , mobile ad - hoc network ( manet ), and the like , or any combination thereof . fig1 is an illustration of the system capable of controlling an appliance and a home , according to one embodiment . the appliances , that the system disclosed here can control , comprise an alarm , a coffee machine , a lock , a thermostat , a bed device , a humidifier , or a light . for example , the system detects that the user has fallen asleep , the system sends a control signal to the lights to turn off , to the locks to engage , and to the thermostat to lower the temperature . according to another example , if the system detects that the user has woken up and it is morning , the system sends a control signal to the coffee machine to start making coffee . fig1 is a flowchart of the process for controlling an appliance , according to one embodiment . in one embodiment , at block 1300 , the process obtains history of biological signals , such as at what time does the user go to bed on a particular day of the week ( e . g . the average bedtime associated with said user on monday , the average bedtime associated with said user on tuesday etc .). the history of biological signals can be stored in a database associated with the user , or in a database associated with the bed device . in another embodiment , at block 1300 , the process also obtains user specified preferences , such as the preferred bed temperature associated with said user . based on the history of biological signals and user - specified preferences , the process , at block 1320 , determines a control signal , and a time to send said control signal to an appliance . it block 1330 , the process determines whether to send a control signal to an appliance . for example , if the current time is within half an hour of average bedtime associated with said user on that particular day of the week , the process , at block 1340 , sends a control signal to an appliance . for example , the control signal comprises an instruction to turn on the bed device , and the user specified bed temperature . alternatively , the bed temperature is determined automatically , such as by calculating the average nightly bed temperature associated with a user . according to another embodiment , at block 1300 , the process obtains a current biological signal associated with a user from a sensor associated with said user . at block 1310 , the process also obtains environment data , such as the ambient light , from an environment sensor associated with a bed device . based on the current biological signal , the process identifies whether the user is asleep . if the user is asleep and the lights are on , the process sends an instruction to turn off the lights . in another embodiment , if the user is asleep , the lights are off , and the ambient light is high , the process sends an instruction to the blinds to shut . in another embodiment , if the user is asleep , the process sends an instruction to the locks to engage . in another embodiment , the process , at block 1300 , obtains history of biological signals , such as at what time the user goes to bed on a particular day of the week ( e . g . the average bedtime associated with said user on monday , the average bedtime associated with said user on tuesday etc .). the history of biological signals can be stored in a database associated with the bed device , or in a database associated with a user . alternatively , the user may specify a bedtime for the user for each day of the week . further , the process obtains the exercise data associated with said user , such as the number of hours the user spent exercising , or the heart rate associated with said user during exercising . according to one embodiment , the process obtains the exercise data from a user phone , a wearable device , fitbit bracelet , or a database associated with said user . based on the average bedtime for that day of the week , and the exercise data during the day , the process , at block 1320 , determines the expected bedtime associated with said user that night . the process then sends an instruction to the bed device to heat to a desired temperature , before the expected bedtime . the desired temperature can be specified by the user , or can be determined automatically , based on the average nightly temperature associated with said user . fig1 is a flowchart of the process for controlling an appliance , according to another embodiment . the process , at block 1400 , receives current biological signal associated with said user , such as the heart rate , breathing rate , presence , motion , or temperature , associated with said user . based on the current biological signal , the process , at block 1410 , identifies current sleep phase , such as light sleep , deep sleep , or rem sleep . the process , at block 1420 also receives a current environment property value , such as the temperature , the humidity , the light , or the sound . the process , at block 1430 , accesses a database , which stores historical values associated with the environment property and the current sleep phase . that is , the database associates each sleep phase with an average historical value of the different environment properties . the database maybe associated with the bed device , maybe associated with the user , or maybe associated with a remote server . the process , at block 1440 , then calculates a new average of the environment property based on the current value of the environment property and the historical value of the environment property , and assigns the new average to the current sleep phase in the database . if there is a mismatch between the current value of the environment property , and the historical average , the process , at block 1450 , regulates the current value to match the historical average . for example , the environment property can be the temperature associated with the bed device . the database stores the average bed temperature corresponding to each of the sleep phase , light sleep , deep sleep , rem sleep . if the current bed temperature is below the historical average , the process sends a control signal to increase the temperature of the bed to match the historical average . biological signals associated with a person , such as a heart rate or a breathing rate , indicate said person &# 39 ; s state of health . changes in the biological signals can indicate an immediate onset of a disease , or a long - term trend that increases the risk of a disease associated with said person . monitoring the biological signals for such changes can predict the onset of a disease , can enable calling for help when the onset of the disease is immediate , or can provide advice to the person if the person is exposed to a higher risk of the disease in the long - term . fig1 is a diagram of a system for monitoring biological signals associated with a user , and providing notifications or alarms , according to one embodiment . any number of user sensors 1530 , 1540 monitor bio signals associated with said user , such as temperature , motion , presence , heart rate , or breathing rate . the user sensors 1530 , 1540 communicate their measurements to the processor 1500 . the processor 1500 determines , based on the bio signals associated with said user , historical biological signals associated with said user , or user - specified preferences whether to send a notification or an alarm to a user device 1520 . in some embodiments , the user device 1520 and the processor 1500 can be the same device . the user device 1520 is any type of a mobile terminal , fixed terminal , or portable terminal including a mobile handset , station , unit , device , multimedia computer , multimedia tablet , internet node , communicator , desktop computer , laptop computer , notebook computer , netbook computer , tablet computer , personal communication system ( pcs ) device , personal navigation device , personal digital assistants ( pdas ), audio / video player , digital camera / camcorder , positioning device , television receiver , radio broadcast receiver , electronic book device , game device , the accessories and peripherals of these devices , or any combination thereof . the processor 1500 is any type of microcontroller , or any processor in a mobile terminal , fixed terminal , or portable terminal including a mobile handset , station , unit , device , multimedia computer , multimedia tablet , internet node , cloud computer , communicator , desktop computer , laptop computer , notebook computer , netbook computer , tablet computer , personal communication system ( pcs ) device , personal navigation device , personal digital assistants ( pdas ), audio / video player , digital camera / camcorder , positioning device , television receiver , radio broadcast receiver , electronic book device , game device , the accessories and peripherals of these devices , or any combination thereof . the processor 1500 can be connected to the user sensor 1530 , 1540 by a computer bus , such as an i2c bus . also , the processor 1500 can be connected to the user sensor 1530 , 1540 by a communication network 1510 . by way of example , the communication network 1510 connecting the processor 1500 to the user sensor 1530 , 1540 includes one or more networks such as a data network , a wireless network , a telephony network , or any combination thereof . the data network may be any local area network ( lan ), metropolitan area network ( man ), wide area network ( wan ), a public data network ( e . g ., the internet ), short range wireless network , or any other suitable packet - switched network , such as a commercially owned , proprietary packet - switched network , e . g ., a proprietary cable or fiber - optic network , and the like , or any combination thereof . in addition , the wireless network may be , for example , a cellular network and may employ various technologies including enhanced data rates for global evolution ( edge ), general packet radio service ( gprs ), global system for mobile communications ( gsm ), internet protocol multimedia subsystem ( ims ), universal mobile telecommunications system ( umts ), etc ., as well as any other suitable wireless medium , e . g ., worldwide interoperability for microwave access ( wimax ), long term evolution ( lte ) networks , code division multiple access ( cdma ), wideband code division multiple access ( wcdma ), wireless fidelity ( wifi ), wireless lan ( wlan ), bluetooth ®, internet protocol ( ip ) data casting , satellite , mobile ad - hoc network ( manet ), and the like , or any combination thereof . fig1 is a flowchart of a process for generating a notification based on a history of biological signals associated with a user , according to one embodiment . the process , at block 1600 , obtains a history of biological signals , such as the presence history , motion history , breathing rate history , or heart rate history , associated with said user . the history of biological signals can be stored in a database associated with a user . at block 1610 , the process determines if there is an irregularity in the history of biological signals within a timeframe . if there is an irregularity , at block 1620 , the process generates a notification to the user . the timeframe can be specified by the user , or can be automatically determined based on the type of irregularity . for example , the heart rate associated with said user goes up within a one day timeframe when the user is sick . according to one embodiment , the process detects an irregularity , specifically , that a daily heart rate associated with said user is higher than normal . consequently , the process warns the user that the user may be getting sick . according to another embodiment , the process detects an irregularity , such as that an elderly user is spending at least 10 % more time in bed per day over the last several days , than the historical average . the process generates a notification to the elderly user , or to the elderly user &# 39 ; s caretaker , such as how much more time the elderly user is spending in bed . in another embodiment , the process detects an irregularity such as an increase in resting heart rate , by more than 15 beats per minute , over a ten - year period . such an increase in the resting heart rate doubles the likelihood that the user will die from a heart disease , compared to those people whose heart rates remained stable . consequently , the process warns the user that the user is at risk of a heart disease . fig1 is a flowchart of a process for generating a comparison between a biological signal associated with a user and a target biological signal , according to one embodiment . the process , at block 1700 , obtains a current biological signal associated with a user , such as presence , motion , breathing rate , temperature , or heart rate , associated with said user . the process obtains said current biological signal from a sensor associated with said user . the process , at block 1710 , then obtains a target biological signal , such as a user - specified biological signal , a biological signal associated with a healthy user , or a biological signal associated with an athlete . according to one embodiment , the process obtains said target biological signal from a user , or a database storing biological signals . the process , at block 1720 , compares current bio signal associated with said user and target bio signal , and generates a notification based on the comparison 1730 . the comparison of the current bio signal associated with said user and target bio signal comprises detecting a higher frequency in the current biological signal then in the target biological signal , detecting a lower frequency in the current biological signal than in the target biological signal , detecting higher amplitude in the current biological signal than in the target biological signal , or detecting lower amplitude in the current biological signal than in the target biological signal . according to one embodiment , the process of fig1 can be used to detect if an infant has a higher risk of sudden infant death syndrome (“ sids ”). in sids victims less than one month of age , heart rate is higher than in healthy infants of same age , during all sleep phases . sids victims greater than one month of age show higher heart rates during rem sleep phase . in case of monitoring an infant for a risk of sids , the process obtains the current bio signal associated with the sleeping infant , and a target biological signal associated with the heart rate of a healthy infant , where the heart rate is at the high end of a healthy heart rate spectrum . the process obtains the current bio signal from a sensor strip associated with the sleeping infant . the process obtains said target biological signal from a database of biological signals . if the frequency of the biological signal of the infant exceeds the target biological signal , the process generates a notification to the infant &# 39 ; s caretaker , that the infant is at higher risk of sids . according to another embodiment , the process of fig1 can be used in fitness training a normal resting heart rate for adults ranges from 60 to 100 beats per minute . generally , a lower heart rate at rest implies more efficient heart function and better cardiovascular fitness . for example , a well - trained athlete might have a normal resting heart rate closer to 40 beats per minute . thus , a user may specify a target rest heart rate of 40 beats per minute . the process fig1 generates a comparison between the actual bio signal associated with said user and the target bio signal 1720 , and based on the comparison , the process generates a notification whether the user has reached his target , or whether the user needs to exercise more 1730 . fig1 is a flowchart of a process for detecting the onset of a disease , according to one embodiment . the process , at block 1800 , obtains the current bio signal associated with a user , such as presence , motion , temperature , breathing rate , or heart rate , associated with said user . the process obtains the current bio signal from a sensor associated with said user . further , the process , at block 1810 , obtains a history of bio signals associated with said user from a database . the history of bio signals comprises the bio signals associated with said user , accumulated over time . the history of biological signals can be stored in a database associated with a user . the process , at block 1820 , then detects a discrepancy between the current bio signal and the history of bio signals , where the discrepancy is indicative of an onset of a disease . the process , at block 1830 , then generates an alarm to the user &# 39 ; s caretaker . the discrepancy between the current bio signal and the history of bio signals comprises a higher frequency in the current bio signal than in the history of bio signals , or a lower frequency in the current bio signal than in the history of bio signals . according to one embodiment , the process of fig1 can be used to detect an onset of an epileptic seizure . a healthy person has a normal heart rate between 60 and 100 beats per minute . during epileptic seizures , the median heart rate associated with said person exceeds 100 beats per minute . the process of fig1 detects that the heart rate associated with said user exceeds the normal heart rate range associated with said user . the process then generates an alarm to the user &# 39 ; s caretaker that the user is having an epileptic seizure . although rare , epileptic seizures can cause the median heart rate associated with a person to drop below 40 beats per minute . similarly , the process of fig1 detects if the current heart rate is below the normal heart rate range associated with said user . the process then generates an alarm to the user &# 39 ; s caretaker that the user is having an epileptic seizure . fig1 is a diagrammatic representation of a machine in the example form of a computer system 1900 within which a set of instructions , for causing the machine to perform any one or more of the methodologies or modules discussed herein , may be executed . in the example of fig1 , the computer system 1900 includes a processor , memory , non - volatile memory , and an interface device . various common components ( e . g ., cache memory ) are omitted for illustrative simplicity . the computer system 1900 is intended to illustrate a hardware device on which any of the components described in the example of fig1 - 18 ( and any other components described in this specification ) can be implemented . the computer system 1900 can be of any applicable known or convenient type . the components of the computer system 1900 can be coupled together via a bus or through some other known or convenient device . this disclosure contemplates the computer system 1900 taking any suitable physical form . as example and not by way of limitation , computer system 1900 may be an embedded computer system , a system - on - chip ( soc ), a single - board computer system ( sbc ) ( such as , for example , a computer - on - module ( com ) or system - on - module ( som )), a desktop computer system , a laptop or notebook computer system , an interactive kiosk , a mainframe , a mesh of computer systems , a mobile telephone , a personal digital assistant ( pda ), a server , or a combination of two or more of these . where appropriate , computer system 1900 may include one or more computer systems 1900 ; be unitary or distributed ; span multiple locations ; span multiple machines ; or reside in a cloud , which may include one or more cloud components in one or more networks . where appropriate , one or more computer systems 1900 may perform without substantial spatial or temporal limitation one or more steps of one or more methods described or illustrated herein . as an example and not by way of limitation , one or more computer systems 1900 may perform in real time or in batch mode one or more steps of one or more methods described or illustrated herein . one or more computer systems 1900 may perform at different times or at different locations one or more steps of one or more methods described or illustrated herein , where appropriate . the processor may be , for example , a conventional microprocessor such as an intel pentium microprocessor or motorola power pc microprocessor . one of skill in the relevant art will recognize that the terms “ machine - readable ( storage ) medium ” or “ computer - readable ( storage ) medium ” include any type of device that is accessible by the processor . the memory is coupled to the processor by , for example , a bus . the memory can include , by way of example but not limitation , random access memory ( ram ), such as dynamic ram ( dram ) and static ram ( sram ). the memory can be local , remote , or distributed . the bus also couples the processor to the non - volatile memory and drive unit . the non - volatile memory is often a magnetic floppy or hard disk , a magnetic - optical disk , an optical disk , a read - only memory ( rom ), such as a cd - rom , eprom , or eeprom , a magnetic or optical card , or another form of storage for large amounts of data . some of this data is often written , by a direct memory access process , into memory during execution of software in the computer 1900 . the non - volatile storage can be local , remote , or distributed . the non - volatile memory is optional because systems can be created with all applicable data available in memory . a typical computer system will usually include at least a processor , memory , and a device ( e . g ., a bus ) coupling the memory to the processor . software is typically stored in the non - volatile memory and / or the drive unit . indeed , storing and entire large program in memory may not even be possible . nevertheless , it should be understood that for software to run , if necessary , it is moved to a computer readable location appropriate for processing , and for illustrative purposes , that location is referred to as the memory in this paper . even when software is moved to the memory for execution , the processor will typically make use of hardware registers to store values associated with the software , and local cache that , ideally , serves to speed up execution . as used herein , a software program is assumed to be stored at any known or convenient location ( from non - volatile storage to hardware registers ) when the software program is referred to as “ implemented in a computer - readable medium .” a processor is considered to be “ configured to execute a program ” when at least one value associated with the program is stored in a register readable by the processor . the bus also couples the processor to the network interface device . the interface can include one or more of a modem or network interface . it will be appreciated that a modem or network interface can be considered to be part of the computer system 1900 . the interface can include an analog modem , isdn modem , cable modem , token ring interface , satellite transmission interface ( e . g . “ direct pc ”), or other interfaces for coupling a computer system to other computer systems . the interface can include one or more input and / or output devices . the i / o devices can include , by way of example but not limitation , a keyboard , a mouse or other pointing device , disk drives , printers , a scanner , and other input and / or output devices , including a display device . the display device can include , by way of example but not limitation , a cathode ray tube ( crt ), liquid crystal display ( lcd ), or some other applicable known or convenient display device . for simplicity , it is assumed that controllers of any devices not depicted in the example of fig9 reside in the interface . in operation , the computer system 1900 can be controlled by operating system software that includes a file management system , such as a disk operating system . one example of operating system software with associated file management system software is the family of operating systems known as windows ® from microsoft corporation of redmond , wash ., and their associated file management systems . another example of operating system software with its associated file management system software is the linux ™ operating system and its associated file management system . the file management system is typically stored in the non - volatile memory and / or drive unit and causes the processor to execute the various acts required by the operating system to input and output data and to store data in the memory , including storing files on the non - volatile memory and / or drive unit . some portions of the detailed description may be presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory . these algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art . an algorithm is here , and generally , conceived to be a self - consistent sequence of operations leading to a desired result . the operations are those requiring physical manipulations of physical quantities . usually , though not necessarily , these quantities take the form of electrical or magnetic signals capable of being stored , transferred , combined , compared , and otherwise manipulated . it has proven convenient at times , principally for reasons of common usage , to refer to these signals as bits , values , elements , symbols , characters , terms , numbers , or the like . it should be borne in mind , however , that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities . unless specifically stated otherwise as apparent from the following discussion , it is appreciated that throughout the description , discussions utilizing terms such as “ processing ” or “ computing ” or “ calculating ” or “ determining ” or “ displaying ” or “ generating ” or the like , refer to the action and processes of a computer system , or similar electronic computing device , that manipulates and transforms data represented as physical ( electronic ) quantities within the computer system &# 39 ; s registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage , transmission or display devices . the algorithms and displays presented herein are not inherently related to any particular computer or other apparatus . various general purpose systems may be used with programs in accordance with the teachings herein , or it may prove convenient to construct more specialized apparatus to perform the methods of some embodiments . the required structure for a variety of these systems will appear from the description below . in addition , the techniques are not described with reference to any particular programming language , and various embodiments may thus be implemented using a variety of programming languages . in alternative embodiments , the machine operates as a standalone device or may be connected ( e . g ., networked ) to other machines . in a networked deployment , the machine may operate in the capacity of a server or a client machine in a client - server network environment , or as a peer machine in a peer - to - peer ( or distributed ) network environment . the machine may be a server computer , a client computer , a personal computer ( pc ), a tablet pc , a laptop computer , a set - top box ( stb ), a personal digital assistant ( pda ), a cellular telephone , an iphone , a blackberry , a processor , a telephone , a web appliance , a network router , switch or bridge , or any machine capable of executing a set of instructions ( sequential or otherwise ) that specify actions to be taken by that machine . while the machine - readable medium or machine - readable storage medium is shown in an exemplary embodiment to be a single medium , the term “ machine - readable medium ” and “ machine - readable storage medium ” should be taken to include a single medium or multiple media ( e . g ., a centralized or distributed database , and / or associated caches and servers ) that store the one or more sets of instructions . the term “ machine - readable medium ” and “ machine - readable storage medium ” shall also be taken to include any medium that is capable of storing , encoding or carrying a set of instructions for execution by the machine and that cause the machine to perform any one or more of the methodologies or modules of the presently disclosed technique and innovation . in general , the routines executed to implement the embodiments of the disclosure , may be implemented as part of an operating system or a specific application , component , program , object , module or sequence of instructions referred to as “ computer programs .” the computer programs typically comprise one or more instructions set at various times in various memory and storage devices in a computer , and that , when read and executed by one or more processing units or processors in a computer , cause the computer to perform operations to execute elements involving the various aspects of the disclosure . moreover , while embodiments have been described in the context of fully functioning computers and computer systems , those skilled in the art will appreciate that the various embodiments are capable of being distributed as a program product in a variety of forms , and that the disclosure applies equally regardless of the particular type of machine or computer - readable media used to actually effect the distribution . further examples of machine - readable storage media , machine - readable media , or computer - readable ( storage ) media include but are not limited to recordable type media such as volatile and non - volatile memory devices , floppy and other removable disks , hard disk drives , optical disks ( e . g ., compact disk read - only memory ( cd roms ), digital versatile disks , ( dvds ), etc . ), among others , and transmission type media such as digital and analog communication links . in some circumstances , operation of a memory device , such as a change in state from a binary one to a binary zero or vice - versa , for example , may comprise a transformation , such as a physical transformation . with particular types of memory devices , such a physical transformation may comprise a physical transformation of an article to a different state or thing . for example , but without limitation , for some types of memory devices , a change in state may involve an accumulation and storage of charge or a release of stored charge . likewise , in other memory devices , a change of state may comprise a physical change or transformation in magnetic orientation or a physical change or transformation in molecular structure , such as from crystalline to amorphous or vice versa . the foregoing is not intended to be an exhaustive list of all exam page on ples in which a change in state for a binary one to a binary zero or vice - versa in a memory device may comprise a transformation , such as a physical transformation . rather , the foregoing is intended as illustrative examples . a storage medium typically may be non - transitory or comprise a non - transitory device . in this context , a non - transitory storage medium may include a device that is tangible , meaning that the device has a concrete physical form , although the device may change its physical state . thus , for example , non - transitory refers to a device remaining tangible despite this change in state . in many of the embodiments disclosed in this application , the technology is capable of allowing multiple different users to use the same piece of furniture equipped with the presently disclosed technology . for example , different people can sleep in the same bed . in addition , two different users can switch the side of the bed that they sleep on , and the technology disclosed here will correctly identify which user is sleeping on which side of the bed . the technology identifies the users based on any of the following signals alone or in combination : heart rate , breathing rate , body motion , or body temperature associated with each user . the foregoing description of various embodiments of the claimed subject matter has been provided for the purposes of illustration and description . it is not intended to be exhaustive or to limit the claimed subject matter to the precise forms disclosed . many modifications and variations will be apparent to one skilled in the art . embodiments were chosen and described in order to best describe the principles of the invention and its practical applications , thereby enabling others skilled in the relevant art to understand the claimed subject matter , the various embodiments , and the various modifications that are suited to the particular uses contemplated . while embodiments have been described in the context of fully functioning computers and computer systems , those skilled in the art will appreciate that the various embodiments are capable of being distributed as a program product in a variety of forms , and that the disclosure applies equally regardless of the particular type of machine or computer - readable media used to actually effect the distribution . although the above detailed description describes certain embodiments and the best mode contemplated , no matter how detailed the above appears in text , the embodiments can be practiced in many ways . details of the systems and methods may vary considerably in their implementation details , while still being encompassed by the specification . as noted above , particular terminology used when describing certain features or aspects of various embodiments should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics , features , or aspects of the invention with which that terminology is associated . in general , the terms used in the following claims should not be construed to limit the invention to the specific embodiments disclosed in the specification , unless those terms are explicitly defined herein . accordingly , the actual scope of the invention encompasses not only the disclosed embodiments , but also all equivalent ways of practicing or implementing the embodiments under the claims . the language used in the specification has been principally selected for readability and instructional purposes , and it may not have been selected to delineate or circumscribe the inventive subject matter . it is therefore intended that the scope of the invention be limited not by this detailed description , but rather by any claims that issue on an application based hereon . accordingly , the disclosure of various embodiments is intended to be illustrative , but not limiting , of the scope of the embodiments , which is set forth in the following claims .

US-201514947685-A

an assembly allowing retraction of soft tissue away from a reference plane ; the assembly including at least one retracting element each having a distal end with a formation allowing anchorage of the at least one retracting element . the assembly also includes a proximal end of the at least one retracting element capable of movement through at least one degree of freedom relative to the anchorage .

the present invention will now be described in more detail according to a preferred embodiment but non limiting embodiment and with reference to the accompanying illustrations . typically according to one method , cervical distraction of vertebrae involves the use of anchor pins temporarily fixed to the vertebrae to be distracted . generally two anchor pins are used one above and one below a disc or vertebral body of interest . traditionally in a caspar system these pins have only been used for distraction purposes via sliding tubes that fit axially over the pins and connect to an associated distraction mechanism . the role of the pin has been expanded to perform one or more of the following roles . the pin acts as x - ray marker to estimate a midline of a spine for cage or prosthetic disc replacement . the known and commonly used caspar type distracter is then secured to the spine . distracter tubes that each slide over respective pins and are secured to the pins via a screw applied at a threaded region . this however , does not have snug hex or square fit at a base of the pin but is round and transfers distraction forces along a length of a round pin . this does not provide optimal load transfer to the spinal vertebrae where distraction force is required but rather applies the load at a moment arm distant from the required load application site . the known technique for distraction force application applies a bending and shear force to the pins which must be transferred down the pin to its point of engagement with the vertebrae . a mechanical advantage during distraction is provided the closer the load is applied to the vertebrae due to a reduced moment arm and elimination of a bending moment on the pins so it is desirable to provide an assembly which meets this objective . in that case a shear force is applied at a base of pins to be distracted . throughout the specification a reference to a retractor arm may be taken to be synonymous with side arms , retractor blade and retraction member . a reference to blades will be taken to include a reference to retractors or retractor arms . to fully appreciate the various embodiments of the invention to be described below a summary of the bone fixation methodology and associated apparatuses and assemblies . this is accomplished by screws or short spikes or a spike / screw combination . spikes are useful where a line of pull is oblique to a line of insertion and where anatomy is unfavorable for screws . multiples screws or spikes may be used . a portion of the screw or spike may engage and link to other components . this portion is referred to as the anchor . anchor recess shapes which may be used ( see figures ) include the following non limiting embodiments : pedestal , integral hinge and sidearm for connection to blade , integral hinge allowing rotation in single plane , integral small ball and socket with shaft for connection to blade . anchor incorporates means of rotation anchor with built in shaft for blade attachment that allows rotation in 1 plane only . anchor with built in ball and socket plus shaft for blade fixation that allows rotation in multiple planes . link blade interface allows rotation either with integral or detachable hinge see fig2 , or as in . anterior cx system fig1 . the various combinations of component include methods for securing components together , that may permit desired free rotation but may limit movement in other planes likely to produce loosening or fall out . it will be obvious to those skilled in the art that the mechanisms shown limiting unwanted motion are non limiting and that more simple versions of the following components with less stability are envisaged which prevents lift out once rotated . according to one embodiment there are links which lock rotation at the desired point such as the splines on retention members as shown in figure ( fig1 , 7 and 8 . flathead with recess for locking pin . once retractor blade rotates to certain angle e . g . 30 degrees recess is exposed allowing pin to be inserted from above down front of the blade . this pin is easily pulled out allowing free rotation of the blade but by insertion prevents blade returning until pin removed . locking the retractor blade in this fashion means external handles for the blades or weights to pull the blade outwards are avoided . this reduces number of instruments around the operative field , frees or avoids totally the need for an assistant and facilitates x - rays . according to one embodiment a retractor blade clicks into position from above which is an alternative to sliding components together but once together resist pull out directly unless slid out sideways . fig1 shows a perspective view of a retractor assembly capable of concurrent retraction and distraction by cooperating anchor pins according to a preferred embodiment . referring to fig1 there is provided a retraction and distraction assembly 110 comprising retractor arms 111 and 112 terminating respectively in joining members 113 and 114 which engage anchor pin assemblies 115 and 116 . various shapes of retractor joining member / side arms are possible as required . retractor arm 111 comprises a first free end portion 117 including a recess 118 and spanning therebetween bridge members 119 and 120 . bridge members 119 and 120 define spaces 121 and 122 which may attach to an operating tool not shown . the operating tool facilitates rotational movement of retractor arm 111 . retractor arm 112 comprises a first free end portion 123 including a recess 124 and spanning therebetween bridge members 125 and 126 . bridge members 125 and 126 define spaces 127 and 128 which may receive an operating tool not shown . as with arm 111 , the operating tool facilitates rotational movement of retractor arm 112 such that arms 111 and 112 cooperate in maintaining retraction of opposing surgical wound margins . arms 111 and 112 are in use disposed against opposing soft tissue wound margins during surgery to facilitate and maintain adjustable rotational retraction . arm 111 further comprises blade region 129 which terminates in a formation 130 which defines a recess 131 which receives and retains therein joining arm 132 of joining member 113 . this allows arm 111 to selectively rotate about joining arm 132 . joining member 113 also comprises a bifurcated portion 133 having two arms which define recess 134 which receives and retains anchorage assembly 115 . anchorage assembly 115 comprises an anchorage pin 135 having a leading end 136 terminating in a sharp point 137 . leading end 136 may have thread like screw or pin like to facilitate penetration in bone and a trailing end 138 providing a driving member 138 a to facilitate bone penetration of point 137 . pin 135 is housed in guide sleeve 139 which compresses bifurcated portion 133 . joining member 113 locates between base 138 a and end 139 a of sleeve 139 . anchorage pin 135 which cooperates with sleeve 139 has a leading end 136 terminating in a sharp point 137 to facilitate penetration in bone . distal end 155 receives a driving member 156 to facilitate compression of sleeve 139 a against bifurcated portion 133 securing joining member 113 . pin 135 is housed in guide sleeve 139 which engages bifurcated portion 133 . guide sleeve 139 has connected thereto an ancillary sleeve 140 which receives in recess 141 a tool ( not shown ) to facilitate distraction i . e . separation of anchorage assemblies 116 and 115 along an axis usually but not exclusively parallel to the axes of rotation of arms 111 and 112 . arm 112 further comprises blade region 112 a which terminates in a formation 142 which defines a recess 143 which receives and retains therein joining arm 144 of joining member 114 . this allows arm 112 to selectively rotate about joining arm 144 . joining member 114 also comprises a bifurcated portion 145 having two arms which define recess 146 which receives and retains anchorage assembly 116 . anchorage assembly 116 comprises an anchorage pin 147 having a leading end 148 terminating in a sharp point 149 to facilitate penetration in bone and a trailing end 150 providing a driving member 151 to facilitate compression of sleeve 152 against 145 securing joining member 114 . pin 147 is housed in guide sleeve 152 which engages bifurcated portion 145 . guide sleeve 152 has connected thereto an ancillary sleeve 153 which receives in recess 154 a tool ( not shown ) to facilitate distraction of anchorage assemblies 116 and 115 along an axis parallel to the axes of rotation of arms 111 and 112 . the sleeves 152 and 139 engage onto square portions of respective pins . the bifurcated elements 133 and 145 also engage snugly around square portions of pins 135 and 147 . this connection prevents independent rotation of elements . combined rotation of all elements is prevented by joining two sleeves and pins together with an external distraction assembly . this distraction assembly ( not shown ) may join with the assembly as shown via recess 154 and 158 or may be integral as in existing caspar systems . with the above described assembly 110 a surgeon may selectively effect both distraction ( of bone ) and retraction ( of soft tissues ). the assembly allows distraction along an axis parallel to the axes of rotation of arms 111 and 112 and selective opposing rotational adjustments of arms 111 and 112 and if required removal of one or other of arms 111 and 112 . fig2 shows a perspective view of a part retractor assembly showing retraction arm 160 anchored to an anchor pin 161 by a joining member 162 according to an alternative embodiment . arm 160 comprises free end portion 163 and blade region 164 which terminates in a formation 165 which defines a recess 166 which receives and retains therein joining arm 167 of joining member 162 . this allows retraction arm 160 to selectively rotate about joining arm 167 . joining member 162 also comprises a bifurcated portion 168 having two arms which define recess 169 which releasably receives and retains head 170 of anchorage pin 161 terminating in a sharp point 171 to facilitate penetration in bone . free end portion 163 includes recess 172 which retains bridge members 173 and 174 . bridge members define openings 176 and 177 which receive an operating tool to facilitate both selective rotation of arm 160 and detachment from either joining member 162 or anchor 161 . fig3 shows an enlarged view of the retractor arm anchor pin 161 of fig2 with corresponding numbering . head 170 includes recess 180 which receives bifurcated portion 168 of joining member 162 . bifurcated portion 168 bears on shoulder 181 and locks against underside surface 182 of head 170 . shoulder 181 is optional and could be removed allowing bifurcated portion 168 of 162 to be positioned securely between 182 and base plate 170 a . fig4 shows an elevation view of the arm anchor pin 161 of fig3 with corresponding numbering . point 171 may further comprises formations 183 which facilitate bone penetration . fig5 shows an elevation view of the arm anchor pin 161 of fig6 . this arrangement of blade secured to anchor pin 161 with mechanism permitting rotation has widespread application in but not limited to orthopaedic and spinal surgery and whenever bone fixation possible . variations of such devices will be obvious to those skilled in the art . referring to fig6 there is shown a perspective view of an assembly 260 including abbreviated retractor arm 261 and joining member 262 including locating spline assembly 263 according to one embodiment . fig6 shows arm 261 at an oblique angle relative to a horizontal plane through joining member 262 . fig7 shows the arrangement of fig6 with arm 261 rotated to an alternative position disposed normally to the plane of joining member 262 . fig8 shows an exploded view of the assembly 260 of fig6 . joining member 262 includes a joining shaft 264 terminating in a free end 265 and having a knurled or bevelled surface . member 262 terminates at its opposite end in a bifurcated member 266 which engages an anchor ( not shown ) similar to the arrangements previously described . shaft 264 includes thereon a radial array of splines 267 extending from its circumferential surface 268 . arm 261 terminates in an enlarged region 269 having a wall 270 which defines a recess 271 adapted to axially receive shaft 264 . wall 270 has at one end 272 a radial array of elements 273 arranged to align with intermediate spaces between individual splines in spline array 267 . this arrangement allows arm 261 to be selectively released from spline array 267 rotated to alternative positions such as shown in fig6 and 7 . this allows a surgeon to selectively position the angle of repose of arm 261 held securely in position by splines 267 . to reposition the angle of arm 261 this is axially released from splines 267 , rotated and then reset . splines provide a strong resistance to rotational loads applied against the arm 261 during use as a retractor . in an alternative embodiment it will be appreciated that position of splines 267 on shaft 268 may be varied to opposite end 265 with a corresponding change of mating profile to other end of recess 271 and in a further embodiment blade could contain splines and the shaft the recesses . opposite gender spline mating may also be employed . the number of splines and teeth angles may be varied according to requirements . in an example of a method of use of the assembly , a surgeon may assemble the combined distracter and retractor assembly of fig1 according to the following regime . typically , the assembly may be employed in an anterior approach to the cervical spine . the first step which is based on a known technique involves insertion of pins in vertebrae to be distracted . preferably there will be two pins 135 and 147 spaced apart which are distracted to allow access to a disc space in the case for instance where a disc is to be replaced . the distracter pins such as those described as in fig1 are inserted into adjacent vertebrae . the surgeon takes a first retractor arm 111 or 112 whose configuration is selected to accommodate patient anatomy and allows it to directly or indirectly engage a first of said pins causing an associated rod and blade to lie generally parallel to a longitudinal axis of a spine . arms 111 and 112 are mounted respectively on arms 132 and 144 of joining members 113 and 114 . sleeves 139 and 152 are positioned over respective pins 135 and 147 . a retractor blade 111 or 112 such as that described with reference to fig1 is attached if not previously done by sliding respective sleeves ( 130 and 142 ) on the blade along the pivot arm of a joining member 132 , 144 until mating splines ( or other mechanically equivalent engagement ) engage . the orientation of the retractor blade is set according to a selected circumferential ( rotational ) engagement of the respective mating opposed splines . the assembly now formed and shown in fig1 provides an ability to both distract vertebrae and retract soft tissue as required , the distraction occurring when a distraction force is applied through the sleeves or tubes 139 and 152 which axially engage the pins 136 and 147 . the degree of retraction is set by engaging the splines at a predetermined position so as to set the retractor arms 111 and 112 at an angle of repose which keeps soft tissue margins apart as required by the surgeon . if the aforesaid description relates to a right side distracter arm and retractor blade assembly there will be a corresponding left hand side arrangement which is preferably symmetrical about a transverse line through a disc space . if the aforesaid description relates to a left side distracter arm and retractor blade there will be a corresponding right hand side arrangement which is again symmetrical about a transverse line through the disc space . the distraction forces are applied at the base of the pins 136 and 147 to optimise mechanical advantage and to eliminate pin bending loads . this assembly described above allows variable distraction poses and movement without removal of retractors — side retractor arms and blades . fig9 shows a retractor arm and joining member assembly 200 according to an alternative embodiment . assembly 200 comprises a retractor arm 201 and joining member 202 with the retractor arm 201 in a substantially vertical orientation . arm 201 includes free end portion 203 and blade 204 . end 203 includes bifurcation 205 defining recess 206 . recess 206 includes bridging members 207 and 208 defining recesses 209 and 210 which receive an operating tool ( not shown ) which in use facilitates arm rotation for retraction of soft tissues . blade portion 204 terminates in an enlarged formation 211 defining a recess 212 having a partially cut away wall exposing the interior of recess 212 . this cut away allows insertion and removal of members 202 and 222 plus rotation once centered . recess 212 receives and retains joining member 202 . fig1 shows the retractor arm 201 of fig9 separated from a joining member 202 . fig1 shows an enlarged view of the joining member of fig1 . joining member 202 is insertable in recess 212 via pivot arm 214 . pivot arm 214 has preferably intermediate its ends a bridge 215 which terminates in a loop 216 which engages an anchor pin ( not shown ). arm 201 may then be rotated through about 30 degrees but it will be appreciated that the wall 217 ( see fig1 ) contains notch 217 a that allows rotation of bridge 215 to occur limiting rotation as desired of recess 212 can be configured to achieve an alternative degree ( more or less ) of rotation . fig1 shows a retractor arm and joining member assembly 220 according to an alternative embodiment . assembly 220 comprises a retractor arm 221 and joining member 222 with the retractor arm 221 abbreviated but in a substantially vertical orientation . blade portion 223 terminates in an enlarged formation 224 defining a recess 225 having a partially cut away wall exposing the interior of recess 225 . fig1 shows an enlarged view of the joining member of fig1 . recess 225 receives and retains pivot retention arm 226 about which retractor arm 221 is free to rotate . pivot arm 226 has preferably intermediate its ends a bridge 227 which terminates in an open saddle 228 which engages an anchor pin ( not shown ). arm 221 may then be rotated as required about pivot arm 226 . fig1 shows a retractor arm and joining member assembly 230 according to an alternative embodiment . assembly 230 comprises a retractor arm 231 and joining member 232 with the retractor arm 231 abbreviated but in a substantially vertical orientation . blade portion 233 terminates in an enlarged formation 234 defining a recess 235 having a partially cut away wall exposing the interior of recess 235 . fig1 shows an enlarged view of the joining member of fig3 . recess 235 receives and retains pivot arm 236 about which retractor arm 231 is free to rotate . pivot arm 236 has preferably at one end a bridge 237 which terminates in an open saddle 238 which engages an anchor pin ( not shown ). retractor arm 231 may then be rotated as required about pivot arm 236 . according to one aspect of the invention once the retractor blades are inserted they are fixed at or adjacent to a location where a tip of an end of the retractor blade is required . this is usually deep in the wound and generally involves firm fixation to an adjacent bony surface via a screw , clamp or other gripping device that connects directly to the blade or via an intermediary linkage . in most situations this connection with the fixation device will allow rotation of the blade about the point of fixation , either because the point of fixation itself can rotate . this fixation with rotation allows retractor blades to be left in situ throughout a procedure but allowing the surgeon to release the pressure and the retraction forces while working on another area thus reducing the tissue trauma but without having to remove the retractor blade or reposition the retractor blade . releasing self retaining retractors leads to repeated tissue trauma every time these are reinserted and / or reopened . this system would therefore reduce tissue trauma and save time . it would also mean that the retractor once appropriately inserted can be secured insitu and not become loose or dislodged and require repositioning . the fixation device described in the cervical assembly utilises a pin with a screw thread into the bone and is first embodiment of this principal . this components described have multiple applications for the purpose of retraction of tissues . such assemblies could also act as components in distraction devices alone or be combined with function as base for rotating retractors as illustrated in fig1 . it will be appreciated by those skilled in the art that the utilisation of this principal could be used in numerous other applications adapting to the different anatomy and retraction requirements throughout the spine , musculoskeletal system or wherever bony fixation can be utilised , e . g . the head . it will be further recognised by persons skilled in the art that numerous variations and modifications may be made to the invention without departing from the overall spirit and scope of the invention broadly described herein . such modifications would allow adaptation of key concepts ( which is that retractor blades are fixed at or close to critical point of retraction and may rotate ) to provide additional retraction devices for use in anterior or posterior spinal surgery throughout length of spine or in orthopaedics or other surgical disciplines where bony fixation is available .

US-201414154610-A

an infusion device for infusion of a fluid from a reservoir into a body , the infusion device being connectable to an infusion set adaptor at a connecting site , the infusion device comprising : a drive mechanism to operatively couple with at least a portion of the reservoir ; a housing being sized to contain at least a portion of the reservoir , wherein the drive mechanism is at least partially or fully contained within the housing ; a sealing device that permits the passage of air into and out of the housing or a housing compartment and inhibits the passage of liquids into the housing or a housing compartment through the sealing device ; wherein the sealing device is arranged at the drive mechanism or at a location between a part of the drive mechanism and the connecting site of the infusion set adaptor or at the connecting site of the infusion set adaptor .

in order to specify the directions within the administering apparatus , designated directions are defined as follows . the distal direction is respectively understood to mean the direction in which the liquid and the drug plug are moved when the drug is administered . as will be described again in more detail below , liquid in the liquid path is diverted in the interior of the administering apparatus and changes its flow direction . the distal direction therefore corresponds to different absolute spatial directions for different parts of the administering device . the proximal direction is correspondingly defined as the opposite direction to the distal direction . a lateral direction is a direction perpendicular to this . fig1 to 6 show an embodiment in accordance with the invention of the device for administering a fluid product . the embodiment shown in the figures is intended to describe the invention by way of an example . other embodiments have already been described in part further above and / or are mentioned repeatedly in the text of the description of the figures , and additional possible embodiments will be apparent to the person skilled in the art on the basis of the description of the invention , such that the embodiments described below are not to be regarded as limiting . the device shown in fig1 a , 1 b and 2 comprises the administering apparatus 1 , shown here as an infusion pump , and the infusion set , wherein only the infusion set adaptor 30 and the infusion line 31 of the infusion set are shown . the front side of the administering apparatus 1 is shown in fig1 a , and the rear side in fig1 b . a touch display 20 is arranged on the front side and comprises at least a display device , in particular an oled or amoled , and a touch - sensitive surface arranged over the display device , in particular a touch screen , wherein the touch display 20 is sunk into the housing 5 of the administering apparatus 1 , such that it ideally forms a continuous and smooth surface with the surface of the housing 5 , wherein the touch display 20 is adhered or fused to the housing 5 or at least joined to the housing 5 in such a way that the join is closed in a liquid - proof seal . the viewing window 6 is arranged in a side wall of the housing 5 and can be an integral part of the housing 5 and enables the person using the device to view the carpule compartment 9 . the function key 10 is arranged on the distal wall 5 a . as shown in fig5 , other elements are arranged on the distal wall 5 a , namely the opening of the carpule compartment 9 on the one hand and the device 8 for ventilating or evacuating the housing on the other . the latter enables the pressure to be equalized between the outside and inside of the administering apparatus 1 . in the embodiment shown in fig2 , the ventilating or evacuating device 8 comprises a membrane 8 a which closes an opening 8 d of the housing . the membrane 8 a allows gases to pass through but prevents liquid from passing through . the membrane 8 a is protected against damage from without by the evacuating protection 8 b . so as not to obstruct the exchange of gas between the inside and outside of the housing , the evacuating protection 8 b comprises apertures 8 c or holes . fig2 shows the carpule compartment 9 in section . the carpule compartment 9 serves to accommodate the product container — in the case shown , the carpule 2 — wherein the carpule 2 is introduced into the carpule compartment 9 with its open end 2 first . the opening of the carpule compartment 9 is closed by means of the infusion set adaptor 30 , as shown in fig1 a and fig2 . the opening of the battery compartment 91 is arranged in the proximal wall 5 b . the opening of the battery compartment 91 can be closed and opened by means of the battery compartment lid 7 , wherein the battery compartment lid 7 is formed such that it can close the battery compartment 91 in a water - proof but e . g . gas - permeable seal . the battery 90 can be introduced into the battery compartment 91 , as shown in fig2 , wherein the primary cell 90 can be a commercially available aaa battery or alternatively a different type of battery or a correspondingly dimensioned rechargeable power pack . in order to obtain a good electrical contact between the battery 90 and the negative contact terminal 93 of the administering apparatus 1 and between the battery 90 and the positive contact terminal 92 of the administering apparatus 1 , the negative terminal 93 can comprise or be formed as a spring , as shown in fig2 , wherein the positive terminal 92 is fixedly attached to the battery compartment lid 7 , such that when the battery compartment 91 is closed , a pressure force which optimizes the electrical contacting is applied to the contacts by the spring force . the administering apparatus 1 shown in fig1 a , 1 b and 2 comprises a drive device . the drive device , which is also shown in detail in fig3 a to 3 g , comprises a motor 40 , a gear system 45 , an advancing sleeve 51 and a piston rod 52 . the drive device also comprises a drive housing 50 in and / or on which the parts of the drive device can be mounted , wherein the drive housing 50 is fixedly connected to the housing 5 . the seals 54 , 57 and 58 seal the drive device off from the carpule compartment 9 in a liquid - proof seal , in order to prevent liquid from crossing into the interior of the drive device . seals 54 , 57 and / or 58 can be made of a material which permits the transmission of air , as described above . the motor 40 is controlled and fed by an electronic control module 80 . when activated , the motor axle 40 a rotates and with it the driven toothed wheel 40 b arranged rotationally fixed on the axle . the driven toothed wheel 40 b transmits the movement onto the gear system 45 . the movement of the motor is geared up or down in the desired ratio via the toothed wheels 45 a to 45 e of the gear system 45 , wherein the toothed wheels 45 a to 45 e of the gear system 45 are rotatably mounted on the axles 45 f and 45 g , respectively . the gear system toothed wheels 45 a to 45 e comprise two coaxially arranged toothings which are arranged sequentially in the axial direction and such that they are fixedly connected to each other , wherein the two toothings typically exhibit a different number of teeth . the first toothing assimilates the movement from the preceding toothed wheel . the second toothing relays the movement to the next toothed wheel , wherein — as the person skilled in the art will be aware — the embodiment of the gear system can vary without deviating from the concept of the invention . in particular , a different number of toothed wheels in the gear system can be chosen and / or the number of teeth on a toothed wheel can be varied . at the output of the gear system 45 , the toothed wheel 45 e transmits the movement onto the toothing 51 a of the advancing sleeve 51 . the advancing sleeve 51 is rotatably mounted in the drive housing 50 with the aid of the ball bearing 55 , wherein a roll bearing , needle bearing or a simple slide bearing would also be possible . the seal 58 is arranged between the drive housing 50 and the advancing sleeve 51 and seals the interior of the drive housing 50 off from the outside of the rotatable advancing sleeve 51 . on its inside , the advancing sleeve 51 comprises an inner thread 51 b which is in engagement with an outer thread 52 b of the piston rod 52 . the piston rod 52 is arranged coaxially with respect to the advancing sleeve 51 and coupled to it via the threaded engagement mentioned . the piston rod 52 also comprises two longitudinal guiding grooves 52 a . the cams 50 a of the drive housing 50 engage with these guiding grooves 52 a and thus allow a movement of the piston rod 52 in the longitudinal direction of the piston rod 52 relative to the drive housing 50 , but prevent a relative rotation between the piston rod 52 and the drive housing 50 . if the advancing sleeve 51 is rotationally set in motion via the gear system 45 , then the threaded engagement between the advancing sleeve 51 and the piston rod 52 in combination with the rotational lock between the drive housing 50 and the piston rod 52 generates an axial shift in the piston rod 52 relative to the drive housing 50 , hence the piston rod 52 is also shifted relative to the housing 5 . during a movement for administering product , the piston rod 52 moves in the distal direction . the described arrangement of the drive can be kinematically reversed , without deviating from the teaching of the invention . in such a reversal , the piston rod 52 would be mounted , such that it can be shifted but is secured against rotating , in the advancing sleeve 51 and would be connected to the drive housing 50 via a threaded connection . if the advancing sleeve 51 were then rotationally set in motion by the gear system 45 , the piston rod 52 would also be rotated and consequently screwed in the axial direction via the threaded connection with the drive housing 50 . an equally advantageous axial advance by the piston rod 52 could thus also be achieved using a kinematically reversed arrangement . a cap flange 53 is attached to the distal end of the piston rod 52 and can mechanically engage with the proximal end of a carpule plug 4 . in the example from fig2 shown , the proximal side of the carpule plug 4 comprises a piston rod receptacle as a blind hole 4 a with an inner thread , which improves the engagement of the cap flange 53 . in an equally advantageous embodiment , a carpule plug 4 with no blind hole 4 a is also conceivable , wherein the shape of the cap flange 53 would be correspondingly adapted . as described above , the carpule 2 is arranged in the housing 5 . when the infusion set adaptor 30 is inserted into the housing 5 , the carpule 2 is mounted axially between the drive housing 50 and the infusion set adaptor 30 , wherein a carpule spring 59 ensures , via a sleeve 59 a which abuts the proximal end of the carpule wall , that the carpule 2 is pressed in the distal direction against the infusion set adaptor 30 . the carpule 2 comprises a cylindrical body which is open at its proximal end 2 a and tapers at its distal end and is closed by a septum 3 , wherein the septum 3 is fastened to the distal end of the carpule 2 by a septum holder 3 a . the carpule plug 4 is mounted , such that it can be axially shifted , in the carpule 2 and forms a moving proximal closure of the carpule 2 , since it also forms a seal with the carpule wall . when the infusion set adaptor 30 is inserted into the housing 5 , a connecting needle — shown as a cannula 33 — pierces the septum 3 of the carpule 2 and thus establishes a liquid connection between the infusion set adaptor 30 and the interior space of the carpule 2 , such that liquid product can pass from the carpule 2 into the infusion set adaptor 30 . shifting the carpule plug 4 by means of an axial movement of the piston rod 52 in the distal direction reduces the interior space of the carpule 2 and displaces product from the carpule 2 and thus conveys it into the infusion set adaptor 30 . as mentioned further above , the advancing sleeve 51 is rotatably mounted in the drive housing 50 . axial movements of the advancing sleeve 51 are possible to a limited extent . the axial movement is limited in the distal direction by the closed end 50 b of the drive housing 50 . the movement of the advancing sleeve 51 is limited in the proximal direction by a bearing plate 60 which is fixedly connected , in particular screwed , to the drive housing 50 . a circular opening 60 a arranged coaxially with respect to the advancing sleeve 51 is provided in the bearing plate 60 and exhibits a diameter which is less than the diameter of the region of the advancing sleeve 51 which bears the toothing 51 a , thus ensuring that the axial movement of the advancing sleeve 51 is limited by the bearing plate 60 , despite the opening 60 a . the proximal end of the advancing sleeve 51 is closed by the closure cap 56 , wherein the closure cap 56 is movably held on the advancing sleeve 51 by the seal 57 — shown for example in fig3 g as an o - ring — which is arranged on the proximal end of the advancing sleeve 51 , wherein the diameter of the closure cap 56 is chosen such that the cap 56 fits through the opening 60 a in the bearing plate 60 . a force sensor 85 is arranged , fastened to the housing on one side , between the closure cap 56 and the housing 5 of the administering apparatus 1 , wherein “ fastened to the housing ” means in particular that the force sensor 85 is mounted such that it cannot be moved laterally relative to the housing 5 . a certain clearance can , but need not , be provided in the axial direction , but which is eliminated when the drive device is put into operation . said force sensor 85 measures forces which are transmitted from the closure cap 56 to the sensor 85 . due to the advantageous embodiment of the closure cap 56 , the advancing sleeve 51 and the piston rod 52 , various forces can be measured using the arrangement shown in fig2 or fig3 g . on the one hand , the reaction force during the axial movement of the piston rod 52 , in particular while product is being administered , can be measured , i . e ., when the piston rod 52 is moved in the distal direction and presses against the carpule plug 4 , the advancing sleeve 51 exerts a force in the proximal direction which is transmitted onto the force sensor 85 via the closure cap 56 . measuring forces in this way enables occlusions , i . e ., for example blockages , in the infusion set to be identified on the basis of an increase in force and / or a force limit value during delivery , wherein the measurement signal generated in the force sensor 85 can be evaluated and stored in the control module 80 . in addition , when carpules 2 are newly inserted , the position of the piston rod 52 at which the piston rod 52 , in particular the cap flange 53 , hits the carpule plug 4 can also be identified ; in this situation , an increase in the reaction force can again be observed at the force sensor 85 . the measurement signals from the force sensor 85 are read and evaluated by the control module 80 . consequently , the control module 80 can for example stop the motor 40 and issue alarm alerts on the display or let the motor 40 continue running . on the other hand , it is possible to measure forces which are transmitted directly from the piston rod 52 to the force sensor 85 via the closure cap 56 . when a new carpule 2 is inserted into the administering apparatus 1 , the piston rod 52 has to be moved back into its initial position before the new carpule 2 is inserted . this is achieved by driving the motor 40 in the opposite direction to the delivery movement . consequently , the corresponding rotation of the advancing sleeve 51 draws the piston rod 52 into the advancing sleeve 51 , i . e ., in the proximal direction . when the piston rod 52 reaches its initial position , it hits the closure cap 56 and presses it in the proximal direction onto the force sensor 85 . the increase in force which this generates can be measured by the sensor 85 and relayed to the control module 80 . the control module 80 can then correspondingly stop the motor 40 , and the new carpule 2 can be inserted . the infusion set adaptor 30 , including a proximal housing 30 a and a distal housing 30 b , can be detachably connected to the housing 5 of the administering apparatus 1 . this may be achieved by the bayonet lock 32 shown in fig5 and 6 . the bayonet lock 32 includes two guiding grooves 32 b and 32 c , which are arranged on the outside of the proximal housing 30 a , and complementarily formed latching elements 9 a ( only one of which is shown in fig5 ) in the carpule compartment 9 . the guiding grooves 32 b and 32 c are of different widths , and the two latching elements 9 a ( only one of which is shown ) are correspondingly also of different widths — to fit the groove width of the guiding grooves 32 b and 32 c , respectively . the proximal housing 30 a of the infusion set adaptor 30 is formed such that it can be inserted into the carpule compartment 9 and such that a cylindrical fit between the proximal housing 30 a and the carpule compartment 9 results . the latching elements 9 a protrude in the radial direction into the interior of the carpule compartment 9 and are accommodated by the guiding grooves 32 b and 32 c , respectively , when the infusion set adaptor 30 is inserted and guide the movement of the infusion set adaptor 30 . due to the different widths of the guiding grooves 32 b and 32 c and the complementarily formed latching elements 9 a , the infusion set adaptor 30 can only be inserted into the carpule compartment 9 in precisely one orientation . fig5 shows the infusion set adaptor 30 and the administering apparatus 1 before the infusion set adaptor 30 is connected to the administering apparatus 1 , wherein the infusion set adaptor 30 is already orientated such that it can be inserted into the carpule compartment 9 . once the infusion set adaptor 30 has been completely inserted , it is rotated in the present example by about 90 ° clockwise , in order to close the bayonet lock 32 . this rotation is also guided by the correspondingly aligned grooves 32 b and 32 c which exhibit a corresponding bend . during this rotation , the infusion set adaptor 30 is drawn slightly further again into the carpule compartment 9 , in order to generate an optimum closure . at the end of this rotation , the infusion set adaptor 30 is detachably snapped onto the carpule compartment 9 via latching cams 32 a , in order to prevent the connection from being undesirably released , wherein a tactile or audible feedback which can be perceived by the person using the device may be generated during said snapping . the infusion set adaptor 30 may be configured so that it does not seal the carpule compartment 9 off in an air - tight manner , in order to allow pressure to be equalized between the carpule compartment 9 and the environment . in another embodiment , the rotational direction of the infusion set adaptor 30 can also be reversed , i . e ., can be anti - clockwise . correspondingly , the run of the grooves 32 b and 32 c of the bayonet lock 32 would also be aligned differently . the rotational angle can also be more or less than 90 °, as long as the adaptor 30 can only be inserted into the carpule compartment 9 in precisely one orientation . in the example shown , the proximal housing 30 a and the distal housing 30 b are adhered to each other in a water - proof seal . alternatively , they could also be fused to each other . the infusion set adaptor 30 of the infusion set ( which is not completely shown ) establishes a liquid connection between the product container , corresponding to the carpule 2 shown , and the infusion set , shown here schematically as an infusion line 31 . to this end , the infusion set adaptor 30 comprises a cannula 33 which serves to pierce the septum 3 of the carpule 2 . the cannula 33 is arranged in the interior of the proximal housing 30 a . the proximal housing 30 a exhibits an approximately cylindrical shape and is open in the proximal direction . when the infusion set adaptor 30 is inserted into the carpule compartment 9 ( and the bayonet lock 32 is latched ), the proximal housing is arranged between the distal end of the carpule 2 and the wall of the carpule compartment 9 . the cannula 33 is arranged coaxially with respect to the proximal housing 30 a . when the infusion set adaptor 30 is inserted into the carpule compartment 9 , the cannula 33 pierces the septum 3 of the carpule 2 which is inserted beforehand into the carpule compartment 9 . this establishes a liquid connection between the carpule 2 and the interior of the infusion set adaptor 30 . the infusion set adaptor 30 comprises a valve device 34 , 35 which is arranged in the liquid path between the cannula 33 and the infusion line 31 . the valve device 34 , 35 has in principle two functions . firstly , it is intended to prevent liquid from flowing back from the infusion line 31 into the administering apparatus 1 . secondly , product is to be prevented from undesirably flowing out , for example due to differences in pressure . while backflow is to be prevented completely , the flow of product for the purpose of administering product is to be possible , but only beyond a certain minimum pressure in the product container , wherein a compromise has to be drawn between safety ( preventing product from undesirably flowing out ) and obstructing the actual administering process as little as possible . the infusion line 31 typically has a length of 30 to 120 cm , which then corresponds to about the distance between the administering apparatus 1 and the administering location on the body of the person using the device . assuming an unfavorable scenario , the difference in height between the administering apparatus 1 and the administering location may be roughly one meter , thus establishing a column of liquid having a corresponding height , which corresponds to a gravitational pressure of about 0 . 1 bar . as already mentioned , the carpule 2 comprises a carpule plug 4 which is movably mounted in the carpule 2 . in order to deliver product from the carpule 2 , the carpule plug 4 is pressed towards the septum 3 , i . e ., in the distal direction , by means of the piston rod 52 and the cap flange 53 . the carpule plug 4 is not retained by the cap flange 53 , i . e ., the connection between the cap flange 53 and the plug 4 cannot absorb any tensile forces . if the friction between the carpule plug 4 and the carpule wall is sufficiently small that the difference in pressure just described can cause the plug to be shifted , then the drug will undesirably leak out . the carpule 2 has a typical inner diameter of about 9 . 25 mm ; at a difference in pressure of 0 . 1 bar , a force of about 0 . 7 n can therefore act on the plug 4 . en iso 11608 - 3 : 2000 specifies that the dynamic frictional force should not exceed 20 n and that the breakaway force of the carpule plug 4 should not exceed 40 n . in practice , however , the values are significantly lower , in the range of about 10 n or less . frictional forces which are as low as possible are desired , so that as little drive energy as possible is lost through frictional losses . optimizing the frictional forces , however , increases the risk of undesirable leakage in accordance with the rough calculation employed above . the valve device 34 , takes account of this risk . in addition to the first function as a reflux valve , the valve device 34 , 35 also functions as a threshold value valve . the valve is configured such that a typical ( example ) minimum pressure of about 0 . 3 bar in the product container has to be reached in order to open the valve and consequently enable the drug to be administered , wherein the minimum pressure can be tailored to a particular application . fig4 shows the infusion set adaptor 30 in an exploded representation . fig6 shows the infusion set adaptor 30 in a sectional representation , wherein the section is taken through the liquid path . the distal end of the cannula 33 feeds into a valve space 34 . a valve membrane 35 is arranged in this valve space 34 . on the right above the valve membrane 35 , the valve space 34 feeds into the intersection 36 a to the receptacle 36 for the infusion line 31 . the infusion line 31 , as well as the distal housing 30 b of the infusion set adaptor 30 , are embodied in materials , in particular plastic , which can be adhered or fused to each other — such that a liquid - proof connection is created . alternatively , the receptacle 36 can also be embodied as a luer cone , wherein the infusion line 31 comprises a corresponding counter - piece . the valve space 34 is designed so as to be rotationally symmetrical , in particular round , relative to the longitudinal axis of the cannula 33 . the valve membrane 35 also comprises a round base area . the valve membrane 35 is clamped between the proximal housing 30 a and the distal housing 30 b , wherein the centering cam 30 c of the distal housing 30 b presses a central region of the valve membrane 35 in the proximal direction . the periphery of the valve membrane 35 lies on a sealing edge 34 a of the valve space 34 . due to the pressure built up by the centering cam 30 c and the corresponding elastic forces in the membrane 35 , the liquid path is closed by the valve membrane 35 along the line of contact between the valve membrane 35 and the sealing edge 34 a . the valve membrane 35 is made of a flexible material , for example rubber or another elastomeric material . the outside of the valve membrane 35 comprises the centering aids 35 a which are important for assembling the infusion set adaptor 30 , see fig4 in this respect . for assembling , the valve membrane 35 is inserted into the distal end of the proximal housing 30 a . the centering aids 35 a , which in the form shown are formed as nubs 35 a , enable the valve membrane 35 to be centrally positioned in the housing without consequently obstructing the transport of product through the infusion set adaptor 30 or impairing the valve characteristics due to the contact between the nubs 35 a and the wall of the infusion set adaptor 30 . as soon as the valve opens due to deformation of the valve membrane 35 , the nubs 35 a of the valve membrane 35 can no longer touch the wall of the infusion set adaptor 30 and thus do not influence the valve characteristics . in order to minimize the volume of the valve space 34 , the wall of the distal housing 30 b on which the centering cam 30 c is arranged is shaped so as to be convex towards the valve space 34 . if pressure is built up on the proximal side of the valve membrane 35 and exceeds a particular threshold value , then the periphery of the valve membrane 35 is deflected in the distal direction and the valve opens in order for product to flow through it in the distal direction . if the pressure falls below the threshold value or a pressure burden is established on the distal side of the valve membrane , then the valve closes itself off , forming a seal , wherein the threshold value corresponds to the minimum pressure mentioned further above and is about 0 . 3 bars of relative pressure difference in the example shown . in order to reduce the danger of the valve membrane 35 sticking to the sealing edge 34 a , the valve membrane 35 in one advantageous embodiment does not completely close at pressures less than 0 . 3 bar . to this end , a small , defined leakage in the form of a micro - channel or micro - notch ( not shown ) is arranged on the sealing edge 34 a , wherein the leakage is dimensioned to be sufficiently small that at the differences in pressure mentioned above , the greatest amount of product per unit time which can leak out is one which is harmless to the person using the device . taking the example of insulin , this would mean a worst - case flow rate of 5 units of insulin per day . in this case , the leakage would exhibit a cross - sectional diameter of roughly 10 to 15 μm . since half the diameter to the fourth power features in the hagen - poiseuille flow equation using which the flow rate is estimated , the greatest attention must be paid to the precise dimensioning of the leakage diameter . the defined leakage in the valve device 34 , 35 has the advantage that , due to the defined leakage , minimal amounts of product can flow out even when the threshold value of the drive pressure has not yet been reached , which enables the valve device 34 , 35 to be prevented from drying out completely . this embodiment presupposes that the product to be administered is compatible with the micro - leakage . suspensions may for example impair the functionality of the leakage . the administering device can be programmed and controlled by the person using the device . to this end , the administering apparatus 1 comprises a touch display 20 and a function key 10 , both of which are connected to the control module 80 . the control module 80 can display a menu structure on the touch display 20 . the person using the device can control the administering apparatus 1 or also for example retrieve and display the administering “ history ” via the touch - sensitive touch display 20 , with the aid of a finger or suitable pointer and the support of the menu structure . the person using the device can also program the types of administering . the person using the device can for example store a basal rate profile in the apparatus 1 , which then controls how product is administered , in a time - controlled way . it is also possible for boluses to be dispensed immediately or with a time delay . as an alternative or complement to controlling the administering device via the touch display 20 , a simplified form of control via the function key 10 is possible . in one function , the function key 10 serves as an on / off key or as a standby key . in another function , the function key 10 serves as a programming and triggering key for so - called blind boluses , i . e . activating the administering device to dispense boluses without the administering device having to be controlled via the touch display 20 . this is advantageous because the person using the device can wear the administering apparatus 1 , hidden from other people , while programming and triggering blind boluses . the boluses can thus be discreetly programmed and triggered . in order to acknowledge inputs or accentuate alerts , the administering apparatus 1 also comprises a vibration device 82 and a buzzer or loudspeaker ( not shown ). when programming and administering blind boluses , the vibration device 82 in particular can discreetly provide the person using the device with feedback regarding the bolus amount set , namely with a particular number of vibration pulses , and that the bolus has been successfully administered . with respect to controlling the touch display 20 by means of a finger , it is also conceivable in one embodiment for gestures using multiple fingers simultaneously to be recorded by the touch display 20 . such gestures are known from the literature as multi - touch gestures . fig7 shows an embodiment of the present invention , wherein reference is made to the above description of fig2 . the embodiment shown in fig7 does not comprise the housing evacuator 8 , the evacuating element 8 a , the evacuating protection 8 b , the aperture 8 c and has no housing opening 8 d . the only way to connect the inside of the housing 5 , in which the battery 80 and the drive mechanism 40 , 45 , 50 , 51 , 52 , 53 , 55 and 56 is arranged , to the outside of the infusion device by allowing the passage of air is through seal 54 and optionally also through seal 57 and / or 58 , which seal 54 is located between an element of the drive mechanism , such as for example the shown drive housing 50 being on the inner side of seal ring 54 , and viewing window 6 or housing 5 being on the outside of seal ring 54 . seal 54 is made from a material allowing the passage of air and inhibiting the passage of liquids or water and may be in tight contact or bonded to the housing 5 , 6 and to the drive housing 50 so that no unsealed opening is present between the housing compartment and the carpule compartment 9 . as mentioned above , seal or o - ring 54 can for example be made of ptfe , hdpe , pes , uhmw polymers or gore - tex ®, porex ®, polyphobe ™ or filtrone . fig8 shows a further embodiment according to the present invention , wherein seal 54 can be made from a material allowing the passage of air and inhibiting the passage of liquids or water or can be a conventional seal . a further location for a seal 54 a is shown on the upper or distal side of the housing 5 . seal 54 a is attached on the inner side or side wall 9 a ( see fig7 ) of the carpule compartment 9 to be in contact with the housing 30 a of the infusion set adaptor 30 as mentioned above , when the infusion set adaptor 30 is placed onto the infusion device . fig9 shows a further embodiment of the invention , wherein seal 54 b being made from a material allowing the passage of air and inhibiting the passage of liquids or water and being a seal ring is attached to the outside of the proximal housing 30 a of the infusion set adaptor 30 and is brought into a position to be in contact with the inner wall 9 a ( see fig7 ) of the carpule compartment 9 once the infusion set adaptor 30 is placed onto the infusion device 1 . fig1 shows a further embodiment wherein two sealing elements 54 c and 54 d both being made from a material allowing the passage of air and inhibiting the passage of liquids or water and being sealing rings are attached to the outside or outer circumference of the proximal housing 30 a of the infusion set adaptor 30 to be in contact with the inside or inner wall 9 a ( see fig7 ) of the carpule compartment 9 when being placed thereon . the invention relates according to a further aspect to an infusion set adaptor 30 for an infusion set , comprising : a housing 30 a , 30 b ; a liquid path which extends through the housing 30 a , 30 b and comprises a liquid inlet 33 and a liquid outlet 36 ; and a membrane valve 34 , 35 which is arranged in the liquid path and comprises an inlet and an outlet , wherein the membrane valve 34 , 35 comprises a valve space 34 , which is limited by walls , and a valve membrane 35 , and wherein a valve seating 34 onto which the valve membrane 35 can be placed is arranged in the valve space 34 , characterized in that at least two centering aids 35 a are arranged on the walls or the periphery of the valve membrane 35 and in particular simplify centrally positioning the valve membrane 35 on the valve seating 34 a when assembling the infusion set adaptor 30 . the infusion set adaptor 30 for an infusion set as described above , wherein the valve membrane 35 comprises the centering aids 35 a at its periphery as radially aligned and nub - shaped centering aids 35 a . the infusion set adaptor 30 for an infusion set as described above , wherein the housing 30 a , 30 b comprises a proximal housing 30 a and a distal housing 30 b , wherein the liquid outlet 36 is arranged on the distal housing 30 b and the liquid inlet 33 is arranged on the proximal housing 30 a . the infusion set adaptor 30 for an infusion set as described above , wherein the walls of the valve space 34 are formed by the proximal housing 30 a and the distal housing 30 b . the infusion set adaptor 30 for an infusion set as described above , wherein the valve membrane 35 is shaped as a circular disc and , when assembling the infusion set adaptor 30 , can be inserted into a space in the proximal housing 30 a which is shaped complementarily with respect to the disc , wherein when the membrane 35 is not mechanically stressed , the centering aids 35 a can touch a wall of the complementarily shaped space . a device for administering a fluid product , comprising an administering apparatus 1 and an infusion set , wherein the infusion set can be detachably connected to the administering apparatus 1 by means of an infusion set adaptor 30 as described above , such that a liquid path between the infusion set and the administering apparatus 1 is created . a device for administering a fluid product , comprising an administering apparatus and an infusion set , wherein the infusion set can be detachably connected to the administering apparatus by means of an infusion set adaptor , such that a liquid path between the infusion set and the administering apparatus is created . the infusion set adaptor comprises a membrane valve , wherein the membrane valve comprises centering aids for simplifying the positioning of the membrane . one common therapy for treating auto - immune diseases ( for example , type 1 diabetes ) involves near - continuously supplying a drug ( for example , insulin ) for the entire duration of the therapy , with the aid of a portable pump . in the case of diabetes , the pump therapy enables a ( variable ) basal rate of insulin to be continuously dispensed , as well as individual boluses which are employed in connection with mealtimes and for correcting excessively high glucose values in the patient &# 39 ; s blood . by continuously dispensing the basal rate in accordance with a user - specific basal rate profile , a more uniform blood sugar level is achieved and the patient &# 39 ; s organism is thus unburdened . infusion systems are correspondingly known which include an infusion pump for insulin ( insulin pump ), a supply line to the body ( infusion set ) and , as applicable , a remote control . in general , the insulin pump is to be formed so as to be as compact as possible , so that it is not too bulky and is comfortable for the user to wear . the pump thus comprises a small pump housing which accommodates a battery , a motor including a gear system and control and communications electronics , and an ampoule which is connected to the infusion tube , forming a seal . the outside of the pump comprises operating keys and in most cases a display . this display , as well as the size and number of the operating keys , is limited by the structural shape which is to be realized . at the same time , operating them should be as simple and intuitive as possible , so that the users of the infusion system can perform the therapy themselves . the conventional displays and keys which have been used hitherto result in solutions involving confusing displays and / or complicated operating steps using various keys . modern touch displays , such as are used in smartphones , make them simpler to operate and clearer , but can hardly be entertained in insulin pumps for reasons of price and space and power consumption . this approach has hitherto only been pursued in remote controls . moreover , the requirement that it also be possible to administer a bolus “ blind ” necessitates the use of keys . the subject of the invention is therefore a concept for realizing a simple and clear way of operating infusion pumps , based on a touch display which exhibits a simple functionality , and an individual and in particular mechanical bolus key . it is a further object of the invention to provide an infusion pump , and a method for controlling a user interface of such a system , which enable a large range of functions and a simple mode of operation , even when using miniaturized components . this object is solved by an administering apparatus , in particular a portable infusion pump comprising a touch - sensitive display and an additional operating element , characterized in that the operating element is a key . the touch screen or touch display can comprise 128 × 256 pixels at most . the administering apparatus can comprise precisely one single additional operating element . the precisely one or single additional operating element can be a mechanical key . the precisely one or single additional operating element can be an electromechanical key . the precisely one or single additional operating element can be a piezo - resistive key . a feedback device can be provided at or in the administering apparatus , which feedback device can generate a tactile , acoustic or optical feedback as a response to the additional operating element being operated . in one example embodiment , four concepts interact which are realized by the components mentioned : an operating concept comprising a touch display , i . e . a touch - sensitive display , and a single operating element , in particular a single mechanical key ; an infusion set comprising an integrated pressure valve and a carpule adaptor ; a drive concept comprising a deflection gear system and an integrated monitor ; and a feed concept comprising a supporting power pack . each of these concepts exhibits particular features in detail , which in their entirety result in a mode of operation which is substantially simplified as compared to conventional infusion pumps , but at the same time can be miniaturized . the operating concept is characterized by : a display of 128 × 256 pixels at most ; a gesture recognition system , in particular a capacitive gesture recognition system , which recognizes taps and swiping movements made by an individual finger ; and an individual and in particular mechanical key which on the one hand enables the touch display to be activated and on the other hand enables a bolus to be programmed without using the display . during normal operation , the display is switched off . it is activated by a keystroke and displays a summary of the current status . a swiping movement switches to a menu displaying a row of symbols . the symbols / sub - menus can be moved in and out of the visible region by left and right swiping movements , and selected by tapping them . the submenus are functional displays or screens which show displaying and setting options depending on the function . a keystroke cancels an initiated input and returns to the next respectively higher level . the operating concept described here can be implemented in both landscape and portrait format . it is also possible to program a “ blind ” bolus using the key , which is in particular a mechanical key , thus circumventing the touch display , wherein a bolus is triggered without the need for eye contact or interaction with the display , for example while carrying the pump in one &# 39 ; s trouser pocket or wearing it beneath one &# 39 ; s clothing . to this end , the key is sequentially operated as follows : 1 . a long keystroke , in order to activate the blind bolus function ; 2 . short keystrokes , acknowledged by tactilely perceivable signals from the pump , in order to input the bolus amount in predefined incremental increases ; 3 . a pause , upon which the pump system acknowledges the programmed amount , via tactile signals , and delivery then commences ; and this series of keystrokes realizes a very simple mode of operation , with a very high level of security against unintentionally triggering the delivery of a bolus . in accordance with the invention , the infusion set includes the following elements : a carpule connector ; a pressure valve ; and a transition line into the patient &# 39 ; s body . the result of integrating these elements is that the infusion system is simpler and more secure to operate . in particular , it enables incompletely filled carpules to be used , a warning to be issued when the system is put into operation with no carpule , and the operation of the system to be monitored during delivery . in accordance with the invention , the drive concept comprising a deflection gear system and an integrated monitor include : a drive comprising a rotary position monitor ( encoder ); a force transmission , arranged parallel thereto , onto the carpule stopper ; and a deflection gear system which deflects the rotational movement of the drive and at the same time converts it into a linear thrust , wherein the deflection gear system is integrated into the pump housing in such a way that the force exerted on the carpule stopper can be measured using a force sensor . this arrangement enables a shorter and therefore more user - friendly structural shape of the pump system . the feed concept comprising a supporting power pack includes a primary and a secondary energy source and a controller . the primary energy source is exchangeable and chosen such that it is as simple as possible for the user to replace ( standard aaa or aaaa battery , operated without any special tools ). the secondary energy source is fixedly installed , rechargeable and fed from the primary cell . this means on the one hand that the primary cell can be exchanged without interrupting the therapy , and on the other hand enables a warning to still be issued if the primary cell fails or an internal line is cut . the arrangement described thus enables a very simple mode of operation and at the same time the highest level of operational security . the components of the infusion system shown in fig1 are a housing 5 , a mechanical drive 40 - 53 , an energy source 90 , a drug reservoir 2 , a transition line to the patient &# 39 ; s body ( infusion set 30 , 31 ), a touch - sensitive display or touch display 20 , a key 10 and a controller 80 . fig1 shows a further aspect being an infusion pump having a display 20 being able to display a code , such as a data matrix code 21 . this data matrix code can be data matrix ecc 200 ( a well - known error checking and correction algorithm ). the data shown or encoded by the data matrix 21 can comprise or include data concerning the infusion pump itself and / or data concerning the functioning or working of the infusion pump , such as the infusion pump history . data included in the infusion pump history can for example be data indicating what amount of medication was delivered over time , such as data concerning the basal rate and data concerning one or more boluses delivered by the infusion pump . this infusion device can be combined with the above described aspects or can be independent thereof . the displayed code can be a bar code instead of the mentioned matrix code and can be any readable code which is able to display information or to transfer information from inside the infusion device , such as information from a memory and / or processor 80 inside the infusion device to the display 20 . the encoded information displayed on the display device can be read with an appropriate reading device having a camera , such as a mobile telephone , a camera connected to a computer or any other kind of camera connected to an electronic device . such a display can also be provided at a medical measuring device , such as at a blood glucose measuring device . in this case the data provided by the blood glucose measuring device and the data provided by the infusion pump can both be read by a camera and can be associated with each other using an electronic device . the data graphically displayed on the display 20 can provide a serial communication where a sequence of information , for example a sequence of matrix codes or bar codes or pixels , e . g . a single blinking pixel , can be displayed . each single code of the sequence can be displayed for a predetermined amount of time , such as for one second , whereafter the next code of the sequence is displayed until the last code required to transmit or display the desired information is reached . this displayed sequence of codes can be scanned by the mentioned camera connected to an electronic device which is able to extract the information from the displayed sequence of codes . in case a single pixel is used , the display and the viewing or receiving device act as optocouplers . it is possible to provide a parallel communication on the display , which parallel communication can be provided using a clock signal and several data pixels or picture elements or picture areas . the display can for example be divided into a predetermined number of fields , such as for example into four , nine or 16 fields . each field can then transmit a specific type of information by displaying a single picture or single data code or by providing a serial communication as described above , such as by providing a sequence of graphical codes . to provide a scannable graphical code the infusion pump includes a graphical code generator , which can be included or be a part of the electronic control module 80 or can be a separate device , which is provided from an internal electronic device of the infusion pump , such as a processor which can be connected to a memory device , with the information to be transformed into the graphical code , matrix code or bar code by the code generator . the input data can be configuration data of the infusion pump , device data , system state data and infusion or delivery history data . the code generator is connected to a display 20 for displaying the code , which display can be a transmissive display , such as a backlit lcd display , or can be a regular lcd display or can be a reflective display , such as an electronic paper . the graphical code can be a bar code or a data matrix code 21 and can in general be any kind of code which is able to transport or transfer information once the code is displayed . the scanning device can include electronics to obtain the information included in the scanned graphical code . according to an embodiment , an appropriate configured scanning device , such as a mobile phone or computer , can include a browser able to view a given web page associated with an uniform resource locator ( url ) included in the displayed graphical code and can display the contents of the thus specified web page . the information included in the graphical code can specify a particular alarm of the infusion pump or indicate malfunction and optionally data associated with the malfunction , such as data specifying the pressure detected by an internal pressure sensor of the infusion pump in case an occlusion is detected . an infusion pump system can comprise a display 20 for rendering a scannable graphical code , such as a one - dimensional or two - dimensional code , for example a bar code or a matrix code . the display 20 may be integrated within the infusion pump . the infusion pump may include a graphical code generator for generating a scannable graphical code based on input information . the input information can be selected from a group consisting of : configuration data , device data , system state data , device history data , infusion history data , device alarm data and / or malfunction data . the graphical code data generated by the code generator can be a static data or can be a serial communication data with a sequence of separate data units , such as a sequence of separate graphical data or can be a parallel communication data providing in parallel graphical code data on specified fields of the display device 20 optionally using a clock signal . a method for displaying a graphical code on a display 20 of an infusion system comprises the steps : obtaining data from an electronic device inside the infusion pump ; transforming this data into a graphical code ; and displaying this graphical code on a display 20 of the infusion pump . the step of displaying can be a static display , for example the display of a single graphical code for a predetermined amount of time or until a specific event , such as pressing a button 10 of the infusion pump . alternatively , the step of displaying includes the display of a sequence of graphical codes including separate individual graphical codes . this sequence can be displayed using a predefined clock signal to display each of a series of graphical displays in sequence , wherein each graphical code is displayed for a predetermined amount of time . alternatively , the sequence can be triggered by an external event , such as by pressing a button 10 on the infusion pump , so that a user can for example flip through the code sequence .

US-201414506197-A

an ankle support for use by persons recovering from an ankle injury or desiring to prevent ankle injury that includes a flexible heel foot support or shoe for fitting around the foot and ankle . a non - stretchable strap , that extends from beneath a fifth metatarsal area of the foot support or shoe and is fitted through a sleeve to pass over the outer ankle bone or lateral malleolus area of the foot support or shoe , and over an instep area and down to a ring mounted to the heel area support on the same side as the sleeve ; and an arrangement to receive and maintain the strap in a taut condition to the ring .

in the illustrated preferred embodiment of the invention shown in fig1 - 4 , the ankle support shown generally at 10 comprises a fabric shell foot support 11 , hereinafter referred to as foot support , which may be made of seamed inner and outer layers of nylon 12 and 13 or other suitably strong material and with a padding material 14 such as cotton , arranged between the inner and outer layers . as shown , the foot support 11 is shaped as a high - topped shoe , that is open at the toe 15 and heel 16 . the front 17 of the foot support is open at 18 with a tongue 19 that is attached to one side of the foot support to extend across the front opening 18 when the foot support is laced onto a user &# 39 ; s foot . spaced eyelets 20 are arranged along opposite sides of the front opening and a shoe lace 21 is provided for threading through the eyelets to secure the foot support to a user &# 39 ; s foot in usual high - top shoe fashion . a non - stretchable strap 25 is included that has one end attached to the outside surface of the foot support 11 in the area that fits over the fifth metatarsal bone of the user . the strap 25 is passed through a sleeve 26 that is secured to the outside of foot support 11 and is positioned to direct the strap 25 across the fifth metatarsal and is curved or angled upwardly and rearwardly over the area of the foot support that covers the outside ankle bone , or lateral malleolus , of a user . the sleeve 26 is curved or angled to direct strap 25 around the back of the foot support or heel cord , or achilles tendon such that the strap will pass over the area of the foot support that covers the inside ankle bone of a user . the strap is secured thereover when it is passed over or above the instep area of the foot support and the strap then passes through a ring 30 . which ring 30 may be but need not be pivotally fixed to the foot support outer surface , or lateral heel area . the ring 30 is held in place by a flap 31 that is passed through the ring and has its ends anchored at the heel area of the foot support 11 . shown in fig1 and 2 the ring is anchored by a rivet 32 though it could as well be secured thereto as by sewing , or the like . the flap 31 and ring 30 may be arranged to pivot about the rivet 32 to accommodate reception of the strap 25 end through ring 30 after the strap 25 has been passed across the instep . adjustability is provided to prevent strap 25 from folding upon itself inside ring 30 . strap 25 is removably attached to the ring 30 by passing a free end 34 of that strap through the ring and turning or bending the strap end back upon itself . a hook and loop fastener 35 , such as that marketed under the trademark &# 34 ; velcro &# 34 ;, is preferably used to secure the end of the strap to the strap surface , after that strap has been pulled tight . the ankle support 10 is adapted for use on previously injured ankles or for protecting ankles against commonly occurring injuries . the foot 39 of a user wearing the ankle support 10 , is shown with curved arrows , in fig4 being turned in a manner that frequently will result in serious ankle injury . the foot 39 is shown rolling to the inside ( inversion ). approximately 80 % of all ankle sprains are sustained when the ankle is stressed in a position of inversion with the foot pointed down . this rolling of the foot and subsequent downward pulling and stretching of the lateral ankle ligaments is countered by the strap 25 that holds the ankle to the foot from the area of the fifth metatarsal bone and from the heel . as the foot rolls under , tension is applied to strap 25 at its origin at the fourth and fifth metatarsal area . if this force is followed along the strap around the ankle to its attachment to the heel buckle , one realizes that , due to the single support strap arrangement , a counterforce is produced at the heel , holding the heel up and out , or opposite to the direction of a force as would cause injury to the lateral ankle ligaments . the ankle support 10 is readily worn inside a conventional shoe . as shown in fig1 - 4 , it is constructed for use on the right foot of a user . it will be apparent that a support for use on the left foot would be constructed as a mirror image of that shown in fig1 - 4 . because the support is open in both the heel and toe areas the support can be used for feet of many sizes . another embodiment of the ankle support is shown in fig5 as ankle support 40 that is constructed for use on either a right or left foot of a user . in this embodiment the fabric shell foot support 41 is constructed the same as the foot support 11 previously described . the foot support 41 is made of seamed inner and outer fabric layers 42 and 43 with a padding material 44 between them . the support is open at toe 45 and heel 46 and has a front opening 48 adapted to be covered by a tongue 49 . spaced eyelets 50 and a lace 51 for threading therethrough allow the support to be laced snugly onto a user &# 39 ; s foot and ankle . a non - stretchable strap 55 , that corresponds to the strap 25 previously described , has one end sewn or otherwise affixed to the center bottom of the support 42 . two flexible sleeves 56 and 56a are respectively attached to opposite sides of the foot support 41 , with each being curved upwardly and rearwardly on the support . the foot support 41 also has a pair of rings 60 and 60a affixed thereto . thus , ring 60 is attached as by a flap 61 and a rivet 62 to one side of the support at the heel thereof and the ring 60a is attached by a flap 61a and a rivet 62a to the other side of the support at the heel area . as in the previously described embodiment , strap 45 is adapted to be passed through one or the other of sleeves 60 or 60a and , as it is inserted through one of said sleeves , depending on whether the support is to be used on a right foot or a left foot of a user , the strap passes beneath and across the fifth metartsal bone of the user . the strap , after running through a sleeve 56 or 56a then passes over the instep area and is secured to a ring 60 or 60a on the same side of the support as the sleeve through which the strap is passed in the manner previously described . the ankle support 40 is accordingly adapted for use on either foot of a user , for use in the same manner as the ankle brace 10 . fig6 shows still another embodiment of an ankle support 70 . in this embodiment , a high top shoe 71 is the foot support , hereinafter referred to as shoe , that may be a canvas or leather high top , such as a basketball shoe , is substituted for the fabric shell foot support 11 of fig1 through 4 . accordingly , as shown in fig6 the non - stretchable strap 25 is secured or attached at one end to the outside surface of shoe 71 in the area that fits over the fifth metatarsal bone of the user . the strap 25 is passed through sleeve 26 that is outside of the shoe 71 to direct the strap 25 across the fifth metatarsal , functioning as described hereinabove with respect to fig1 and 4 . the strap 25 , directed by sleeve 26 , passes around the back of the wearer &# 39 ; s foot , or achilles tendon , and over the inside ankle bone and across the top of the foot and through ring 30 which ring is shown attached by a flap that is secured to the shoe and is fitted through the ring , and folded back upon itself . the overlapping lap sections are sewn at 32 to fix the ring 30 to the shoe &# 39 ; s outer surface , or lateral heel area . which ring in this embodiment may also be pivotally fixed to the shoe , rather than sewn within the scope of this disclosure . the strap 25 is fitted through ring 30 and is folded back in itself . a velcro type hook section 34 is provided on the strap for coupling to an opposite velcro type mat surface 35 to maintain the strap end to the strap body , functioning as described above with respect to a discussion of fig1 through 4 . although a preferred form of my invention has been herein disclosed , it is to be understood that the present disclosure is by way of example only and that variations are possible without departing from the subject matter coming within the scope of the following claims and a reasonable equivalency thereof , which subject matter i regard as my invention .

US-49331790-A

a surgical instrument for endoscopic surgery is provided which is capable of articulation in the endoscopic arm portion of the instrument to supply the surgeon with improved adjustability in the orientation of the arm . the instrument provides means through which the surgeon can change the angle at which the instrument actuates . this articulation functions without disruption of the rotatability of the arm or the mechanism for applying staples , clips , and the like . because this articulation can be performed in conjunction with a rotation feature , a large degree of adjustment is generated .

turning now to the drawings , fig1 and 3 show one embodiment of the surgical instrument in perspective , top and front views , respectively . generally speaking , a surgical instrument , particularly those used in endoscopic surgery , includes a long endoscopic arm portion 1 , an actuation mechanism 2 located at the end of the endoscopic arm portion 1 and a handle area 3 with a trigger 4 . the operation of the trigger 4 causes a linear force to travel through the length of the arm 1 to the actuation mechanism 2 . this linear force activates the actuation mechanism 2 . the actuation mechanism 2 can include , but is not limited to , staplers , clip appliers , scissors , linear staplers , gia stapling and dividing devices , graspers , or other such instruments . as depicted in fig4 - 6 , the invention also comprises an articulation mechanism or joint 5 which includes an articulation rod 20 , a backstop 21 , two pivot gears 22 and 24 , and two pivot gear racks 23 and 25 . further , the actuation mechanism or cartridge 2 is connected to the endoscopic arm 1 at the joint 5 . a drive cable 40 runs through the center of the joint 5 between the endoscopic arm 1 and into the cartridge 2 as shown in fig4 a , 5 and 5a . the drive cable 40 consists of a flexible but strong material , such as stainless steel with a thin plastic coating . in the present embodiment of the invention , movement of the trigger 4 forces a long push rod 41 to move forward pushing a short push rod 42 . the short push rod 42 is secured to the drive cable 40 . the drive cable 40 will consequently move forward , regardless of any bending in the drive cable 40 . the long push rod 41 and the short push rod 42 are rigid to prevent any unwanted bending . the long push rod 41 is contained within a cylindrical aperture 43 concentric to and in the center of the arm 1 which comprises arm halves 1a , 1b . the long push rod 41 is rotatably secured in a pivot bearing 45 which is located on the trigger 4 . articulation of the invention is caused by the saddle 10 which is linked to the articulation rod 20 . at zero degrees articulation , as shown in fig4 the backstop 21 , pivot gears 22 and 24 and pivot gear racks 23 and 25 do not perform any particular function . the drive cable 40 passes through the center of the pivot gear 22 and the centerline of the arm 1 . as shown in fig4 a , 5 , 5a and 6 , the racks 23 and 25 are secured within the arm halves 1a , 1b . each rack 23 , 25 is positioned within molded openings 26 , 27 which have a geometry corresponding to the shape of the racks . the gears 22 , 24 are attached to each half of the knuckle 36 by inserting a t - shaped or other shaped protrusion on the gears 22 , 24 into a t - shaped or correspondingly shaped opening in each half of the knuckle 36 . the molded openings 26 , 27 also have an area corresponding to the gears 22 and 24 , but the gears 22 and 24 are allowed to rotate up the teeth of the racks 23 and 25 . at an articulated angle , however , the functioning of these pieces is critical to this invention . the operation occurs when the saddle 10 is moved laterally . the articulation rod 20 is operably attached to the saddle 10 at one end and rotatably attached at opening 35 in the knuckle 36 of the cartridge 2 . when the saddle 10 is moved laterally , the articulation rod 20 , which travels the length of the arm 1 , causes the cartridge 2 to move angularly relative to the arm 1 as shown in fig5 and 5a . this angular movement of the cartridge 2 is achieved because the lateral movement of the articulation rod 20 pulls the cartridge 2 toward the arm 1 . the cartridge 2 begins to articulate as the gear 22 climbs the gear rack 23 . the joint 5 is predeterminately designed to provide a predictable degree of articulation depending on the position of the articulation rod 20 . fig5 shows the joint 5 in full articulated position . thus , when the trigger 4 of the instrument is squeezed , the drive cable 40 moves forward through the joint 5 . the leading edge of the cable 40 is connected to a member in the actuation mechanism or cartridge 2 for accepting the linear force transmission . as the trigger force increases , the cable 40 tends to bow outward in the joint area until the outer tangent surface comes into contact with the backstop 21 as shown in fig5 and 5a . the cable 40 then resumes its forward motion . the backstop 21 has a fixed pivot point 15 in the arm 1 and follows a track 16 in the knuckle 36 . this track 16 causes the backstop 21 to move in accordance with the articulation angle , thereby providing support at all angles . the pivot gear 22 and rack 23 acts as a moment balancing joint . as the articulation angle changes , the pivot gear 22 climbs up the gear rack 23 , changing the effective pivot point . the importance of this design is that the cable 40 always passes through the center of the pivot point in order to eliminate any moment that would be caused during force transmission . another function of the pivot gear system is to eliminate cable compression above the pivot point . this compression occurs naturally with a fixed pivot point on the centerline and tends to alter the firing stroke of the trigger and also the pre - cock system . to provide stability to the articulated position of the cartridge 2 , the saddle 10 is fastened to a detent slide 55 with a protrusion 57 . the protrusion 57 fits within a groove 58 , which is part of a linear series . when the saddle 10 moves laterally , the detent slide 55 likewise moves . however , a detent compression spring 56 , secured by ribs 59 in the handle 3 , applies an upward pressure on the detent slide 55 to force the protrusion 57 to fit within one of the molded grooves 58 . the spring 56 allows the saddle 10 to move when a surgeon applies a reasonable pressure to the saddle 10 . nonetheless , the spring 56 applies sufficient pressure to provide stability to the position of the saddle 10 , and consequently , the articulated position of the cartridge 2 . fig7 a and 8 illustrate the rotation feature of the invention . the arm 1 is free to rotate because it is not fixedly secured to the handle 3 , but is positioned within a tube - like protrusion 50 on the handle 3 . the long push rod 41 travels into the handle 3 and is attached to a pivot bearing 45 in the trigger 4 . the pivot housing 46 which includes housing halves 46a , 46b is fixedly attached to the arm 1 and rotatably attached to the protrusion 50 . thus , the surgeon can rotate the arm 1 without affecting the position of the handle 3 by rotating the pivot housing 46 . the articulation rod 20 maintains its relative position in the arm 1 , but slides within an annular channel 68 in an articulation disk 70 . the mount 72 which is operably attached to the saddle 10 by saddle linkage 74 acts on the articulation rod 20 through the articulation disk 70 regardless of the rotated position of the arm 1 . the rotation feature is provided with a detent mechanism in order to maintain the position selected by the user similar to the function of the detent mechanism for the articulation feature . referring to fig7 a and 8 , a resilient , u - shaped wire 80 is secured within the pivot housing 46 by two ribs 82 , 84 on housing half 46a and two ribs 86 , 88 on housing half 46b . as the pivot housing 46 is rotated , one leg 94 of the wire 80 deflects over the annular series of grooves 98 on the tube - like protrusion 50 . consequently , the pivot housing 46 which is ultimately connected to the actuation mechanism 2 can be held in the position selected by the user because the leg 94 will be held in one of the grooves 98 until the user selects a new position . there are two main advantages of this detent mechanism . the first advantage is that the design minimizes the number of parts required since the u - shaped wire 80 provides both the contact surface and the spring force . the second advantage is that the detent force , i . e . the force required to rotate the device as the leg 94 deflects over one peak between the grooves 98 , can easily be altered . the detent force is altered by changing the bend angle of the leg 94 in the u - shaped wire 80 , without altering the annular series of grooves 98 . referring to fig7 and 7a , the trigger 4 is attached to the handle 3 at pivot point 106 . the trigger 4 is held in the open position by extension spring 108 which is attached to the trigger 4 and the handle 3 . in order to move the long push rod 41 forward , the user pulls the trigger 4 rearward against the handle 3 to overcome the biasing force of the extension spring 108 . in order to ensure that the user pulls the trigger 4 through its required stroke or movement , the handle 3 includes a pre - cock system 112 . referring to fig7 a , the pre - cock system 112 includes pre - cock spring 114 , a pre - cock latch 116 and a series of ridges 118 on the trigger 4 . as the trigger 4 is pivoted rearward the ridges 118 engage the latch 116 . the latch 116 deflects over each ridge 118 as the spring 114 biases the latch 116 towards the ridges 118 . due to the shape of the ridges 118 and the angular edge 120 on the latch 116 , the trigger 4 can be held in a fixed position with respect to the handle 3 as the latch 116 engages each ridge 118 . consequently , the user can partially depress the trigger 4 and the pre - cock system 112 will hold the trigger 4 in the partially depressed position . furthermore , due to the pre - cock system 112 , the trigger 4 can only move in a rearward position , and cannot be moved in a forward position , until the latch 116 deflects over the last ridge 118 . after the latch 116 deflects over the last ridge 118 , the latch 116 achieves a different orientation and permits the trigger 4 to move forward . thus , the pre - cock system 112 ensures that the user pulls the trigger 4 through its required stroke or movement in order to prevent double actuation of the actuation mechanism 2 . it will be appreciated , of course , that the foregoing arrangement is suitable for any instrument that requires transmission of force to an actuation mechanism 2 and requires an articulation feature . furthermore , it will be appreciated that the foregoing invention is suitable for any instrument which requires a rotational feature which allows the user to maintain a selected rotational position .

US-13452293-A

the subcutaneous injection device contains a pump and a mechanism for inserting a cannula into the patient &# 39 ; s skin . the cannula is fixedly positioned relative to the pump and the insertion mechanism has a flexible surface adhering to the skin . the flexible surface is positioned relative to the cannula in such a way that in a first position the tip of the cannula is concealed by the surface and in a second position the cannula is exposed beyond the surface . the insertion mechanism brings the surface from the first to the second position , thereby pulling the skin against the tip of the cannula .

the injection device shown in fig1 has a casing having a cylindrical side - wall 1 housing a barrel in form of a segment of a toroidal tube 2 . one end 3 of the barrel is provided with a connecting channel to a cannula ( not shown ). the barrel has a circular cross section . a piston 4 is arranged in the interior of the barrel and is provided with a seal fitting tightly at the inner wall of the barrel . the piston is connected to a driving rod 6 which is circularly shaped for driving the piston through the entire length of the barrel . using established technologies for manufacturing of a toroidal cylinder the fit between its curvature and the driving rod of the piston will not be perfect . to correct for this the mechanism 5 disclosed here connecting the piston to the rod 6 allowing radial adaptation of the piston represents an improvement as compared to the state of the art solutions e . g . as described by m . p . loeb and a . m . olson in u . s . pat . no . 4 , 525 , 164 , using a resilient spherical piston which is slidably contacted by a cupped distal end of a driving stem allowing it to rotate within the barrel , since such a construction has intrinsic problems of sealing and friction . at its end opposite the piston the driving rod has a perpendicularly bent arm 7 extending to a central pivot , thereby reducing the radial component of the force and the resulting friction by moving the piston through the barrel . the inner side of the rod has a gear rim 8 which is driven by a gear drive 9 . the gear drive is driven e . g . by a gear train and an electrical motor ( for example a watchwork drive ) which can be regulated for controlled delivery by signals from inbuilt and / or remote control elements ( not shown in the figure ). alternatively , other drives , as known in prior art , can be employed . using standard manufacturing technologies for the toroidal barrel such as e . g . plastics - technologies with an injection molding tool having a mandrel which has to be removed by a rotary motion , deviations from a perfect circular shape and variations in its shape are unavoidable due to inherent differences in shrinkage e . g . of the proximal and distal part of the torus wall during manufacturing . because of this almost unavoidable deviation from an ideal circular shape for the manufactured torus the exact geometric fit between the barrel and the driving rod of the piston moved by a rotary motion can not be secured . even if the driving rod of the piston is manufactured using steel - technologies with a high level of form - stability , the fit of the attached piston to the barrel &# 39 ; s shape along its longitudinal axis becomes variable . indeed , e . g . a difference of only 2 % between the radius of the barrel and of the driving rod causes a serious relative shift which can lead to collision between barrel wall and driving rod for torus arcs of e . g . 150 . degree .- 160 . degree . which can be manufactured with standard technologies and are aimed at in order to sufficiently reduce the footprint of the syringe - type pump . in addition , the plastics parts usually used to manufacture the housing holding the barrel and the guideways for the driving rod are not absolutely rigid and can slightly deform especially under the applied forces necessary to provide the pressures of several bar to overcome tissue resistance . the resulting radial and axial forces to correct for the actual shape differences between axis of barrel and driving rod can become very substantial with a rigid driving rod which is used for arcuate piston - drive mechanisms described so far . these forces have to be absorbed by the sealing of the piston leading to its deformation causing high friction with resulting stick - slip phenomena up to blockage and / or problems with tightness of the piston . even if the piston can adapt slightly to correct for the deviation between the axis of the barrel and of the driving rod as described in prior art and with the improvement discussed and exemplified in fig1 the worst case scenario of blockage by clamping between the rigid driving rod and the barrel wall cannot be excluded . therefore , for medical use of controlled and precise fluid delivery constructions according to prior art in which a driving mechanism with a rigid driving rod is used to move the piston in an arcuate barrel are not sufficiently safe . these problems get even more pronounced at low barrel diameters required for syringe - type pumps intended for the precise delivery of small volumes such as e . g . insulin for diabetic patients . according to the subject invention , the solution to avoid stick - slip phenomena and / or problems with tightness or even blockage of the piston or clamping between the rigid driving rod and the barrel wall is to use a driving rod of the piston which adapts to the actual curvature of the barrel , being guided and supported by the inner wall of the barrel . in contrast to constructions described in prior art the rod guided and supported by the inner wall of the barrel of the subject invention can adapt to all deviations from the ideal shape and geometry which are unavoidable using cost - effective manufacturing technologies and materials . a preferred embodiment of the subject invention , which can be adapted for both , fluid delivery and fluid withdrawal , is exemplified in fig2 . fig2 shows a combined injection and analysis fluid removal device with two independent circular syringe pumps in top view of a horizontal section . the pump for delivery of injection fluid is shown in the more peripheral part of the drawing , whereas in the more central part a pump for removal of analysis fluid is shown . in fig2 parts corresponding to fig1 are given the same reference numbers . the embodiment in fig2 does not have a rigid driving rod . instead , the driving rod 6 of the piston is formed in such a way that its movement is guided and supported by the inner surface of the barrel wall as shown in cross section in detail a . importantly , a brace 11 of optimized form and material for even movement with low friction to increase precision and to reduce the necessary forces for piston movement forms the gliding zone between driving rod of the piston and inner surface of the barrel wall . this can be achieved by using for the driving rod plastics with suitable gliding properties or by attaching a rim of suitable material , e . g . a steel wire , but other possibilities of friction reduction like e . g . a construction with a number of rolls the axis of which is held by the brace can be implemented in order to avoid gliding resistance and replace it by rolling resistance . the radial and axial flexibility of the driving rod exemplified in detail a can be further increased e . g . by using a segmented structure of the brace holding glidingly a steel wire or the rolls or even a back - bone like structure of the flexible driving rod with segments linked by hinge regions . to ensure safe transmission of the power to the gear rim 8 to move the piston , the gear drive 9 is supported by a radially opposing brace 10 , preferentially in the form of an antifriction bearing , pressing against the contact rim 11 of the driving rod , but other constructions like e . g . a side - wall attached to the housing are also possible . the piston 4 with its sealing , e . g . an o - or an x - ring is held in a defined distance from the inner surface of the barrel wall by the brace of the driving rod and transmits only the tangential driving force to the piston . in addition , to allow self - centering of the piston in the lumen of the barrel , in an alternative construction the piston is not directly fused rigidly with the end of the driving rod , but movably attached to an end - piece of the driving rod which is held by the brace in a defined distance from the barrel wall . this can be achieved e . g . by a low - friction sliding surface contact between the end - piece of the driving rod and the piston or by balls rolling at the interface . such a self - centering construction might be useful to improve the performance of the pump in case of significant manufacturing process derived variability in the inner shape and diameter of the barrel along its axis . for delivery of injection fluid the driving rod of the piston is pushing , while guided and supported by the distal inner surface of the barrel ( shown in detail a ). in contrast , the circular syringe pump for removal of analysis fluid is operated in suction mode and the driving rod of the piston is pulling , guided and supported by the proximal inner surface of the barrel ( mirror image of detail a , not shown as detail ). a proximally located gear rim 8 to move the piston can also be used e . g . in a construction in which the gear rim is double - tracked and set back respective to the brace 11 and the gear drive 9 has a slit to accommodate the protruding brace . fig3 is the central part of a tangential cut of the device through the end portion 3 of the barrel . a first channel 15 is leading to the upper side of the device and is closed by a septum 14 . for filling the barrel with injection fluid a syringe ( not shown ) having a needle 13 is pierced through the septum 14 . before filling , the piston is touching the end portion 3 of the barrel ( not shown ). the injection fluid is introduced through channel 15 , thereby pushing the piston towards the opposite end of the barrel . a second channel 17 is leading from the interior of barrel 2 to an injection cannula 16 for delivery of injection fluid into the skin . the cannula 16 is closed at the other end with a septum - seal 18 which is held in a housing 19 . the overall construction is such that the dead volume is minimal and no significant volume of air is in the system after filling with injection fluid . in the exemplified embodiment the insertion means into the skin of the cannula 16 has a flexible base plate 20 which is attached to the skin by an adhesive layer 21 . in the ready - to - use mode shown in the figure this flexible base plate is deformed to a convex shape covering the cannula 16 . the base plate is preferentially annular or oval and in order to insert a cannula which is remote from the center of the device consists preferentially of two segments with a diagonal slit , forming a gable upon bending . this configuration allows also to use this insertion means for more than one cannula simultaneously which are positioned along the diagonal slit , e . g . if more than one infusion pumps for more than one infusion fluid is used and / or for the combination with insertion of a diagnostic probe into the skin . by the spring - type mechanism , in addition the septum - seal 18 is pierced by the cannula before it enters the skin . the segments are attached to the circumference of the casing 1 by springy hinge regions and are in addition preferentially made of a flexible material . alternative forms like a radial segmentation , preferably into 5 to 8 segments with a spacing between them and a central opening , forming a cone upon central bending are also possible if the cannula is placed close to the center of the device . on its underside , the flexible base plate has an annular or oval adhesive layer for securing the device to the patient &# 39 ; s skin with a diagonal slit or a concentric central opening , respectively similar to the base plate . this adhesive layer is composed of three parts , a glue for fixing to the flexible base plate , a textile providing the necessary flexibility and a glue for fixing onto the skin . suitable materials with low allergenicity potential are commercially available . the adhesive layer can have a larger circumference than the device but it could have also the same circumference if the attachment to the base plate leaves an outer zone where it is not connected to the housing . upon release of the pre - stressed base plate actuated e . g . by a sliding bolt mechanism ( not shown ) it rapidly relaxes to a flat shape towards the bottom of the housing of the device 1 , pushes the housing 19 of the septum - seal 18 , and the cannula 16 pierces through the septum - seal 18 and through the skin attached by the adhesive layer . upon reading this specification , various alternative embodiments will become obvious to the skilled artisan . for example , the drive means for moving the piston or the implantation mechanism of the cannula for delivery of injection fluid into a patient , or for removal of analysis fluid of a patient could be achieved via numerous chemical , mechanical , or electrical means . further , a large variety of diagnostic elements for the online analysis or for sampling of analysis fluid for removed analysis as well as control and measuring means can be accommodated with the device . the major advantages of a device with a toroidal syringe - type pump described above are its reduced footprint - size by which it can be comfortably worn and operated by the patient and at the same time the inherent high precision of a syringe type pump . the intrinsic problems of such pumps exemplified in prior art of sealing , friction causing stick - slip phenomena , and even blockage caused by lack of exact fit between the actual form of the arcuate barrel and of the plunger unavoidable in manufacturing of the toroidal barrel and the device using standard cost - effective technologies are solved by using as the drive for the piston a driving rod which is guided and supported by the inner wall of the barrel and therefore can adapt to all deviations from the ideal shape and in geometry . a further advantage is the absence of the problems with connecting tubings between a syringe pump and the cannula penetrating the skin . in addition , the device according to the invention has almost no dead volume thus avoiding complicated mechanisms to move air out of the system during filling of the pump with injection fluid .

US-201514738995-A

exercise weights and method , regarding belts , handweights , arm weights , ankle weights , and knuckles weights .

referring now to the drawings wherein like reference numerals refer to similar or identical parts throughout the several views , and more specifically to fig1 and 3 thereof , there is shown an ankle weight system 10 . the ankle weight system 10 comprises an adjustable weighting system 12 . the ankle weight system 10 comprises a mechanism 14 for holding the weighting system 14 to an ankle of the user . preferably , the weighting system 12 includes a first weight 16 of at least one pound and at least a second weight 18 of at least one pound . the holding mechanism 14 preferably includes a first cell 20 and at least a second cell 22 which is attachable and separable from the first cell 20 . the first cell 20 holds the first weight 16 , and the second cell 22 holds the second weight 18 . preferably , each cell has a strap 24 which is adapted to wrap around the leg of a user . the first cell 20 preferably includes a first zipper mechanism 20 , and the second cell 22 includes a second zipper mechanism 28 which zips with the first zipper mechanism 26 . the present invention pertains to a method for exercising . the method comprises the steps of zipping a first cell 20 having a first weight 16 to a second cell 22 having a second weight 18 . then there is the step of placing the first cell 20 and second cell 22 around the leg . next there is the step of pulling a strap 24 of the first cell 20 tight around the leg . then there is the step of pulling a strap 24 of the second cell 22 tight around the leg . in the operation of the ankle weight system 10 , as shown in fig1 and 3 , there is a first weight 16 disposed in a first cell 20 . the first cell 20 has a first zipper mechanism 26 attached to it . a second cell 22 has a second weight 18 and a second zipper mechanism 28 attached to it . the first cell 20 is connected to the second cell 22 by zipping together at the first and second zipper mechanisms . if desired , additional cells with additional weights having the zipper mechanisms attached to the perspective cells can be combined with the second cell 22 to extend the ankle weight system 10 and add weight to the ankle weight system 10 . typically the third cell 29 having a third weight 30 with a third zipper mechanism 31 is attached through the zipper mechanisms to the second cell 22 , as shown in fig1 and fig3 . when the user wishes to use the ankle weight system 10 . the user determines how much weight is to be included on the ankle weight system 10 . the user then combines a desired number of cells to attain this weight . the cells , connected together through the zipper mechanisms are wrapped around an ankle and held in place by hook and loop fasteners 32 which connect opposite ends of the cells together to form a closed loop around the ankle . the present invention pertains to a wrist weight system 40 . the system 40 comprises a weight portion 41 weighing at least 15 ounces having a first end 42 and a second end 43 . the system 40 comprises a stretchable band portion 44 that connects with the first end 42 and the second end 43 of the weight portion 41 and together with the weight portion 41 forms a closed continuous essentially cylindrical shape with an opening 45 having a diameter through which the user inserts the wrist . the system 40 comprises an adjustable tensioning portion 46 connected to the weight portion 41 which varies the tension of the weight portion 41 about the wrist . preferably , the tensioning portion 46 includes a strap 47 having a fixed strap end 48 connected to the first end 42 of the weight portion 41 and a free strap end 49 . the strap 47 has a first connector portion 50 adjacent the free strap end 49 . the tensioning portion 46 includes a second connector portion 51 disposed adjacent the second end 43 of the weight portion 41 which mates with the first connector portion 50 to maintain the weight portion 41 at a desired tension about the wrist of the user . the first connector portion 50 and second connector portion 52 are preferably hook and loop fasteners , respectively . the present invention pertains to a method for exercising . the method comprises the steps of inserting a wrist through an opening 45 of a wrist weight 40 having an essentially cylindrical shape . then there is the step of pulling a tensioning portion 46 of the wrist weight 40 so a weighted portion 41 of the wrist weight 40 is tightened about the rest . next there is the step of securing the tensioning portion 46 to the weighted portion 41 to maintain the tension of the weighted portion 41 . in the operation of the wrist weight system 40 , the hand of a user is inserted through the opening 45 of the weight portion 41 until the wrist weight system 40 is positioned about the wrist of the user . see fig5 . the weight portion of 41 has a first end 42 and a second end 43 that are connected together through a band portion 44 which stretches to allow the first end 42 and second end 43 to separate from each other and still be connected to each other as a hand moves through the opening 45 . the band portion 44 serves to maintain the weight portion 41 in the desired cylindrical shape to facilitate easy positioning of the wrist weight system 40 by the user . see fig4 . once the wrist weight system 40 is in a desired position around the wrist of the user , a strap 47 which is attached to the first end 42 at a fixed strap end 48 is pulled to in turn pull the first end 42 toward the second end 43 . this serves to tension the weight portion 41 onto the wrist . the free strap end 49 of the strap 47 is then placed down onto the weight portion 41 . at the free strap end 49 is a first connection portion 50 . adjacent to the second end 43 of the weight portion 41 is a second connector portion 51 . the first connector portion 50 , when placed against the second connector portion 51 is held in place and maintains the weight portion 41 in a desired tension . see fig6 . the first connector portion 50 and second connector portion of 51 can be hook and loop fasteners . the present invention pertains to a belt - ankle - wrist - thigh weight system 55 . the system 55 comprises a first weight portion 56 . the system 55 comprises a first attachment portion 57 connected to the first weight portion 56 which is attachable to a user . the system 55 comprises a second weight portion 58 . the system 55 comprises a second attachment portion 59 connected to the second weight portion 58 which is attachable to a user . the second attachment portion 59 is attachable and separable with the first attachment portion 57 to form a third weight portion 60 of the first and second weight portions which is attachable to a user . preferably , the first weight portion 56 and the second weight portion 58 each have a plurality of weights 61 that are held by the respective attachment portion . each attachment portion preferably has a plurality of pockets 62 , each pocket holding a weight 61 . preferably , the first attachment portion 57 includes a first strap 63 to which pockets 62 are attached . the first strap 63 has hook and loop fasteners 64 which holds the first weight portion 56 to the user . the second attachment portion 59 includes a second strap 65 to which pockets 62 are attached . the second strap 65 has hook and loop fasteners 64 which hold the second weight portion 58 to the user and to the first attachment portion 57 . the first and second attachment portions preferably each have a loop 66 through which a strap passes to form an attachment . the present invention pertains to a method for exercising . the method comprises the steps of attaching a first weight portion 36 to a second weight portion 58 . then there is the step of strapping the first and second weight portions around the hips of a user so the first and second weight portions are situated over the right and left hips , respectively . next there is the step of removing the first and second weight portions from the user . then there is the step of separating the first and second weight portions . next there is the step of strapping the first weight portion 56 to the right thigh of the user . then there is the step of strapping the second weight portion 58 to the left thigh of the user . in the operation of the belt - angled - wrist - thigh system 55 , a first weight portion 56 and second weight portion 58 are connected together through a first attachment portion 57 connected to the first weight portion of 56 and a second attachment to portion 58 connected to the second weight portion 58 . see fig7 and fig8 . each attachment portion has pockets 62 . the first attachment portion 57 includes a first strap 63 along which pockets 62 are sewn . the second attachment portion 59 includes a second strap 65 which also has pockets 62 sewn to it . the first weight portion 56 includes weights 61 that are inserted into the pockets 62 along the first strap 63 , as shown in fig9 . similarly , the second weight portion 58 includes weights 61 that are inserted into pockets 62 along second strap 65 . the weight 61 can be chosen to be a certain weight so the overall weight of the respective weight portions is attained . the first weight portion of 56 and second weight portion 58 are connected together by the first strap 63 passing through a loop 66 of the second attachment portion 59 and the first strap 63 then bring brought back upon itself and fixed to itself through hook and loop fasteners 64 . the second strap 65 of the second attachment portion 59 is then brought around to pass through the loop 66 of the first attachment portion 57 and brought back upon itself to be fixed in place through hook and loop fasteners 64 . during positioning by a user onto the body , the first strap 63 is passed through loop 66 of the second attachment portion 59 and fastened back onto itself with the hook and loop fasteners 64 . with the second strap 65 still loose , the first and second weight portions , which are now connected together and form a third weight portion 60 whose weight is the sum of the total weight of the first weight portion 56 and second weight portion 58 , are positioned around the waist so the first weight portion 56 is situated about the right hip and the second weight portion 58 is situated about the left hip . then the second strap 65 is passed through the loop 66 of the first attachment portion and fastened upon itself through hook and loop fasteners 64 . when the user decides to remove the weight system 55 , the second strap 65 is separated from itself and pulled back through the loop 66 of the first weight portion 56 . the first and second weight portions can then be removed from the body of the user . the user can then separate the first strap 63 from the loop of the second attachment portion 59 and thus separate the first weight portion 56 from the second weight portion 58 . each weight portion can then serve as a separate weight system that can be used to wrap around an ankle or wrist or thigh . see fig1 , 11 , and 12 . in each case , the respective strap is simply passed through the loop 66 of its own attachment portion and pulled to create a desired tension around the given appendage of the user so it fits properly during exercise . the present invention pertains to an exercise apparatus 70 . the apparatus 70 comprises a weight 71 . the apparatus 70 comprises a holder 72 for a weight 71 . the holder 72 has a pocket 73 which holds the weight 71 . the pocket 73 has a slot 74 through which the weight 71 is placed into or removed from the pocket 73 . the pocket 73 has a smooth outer surface 75 with no protrusions or flap or zipper extending from the surface 75 . in the operation of the exercise device 70 , a continuous weight 71 , is inserted into a pocket 73 through a slot 74 in the pocket 73 . see fig1 . when the weight 71 is disposed in the pocket 73 it is fully surrounded by the pocket 73 . the pocket 73 is sewn onto a holder 72 . the slot 74 in the pocket 73 is flush with the outer surface 75 so the outer surface 75 is smooth and there are no flaps or zippers or hooks to extend from the outer surface 75 to rub or scratch the user . if the weight 71 is desired to be changed , the weight is simply removed through the slot 74 from the pockets 73 and a different weight 71 can be introduced back into the pocket 73 . the present invention pertains to a handweight . the handweight comprises a holder portion 81 which is adapted to fit about the hand and wrist of a user . the holder portion 81 holds a first weight 82 about the hand and a second weight 83 about the wrist . the first and second weights are adjustable . the handweight 80 comprises a first weight 82 . the handweight 80 comprises a second weight 83 . preferably , the holder portion 81 includes a first holder portion 84 disposed about the hand in which the first weight 82 can be changed and a second holder portion 85 disposed about the wrist in which the second weight 83 can be changed . the first holder portion 84 preferably is a first pocket 86 with a slot 87 , and the second holder portion 85 is a second pocket 88 with a slot 87 . the first weight 82 is inserted into or removed from the first pocket 86 through the slot 87 . the second weight 83 is inserted into or removed from the second pocket 88 through the slot 87 . preferably , the holder portion 81 includes a third pocket 89 disposed about the hand , and a fourth pocket 90 disposed about the wrist , and a third weight 91 which is removably installable in the third pocket 89 and a fourth weight 92 which is newly installed in the fourth pocket 90 . the holder portion 81 is preferably one piece . preferably , the holder portion 81 has a first side 93 and a second side 94 and a first strap 95 and a second strap 96 on the first side 93 . the first strap 95 and the second strap 96 connects with the second side 99 when the holder portion 81 is about the hand of the user . the first strap 95 and second strap 96 and second side 94 preferably have hook and loop fasteners 97 which mate to connect the first and second straps with the second side 94 . preferably , the holder portion 81 has an inner surface 98 which is smooth and has no seams . the first weight can be magnetic for medical applications . the present invention pertains to a method for exercising . the method comprises the steps of placing a holder portion 81 about the hand and wrist of a user . then there is the step of removing a first weight 82 from a first pocket 86 over the hand of the holder portion 81 . next there is the step of removing a second weight 83 from a second pocket 88 over the wrist of the holder portion 81 . then there is the step of inserting a new first weight 82 having a different weight than the first weight 82 into the first pocket 86 . next there is the step of inserting a new second weight 83 having a different weight then the second weight 83 into the second pocket 88 . in the operation of the handweight 80 , there is a holder portion 81 having a first holder portion 84 which holds a first weight 82 , and a second holder portion 85 with holds a second weight 83 , as shown in fig1 . the first holder portion 84 has a first pocket 86 with a slot 87 , and the second holder portion 85 has a second pocket 88 with a slot 87 . the first weight 82 is disposed in the first pocket 86 and is inserted into or removed from the first pocket 86 through the slot 87 . similarly , the second weight 83 is disposed in the second pocket 88 and is inserted into or removed from the second pocket 88 through the slot 87 in the second pocket 88 . the first pocket 86 is disposed on the holder portion 81 so that it is positioned on the inside of the hand of a user . the second pocket 88 is disposed on the holder portion 81 so that it is positioned on the inside of the wrist of the user . the first holder portion 84 also includes a third pocket 89 disposed on the holder portion 81 so that it is positioned on the outside of the hand , and the second holder portion 85 includes a fourth pocket 90 that is disposed on the holder portion of 81 so that it is positioned on the outside of the wrist . a third weight 91 is held by the third pocket 89 and a fourth weight 92 is held by the fourth pocket 90 . the holder portion 81 has a first side 93 and a second side 94 with a thumb hole 99 located approximately in the center of the holder portion 81 . when the handweight 80 is put on to the hands of the user , the thumb of the hand extends through the thumb hole 99 , the first side 93 is positioned on the inside of the hand and wrist and the second side 94 is positioned on the outside of the hand and wrist . there is a first strap 95 and a second strap 96 that are sewn to the first side 93 of the holder portion 81 . at the ends of the first strap 95 and second strap 96 are hook and loop fasteners 97 which mate with hook and loop fasteners 97 on the second side 94 of the holder portion 81 . the straps and hook and loop fasteners 97 serve to connect and maintain tension of the holder portion 81 about the hand and the wrist . see fig1 and 16 . the pockets allow for the easy introduction and removal of weights so desired weights can be used with the handweight at any given time . the weights are located around the wrist and the hand to provide resistance to both areas for exercise purposes . as shown an fig1 , the holder portion 81 is one continuous piece with the pockets formed into it . during manufacture , the pockets are folded inwards about the shown dotted lines in fig1 and the weights are inserted into or removed from the respective pockets as shown in fig1 . the holder portion 81 is sewn together at the zig zag points shown in fig1 . once the sewing is complete , the holder portion 81 is turned inside out , as shown in a fig2 so the inner surface 98 that is in contact with the hand and wrist of the user is smooth without any seams or edges to irritate our cause a blister to a user during exercise with the handweight 80 . the presence of the first pocket 86 on the inside of the hand when the holder portion 81 is in place , allows a squeezable or pliable weight to the inserted into the first pocket 86 . this not only provides weights to the hand for exercise purposes but also serves to hold the weight 82 so the user can squeeze the weight 82 an exercise the fingers and tendons and muscles associated with the gripping action of the hand . alternatively , the first weight 82 , second weight 83 , third weight 91 and fourth weight 92 , either all or any one of them , can be magnetic to use in medical applications . see for instance page 323 of natural healing basics , and the chapter titled “ magnets : stop pain . . . ease arthritis . . . help heal broken bones and more ”, incorporated by reference , herein . the presence of the magnet causes the blood to be drawn to the area in the hand about the magnet to increase blood flow and diminish pain due to a combination of the hall effect and stabilizing influence on the nervous system . typically , the medical magnet is rated at 200 to 800 gauss . the present invention pertains to a handweight 110 . the handweight 110 comprises a holder portion 112 which fits about the hand and has a plurality of pockets 114 . each pocket 114 has a slot 116 . the pockets 114 are adapted to be disposed about the knuckles of a user . the handweight 110 comprises a plurality of weights 118 which are removably disposed in respective pockets 114 . each weight 118 is inserted in and removed from the pocket 114 through respective slots 116 in the pockets 114 . in the operation of handweight 110 , as is shown in fig2 and 22 , there is a one - piece holder portion 112 that has a pocket 114 . the pocket 114 inside the holder portion 112 is accessed through a slot 116 through which a one piece weight 118 is inserted or removed . the holder portion 112 has straps 120 and a thumb opening 122 which allows the holder portion 112 to be placed about the hand . the weight 118 is flexible so that it can bend around the hand when the handweight 110 is connected to the hand by the straps being connected together through hook and loop fasteners . the holder portion 112 is formed by first folding the holder portion 112 along the dotted line in fig2 . then , the holder portion 112 is sewn along the zig zag lines shown in fig2 to form the pockets 114 . the holder portion 112 is then turned inside out , as shown in the fig2 . this allows the smooth outer surface of the holder portion 112 to contact the hand of the user to minimize blistering or irritation of the skin of the user . then , the weight 118 is inserted through the slot 116 into the pocket 114 . if it is desired to change the weight 118 , then the weight of 118 is removed from the pocket 114 through the slot 116 and a new and different weight 118 is inserted back into the pocket 114 through the slot 116 . to facilitate the weight being inserted or removed from the pocket 114 , the weight 118 is covered with a lycra or tricot fabric so the weight will slide in or out of the pocket easily . generally , this is done with all weights and pockets . the present invention pertains to a handweight 140 . the handweight 140 comprises a one - piece holder portion 142 with a pocket 144 . the handweight 140 comprises a one - piece continuous foldable weight 146 which is disposed in the holder portion 142 and extends about the hand of a user when the handweight 140 is on the hand of the user . in the operation of the handweight 140 , shown in fig2 and 28 , there is a one piece holder 142 that has pockets 144 . each pocket 144 has a weight 146 in it . the weight 146 is inserted into or removed from the pockets through a slot 147 . the holder 142 is configured so that when it is around the hands of the user , the weights 146 in the pockets 144 are aligned over the knuckles of the back of the hand of the user and also in front of the hand and below the fingers . the handweight 140 has straps 148 with hook and loop fasteners 149 on them . on the corresponding symmetrically opposite location the one piece holder 142 are also hook and loop fasteners which mate with the corresponding hook and loop fasteners on the straps 148 to tension and hold the handweight 140 in place around the hands . there is a thumb opening 150 in which the thumb is discloses when the handweight 140 is in place . the present invention pertains to an exercise apparatus 160 . the exercise apparatus 160 comprises a vest 162 adapted to fit about the chest and back of a user . the vest has pockets 164 which hold weights 166 . the exercise apparatus 160 comprises an adjustable fitting mechanism 168 which can tighten the vest 162 about the user from the right and left sides of the user . preferably , the pockets 164 are disposed on the inner surface 170 of the vest 162 . the weights 166 preferably can be changed to vary the total weight of the vest 166 . preferably , the vest 162 has a back 172 and a front 174 with a right side 176 and left side 178 , and the vest 162 has a zipper 180 which connects the right side 176 and left side 178 together . the fixing mechanism 168 preferably includes a first loop and strap mechanism 182 connected to the right side 176 and the back 172 , and a second loop and strap mechanism 184 connected to the left side 178 and the back 172 . each loop and strap mechanism is adjustable to vary the tension of the vest 162 about the user . in the operation of the exercise apparatus 160 , shown in fig2 , there is a vest 162 having a front 174 and a back 172 . the vest 162 has pockets 164 that are on the back 172 and the right side of 176 and the left side 178 of the front 174 . the vest covers the chest and back of the user and can be worn under clothing or during sports activity such as basketball or soccer besides the more standard jogging or walking exercises as well as aerobic exercise . each pocket 164 has a weight 166 disposed in them . each pocket 164 has a slot 186 through which a weight 166 is inserted or removed . the pockets 164 or disposed on the inner surface 170 of the vest 162 . see fig3 . the right side 176 and left side 178 of the front 174 have a zipper mechanism 180 connected to them which allows the right side 176 and left side 178 to be zipped together when in place around the body of the user . there is a first loop and strap mechanism 182 connected to the right side 176 and the back 172 , and a second loop and strap mechanism 184 connected to the left side 178 and back 172 . the first and second loop and strap mechanisms are used to tension the vest about the user when the vest is place . the first and second loop and strap mechanisms allow the vest to be tightened from both the right and left sides of the user so the vest tensions uniformly about the user . see fig3 and 32 . instead of a zipper used to connect the right side 176 and left side 78 , there can be fasteners 194 on the right side 176 and left site 178 which are used to connect the right side 176 and left side 178 together , as shown in fig3 . each loop and strap mechanism 182 has a strap 188 and a loop 190 through which a strap 188 passes , as shown and fig2 and 31 . after the strap 188 passes through the loop 190 , it is passed through a second loop 192 adjacent the first loop 190 in the direction from which it came . each of the straps of the loop and strap mechanisms are then pulled forward causing the right side 176 and left side 178 and back 172 to come together to the desired tension . the weights 166 are about 0 . 5 inches thick to 1 inch thick and are 0 . 5 pounds to 1 pound , respectively , in weight . they are two inches wide and 4 inches high . the thickness of the fabric is 0 . 0625 , and is made of a wearnyle teflon coated nylon . these weights can be used in all embodiments described above with pockets . in regard to the handweight covering the knuckles , the weights can be longer and narrower but of the same thickness . the weight can be as little as 0 . 25 pounds . for the weights in cells such as the ankle and wrist weights , the weight itself can be between 0 . 5 pounds to 7 pounds each . generally , the holder portions are made of nylon covered in neoprene made by rubatex that is { fraction ( 1 / 8 )} inches thick . materials for the weights and holder portions or cells are also described in u . s . patent application ser . no . 08 / 555 , 771 , filed nov . 9 , 1995 , titled “ reinforced thermoplastic elastomeric gel ”; u . s . patent application ser . no . 08 / 694 , 993 filed aug . 9 , 1996 , titled “ high friction interface for weights ”; u . s . patent application ser . no . 08 / 619 , 330 filed mar . 21 , 1996 , titled “ exercise and therapy device ”; and u . s . patent application ser . no . 08 / 555 , 772 filed nov . 9 , 1995 , titled “ concealable arm and leg weight ”, all of which are incorporated by reference herein . although the invention has been described in detail in the foregoing embodiments for the purpose of illustration , it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention except as it may be described by the following claims .

US-85176001-A

an improved canister - type aquarium filter design which includes , in various combinations , a motor which is contained within the canister , a discharge tube arranged approximately along the longitudinal axis of the canister , a pump section from which water exits from the top , a cover securing device which applies force to the top of the cover , a clamp arrangement for securing tubes to ports on the cover , and an adjustable mounting system for mounting the filter to an aquarium frame . the improved design provides easy access to the filter cartridge , improves efficiency , and eliminates the need for flexible hoses traditionally used to connect the filter to an aquarium .

the following is a detailed description of the best presently known 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 defined by the appended claims . as illustrated for example in fig1 a preferred embodiment of the filter unit may include a filter canister 10 having a filter cartridge 12 contained therein . as depicted in the embodiment illustrated in fig1 the filter cartridge 12 may be a fine mesh type , such as a pleated cylindrical cartridge formed of a fibrous material 12a . one example of such a filter is the reemay ™ filter sold by the reemay corporation . alternatively , the filter cartridge 12 may be a conventional cartridge formed of a pair of plastic or wire mesh screens having carbon granules or other appropriate media sandwiched between the screens . the filter canister 10 may include a removable cover 14 . the cover 14 includes an inlet port 20a and an outlet port 20b . an inlet tube 22 , which may be secured to the inlet port 20a , transfers water from an aquarium 23 to the canister 10 . an outlet tube 24 , which may be secured to the outlet port 20b , returns water from the canister 10 to the aquarium . in the preferred embodiment illustrated for example in fig1 a cover clamping mechanism indicated generally at 25 including a latch 18 and a clamp wire 16 may be employed to secure the cover 14 to the top of canister 10 . additionally , a generally l - shaped hanger wire 28 , which extends horizontally behind the canister 10 , may be used to adjustably hang the filter assembly on an aquarium frame 29 . in the illustrated embodiment , the canister 10 is shaped generally as a half cylinder having a generally flat side 31 ( fig2 ) to abut the side of the aquarium 23 . a collar 26 may be used to provide locational and structural support for the clamp wire 16 and the hanger wire 28 . the collar 26 may be a generally ring - like structure conforming to the shape of the canister 10 and may also include an inwardly facing projection 26a ( visible in fig2 ). during assembly , the collar 26 may be placed around the bottom portion of the canister 10 and slid upwardly until the inwardly facing projection 26a abuts a step 11 provided on the canister 10 and located approximately 11 / 2 &# 34 ; from the top of the canister . as illustrated for example in fig1 in a preferred embodiment the hanger wire 28 may include horizontal legs 28a and 28b and a rear portion 28c which extends between legs 28a and 28b . the hanger wire 28 may be slidably coupled to the collar 26 by inserting the horizontal legs 28a and 28b into respective apertures 29 of the collar , only one of which is visible in fig1 . the gap between the rear portion 28c and the collar 26 may be easily adjusted by sliding the hanger wire 28 horizontally in apertures 29 . the position of the hanger wire 28 is maintained by friction between the horizontal legs 28a and 28b and the apertures 29 . thus , the filter assembly can be tightly attached to an aquarium frame or allowed to hang loosely . additionally , a vertical orientation of the filter may be easily accomplished . referring to the numbered elements in the embodiment illustrated for example in fig2 and 3 , the lower section of canister 10 may be enclosed by a bottom cover 30 . the bottom cover 30 may be secured to the canister 10 by an adhesive or by a mechanical fastener . an adjustable stop 32 for leveling the canister filter may be slidably coupled to the bottom cover 30 . the bottom cover 30 also provides a cosmetic finish to the canister assembly by shrouding the portion of the canister that contains the motor . as best seen in fig1 , the adjustable stop 32 includes a generally c - shaped spring 33 which is slidingly received by a pair of slots 35 formed in the bottom cover 30 . the spring 33 has a plurality of detents 37 formed on the exterior of the legs 39 of the spring 33 , which interact with a pair of ridges 41 formed in the cover 30 to selectively &# 34 ; lock &# 34 ; the spring 33 in place . as the legs 39 of the spring 33 are inserted into the slots , the legs 39 deflect inwardly and then spring outwardly as the ridges 41 of the cover 30 successively exit and enter the detents 37 formed in the spring 33 . a v - shaped wall 43 aligned with the slots 35 of the cover 30 guides the legs 39 of the spring 33 and limits their inward deflection . when the spring 33 is inserted to the desired depth to space the bottom of the canister 10 from the aquarium frame the desired distance , the ridges 41 engaging an associated pair of dents 37 releasably hold the spring 33 in place . in the illustrated embodiment , the spring 33 has eight pairs of detents 37 . consequently , the spring 33 of the stop 32 may be selectively &# 34 ; locked &# 34 ; in any one of eight positions , as desired . in this manner the desired vertical orientation of the canister 10 may be readily achieved . in the illustrated embodiment , the spring 33 has a foam pad 43 at the end of the spring 33 as shown in fig2 . as illustrated for example in fig2 , 7 , 9 and 10 , a pump impeller assembly 48 may include a magnet 62 ( enclosed in a sleeve 66 as illustrated in fig7 ) which may be located in a closed bottom portion 40 of the canister 10 . thus , water within the canister 10 will surround the magnet 62 . as best seen in fig9 and 10 , a stator 34 includes flux carrying laminations 38 which define a gap 38a which may be centered at the closed bottom portion 40 . the stator laminations 38 are supported by locating ribs 42 . the stator also includes a winding 34a . a canister extension 39 together with the bottom portion 40 forms a cavity 36 which is filled with an encapsulant that retains the motor stator 34 and provides electrical insulation and good thermal conductivity . a motor cover 37 may be attached to the end of the extension 39 to completely enclose the motor stator 34 and the encapsulant . as illustrated for example in fig3 and 8 , a 3 - part generally &# 34 ; onion shaped &# 34 ; impeller housing 46 and the pump impeller assembly 48 may be positioned inside the canister 10 . a stationary center diffuser 46b having three vanes snaps into a top housing portion 46a . as the impeller 52 of the assembly 48 is larger in diameter than an inlet hole 54 of a housing base portion 46c , the impeller assembly 48 must be attached to the center diffuser 46b before final assembly of the impeller housing 46 . the impeller assembly 48 may be attached to center diffuser 46b by pressing a rubber sleeve 50a on the impeller assembly into a blind hole 47 in center diffuser 46b . the rubber sleeve 50a supports one end of a rod 51 . the magnet 62 is rotatably supported by the rod 51 . finally , the base 46c may be snapped into the top housing 46a . the impeller assembly 48 and the housing 46 are then placed in the canister 10 such that the rotor portion 49 of the impeller assembly 48 is received on the inside of the bottom portion 40 of the canister 10 ( fig3 ) and a rubber sleeve 50b on impeller assembly is received in a pocket 56 at the bottom of the bottom portion 40 . the rubber sleeve 50b supports the other end of the rod 51 . the base 46c of the impeller housing 46 abuts ribs 58 ( fig3 ) of the canister 10 . the center diffuser 46c and top housing 46a are centered by ribs 60 of the canister 10 . the magnet 62 may be secured to the impeller 52 of the impeller assembly 48 by inner and outer sleeves 64 and 66 , respectively , and aligned with the laminations 38 of the stator 34 . the inner sleeve 64 includes a bearing surface in contact with the rod 51 . to drive the impeller 52 , an alternating current is supplied to the windings 34a , creating an alternating magnetic field in the laminations 38 . the magnetic field causes the magnet 62 to rotate at synchronous speed , thus driving the impeller 52 via the inner and outer sleeves 64 and 66 . the closed bottom portion 40 of the canister 10 between the laminations 38 and the rotor 49 seals the stator 34 from the water flowing through the canister 10 . referring to the numbered elements in the embodiment illustrated in fig2 and 3 , immediately above the impeller housing 46 , a bottom plate 68 having a circular opening 72 is supported by a shoulder 70 in the canister 10 . the shoulder 70 centers bottom plate 68 within the canister . a supporting structure 12b of the filter cartridge 12 may be arranged on top of bottom plate 68 . a discharge tube 74 is placed within filter cartridge 12 with a bottom end 74a of the discharge tube 74 being received by a tubular opening 46e at the top of top housing portion 46a . the bottom end 74a of the discharge tube 74 is supported by a shoulder 46d of the top of top housing portion 46a . a pre - filter media such as a sponge 80 may be placed in the canister 10 such that the inside diameter of the media 80 fits around the top portion of the discharge tube 74 . when the cover 14 is installed , a lower flange 76 on the discharge tube 74 presses against a foam gasket 78a located between a top surface 79 of the filter cartridge 12 and the flange . the gasket 78a provides sealing between the discharge tube 74 and the filter cartridge 12 to ensure that water drawn into the canister does not bypass the filter cartridge 12 . as illustrated for example in fig2 and 4 , the cover 14 includes the sealed flow path 82 formed by wall members 84 and 86 . the sealed flow path 82 connects the outlet port 20b to the inside of a cylindrical projection 88 on the wall member 84 . the cylindrical projection 88 may be received within the discharge tube 74 thereby coupling the discharge tube 74 and the sealed flow path 82 . a surface 90 on the wall member 84 presses against a foam gasket 78b located between a top flange 92 on the discharge tube 74 and the cover 14 . the gasket 78b provides sealing between the discharge tube 74 and the flow path 82 . a seal 94 received in a channel 95 found in the cover 14 provides sealing between the cover 14 and the canister 10 . the filter cartridge 12 includes a perforated center tube 96 . the center tube 96 may be located against the top of circular opening 72 . ribs 98 on the discharge tube 74 abut the center tube 96 , thus causing the filter cartridge 12 to be centered relative to , i . e . coaxial with , the impeller housing 46 . referring to the numbered elements in the embodiment illustrated for example in fig2 when the impeller assembly 48 begins rotating , water will flow in the direction of the arrows from the impeller housing 46 , through the discharge tube 74 , through the sealed flow path 82 in the cover 14 , through the outlet port 20b , and finally back to the aquarium through the outlet tube 24 . accordingly , the water level in the canister 10 drops , thereby creating a vacuum within canister 10 . the vacuum reaches a level sufficient to draw water from the aquarium through inlet tube 22 and inlet port 20a , and the vacuum increases until the flow of water through the inlet tube 22 to the canister 10 equals the flow of water discharged through the outlet tube 24 . additionally , the pumping action creates a differential pressure across the filter cartridge 12 , with the pressure in open space 100 between the perforated center tube 96 and the discharge tube 74 being less than the pressure around cartridge 12 in canister 10 . this causes water to flow radially inwardly in canister 10 through the filter cartridge 12 and into the open space 100 . the water in the open space 100 is drawn in an intake flow which flows from the open space 100 down and around the outside of the impeller housing 46 and then through the inlet hole 54 in the base 46c of impeller housing 46 . at that point the impeller 52 acts on the water causing it to flow up through the inside of the impeller housing 46 in a discharge flow into the discharge tube 74 from the top of the impeller housing 46 . the discharge flow of water exits the discharge tube 74 and enters the sealed flow path 82 in the cover 14 at the cylindrical projection 88 . from the sealed path 82 of the cover 14 the flow of water is discharged into the aquarium through the outlet port 20b . it should be appreciated from the above that the discharge flow below the cover 14 is coaxially aligned with the intake flow from the filter cartridge 12 and is separated from the co - axial intake flow by the impeller housing 46 and the discharge tube 74 . because the discharge tube 74 is centered within the interior of the filter cartridge , the space available within the canister for filter media has been substantially increased . in addition , it has been found that the coaxial stacked arrangement of the rotor 49 , the impeller 52 , the impeller housing 46 , the discharge tube 74 , and the cylindrical intake projection 88 of the cover 14 has several other advantages . for example , the latch 18 may be positioned relative to the discharge tube 74 such that the resultant clamping force applied by the latch 18 is substantially evenly distributed and substantially vertically oriented , even though the latch 18 is a singular device . as a consequence , the clamping force is centered and aligned with the annular surface 90 of the cover 14 and the top annular flange 92 of the discharge tube 74 so that the gasket 78b therebetween is firmly clamped to provide a good seal between the discharge tube 74 and the cover 14 . in a similar manner , the clamping force is centered and aligned with the lower annular flange 76 of the discharge tube and the top annular surface 79 of the filter cartridge 12 so that the gasket 78a therebetween is firmly clamped to provide a good seal between the discharge tube 74 and the filter cartridge 12 . still further , the impeller 52 , the impeller housing 46 and the discharge tube 74 are coaxially aligned so that the discharge flow of water through these elements is straight . it is believed that reducing changes in direction of the flow path increases the efficiency of the overall system . the filter system may be supplied without inlet tube 22 and outlet tube 24 installed . as illustrated for example in fig4 - 6 , the inlet tube 22 and the outlet tube 24 are identical in the areas that are inserted into the inlet port 20a and the outlet port 20b , respectively . each tube may include an o - ring 102 assembled in a groove 104 on one side of a chamfered annular projection , or flange , 106 . the groove 104 and the projection 106 are arranged such that the o - ring 102 seals within a bore 108 before the projection 106 snaps past a locking ring 110 . the locking ring 110 includes a c - shaped plastic ring portion 113 that can resiliently open to receive and then close to partially encircle one of the tubes ( 22 or 24 ) as the ring portion 113 slides vertically between cylindrical ribs 112 and 114 . when one of the tubes ( 22 or 24 ) is inserted into one of the ports ( 20a or 20b ), the chamfer of projection 106 deflects a resilient integral catch portion 111 of locking ring 110 and then moves past portion 111 . the catch portion 111 is coupled to the ring portion 113 of the locking ring 110 by an integral stem portion 115 . after the projection 106 passes the portion 111 , portion 111 resiliently moves up behind projection 106 to retain the tube ( 22 or 24 ). similarly , when removing one of the tubes ( 22 and 24 ), one presses down on finger tabs 117 of locking ring 110 which moves the catch portion 111 out of the path of the projection 106 which allows the tube to be pulled out of the port . once the finger tabs 117 are released , the ring portion 113 resiliently reseats the ring 110 in the cylindrical ribs 112 and 114 of the tube . when removing the filter of the illustrated embodiment from the tank for cleaning , one simply disconnects the power cord from the wall receptacle , removes the inlet tube 22 and the outlet tube 24 from the cover 14 , lifts the filter off the aquarium frame and carries it to a sink . in another aspect of the invention , as best seen in fig2 the latch 18 includes a latch arm 120 which is pivotally coupled at one end 122 to the cover 14 by a pivot pin 124 . the pivot end 122 of the latch arm 120 has a rounded bearing surface 126 which is received by a concave bearing surface 128 recessed in the cover 14 . the pivot end 122 also has a pair of ridges 130 which define a groove 132 . rotation of the latch arm 120 in the clockwise direction is limited by the forward ridge 130 which engages a stop surface 134 of the concave bearing surface 128 when the tab end 136 of the latch arm 120 is lifted to the maximum upward position . in this position of the latch arm 120 , the clamp wire 16 which is pivotally coupled to the collar 26 , may be pivoted so that the top horizontal portion 16a of the clamp wire 16 may be received by the groove 132 of the latch arm 120 . to clamp the cover 14 in place , the tab end 136 of the latch arm 120 is rotated downwardly which causes the groove 132 at the pivot end of the latch arm 120 to lift the clamp wire portion 16a of the clamp wire 16 upward , which applies a downward , clamping force on the cover 14 in response . as best seen in fig1 the clamp wire 16 includes two generally c - shaped portions 16b , each of which is joined to the central portion 16a at one end and is pivotally received by a bore 140 in the collar 26 at the other end . as the central portion 16a of the clamp wire 16 is lifted by the latch arm 120 of the latch 18 , the c - shaped portions 16b of the clamp wire flex and open , which applies a spring tension to the cover 14 . to unlatch the cover 14 , the tab end 136 of the latch arm 120 is rotated upwardly which pivots the central portion 16a of the clamp wire 16 downwardly . this releases the tension on the clamp wire 16 , allowing the clamp wire 16 to be pivoted away and the cover 14 removed . thus , in order to remove the filter cartridge 12 for cleaning or replacement while the filter remains on the tank , one simply disconnects the power cord from the wall receptacle , lifts the latch 18 and swings the clamp wire 16 to the back of the cover 14 , i . e . to the right in fig2 . the cover 14 may then be removed . next , the discharge tube 74 and the pre - filter media 80 can be removed so that the filter cartridge 12 is accessible . after returning the cover 14 to the canister 10 , the latch 18 may be lifted until the groove 132 is adjacent to the top of cover 14 so that the clamp wire 16 may be rotated into groove 132 . the latch 18 may then be lowered in order to produce tension in the clamp wire 16 and secure the cover 14 to the canister 10 . as the top of the filter may be mounted above the water level of the aquarium , all of the above may be performed without leaks or spills . a system for expelling gas which may accumulate is described in copending and contemporaneously filed application ( our docket pd - 2449 ), co - owned by the assignee of this application and entitled &# 34 ; gas expelling device &# 34 ; the subject matter of which is incorporated herein by reference . although the present invention has been described in terms of a preferred embodiment above , numerous modifications and additions to the above - described preferred embodiment would be readily apparent to one skilled in the art . it is intended that the scope of the present invention extends to all such modifications and additions and that the scope of the present invention is limited solely by the claims set forth below .

US-380393-A

an exemplary surgical instrument for inserting a spinal implant includes an inserter portion , a coupling member , a first actuator , and a second actuator . the inserter portion includes at a proximal end a receiving block , at a distal end a sleeve , and a channel extending therethrough . the coupling member includes at a proximal end movably coupled with the receiving block , a middle portion that slides within the channel , a distal end that couples the spinal implant , and a first axial bore extending therethrough . the first actuator includes a proximal end with a first projection for engaging the receiving block , a first shaft extending through the first axial bore , and a distal end with a first engagement feature for engaging a first deployment feature of the implant . the second actuator includes a proximal lend with a second projection for engaging the receiving block , a second shaft extending through a second axial bore of the first shaft , and a distal end with a second engagement feature for engaging a second deployment feature of the implant .

implants or vertebral body replacements may be placed in the interdiscal space between adjacent vertebrae of the spine . the implants may include one or more features that are deployed to affix the implants to the adjacent vertebrae . for example , a stand - alone interbody fixation system , as disclosed in commonly assigned u . s . continuation - in - part application ser . no . 13 / 633 , 301 to vishnubhotla et al . filed oct . 2 , 2012 , which is a continuation - in - part of u . s . pat . no . 8 , 328 , 870 , to patel et al ., both of which are incorporated by reference in their entirety , provides a solid fixation in all aspects by using counter - rotating blades that provide fixation to the vertebrae . such implants may be inserted , positioned , and deployed by various embodiments of the instrument of the present disclosure . as can be understood by one skilled in the art , these embodiments are shown for illustrative purposes and are not intended to limit the scope of the invention . embodiments of the invention will now be described with reference to the figures , wherein like numerals reflect like elements throughout . the terminology used in the description presented herein is not intended to be interpreted in any limited or restrictive way , simply because it is being utilized in conjunction with detailed description of certain specific embodiments of the invention . furthermore , embodiments of the invention may include several novel features , no single one of which is solely responsible for its desirable attributes or which is essential to practicing the invention described herein . the words proximal and distal are applied herein to denote specific ends of components of the instrument described herein . a proximal end refers to the end of an instrument nearer to an operator of the instrument when the instrument is being used . a distal end refers to the end of the instrument further from the operator and extending towards the surgical area of a patient and / or the implant . referring to fig1 and 2 , a surgical instrument 100 according to the principles of the present disclosure is shown . the instrument 100 includes features to enable insertion of an implant 300 into the spinal area of a patient and to enable actuation of additional features of the implant 300 after insertion . the instrument includes a housing 102 , a handle assembly 104 , a sleeve 106 , a clamping member 108 , an outer shaft 110 , and an inner shaft 112 . the clamping member 108 includes features that enable coupling of the instrument 100 with the implant 300 . the sleeve 106 includes features that actuate the coupling member 108 to couple the implant 300 . when the implant 300 is coupled , the instrument 100 may be used to position the implant 300 in the spinal area of the patient . the outer shaft 110 and the inner shaft 112 include features that actuate the additional features of the implant 300 . for example , once the implant 300 has been positioned in the spinal area , the outer shaft 110 and the inner shaft 112 may be rotated to deploy features of the implant 300 that engage with vertebrae in the spinal area . referring now to fig2 , a partial exploded view shows additional features of the instrument 100 . the housing 102 includes features for attachment of the sleeve 106 , the clamping member 108 , the outer shaft 110 , and the handle assembly 104 . the housing 102 includes a wheel 114 that freely rotates on the distal end of the housing 102 and includes features that engage with the sleeve 106 . for example , the wheel 114 may include a thread 116 on an inner surface of the wheel 114 that engages with a corresponding threaded portion 118 on the proximal end of the sleeve 106 . the housing 102 may include a threaded portion 120 at the proximal end for attachment of the handle assembly 104 . for example , the threaded portion 120 may engage with threads of a cap 122 on the handle assembly 104 . the sleeve 106 includes a channel 124 that extends the length of the sleeve 106 and is configured to receive the clamping member 108 . the channel 124 may be formed by boring a first series of windows 126 on a first side of the sleeve . the windows 126 may be cut into the sleeve 106 until a wall of material remains on a second side of the sleeve opposite the first side . after the first series of windows 126 has been cut , a second series of windows may be cut through the second side of the sleeve until cross members 128 of material remain on the first side of the sleeve . the second series of windows may be spaced to remove remaining material between the first series of windows 126 . the resulting channel 124 is configured to permit sliding engagement with the clamping member 108 . the sleeve 106 forms an opening 130 at the proximal end to permit passage of the clamping member 108 through the channel 124 into the housing 102 . the sleeve 106 forms a mouth 132 at the distal end that allows for sliding engagement with the clamping member 108 . the mouth 132 may include flared portions 134 that flare away from a center line of the instrument 100 . the flared portions 134 are configured to engage with the clamping member 108 and to couple the implant 300 to the instrument 100 as described below . continuing with fig2 , the clamping member 108 includes an elongated portion 136 and a pair of arms 138 . the elongated portion 136 extends through the channel 124 to engage with the housing 102 . at the proximal end of the elongated portion 136 , a locking feature 140 is configured to fixedly attach the clamping member 108 to the housing 102 . for example the locking feature 140 may include a notch cut into the clamping member 108 that engages with a lock pin ( not shown ) inside the housing 102 . the elongated portion 136 may further include one or more holes 142 to facilitate cleaning of the instrument 100 and to reduce the weight . the pair of arms 138 extends from the distal end of the elongated portion 136 and terminates in a pair of tips 144 . the tips 144 may flare away from the center line of the instrument 100 similar to the flared portions 134 of the sleeve 106 . the tips 144 may include projections 146 that partially extend towards the center line of the instrument 100 . in other features , the projections 146 may partially extend towards the distal end of the instrument 100 . the clamping member 108 further includes a first axial bore 148 that extends the length of the elongated portion 136 to enable the outer shaft 110 to pass through the clamping member 108 as depicted in fig8 and 9 . once the sleeve 106 and clamping member 108 are coupled within the housing 102 and the wheel 114 on the housing is rotated , the threaded portion 118 of the sleeve 106 advances along the thread 116 of the wheel 114 causing the sleeve 106 to slide relative to the clamping member 108 . for example , rotating the wheel 114 in a first direction advances the sleeve 106 towards the distal end of the instrument 100 while rotating the wheel in a second direction retracts the sleeve 106 towards the proximal end of the instrument 100 . as the sleeve 106 advances towards the distal end of the instrument 100 , the flared portions 134 engage with the tips 144 . the flared portions 134 compress the tips 144 towards the center line of the instrument 100 causing the arms 138 to flex inwardly towards the center line . as shown in fig1 , the tips 144 are configured to engage with corresponding holes 302 on the implant 300 . as the tips 144 are compressed , the projections 146 provide a clamping force on the implant 300 to couple the implant 300 to the instrument 100 . continuing with fig2 , the outer shaft 110 extends from the housing 102 through the first axial bore 148 in the clamping member 108 . the outer shaft 110 may freely rotate in the first axial bore 148 relative to the clamping member 108 . referring to fig2 and 3 , the proximal end of the outer shaft 110 may couple with a follower gear 150 inside the housing 102 and the distal end extends through the axial bore 148 and past the mouth 132 of the sleeve 106 . the distal end of the outer shaft 110 includes a first engagement feature 152 configured to actuate a first deployment feature , such as a first blade 304 of the implant 300 as depicted in fig1 - 12 . for example , the first engagement feature 152 may include a hexagonal projection . the outer shaft 110 further includes a second axial bore 154 extending through the length of the outer shaft 110 from the proximal end to the distal end . referring now to fig2 and 4 , the inner shaft 112 extends from the handle assembly 104 through the second axial bore 154 in the outer shaft . the inner shaft 112 freely rotates in the second axial bore 154 relative to the outer shaft 110 . the proximal end of the inner shaft 112 may couple with a handle 156 and a distal end may extend past an opening 158 in the first axial bore 148 . the distal end of the inner shaft 112 includes a second engagement feature 160 configured to actuate a second deployment feature , such as a second blade 306 of the implant as depicted in fig1 - 12 . for example , the second engagement feature 160 may include a splined projection . referring now to fig3 and 4 , exploded views of the handle assembly 104 , inner shaft 112 , housing 102 , and outer shaft 110 are shown in greater detail . the handle assembly 104 includes the cap 122 , the handle 156 , and a striking member 164 . the inner shaft 112 may pass though the cap 122 and the handle 156 to connect with the striking member 164 using a screw 166 or other fixation member . the cap 122 couples the handle assembly 104 to the housing 102 and allows rotation of the handle 156 and inner shaft 112 . when the operator applies torque to rotate the handle 156 , the inner shaft 112 rotates together and in the same direction as the handle 156 . in addition , the operator may apply a striking force to the striking member 164 to drive the implant 300 further into the spinal area . the striking member 164 transfers the striking force to the inner shaft 112 . a drive gear 167 and an alignment block 168 are disposed along the proximal end of the inner shaft 112 . the drive gear 167 may be fixedly attached to the inner shaft 112 to rotate with the inner shaft 112 . the alignment block 168 may be fixedly attached to or formed on the inner shaft 112 and positioned to align the inner shaft 112 and the outer shaft 110 during assembly of the instrument 100 . the alignment block 168 may include notches 170 to align the inner shaft 112 relative to the outer shaft 110 as described below . in addition , when the operator applies a striking force to the striking member 164 , the alignment block 168 may transfer the striking force to the follower gear 150 and the housing 102 rather than to the distal end of the inner shaft 112 . the housing 102 then transfers the striking force to the sleeve 106 to position the implant 300 deeper into the spinal area . this may prevent damage to the engagement features of the shafts . as depicted in fig3 , the housing 102 includes a gear set that transfers torque from the drive gear 167 to the outer shaft 110 . the gear set includes one or more transfer gears 172 configured to be driven by the drive gear 167 on the inner shaft 112 . the transfer gears 172 may be , for example , beveled gears . the transfer gears 172 may be rotatably fixed in removable sleeves 174 disposed in u - shaped channels 176 of the housing 102 . a clip 178 may lock the sleeves 174 into the u - shaped channels 176 . when the operator applies torque to the handle 156 , the drive gear 167 rotates in the same direction as the handle 156 . the inner shaft 112 , also attached to the handle 156 , rotates in the same direction . the drive gear 167 causes the transfer gears 172 to rotate and transfer torque to the follower gear 150 attached to the proximal end of the outer shaft 110 . the transfer gears 172 cause the follower gear 150 to rotate in the opposite direction as the drive gear 167 . thus , the outer shaft 110 , which is attached to the follower gear 150 , rotates in the opposite direction as the inner shaft 112 . thus , when the operator rotates the handle 156 in one direction , the inner shaft 112 and the outer shaft 110 counter - rotate . one or more anti - rotation pins 179 may be used attach the follower gear 150 and to prevent the inner shaft 112 and the outer shaft 110 from rotating beyond a predetermined angle . for example , the anti - rotation pins 179 may radially extend away from the center line of the instrument 100 in a cavity 180 of the housing 102 . the cavity 180 may prevent rotation of the pins 179 beyond the predetermined angle . for example , the anti - rotation pins 179 may prevent over - rotation of the first and second deployment features 304 , 306 of the implant 300 . the transfer gears 172 may also include one or more alignment nibs 182 that extend from the center of the transfer gears 172 towards the inner shaft 112 . the alignment nibs 182 may be used in conjunction with the notches 170 of the alignment block 168 to align the inner shaft 112 with the outer shaft 110 during assembly . for example , the inner shaft 112 may not extend through the opening 158 unless the alignment nibs 182 are lined up with the notches 170 . when the alignment nibs 182 pass through the notches 170 , then the first and second engagement features 152 and 160 are properly aligned for engagement with corresponding features on the implant 300 . referring now to fig5 - 7 the sleeve 106 and clamping member 108 are shown in greater detail . the sleeve 106 may include a first set of guide pins 184 on an inner surface of the mouth 132 . the sleeve 106 may include a second set of guide pins 186 on an inner surface of the channel 124 . the guide pins 184 , 186 slidably engage with a track 188 on the clamping member 108 . the guide pins 184 , 186 prevent over - deflection of the arms 138 when the sleeve 106 advances towards the distal end of the clamping member 108 . additional guide pins may be provided at other locations inside the channel 124 to engage with the track 188 and maintain structural integrity of the clamping member 108 . the clamping member 108 may include a positioning marker 190 on the tips 144 to aid in locating the position of the implant 300 relative to the spinal area under fluoroscopy . the positioning marker 190 may be a cutout or notch in a sidewall of the tips 144 . in additional features , the clamping member 108 may attach to the distal end of the housing 102 using the locking feature 140 . for example , the clamping member 108 may be inserted into a receptacle in the distal end of the housing 102 as seen in fig3 . the locking feature 140 may then engage with a lock pin 194 disposed in the housing 102 . the lock pin 194 may include a spring 196 to facilitate locking and release of the lock pin 194 from the locking feature 140 . referring to fig8 - 10 , the instrument 100 may be used to couple the implant 300 to the distal end of the instrument 100 and actuate features of the implant 300 . in fig8 , the distal ends of the first shaft 110 and the second shaft 112 project from the axial bore 148 in the clamping member 108 so that the first and second engagement features 152 and 160 may engage with corresponding features of the implant 300 . the sleeve 106 is retracted so that the flared portions 134 do not compress the tips 144 of the clamping member 108 . thus , the projections 146 on the tips 144 may engage with the holes 302 in the implant 300 . in fig9 , the projections 146 are engaged with the implant 300 and the sleeve 106 may be advanced towards the distal end of the instrument 100 using the wheel 114 . the coupling member 108 holds the implant 300 to the outer shaft 110 and the inner shaft 112 , enabling the first and second engagement features 152 and 160 to engage with corresponding receptacles in the implant 300 . in fig1 , the operator applies torque to rotate the handle 156 which causes the inner shaft 112 to rotate and actuate the first deployment feature 304 of the implant . the gear set coupling the inner shaft 112 and the outer shaft 110 transfers torque from the inner shaft 112 to the outer shaft 110 . the outer shaft 110 thus rotates in the opposite direction to actuate the second deployment feature 306 of the implant 300 . referring now to fig1 , another exemplary surgical instrument 200 includes features to enable insertion of the implant 300 into the spinal area of a patient and to enable actuation of the deployment features of the implant 300 after insertion . the instrument 200 shares similar features as the first exemplary instrument 100 such as housing 102 , handle 104 , sleeve 106 , and clamping member 108 as well as the counter - rotating outer shaft 110 and inner shaft 112 . therefore , similar numerals are used with reference to similar features . for example , the instrument 200 includes a housing 202 , handle assemblies 204 a and 204 b ( collectively handle assemblies 204 ), a sleeve 206 , a clamping member 208 , an outer shaft 210 , and an inner shaft 212 . the instrument 200 includes features that enable coupling of with the implant 300 in a similar fashion as instrument 100 . for example , the instrument 200 includes a positioning wheel 214 similar to the wheel 114 . however , the sleeve 206 may not move in the present exemplary instrument 200 but may be rigidly secured to the housing 202 . for example , the positioning wheel 214 may act on a proximal threaded end ( not shown ) of the clamping member 208 extending through the housing 202 in order to position the clamping member 208 within the attached sleeve 206 . the sleeve 206 includes features that force portions of the clamping member 208 together to clamp the implant 300 similar to the sleeve 106 . when the implant 300 is coupled to the clamping member 208 , the instrument 200 may be used to position the implant 300 in the spinal area of the patient similar to instrument 100 . the outer shaft 210 and the inner shaft 212 include features that actuate the blades 304 and 306 of the implant 300 . for example , once the implant 300 has been positioned in the spinal area , the outer shaft 210 and the inner shaft 212 may be rotated to deploy features of the implant 300 that engage with vertebrae in the spinal area . the distal ends of the shafts 210 and 212 may include various driving features including hexalobe , star - shaped , allen - wrench , spline drives or any other suitable pattern that mates with features of the implant 300 . in some examples , the distal ends of the shafts 210 and 212 may include one or more detachable tips such as inner shaft tip 260 and outer shaft tip 252 respectively as shown in fig1 . the detachable tips may deform under a predetermined amount of torque to prevent over deployment or rotation of the blades 304 or 306 . the detachable tips may include various sizes for various sizes of implants 300 . the detachable tips may be disposable or reusable . continuing now to fig1 , a partial exploded view shows additional features of the instrument 200 . the housing 202 may include features for attachment of the sleeve 206 and / or the clamping member 208 . in some examples , the sleeve 206 may be integral with the housing 202 . the outer shaft 210 and the inner shaft 212 may pass through the housing 202 similar to the shafts 110 and 112 and housing 102 . for example , the outer shaft 210 may include an outer diameter smaller than the diameter of a cannula or channel extending through the housing 202 . the outer shaft 210 may include an axial bore similar to the axial bore 154 of instrument 100 . the inner shaft 212 may be inserted through the axial bore of the outer shaft 210 and rotate freely therein . the housing 202 may include the positioning wheel 214 on a proximal end which freely rotates and includes features that engage the proximal end of the clamping member 208 to position the clamping member 208 within the sleeve 206 . for example , an inner surface of the wheel 214 may include a thread ( not shown ) that engages with a corresponding threaded portion ( not shown ) on the proximal end of the clamping member 208 similar to the thread 118 on the proximal end of the sleeve 106 of the instrument 100 . rotation of the wheel 214 may position the clamping member 208 relative to the sleeve 206 . for example , as the wheel 214 rotates in one direction , the inner thread of the wheel 214 engages more of the threaded portion on the clamping member 208 and pulls the clamping member 208 proximally into the sleeve 206 to clamp the implant 300 . various features may be used to pull the clamping member 208 into the sleeve 206 to retain the implant 300 as described above with reference to the instrument 100 . rotation of the wheel 214 in the opposite direction positions the clamping member 208 distally to release the implant 300 . the proximal end of the housing 202 may include or couple with a receiving block 215 that receives the outer shaft 210 . the receiving block 215 may include a generally cylindrical , cannulated shape from its proximal end to its distal end . referring now also to fig1 - 16 , the outer shaft 210 may be inserted through an aperture , channel , or cannula 217 in the block 215 extending from a proximal end to a distal end . the distal end may couple with the housing 202 through various means including welding , threaded connection , pins , etc . either removably or permanently . the receiving block 215 may include markings 219 a and 219 b ( collectively markings 219 ) on a proximal surface 221 that assist with aligning the handle assemblies 204 during a deployment procedure . the receiving block 215 may include various features that act on the handle assemblies 204 to align and / or limit rotation of the outer shaft 210 and the inner shaft 212 . these features may control a deployment angle between the concentric shafts as described herein . thus , actuation of the deployment features 304 and 306 of the implant 300 may be limited to prevent over - rotation . further , full actuation of the deployment features 304 and 306 may correspond to tactile feedback provided by the features . for example , the receiving block 215 may include a plurality of features such as markings , slots , ramps , and tabs that aid with alignment of the handle assemblies 204 and engage features of the handle assemblies 204 to guide and limit rotation of the shafts 210 and 212 as described below . the plurality of features above may be repeated along the circumference of the receiving block 215 . for example , the features may be repeated 180 degrees apart from one another . for purposes of illustration , most features will be primarily discussed with reference to a first set of the features denoted with numerals ending in suffix “ a .” a second set of the features , each of which may be repeated 180 degrees from the first set of features about the circumference of the receiving bock 215 , will be denoted with numerals ending in suffix “ b .” features of the receiving block 215 may include the markings 219 , the first surface 221 , initial slots 223 , an outer surface 225 , first ledges 227 , deployed slots 229 , ramped portions 231 , second ledges 233 , and stops 235 . a first marking 219 a may indicate a desired initial position of the first handle assembly 204 a prior to deployment of the implant 300 . a second marking 219 b may indicate an initial position of the second handle 204 b prior to deployment of the implant 300 . the first marking 219 a may be diametrically opposed 180 degrees from the second marking 219 b . either of the handle assemblies 204 a and 204 b may initially be aligned with either of the markings 219 a and 219 b . for example , the first handle assembly 204 a may initially align with the first marking 219 a or the second marking 219 b . likewise , the second handle assembly 204 b may initially align with the first marking 219 a or the second marking 219 b . for purposes of clarity , the instrument 200 will be described with the first handle assembly 204 a initially aligned with the first marking 219 a and the second handle assembly 204 b initially aligned with the second marking 219 b . each of the markings 219 may be radially aligned with first and second initial slots 223 a and 223 b ( collectively initial slots 223 ) on a proximal portion of the receiving block 215 that engage features of at least one of the handle assemblies 204 . the initial slots 223 may include a depth extending radially inward from the outer surface 225 for receiving retractable portions of the handle assemblies 204 . the initial slots 223 may include a length extending axially parallel along the outer surface 225 . the initial slots 223 may include a width extending along a portion of the circumference of the outer surface 225 . for example , first initial slot 223 a may extend from the proximal surface 221 distally a first length l1 along the outer surface 225 of the receiving block 215 . first initial slot 223 a may terminate at the first ledge 227 a which extends circumferentially around at least a portion of the outer surface 225 of the receiving block 215 . the first handle assembly 204 a includes features that engage the first initial slot 223 a . the first handle assembly 204 a may engage the first initial slot 223 a when the instrument 200 is in a non - deployed configuration or an initial configuration prior to deploying the blades 304 and 306 of the instrument as illustrated in fig1 . the initial slots 223 limit rotation of the first handle assembly 204 a in a first direction , such as a clockwise direction as described below . the receiving block 215 further includes first and second deployed slots 229 a and 229 b ( collectively deployed slots 229 ) that engage features of at least one of the handle assemblies 204 . the deployed slots 229 may include depth , width , and length similar to the initial slots 223 . for example , first deployed slot 229 a may extend from the proximal surface 221 distally the first length l1 along the outer surface 225 of the receiving block 215 . first deployed slot 229 a may terminate at the first ledge 227 . the first handle assembly 204 a includes features that engage the first deployed slot 229 a . the first handle assembly 204 a may engage the first deployed slots 229 a when the instrument 200 is in a deployed configuration or a final configuration after deploying the blades 304 and 306 of the implant 300 as illustrated in fig2 . the deployed slots 229 limit rotation of the first handle assembly 204 a in a second direction , such as a counter - clockwise direction as described below . the slots 223 and 229 may be disposed along the circumference of the receiving block 215 at various angles to control an amount of deployment of at least one of the blades 304 and 306 of the implant 300 . the initial slots 223 , the first ledge 227 , and the deployed slots 229 may engage portions of the first handle assembly 204 a to limit rotation of the handle assembly 204 a . for example , initial slot 223 a may be separated from a corresponding deployed slot 229 a by an angle a correlated to the amount of rotation required to deploy a first blade 304 . the outer surface 225 may further include radially ramped portions 231 extending from each initial slot 223 to each corresponding deployed slot 229 . the radially ramped portions 231 include an increasing radius . for example , ramped portion 231 a may include a first radius r1 of outer surface 225 corresponding to a depth of the initial slot 223 a and increase to a second radius r2 just before the deployed slot 229 a as shown in fig1 and 14 . the ramped portions 231 provide increasing resistance on a feature of the first handle assembly 204 a as it rotates from the initial slot 223 to the deployed slot 229 . the increasing resistance may provide tactile feedback to the user . the increasing radius may cause a feature of the first handle assembly 204 a to snap into the deployed slot 229 a providing audible feedback . the receiving block 215 includes additional features that may engage with the second handle assembly 204 b . the receiving block 215 may include a second ledge 233 and first and second stops 235 a and 235 b ( collectively stops 235 ). for example , the second ledge 233 may be proximally disposed from the first ledge 226 a distance l2 and engage with features of the second handle assembly 204 b to limit distal travel of the inner shaft 206 . the stops 235 may be disposed along the second ledge 233 and limit rotation of the second handle assembly 204 b . the second handle assembly 204 b includes features that engage the second stop 235 b . the second handle assembly 204 b may engage the second stop 235 b when the instrument 200 is in a deployed configuration or a final configuration after deploying the blades 304 and 306 of the implant 300 as illustrated in fig2 . the stops 235 limit rotation of the second handle assembly 204 b in a first direction , such as a clockwise direction as described below . referring now to fig1 and 18 , the first and second handle assemblies 204 a and 204 b include similar features such as first and second handles 256 a / b ( collectively handles 256 ), triggers 257 a / b ( collectively triggers 257 ), and housings 259 a / b ( collectively housings 259 ) that engage various features of the handle assemblies 204 and the receiving block 215 . the handles 256 may include a gripping surface such as a silicone wrap or other textured surface to enhance the user &# 39 ; s grip on the instrument 200 . the housings 259 may house the triggers 257 , each of which may include first and second projections 261 a / b ( collectively projections 261 ) extending outside the housings 259 . the triggers 257 may be biased by one or more bias mechanisms such as a spring to extend the projections 261 away from proximal ends of the housings 259 . in fig1 , the first handle assembly 204 a includes first trigger 257 a with first projection 261 a extending away from first housing 259 a for engaging initial slots 223 , first ledge 227 , ramped portions 231 , and deployed slots 229 . the first housing 259 a may be rigidly coupled with a receiving end 263 of the outer shaft 210 and extend radially way from the outer shaft 210 . the receiving end 263 includes an aperture 265 through which the inner shaft 210 may be inserted . the receiving end 263 may include a circular outer profile with one or more notches and pathways about the perimeter for receiving features of the second handle assembly 204 b . for example , a first notch 267 may be disposed at a point along the circumference of the receiving end 263 that is diametrically opposite of point of attachment of the first housing 259 a . when the first handle assembly 204 a is inserted into the receiving block 215 and aligned with the first marking 219 a , the first notch 267 may be aligned with the second marking 219 b . the first notch 267 may extend from a proximal side of the receiving end 263 to a distal side that engages the proximal surface of the receiving block 215 . for example , the first notch 265 may extend a length l3 . a second notch 269 may be disposed at a point along the circumference of the receiving end 263 that is proximate to the point of attachment of the first housing 259 a . for example , the second notch 269 may be disposed at some angle relative to the first housing 259 a and / or the first notch 267 . the first and second notches 267 and 269 may also extend the length l3 . a radially ramped portion 271 may extend between the first notch 267 and the second notch 269 similar to the increasing radius of radially ramped portion 231 of the receiving block 215 to provide tactile and audible feedback similar to the slots 223 and 229 above . in fig1 , the second handle assembly 204 b includes second trigger 257 b with second projection 261 b extending away from the second housing 259 b for engaging the first notch 267 , second notch 269 , and radially ramped portion 271 . the second housing 259 b may be coupled with a top portion 273 of the inner shaft 212 . a release mechanism 275 may be pivotally coupled to the top portion 273 . the release mechanism 275 may include a lever arm 277 with a cam portion 279 that engages the receiving end 263 of the outer shaft 210 . as the lever arm 277 rotates , the cam portion 279 forces the top portion 273 of the inner shaft 212 away from the receiving end 263 of the outer shaft 210 to separate the surfaces therebetween . fig1 and 20 illustrate actuation of the instrument 200 for deploying features of the implant 300 . initially , the first handle assembly 204 a and second handle assembly 204 b may be diametrically opposed 180 degrees to form a generally t - shaped configuration in an initial position . the first projection 261 a of the first handle assembly 204 a may be aligned with the first initial slot 223 a . the second projection 261 b of the second handle assembly 204 b may be aligned with the first notch 267 of the receiving end 263 of the outer shaft 210 . the user may apply torque to the handles 256 a and 256 b causing the inner and outer shafts 210 and 212 to counter - rotate about their common axis . as the handle assemblies 204 rotate towards one another , the first projection 261 a may engage along the ramped portion 231 of the receiving block 215 and the second projection 261 b may engage along the ramped portion 271 of the receiving end 263 of the outer shaft 210 . when the handle assemblies 204 are fully rotated , the instrument may form a more generally v - shaped appearance viewed from the proximal end in a final position . upon full deployment of the features of the implant 300 , the first projection 261 a may engage the first deployed slot 229 a . the second projection 261 b may engage the stop 235 of the receiving block as well as the second notch 269 . the projections 261 may snap into place due to force applied by a bias member . thus , the instrument 200 may provide tactile and audible feedback when full deployment of the features of the implant are complete . upon deployment , the instrument 200 may be removed by actuating the release mechanism 275 to pry apart the second handle assembly 204 b from the first handle assembly 204 a and thus , to separate the inner shaft 212 from the implant 300 . the outer shaft 210 may subsequently be removed from the implant 300 . although the instrument 200 is described with reference to the sleeve 206 , clamping member 208 , and alignment block 215 , the features of the implant 300 may be deployed using only the handle assemblies 204 and their respective shafts 210 and 212 . for example , the implant 300 may be inserted into the disc space between adjacent vertebrae using any of a variety of instruments . once within the disc space , the additional diameter of the sleeve 206 may create difficulty in maneuvering the instrument 200 within the patient , especially in lower regions of the spine near the pelvic bone . the shafts 210 and 212 may be inserted directly into the implant 300 to deploy the blades 304 and 306 . surfaces of the handles 204 a and 204 b may prevent some over deployment . however , ideally , the full system including the alignment block 215 would be used to prevent uniform deployment of the blades 304 and 306 . example embodiments of the methods and components of the present invention have been described herein . as noted elsewhere , these example embodiments have been described for illustrative purposes only , and are not limiting . other embodiments are possible and are covered by the invention . such embodiments will be apparent to persons skilled in the relevant art ( s ) based on the teachings contained herein . thus , the breadth and scope of the present invention should not be limited by any of the above - described exemplary embodiments , but should be defined only in accordance with the following claims and their equivalents .

US-201213718092-A

a modular bone plating system in one embodiment is a bone plate kit including a plurality of bone plates , each of the plurality of bone plates including a male coupling portion , a female coupling portion and a shaft extending between the male coupling portion and the female coupling portion , wherein each of the male coupling portions of each of the plurality of bone plates is configured to couple with each of the female coupling portions of each of the other of the plurality of bone plates .

fig1 shows a bone plate module 100 . the bone plate module 100 includes a shaft 102 extending between two end portions 104 and 106 . a male coupling portion 108 is positioned at the end portion 104 and a female coupling portion 110 is positioned at the end portion 106 . two notches 112 and 114 are located on the end portion 104 next to the male coupling portion 108 . the end portion 104 terminates at a curved outer perimeter 116 and the end portion 106 terminates at a curved outer perimeter 118 . the male coupling portion 108 includes a taper 120 which extends upwardly from a plateau 122 . a ridge 124 extends around the perimeter of and outwardly from the taper 120 . two slots 126 and 128 are formed in the taper 120 and the ridge 124 . the inner surface 130 of the taper 120 curves downwardly and inwardly to a threaded portion 132 as shown in fig2 . two rotation stops 134 and 136 are located at one end of the shaft 102 near the male coupling portion 108 . referring to fig3 , the shaft 102 includes side walls 138 and 140 which extend from the end portion 104 to the end portion 106 . an inwardly curved wall 142 is located at the end of the shaft 106 nearest the end portion 104 and extends downwardly from the upper surface 144 of the bone plate module 100 . another inwardly curved wall 146 which is located at the end of the shaft 106 nearest the end portion 106 extends upwardly from the bottom surface 148 of the bone plate module 100 . the female coupling portion 110 includes a bore 150 which extends downwardly from the upper surface 144 and opens to an overhang 152 . the overhang 152 is located between the curved wall 146 and the outer perimeter 118 . a groove 154 extends about the perimeter of the bore 150 . the bore 150 is sized to be slightly smaller in diameter than the diameter of the taper 120 . the groove 154 , which is sized complementary to the ridge 124 , is located at a distance away from the opening of the bore 150 to the overhang 152 that is about the same a as the distance at which the ridge 124 is positioned on the taper 120 above the plateau 122 . additionally , the curvature of the inwardly curved wall 146 is complementary to the curvature of the outer perimeter 116 and the curvature of the inwardly curved wall 142 is complementary to the curvature of the outer perimeter 118 . the complementary configuration of the end portion 104 and the end portion 106 along with the configuration of the male coupling portion 108 and the female coupling portion 110 allow two or more bone plate modules like the bone plate module 100 to be rigidly coupled . by way of example , fig4 shows a bone plate module 200 which is identical to the bone plate module 100 in all respects . the bone plate module 100 and the bone plate module 200 may be rigidly coupled as shown in fig5 . coupling of the bone plate module 100 with the bone plate module 200 to obtain the bone plate 156 shown in fig5 is accomplished by aligning the male coupling portion 202 of the bone plate module 200 with the female coupling portion 110 of the bone plate module 100 . the male coupling portion 202 and the female coupling portion 110 are then pressed together . the diameter of the bore 150 is slightly smaller than the diameter of the taper 204 . accordingly , the taper 204 is placed under a compressive force . the bone plate module 200 is made from a biocompatible material . such materials include stainless steel , titanium alloy and polymers . these materials exhibit some amount of flexibility when formed with a thin cross section . thus , the thin walls of the taper 204 , particularly at the upper portion of the taper 204 , allow the taper 204 to flex inwardly . moreover , the slots 206 and 208 allow additional flexure . depending upon the materials used and the particular design , more , fewer or even no slots may be incorporated . inward flexure of the taper 204 allows the taper 204 to slide into the bore 150 . as the ridge 210 contacts the opening of the bore 150 to the overlap 152 , additional force is required to flex the taper 204 farther in the inward direction so that the ridge 210 can enter into the bore 150 . as the taper 204 is inserted more fully into the bore 150 , the ridge 210 aligns with the groove 154 . the increased diameter of the groove 154 compared to the remainder of the bore 150 allows the taper 204 to flex outwardly , thereby forcing the ridge 210 into the groove 154 resulting in the configuration shown in fig6 . in fig6 , the ridge 210 is located within the groove 154 and the portion of the bone plate module 100 between the bore 150 and the outer perimeter 118 fits within the gap between the taper 204 and the inwardly curved wall 212 . additionally , the overhang 152 rests upon the plateau 214 and the outer perimeter 216 is adjacent to the inwardly curved wall 142 . additionally , the bottom surface 218 of the bone plate module 200 is aligned with the bottom surface 148 of the bone plate module 100 . accordingly since the snap - fit provided in this embodiment results in a rigid connection between the module 100 and the module 200 , the combination of the bone plate module 100 and the bone plate module 200 provides a single straight bone plate 156 . as described above , the curvature of the inwardly curved wall 146 is complementary to the curvature of the outer perimeter 116 and the curvature of the inwardly curved wall 142 is complementary to the curvature of the outer perimeter 118 . thus , since the bone plate module 200 is identical to the bone plate module 100 , the bone plate modules 100 and 200 may be coupled at an angle to each other . as shown in fig7 and 8 , the bone plate modules 100 and 200 may be used to build an angled bone plate 158 . this is accomplished by aligning the male coupling portion 202 of the bone plate module 200 with the female coupling portion 110 of the bone plate module 100 such that the longitudinal axis 161 of the plate 100 is set at the angle α with respect to the longitudinal axis 220 of the plate 200 and then pressing the bone plate modules 100 and 200 together in the manner discussed above with respect to the bone plate 156 . the bone plate modules 100 and 200 are not constrained to forming a bone plate with a single angle . for example , in the bone plate 160 shown in fig9 , the longitudinal axis 162 of the plate 100 is set at an angle β with respect to the longitudinal axis 220 of the plate 200 that is larger than the angle α . the range of angles which can be formed in this embodiment is limited in one direction by the rotation stop 222 which impinges on the side wall 140 and in the other direction by the rotation stop 224 which impinges on the side wall 138 . fig1 shows a bone plate 170 that includes bone plate modules 100 and 200 and a male end cap 178 . the bone plate 170 may be fastened to a bone using bone screws 172 and 174 . the bone screw 172 is inserted through the taper 120 . the head 176 of the bone screw 172 may be threaded to engage the threaded portion 132 of the taper 120 . the threaded portion 132 may be triple lead threaded to provide for use of both locking and non - locking screws . a compression screw may be used either with or without a threaded portion 132 . the screw 174 extends through the bore 226 . the bore 226 , however , has no threads to engage the screw 174 . the male end cap 178 , however , is threaded as shown in fig1 . specifically , the male end cap 178 includes a male coupling portion 180 with a threaded portion 182 that extends upwardly from a plateau 184 . two notches 186 and 188 are provided in the plateau 184 . a base 190 includes a bottom that is formed in like manner to the bottom surface 148 of the bone plate 100 . the base 190 has a curved outer perimeter portion 192 that is substantially identical to the outer perimeter 118 and another curved outer perimeter portion 194 that is complementary to the inwardly curved wall 146 . thus , when the male end cap 178 is installed as shown in fig1 , the end portion of the bone plate module 200 is supported as if the bone plate module 200 were coupled with the male coupling portion of another bone plate module . additionally , the bottom surface of the bone plate 170 provides a uniform contact surface from one end of the plate 170 to the opposites end . fig1 shows a female end cap 240 that may be used with the bone plate modules 100 and 200 . the female end cap 240 includes a female coupling portion 242 with a bore 244 that extends through the female end cap 240 . a groove 246 extends around the groove 246 . the female end cap 240 has a curved outer perimeter portion 248 that is substantially identical to the outer perimeter 116 and a curved outer perimeter portion 250 that is complementary to the inwardly curved wall 142 . thus , when the female end cap 240 is installed on the male coupling portion 108 , the upper surface of the bone plate 170 provides a uniform upper surface , thereby reducing the potential for irritation to soft tissue adjacent to the plate 170 . additionally , any male coupling portions that are not filled with a screw may be filled , for example , with a threaded plug . a decoupler 260 is shown in fig1 and 14 that may be used to be decouple two bone plate modules . the decoupler 260 includes a shaft 262 and a yoke 264 . two stubs 266 and 268 are provided on arms 270 and 272 , respectively . the arms 270 and 272 are spaced apart by a distance which is approximately equal to the width of the bone plate module . the stubs 266 and 268 are canted with respect to the shaft 262 and are sized slightly smaller than the notches of the bone plate module with which the decoupler 260 is to be used . operation of the decoupler 260 is explained with further reference to fig1 . in this example , the decoupler 260 will be used to decouple the bone plate 180 which was formed by coupling the bone plate modules 100 and 200 . initially the decoupler 260 is placed generally perpendicularly to the bone plate module 100 and the yoke 264 moved toward the upper surface 144 of the bone plate module . as noted above , the arms 270 and 272 are separated by about the same distance as the width of the bone plate module 100 . accordingly , the distance between the stubs 266 and 268 is shorter than the width of the bone plate module 100 . therefore , pushing the yoke - 1 - 64 264 toward the bone plate module 100 forces the stubs 266 and 268 against the bone plate module 100 causing the arms 270 and 272 to flex apart thereby allowing the stubs 266 and 268 to slide along sidewalls 138 and 140 . as the stubs 266 and 268 approach the notches 114 and 112 , the shaft 262 is moved toward a more parallel position with respect to the bone plate module 100 . this movement brings the canted stubs 266 and 268 into alignment with the notches 114 and 112 . once aligned the yoke 264 flexes toward its original shape thereby forcing the stubs 266 and 268 into the notches 114 and 112 , respectively . the cant of the stubs 266 and 268 with respect to the shaft 262 ensures that the stubs 266 and 268 enter the notches 114 and 112 before the shaft 262 of the decoupler 260 is in contact with the upper surface 144 of the bone plate module 100 . additionally , the arms 270 and 272 are sized such that as the stubs 266 and 268 enter the notches 114 and 112 , the yoke 264 is close to , if not touching , the upper surface 144 of the bone plate module 100 . application of force to the shaft 262 thus causes the yoke 264 to contact the bone plate module 100 and provide a pivot point for the decoupler 260 . pressure on the shaft 262 thus forces the stubs 266 and 268 against the female coupling portion of the bone plate module 200 thereby forcing the groove of the bone plate 200 against the ridge 124 thereby flexing the taper 120 inwardly . as the ridge 124 exits the groove of the bone plate module 200 , the bone plate module 200 may be lifter clear of the bone plate module 100 . a kit may include a number of bone plate modules , male end caps , female end caps and a decoupler . additionally , a template may be provided to assist the surgeon in determining the desired number and orientation of bone plate modules to be used to form a bone plate . in one embodiment , bone plate modules are provided in various lengths . for example , one group of bone plate modules may have a length of about 25 millimeters while a second group has a length of about 30 millimeters , and additional groups may have larger lengths . a bone plate module with a length of about 25 millimeters provides sufficient length to incorporate both a male and a female coupling portion of a size that provides a robust coupling force to obtain a bone plate with the desired rigidity . fig1 - 21 show various bone plate modules that may be provided either separately or in a kit with other bone plate modules . fig1 shows a “ y ” shaped bone plate module 300 that includes two female coupling portions 302 located at end portions 304 and 306 and one male coupling portion 308 at an end portion 310 . alternatively , the bone plate module 300 may include two male coupling portions , all female coupling portions or all male coupling portions . a shaft 312 extends between each of the end portions 304 , 306 and 310 . the end portions 304 and 306 have the same configuration as the end portion 106 and the end portion 310 has the same configuration as the end portion 104 . likewise , the female coupling portions 302 and the male coupling portion 308 have the same configuration as the female coupling portion 110 and the male coupling portion 108 , respectively . additionally , the shaft 312 , at each end portion 304 , 306 and 310 , has the same configuration as the shaft 102 for the corresponding coupling portion . thus , since the end portion 310 has a male coupling portion 308 and the end portion 104 of fig1 has a male coupling portion 108 , the shaft 312 includes an inwardly curved wall 314 at the end portion 310 that has the same configuration as the inwardly curved wall 142 of fig1 . accordingly , the bone plate module 300 may be used with the bone plate modules 100 and 200 , the male end cap 178 and female end cap 240 . additionally , the decoupler 260 may be used with the bone plate module 300 . finally , the bone plate modules 100 , 200 or another bone plate module 300 may be coupled to either of the female coupling portions 302 or the male coupling portion 308 in the same manner that the bone plates 100 and 200 may be coupled together . other bone plate modules include the “ s ” shaped bone plate module 320 of fig1 , the “ t ” shaped bone module 322 of fig1 which is configured with three female coupling portions 324 , the “ t ” shaped bone module 326 of fig1 which is configured with three male coupling portions 328 , the curved bone plate module 330 of fig2 and the cross shaped bone plate module 332 of fig2 . each of these bone plate modules , as well as bone plate modules of other shapes , may be configured with various combinations of coupling portions and in various sizes to allow a bone plate to be quickly and easily configured for a particular patient . while the present invention has been illustrated by the description of exemplary processes and system components , and while the various processes and components have been described in considerable detail , the applicants do not intend to restrict or in any way limit the scope of the appended claims to such detail . additional advantages and modifications will also readily appear to those ordinarily skilled in the art . the invention in its broadest aspects is therefore not limited to the specific details , implementations , or illustrative examples shown and described . accordingly , departures may be made from such details without departing from the spirit or scope of the applicants &# 39 ; general inventive concept .

US-90407807-A

a device for the production of confectionery , in particular , pralines , in moulds , with at least one upper die which may be lowered relative thereto , mounted on a die plate whereby the die plate has a flexible mounting .

a corresponding device is described for example in de 197 32 036 . 8 , particular reference being made to this application and this application also being incorporated in the present utility model application for the general description . there , as also in the case of the present application , a die plate 1 can be seen , on which a plurality of dies 2 are located . these dies 2 enter impressions 3 of a mold 4 when the die plate 1 is lowered , and can mold a mass of chocolate poured in there . according to the invention , the die plate 1 hangs on a fixed machine part 5 and is supported with respect to this machine part 5 by means of rubber buffers 6 . 1 and 6 . 2 . furthermore , the die plate 1 hangs by means of bolts 7 . 1 and 7 . 2 on a machine frame 8 , each bolt 7 . 1 , 7 . 2 passing through a bore ( not shown any more specifically ) in a carrier 9 . at least the part of the bolt 7 passing through the bore has a thread , on which a nut 10 is screwed , fixed by a lock nut 11 . the way in which the present invention functions is as follows : liquid chocolate , for example , is introduced into the impressions 3 of the mold 4 . the mold 4 passes , for example on a conveyor belt , under the die plate 1 . to deform the mass of chocolate in the impressions 3 , the die plate 1 is lowered , so that the dies 2 enter the impressions 3 . in the end position , a die face 12 lies on a surface 13 of the mold 4 . should the conveyor belt , or a table under the die plate 1 on which the mold 4 is located , then happen to be uneven or the mold itself warped , there is no canting between the die plate 1 and the mold 4 , since the die plate 1 gives way against the rubber buffers 6 . 1 and 6 . 2 . the bolts 7 . 1 and 7 . 2 have the task of holding the die plate 1 , in order that the die plate 1 does not hang on the rubber buffers 6 . 1 and 6 . 2 , whereby this connection may be permanently damaged . when the die plate 1 gives way , the bolts 7 . 1 and / or 7 . 2 move a little upward in the corresponding bore in the carrier 9 , so that they do not oppose giving way of the die plate 1 . if the entire apparatus is then raised again , the bolts 7 . 1 and 7 . 2 slide back into their starting position , the die plate 1 hanging on the corresponding nuts 10 . moreover , these nuts 10 also provide a very simple possibility for adjusting the die plate 1 with respect to the mold 4 and / or a table / conveyor belt .

US-91215606-A

an endo luminal support structure includes strut members interconnected by swivel joints to form a series of linked scissor mechanisms . the structure can be remotely actuated to compress or expand its shape by adjusting the scissor joints within a range of motion . in particular , the support structure can be repositioned within the body lumen or retrieved from the lumen . the support structure can be employed to introduce and support a prosthetic valve within a body lumen .

particular embodiments of the invention include endoluminal support structures ( stents ) and prosthetic valves . fig1 is a perspective view of a particular endoluminal support structure . as shown , the support structure 10 is a medical stent that includes a plurality of longitudinal strut members 11 interconnected by a plurality of swivel joints 15 . in particular , the swivel joints 15 allow the interconnected strut members 11 to rotate relative to each other . as shown , there are eighteen struts 11 . the strut members 11 are fabricated from a rigid or semi - rigid biocompatible material , such as plastics or other polymers and metal alloys , including stainless steel , tantalum , titanium , nickel - titanium ( e . g . nitinol ), and cobalt - chromium ( e . g . elgiloy ). the dimensions of each strut can be chosen in accordance with its desired use . in a particular embodiment , each strut member is made from stainless steel , which is 0 . 005 - 0 . 020 inch thick . more particularly , each strut is 0 . 010 inch thick 300 series stainless steel . while all struts 11 are shown as being of uniform thickness , the thickness of a strut can vary across a strut , such as a gradual increase or decrease in thickness along the length of a strut . furthermore , individual struts can differ in thickness from other individual struts in the same support structure . as shown , each strut member 11 is bar shaped and has a front surface 11 f and a back surface 11 b . the strut members can however be of different geometries . for example , instead of a uniform width , the struts can vary in width along its length . furthermore , an individual strut can have a different width than another strut in the same support structure . similarly , the strut lengths can vary from strut to strut within the same support structure . the particular dimensions can be chosen based on the implant site . furthermore , the struts can be non - flat structures . in particular , the struts can include a curvature , such as in a concave or convex manner in relationship to the inner diameter of the stent structure . the struts can also be twisted . the non - flatness or flatness of the struts can be a property of the material from which they are constructed . for example , the struts can exhibit shape - memory or heat - responsive changes in shape to the struts during various states . such states can be defined by the stent in the compressed or expanded configuration . furthermore , the strut members 11 can have a smooth or rough surface texture . in particular , a pitted surface can provide tensile strength to the struts . in addition , roughness or pitting can provide additional friction to help secure the support structure at the implant site and encourage irregular encapsulation of the support structure 10 by tissue growth to further stabilize the support structure 10 at the implant site over time . in certain instances , the stent could be comprised of struts that are multiple members stacked upon one another . within the same stent , some struts could include elongated members stacked upon one another in a multi - ply configuration , and other struts could be one - ply , composed of single - thickness members . within a single strut , there can be areas of one - ply and multi - ply layering of the members . each strut member 11 also includes a plurality of orifices 13 spaced along the length of the strut member 11 . on the front surface 11 f , the orifices are countersunk 17 to receive the head of a fastener . in a particular embodiment , there are thirteen equally spaced orifices 13 along the length of each strut member 11 , but more or less orifices can be used . the orifices 13 are shown as being of uniform diameter and uniform spacing along the strut member 11 , but neither is required . the strut members 11 are arranged as a chain of four - bar linkages . the strut members 11 are interconnected by swivelable pivot fasteners 25 , such as rivets , extending through aligned orifices 13 . it should be understood that other swivelable fasteners 25 can be employed such as screws , bolts , ball - in - socket structures , nails , or eyelets , and that the fasteners can be integrally formed in the struts 11 such as a peened semi - sphere interacting with an indentation or orifice , or a male - female coupling . in addition to receiving a fastener , the orifices 13 also provide an additional pathway for tissue growth - over to stabilize and encapsulate the support structure 10 over time . fig2 is a perspective view of a four strut section of the stent of fig1 . as shown , two outer strut members 11 - 1 , 11 - 3 overlap two inner strut members 11 - 2 , 11 - 4 , with their back surfaces in communication with each other . in particular , the first strut member 11 - 1 is swivelably connected to the second strut member 11 - 1 by a middle swivel joint 15 - 1 using a rivet 25 - 1 , which utilizes orifices 13 that bisect the strut members 11 - 1 , 11 - 2 . similarly , the third strut member 11 - 3 is swivelably connected to bisect the fourth strut member 11 - 4 by a middle swivel joint 15 - 7 using a rivet 25 - 7 . it should be understood that the middle swivel joints 15 - 1 , 15 - 7 function as a scissor joint in a scissor linkage or mechanism . as shown , the resulting scissor arms are of equal length . it should also be understood that the middle joint 15 - 1 , 15 - 7 need not bisect the joined strut members , but can instead utilize orifices 13 offset from the longitudinal centers of the strut members resulting in unequal scissor arm lengths . in addition to the middle scissor joint 15 - 1 , the first strut member 11 - 1 is swivelably connected to the third strut member 11 - 3 by a distal anchor swivel joint 15 - 5 , located near the distal ends of the strut members 11 - 1 , 11 - 3 . similarly , the first strut member 11 - 1 is swivelably connected to the fourth strut member 11 - 4 by a proximal anchor swivel joint 15 - 3 , located near the proximal ends of the strut members 11 - 1 , 11 - 4 . to reduce stresses on the anchor rivets 25 - 3 , 25 - 5 , the distal and proximal ends of the struts 11 can be curved or twisted to provide a flush interface between the joined struts . as can be seen , the support structure 10 ( fig1 ) is fabricated by linking together a serial chain of scissor mechanisms . the chain is then wrapped to join the last scissor mechanism with the first scissor mechanism in the chain . by actuating the linkage the links can be opened or closed , which results in expanding or compressing the stent 10 ( fig1 ). returning to fig1 , by utilizing the swivel joints 15 , the diameter of the stent can be compressed for insertion through a biological lumen , such as an artery , to a selected position . the stent can then be expanded to secure the stent at the selected location within the lumen . furthermore , after being expanded , the stent can be recompressed for removal from the body or for repositioning within the lumen . fig3 is a perspective view of a compressed support structure of fig1 . when compressed , the stent 10 is at its maximum length and minimum diameter . the maximum length is limited by the length of the strut members , which in a particular embodiment is 15 mm . the minimum diameter is limited by the width of the strut members , which in a particular embodiment is 0 . 052 inch . fig4 is a perspective view of the support structure of fig1 in a fully expanded state . as shown , the fully expanded support structure 10 forms a ring , which can be used as an annuloplasty ring . in particular , if one end of the stent circumference is attached to tissue , the compression of the stent will enable the tissue to cinch . because the stent has the ability to have an incremental and reversible compression or expansion , the device could be used to provide an individualized cinching of the tissue to increase the competency of a heart valve . this could be a useful treatment for mitral valve diseases , such as mitral regurgitation or mitral valve prolapse . while the support structure 10 can be implanted in a patient during an open operative procedure , a closed procedure will often be more desirable . as such , the support structure 10 can include an actuation mechanism to allow a surgeon to expand or compress the support structure from a location remote from the implant site . due to the properties of a scissor linkage wrapped into a cylinder ( fig1 ), actuation mechanisms can exert work to expand the stent diameter by either increasing the distance between neighboring scissor joints , and decreasing the distance between the anchor joints . fig5 is a perspective view of the support structure of fig2 having a particular actuator mechanism . as shown , the actuator mechanism 30 includes a dual - threaded rod 32 positioned on the inside of the support structure 10 ( fig1 ). it should be understood , however , that the actuator mechanism 30 can instead be positioned on the outside of the support structure 10 . whether positioned on the inside or outside , the actuator mechanism 30 operates in the same way . the rod includes right - hand threads 34 r on its proximal end and left - hand threads 34 l on its distal end . the rod 32 is mounted the anchor points 15 - 3 , 15 - 5 using a pair of threaded low - profile support mounts 35 - 3 , 35 - 5 . each end of the rod 32 is terminated by a hex head 37 - 3 , 37 - 5 for receiving a hex driver ( not shown ). as should be understood , rotating the rod 32 in one direction will urge the anchor points 25 - 3 , 25 - 5 outwardly to compress the linkages while rotating the rod 32 in the opposite direction will urge the anchor points 25 - 3 , 25 - 5 inwardly to expand the linkages . fig6 is a perspective view of the support structure of fig2 having another particular actuator mechanism . as shown , the actuator mechanism 30 ′ includes a single - threaded rod 32 ′ positioned on the inside of the support structure 10 ( fig1 ). the rod 32 ′ includes threads 34 ′ on one of its ends . the rod 32 ′ is mounted to low - profile anchor points 15 - 3 , 15 - 5 using a pair of support mounts 35 ′- 3 , 35 ′- 5 , one of which is threaded to mate with the rod threads 34 ′. the unthreaded end of the rod 32 ′ includes a retaining stop 39 ′ that bears against the support mount 35 ′- 5 to compress the support structure . each end of the rod 32 ′ is terminated by a hex head 37 ′- 3 , 37 ′- 5 for receiving a hex driver ( not shown ). again , rotating the rod 32 ′ in one direction will urge the anchor points 25 - 3 , 25 - 5 outwardly to compress the linkages while rotating the rod 32 ′ in the opposite direction will urge the anchor points 25 - 3 , 25 - 5 inwardly to expand the linkages . in addition , because the struts overlap , a ratcheting mechanism can be incorporated to be utilized during the sliding of one strut relative to the other . for example , the stent could lock at incremental diameters due to the interaction of features that are an integral part of each strut . an example of such features would be a male component ( e . g . bumps ) on one strut surface which mates with the female component ( e . g . holes ) on the surface of the neighboring strut surface , as the two struts slide pass one another . such structures could be fabricated to have an orientation , such that they incrementally lock the stent in the expanded configuration as the stent is expanded . such a stent could be expanded using a conventional balloon or other actuation mechanism described in this application . because the support structure 10 of fig5 and 6 are intended to be implanted during a closed surgical procedure , the actuator mechanism is controlled remotely by a surgeon . in a typical procedure , the support structure 10 is implanted through a body lumen , such as the femoral artery using a tethered endoluminal catheter . as such , the actuator mechanism 30 can be controlled via the catheter . fig7 is a perspective view of a particular support structure and control catheter assembly usable with the actuator mechanisms of fig5 and 6 . the control catheter 40 is dimensioned to be inserted with the support structure through a biological lumen , such as a human artery . as shown , the control catheter 40 includes a flexible drive cable 42 having a driver 44 on its distal end that removably mates with a hex head 37 , 37 ′ of the actuator mechanism ( fig5 and 6 ). the proximal end of the cable 42 includes a hex head 46 . in operation , the proximal hex head 46 of the cable 42 is rotated by a surgeon , using a thumb wheel or other suitable manipulator ( not shown ). rotation of the hex head 46 is transferred by the cable 42 to the driver head 44 to turn the actuator rod 30 , 30 ′ ( fig5 and 6 ). the cable 42 is encased by a flexible outer sheath 48 . the distal end of the outer sheath 48 includes a lip or protuberance 49 shaped to interface with the support structure 10 . when the cable 42 is turned , the outer sheath lip 49 interacts with the support structure 10 to counteract the resulting torque . by employing threads , the rod is self - locking to maintain the support structure in the desired diameter . in a particular embodiment , the rod 32 , 32 ′ has a diameter of 1 . 0 mm and a thread count of 240 turns / inch . while a threaded rod and drive mechanism are described , other techniques can be employed to actuate the linkages depending on the particular surgical application . for example , the actuator mechanism can be disposed within the thickness of the strut members , instead of inside or outside of the stent . for example , worm gears or a rack and pinion mechanism can be employed as known in the art . one of ordinary skill in the art should recognize other endoluminal actuation techniques . in other situations , the support structure can be implanted during an open procedure , which may not require an external actuation mechanism . although there are other uses for the described support structure , such as drug delivery , a particular embodiment supports a prosthetic valve . in particular , the support structure is used in combination with a prosthetic valve , such as for an aortic valve replacement . fig8 is a perspective view of a particular rotating prosthetic valve assembly . the prosthetic valve 100 comprises a three leaflet configuration shown in an open position . the leaflets are derived from a biocompatible material , such as animal pericardium ( e . g . bovine , porcine , equine ), human pericardium , chemically - treated pericardium , gluteraldehyde - treated pericardium , tissue engineered materials , a scaffold for tissue engineered materials , autologous pericardium , cadaveric pericardium , nitinol , polymers , plastics , ptfe , or any other material known in the art . the leaflets 101 a , 101 b , 101 c are attached to a stationary cylindrical member 105 and a non - stationary cylindrical member 107 . one side of each leaflet 101 is attached to the non - stationary cylindrical member 107 . the opposing side of each leaflet 101 is attached to the stationary cylindrical member 105 . the attachment of each leaflet 101 is in a direction generally perpendicular to the longitudinal axis of the cylindrical members 105 , 107 . in this embodiment , each leaflet 101 is pliable , generally rectangular in shape , and has a 180 degree twist between its attachments to stationary member 105 and non - stationary member 107 . each leaflet 101 has an inner edge 102 and an outer edge 103 , with the edges 102 c , 103 c of one leaflet 101 c being referenced in the figure . as known in the art , the leaflets can be fabricated from either biological or non - biological materials , or a combination of both . one way to actuate the valve to close is by utilizing the forces exerted by the normal blood flow or pressure changes of the cardiac cycle . more specifically , the heart ejects blood through the fully open valve in the direction of the arrow shown in fig8 . shortly thereafter , the distal or downstream blood pressure starts to rise relative to the proximal pressure across the valve , creating a backpressure on the valve . fig9 is a perspective view of the valve assembly of fig8 while being closed . that backpressure along the direction of the arrow causes the axially displacement of the leaflets 101 and non - stationary member 107 towards the stationary cylindrical member 105 . as the leaflets 101 move from a vertical to horizontal plane relative to the longitudinal axis , a net counter - clockwise torque force is exerted on the non - stationary member 107 and leaflets 101 . the torque force exerts a centripetal force on the leaflets 101 . fig1 is a perspective view of the valve assembly of fig8 once completely closed . complete closure of the valve 100 occurs as the leaflets 101 displace to the center of the valve and the non - stationary cylindrical member 107 rests upon the stationary member 105 , as shown . the function of the valve 100 opening can be understood by observing the reverse of the steps of valve closing , namely following the sequence of drawings from fig1 to fig8 . in considering the valve 100 as an aortic valve replacement , it would remain closed as shown in fig1 , until the heart enters systole . during systole , as the myocardium forcefully contracts , the blood pressure exerted on the valve &# 39 ; s proximal side ( the side closest to the heart ) is greater than the pressure on the distal side ( downstream ) of the closed valve . this pressure gradient causes the leaflets 101 and non - stationary cylindrical member 107 to displace away from the stationary member 105 along the axial plane . the valve 100 briefly assumes the half - closed transition state shown in fig9 . as the leaflets 101 elongate from a horizontal to vertical orientation along the axial plane , a net torque force is exerted on the leaflets 101 and non - stationary cylindrical member 107 . since the valve 100 is opening , as opposed to closing , the torque force exerted to open the valve is opposite to that exerted to close the valve . given the configuration of embodiment shown in fig9 , the torque force that opens the valve would be in clockwise direction . the torque forces cause the leaflets 101 to rotate with the non - stationary member 107 around the longitudinal axis of the valve 100 . this , in turn , exerts a centrifugal force on each leaflet 101 . the leaflets 101 undergo radial displacement away from the center , effectively opening the valve and allowing blood to flow away from the heart , in the direction shown by the arrow in fig8 . to summarize , the valve passively functions to provide unidirectional blood flow by linking three forces . axial , torque , and radial forces are translated in a sequential and reversible manner , while encoding the directionality of prior motions . first , the axial force of blood flow and pressure causes the displacement of the leaflets 101 and non - stationary members 107 relative to the stationary member 105 along the axial plane . this is translated into a rotational force on the leaflets 101 and non - stationary member 107 . the torque force , in turn , displaces the leaflets 101 towards or away from the center of the valve , along the radial plane , which closes or opens the valve 100 . the valve 100 passively follows the pathway of opening or closing , depending on the direction of the axial force initially applied to the valve by the cardiac cycle . in the body , the stationary cylindrical member 105 can secured and fixed in position at the implant site , while the non - stationary member 107 and distal ends of leaflets 101 are free to displace along the axial plane . in using the prosthetic valve as an aortic valve replacement , the stationary member 105 would be secured in the aortic root . as the blood pressure or flow from the heart , increases , the valve 100 changes from its closed configuration to the open configuration , with blood ejecting through the valve 100 . specific advantages of the rotating valve of fig8 - 10 , along with further embodiments , are described in the above - incorporated parent provisional patent application . fig1 is a perspective view of the valve of fig8 - 10 in combination with the support structure of fig1 . as shown in the closed position , the valve &# 39 ; s stationary member 105 is attached to the support structure 10 . the valve &# 39 ; s non - stationary member 107 is not attached to the support structure 10 . this enables the non - stationary member 107 to displace along the axial plane along with the leaflets 101 during valve opening or closing . in this particular embodiment , the valve 100 occupies a position that is closer to one end of the support structure 10 , as shown . fig1 is a perspective view of the valve of fig1 in the open position . as noted above , the non - stationary member 107 is not attached to support structure 10 , and is thus free to displace along the axial plane , along with the leaflets 101 . in this particular embodiment , during full opening , non - stationary member 107 and the leaflets 101 remain within the confines of the support structure 10 . the stented valve 110 can be implanted during a closed procedure as described above . however , because of the operation of the non - stationary member within the body of the stent , the actuator mechanism to compress and expand the stent would not be disposed within the stent . further embodiments of the stented valve 110 , positioning of the valve in the body , and procedures for implantation are described in the above - incorporated parent provisional patent application . in addition , a tissue valve can be draped on the support structure . additional embodiments should be apparent to those of ordinary skill in the art . fig1 is a perspective view of a traditional tissue valve mounted to the support structure of fig1 . as shown , a stented valve 120 includes a prosthetic tissue valve 121 attached to a support structure 10 , such as that described above . the tissue valve 121 includes three pliable semi - circular leaflets 121 a , 121 b , 121 c , which can be derived from biocompatible materials as noted with reference to fig8 . adjacent leaflets are attached in pairs to commissures 123 x , 123 y , 123 z on the support structure 10 . in particular , the commissures 123 x , 123 y , 123 z correspond with spaced - apart distal anchor points 13 x , 13 y , 13 z on the support structure 10 . in an 18 - strut stent , the commissures are attached the structure 10 via corresponding fasteners 25 at every third distal anchor point . from the commissures , the leaflet sides are connected to the adjacent diagonal struts . that is , the sides of the first leaflet 121 a are sutured to the struts 11 - xa and 11 - za , respectively ; the sides of the second leaflet 121 b are sutured to the struts 11 - xb and 11 - yb , respectively ; and the sides of the third leaflet 121 c are sutured to the struts 11 - yc and 11 - zc , respectively . those sutures end at the scissor pivot points on the diagonal struts . in the configuration shown , neighboring struts 11 are attached to one another in a manner that creates multiple arches 128 at the ends of the stent . posts for leaflet attachment , or commissures , are formed by attaching neighboring leaflet to each of the struts that define a suitable arch 128 x , 128 y , 128 z . in the configuration shown , there are three leaflets 121 a , 121 b , 121 c , each of which is attached to a strut along two of its opposing borders . the commissures are formed by three equi - distance arches 128 x , 128 y , 128 z in the stent . the angled orientation of a strut in relationship to its neighboring strut enables the leaflets 121 a , 121 b , 121 c to be attached to the stent in an triangular configuration . this triangular configuration simulates the angled attachment of the native aortic leaflet . in the native valve this creates an anatomical structure between leaflets , known as the inter - leaflet trigone . because the anatomical inter - leaflet trigone is believed to offer structural integrity and durability to the native aortic leaflets in humans , it is advantageous to simulate this structure in a prosthetic valve . one method of attachment of the leaflets to the struts is to sandwich the leaflet between a mutli - ply strut . the multiple layers are then held together by sutures . sandwiching the leaflets between the struts helps to dissipate the forces on leaflets and prevent the tearing of sutures through the leaflets . the remaining side of each leaflet 121 a , 121 b , 121 c is sutured annularly across the intermediate strut members as shown by a leaflet seam . the remaining open spaces between the struts are draped by a bio compatible skirt 125 to help seal the valve against the implant site and thus limit paravalvular leakage . as shown , the skirt 125 is shaped to cover those portions of the stent below and between the valve leaflets . in more detail , the skirt 125 at the base of the valve is a thin layer of material that lines the stent wall . the skirt material can be pericardial tissue , polyester , ptfe , or other material or combinations of materials suitable for accepting tissue in growth , including chemically treated materials to promote tissue growth or inhibit infection . the skirt layer functions to reduce or eliminate leakage around the valve , or “ paravalvular leak ”. to that end , there are a number of ways to attach the skirt material layer to the stent , including : the skirt layer can be on the inside or the outside of the stent ; the skirt layer can occupy the lower portion of the stent ; the skirt layer can occupy the lower and upper portion of the stent ; the skirt layer can occupy only the upper portion of the stent ; the skirt layer can occupy the area between the struts that define the commissure posts ; the skirt layer can be continuous with the leaflet material ; the skirt layer can be sutured to the struts or a multitude of sites ; or the skirt layer can be secured to the lower portion of the stent , and pulled or pushed up to cover the outside of the stent during the deployment in the body . the above list is not necessarily limiting as those of ordinary skill in the art may recognize alternative draping techniques for specific applications . fig1 is a perspective view of the valve structure of fig1 having a full inner skirt . a stented valve 120 ′ includes a prosthetic tissue valve 121 ′ having three leaflets 121 a ′, 121 b ′, 121 c ′ attached to a support structure 10 . a skirt layer 125 ′ covers the interior surface of the stent 10 . as such , the valve leaflets 121 a ′, 121 b ′, 121 c ′ are sutured to the skirt layer 125 ′. fig1 is a perspective view of the valve structure of fig1 having a full outer skirt . a stented valve 120 ″ includes a prosthetic tissue valve 121 ″ having three leaflets 121 a ″, 121 b ″, 121 c ″ attached to a support structure 10 , such as that described in fig1 . a skirt layer 125 ″ covers the exterior surface of the stent 10 . the tissue valve structures 120 , 120 ′, 120 ″ can also be implanted during a closed procedure as described above . however , the actuator mechanism to compress and expand the stent would be attached to avoid the commissure points and limit damage to the skirt layer 125 , 125 ′, 125 ″, such as by mounting the actuator mechanism on the outer surface of the stent 10 . while the above - described embodiments have featured a support structure having linear strut bars and equal length scissor arms , other geometries can be employed . the resulting shape will be other than cylindrical and can have better performance in certain applications . fig1 is a perspective view of the arrangement of strut members in a conical - shaped support structure configuration . in the conical structure 10 ′, the strut members 11 are arranged as shown in fig2 , except that the middle scissor pivots do not bisect the struts . in particular , the middle scissor pivots ( e . g . 15 ′- 1 , 15 ′- 7 ) divide the joined strut members ( e . g . 11 ′- 1 , 11 ′- 2 and 11 ′- 3 , 11 ′ 4 ) into unequal segments of 5 / 12 and 7 / 12 lengths . when fully assembled , the resulting support structure thus conforms to a conical shape when expanded . for illustration purposes , the stent 10 ′ is shown with a single - threaded actuator rod 32 ′ ( fig6 ), but it is not a required element for this stent embodiment . the stent 10 ′ can also assume a cone shape in its expanded configuration by imposing a convex or concave curvature to the individual strut members 11 that comprise the stent 10 ′. this could be achieved by using a material with memory , such as shape - memory or temperature sensitive nitinol . a valve can be orientated in the cone - shaped stent 10 ′ such that the base of the valve was either in the narrower portion of the cone - shaped stent , with the non - base portion of the valve in the wider portion of the cone . alternatively , the base of the valve can be located in the widest portion of the stent with the non - base portion of the valve in the less - wide portion of the stent . the orientation of a cone - shaped stent 10 ′ in the body can be either towards or away from the stream of blood flow . in other body lumens ( e . g . respiratory tract or gastrointestinal tract ), the stent could be orientated in either direction , in relationship to the axial plane . fig1 is a perspective view of an hourglass - shaped support structure configuration . in this configuration , the circumference around the middle pivot points 15 ″- 1 , 15 ″- 7 , 15 ″- 9 ( the waist ) is less than the circumference at either end of the stent 10 ″. as shown , the hourglass shaped support structure 10 ″ is achieved by reducing the number of strut members 11 ″ to six and shortening the strut members 11 ″ in comparison to prior embodiments . as a result of the shortening , there are fewer orifices 13 ″ per strut member 11 ″. because of the strut number and geometry , each strut member 11 ″ includes a twist at points 19 ″ along there longitudinal planes . the twists provide a flush interface between joined strut 15 ″- 3 . an hourglass stent configuration could also be achieved by imposing concave or convex curvatures in individual bars 11 ″. the curvature could be a property of the materials ( e . g . shape - memory or heat - sensitive nitinol ). the curvature could be absent in the compressed stent state and appear when the stent is in its expanded state . it should be noted that any of the above - described support structures can be extended beyond the anchor joints at either of both ends of the stent . by coupling a series of stents in an end - to - end chain fashion , additional stent lengths and geometries can be fabricated . in particular , an hourglass - shaped stent could be achieved by joining two cone - shaped stents at their narrow ends . the hourglass shape can also be modified by assembling the middle scissor pivots off center as shown in fig1 . particular embodiments of the invention offer distinct advantages over the prior art , including in their structure and applications . while certain advantages are summarized below , the summary is not necessarily a complete list as there may be additional advantages . the device allows the user to advert the serious complications that can occur during percutaneous heart valve implantation . because the device is retrievable and re - positionable during implantation into the body , the surgeon can avoid serious complications due to valve mal - positioning or migration during implantation . examples of these complications include occlusion of the coronary arteries , massive paravalvular leakage , or arrthymias . the device can also decrease vascular access complications because of the device &# 39 ; s narrow insertion profile . the device &# 39 ; s profile is low , in part , due to its unique geometry , which allows neighboring struts in the stent to overlap during stent compression . the device &# 39 ; s low profile is further augmented by eliminating the necessity for a balloon or a sheath . the device &# 39 ; s narrow profile offers the advantage of widening the vascular access route options in patients . for instance , the device can enable the delivery of the prosthetic valve through an artery in the leg in a patient whom would have previously been committed to a more invasive approach through the chest wall . the device therefore aims to decrease complications associated with the use of large profile devices in patients with poor vascular access . the tissue valve embodiments can offer improved durability by allowing for attachment of the leaflets to flexible commissural posts . the flexible posts allow dissipation of the stress and strain imposed on the leaflet by the cardiac cycle . the use of multi - ply struts enables the leaflets to be sandwiched in between the struts , which re - enforces the leaflet attachments and prevents tearing of sutures . the valve further assumes a desirable leaflet morphology , which further reduces the stress and strain on leaflets . namely , the angled leaflet attachment to the stent is similar to the native human aortic valve &# 39 ; s inter - leaflet trigone pattern . these properties significantly improve the longevity of percutaneous heart valve replacement therapies . the device could reduce or eliminate arrthymia complications due to the incremental expansion or compression of the stent . the stent can employ a screw mechanism for deployment , which enables the stent to self - lock or un - lock at all radii . this enables more controlled deployment and the potential for individualizing the expansion or compression of the device in each patient . because the expansion or compression of the device is reversible at any stage during the procedure , the surgeon can easily reverse the expansion of the device to relieve an arrythmia . in addition , if an arrythmia is detected during implantation , the device can be re - positioned to further eliminate the problem . the device can reduce or eliminate paravalvular leak due to the device &# 39 ; s ability to be accurately positioned , and re - positioned , if necessary . that can considerably decrease the occurrence and severity of paravalular leaks . the device eliminates balloon - related complications . the screw mechanism of deployment exploits the mechanical advantage of a screw . this provides for forceful dilation of the stent . the lever arms created by the pivoting of the struts in the scissor linkage of the stent , transmits a further expansion force to the stent . the stent is expanded without the need for a balloon . in addition , the ability of the device to be forcefully dilated reduces or eliminates the need for pre - or post - ballooning during the implantation procedure in patients . the device has more predictable and precise positioning in the body because the difference between the height of the stent in the compressed and expanded position is small . this “ reduced foreshortening ” helps the surgeon to position the device in the desirable location in the body . the ability to re - position the device in the body further confers the ability to precisely position the device in each individual . in addition to the mechanical advantages , the device enables a wider population of patients to be treated by a less invasive means for valve replacement . for example , the device enables patients with co - morbidites , whom are not candidates for open chest surgical valve replacement , to be offered a treatment option . the device &# 39 ; s ability to assume a narrow profile also enables patients who were previously denied treatment due to poor vascular access ( e . g . tortuous , calcified , or small arteries ), to be offered a treatment option . the durability of the valve should expand the use of less - invasive procedures to the population of otherwise healthy patients , whom would otherwise be candidates for open chest surgical valve replacement . the device &# 39 ; s ability to be forcefully expanded , or assume hourglass , or conical shapes , potentially expands the device application to the treatment of patients diagnosed with aortic insufficiency , as well as aortic stenosis . the device can also provide a less invasive treatment to patients with degenerative prosthesis from a prior implant , by providing for a “ valve - in - valve ” procedure . the device could be accurately positioned inside the failing valve , without removing the patient &# 39 ; s degenerative prosthesis . it would help the patient by providing a functional valve replacement , without a “ re - do ” operation and its associated risks . while this invention has been particularly shown and described with references to particular embodiments , it will be understood by those skilled in the art that various changes in form and details may be made to the embodiments without departing from the scope of the invention encompassed by the appended claims .

US-200913055441-A

formulations for topical application of aripiprazole are provided . the formulations , when applied topically to the skin of a subject , provide a therapeutic amount of aripiprazole in the blood for a sustained period of time for treatment of conditions responsive to aripiprazole including but not limited to depression , schizophrenia , and bipolar disorder .

various aspects now will be described more fully hereinafter . such aspects may , however , be embodied in many different forms and should not be construed as limited to the embodiments set forth herein ; rather , these embodiments are provided so that this disclosure will be thorough and complete , and will fully convey its scope to those skilled in the art . where a range of values is provided , it is intended that each intervening value between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the disclosure . for example , if a range of 1 μm to 8 μm is stated , it is intended that 2 μm , 3 μm , 4 μm , 5 μm , 6 μm , and 7 μm are also explicitly disclosed , as well as the range of values greater than or equal to 1 μm and the range of values less than or equal to 8 μm . as used in this specification , the singular forms “ a ,” “ an ,” and “ the ” include plural referents unless the context clearly dictates otherwise . thus , for example , reference to a “ polymer ” includes a single polymer as well as two or more of the same or different polymers , reference to an “ excipient ” includes a single excipient as well as two or more of the same or different excipients , and the like . formulations for topical application for transdermal delivery of aripiprazole are provided . the formulations provide delivery of aripiprazole transdermally in an amount sufficient for therapy for conditions responsive to aripiprazole . exemplary formulations were prepared and are described in example 1 . in one embodiment , a formulation is provided , where the formulation comprises aripiprazole and a delivery vehicle that consists or consists essentially of glycerol ; a glycol ; lauryl lactate ; lactic acid ; water or a surfactant ; and a polymeric vehicle . aripiprazole is typically included in the formulation in an amount between 1 - 25 wt %. aripiprazole is present in the formulation as a base , in one embodiment . salt forms of aripiprazole are contemplated . the components of the delivery vehicle are tailored to provide transdermal absorption of aripiprazole in an amount sufficient for therapy for a period of at least about 1 day , 3 days , 4 days , 5 days , 6 days or 7 days ; alternatively for a period of between about 3 - 7 days , 4 - 7 days , 5 - 7 days or 6 - 7 days . the components of the delivery vehicle that provide release for this period are now described . glycerol is present in the delivery vehicle or formulation in an amount between 5 - 25 wt %, or between about 8 - 20 wt % or between about 8 - 18 wt %. in the formulations prepared and tested for in vitro permeation described herein glycerol was present in amounts of 10 wt %, 11 wt %, 13 - 13 . 5 wt % and 15 - 15 . 5 wt %. a glycol is present in the delivery vehicle or formulation in a total amount of between 15 - 50 wt %. in one embodiment , the glycol is hexylene glycol ( 2 - methyl - 2 , 4 - pentanediol ), propylene glycol , or a mixture of hexylene glycol , propylene glycol . typically , the mixture comprises hexylene glycol and propylene glycol in a ratio of between about 1 : 1 to 1 : 0 . 5 . hexylene glycol is present in the vehicle or formulation , in one embodiment , in an amount between 3 - 30 wt %. propylene glycol is present in the vehicle or formulation in an amount between 3 - 30 wt %. in the formulations and vehicles prepared and tested for in vitro permeation described herein a mixture of hexylene glycol and propylene glycol was included , where the ratio of hexylene glycol to propylene glycol was 1 : 0 . 9 , 1 : 0 . 94 , 1 : 0 . 65 and 1 : 0 . 67 . stated alternatively , the amount of hexylene glycol in the formulations and vehicles was about 11 wt %, about 12wt %, and about 15wt %. the amount of propylene glycol in the formulations and vehicles described herein was about 7 wt %, about 8 wt %, about 13 wt % and about 14 wt %. it will be appreciated that other glycols may be suitable , such as dipropylene glycol and tripropylene glycol . the formulations and vehicles also comprise lauryl lactate in an amount between about 0 . 5 - 10 wt %. the amount of lauryl lactate in the formulations and vehicles described herein was about 2 wt % or about 4 wt %. lactic acid is included in the formulations and vehicles in an amount between 0 . 5 - 10 wt % or between about 1 - 7 wt % or between about 1 . 5 - 5 . 5 wt %. in one embodiment , the molar ratio of lactic acid to aripiprazole is not from 0 . 5 : 1 to 3 : 1 . in another embodiment , the molar ratio of lactic acid to aripiprazole is between 0 . 5 : 1 to 3 : 1 and the formulation or delivery vehicle does not include n , n - dimethylformamide , n , n - dimethylacetamide , or n - methyl - 2 - pyrrolidone or does not include isopropyl myristate , diethyl sebacate , medium - chain triglyceride , propylene carbonate . in the exemplary formulations and vehicles prepared herein , lactic acid was included at about 2 wt % and at about 5 wt %. a polymeric vehicle is present in the formulation or vehicle . in one embodiment , the polymeric vehicle is a polyvinylpyrrolidone or a hydroxyalkylcellulose or a polyacrylate copolymer . in another embodiment the polymeric vehicle is a combination of a polyvinylpyrrolidone or a hydroxyalkylcellulose . in another embodiment , the polymeric vehicle is a mixture of a hydroxyalkylcellulose and at least one or both of a polyvinylpyrrolidone and a polyacrylate copolymer . in one embodiment , the hydroxyalkylcellulose is selected from hydroxymethylcellulose , hydroxyethylcellulose , and hydroxypropylcellulose . in one embodiment , the hydroxyalkylcellulose functions as a gelling agent or thickening agent and is present in the vehicle or composition in an amount sufficient to achieve this function . the polyvinylpyrrolidone is selected from polyvinylpyrrolidone homopolymers and polyvinylpyrrolidone copolymers . a polyvinylpyrrolidone homopolymer with an average molecular weight of about 40 , 000 daltons is included in the formulation or vehicle , in one embodiment . the polyacrylate copolymer is , in one embodiment , a copolymer of methacrylic acid and methyl methylacrylate monomers . in one embodiment , the copolymer is poly ( methacylic acid - co - methyl methacrylate ) having a 1 : 1 ratio of the monomers ( eudragit l - 100 ). the formulation or vehicle also comprises water or a surfactant as an optional component . in one embodiment , the optional water or the surfactant is present , and is present in an amount between about 3 - 15 wt %. the surfactant when present is , in one embodiment , a sorbitan monolaurate . the formulation , composition or vehicle further comprises or consists of dimethyl sulfoxide , in one embodiment . when present , dmso is included in an amount between about 15 - 25 wt %, preferably between about 18 - 22 wt %. the formulation , composition or vehicle may further comprise oleic acid or another fatty acid , in some embodiments . when present , a fatty acid , such as oleic acid , is present in an amount between about 1 - 10 wt %, or 2 - 8 wt % or 2 - 6 wt %. in another aspect , a formulation consisting essentially of the following components is provided : between about 1 - 12 wt %; aripiprazole ; between about 5 - 40 wt % of a glycol selected from hexylene glycol , propylene glycol , or a mixture thereof ; between about 10 - 25 wt % glycerol ; between about 0 . 5 - 10 wt % lauryl lactate ; between about 0 . 5 - 10 wt % lactic acid ; between about 2 - 15 wt % water or a surfactant ; and between about 5 - 40 wt %, or between about 5 - 35 wt %, or between about 20 - 35 wt %, or between about 20 - 40 wt % of a polymeric vehicle comprising a polyvinylpyrrolidone or a hydroxyalkylcellulose or both . formulations prepared with the components described above were tested for in vitro skin flux . fig1 - 4 are graphs showing the flux of the formulations identified herein as formulation no . 13 ( fig1 ), formulation no . 15 ( fig2 ), formulation no . 19 ( fig3 ) and formulation no . 21 ( fig4 ). the in vitro skin flux of aripiprazole provided by the formulations described herein is between about 10 - 20 μg / cm 2 · hr at steady state , which is typically reached within about 48 hours of topical application . the steady state flux is maintained for a period of at least about 3 days or at least about 4 days . accordingly , the formulations provide a means for administration of aripiprazole transdermally in a device or composition that lasts for at least about 1 day , 3 days , or at least about 4 days , or at least about 5 , 6 , or 7 days . in one embodiment , the formulation is applied topically to the skin of a subject and achieves transdermal administration of aripiprazole as evidenced by aripiprazole concentration in the blood of the subject . a method for treating a condition responsive to aripiprazole is contemplated , where a formulation as described herein is provided along with instructions to apply the formulation to skin of a subject in need . in some embodiments , the condition responsive to aripiprazole is depression , schizophrenia , or bipolar disorder . the formulations described herein can , of course , be applied directly to the skin or can be incorporated into a transdermal patch that comprises a backing layer and other materials as needed , such as a porous membrane , an adhesive . when incorporated into a patch , it is desired that the materials be non - rate limiting to aripiprazole permeation , so that the device permits release of aripiprazole from the formulation to achieve an aripiprazole concentration in the blood sufficient for therapy for a period of at least about 1 day , 3 days , 4 , days , 5 days , 6 days or 7 days . in another embodiment , the materials of the transdermal patch , such as a microporous membrane positioned between the skin and the reservoir in which the aripiprazole formulation is retained , influences or controls aripiprazole permeation from the device . in this embodiment , the device provides an aripiprazole concentration in the blood sufficient for therapy for a period of at least about 1 day , 3 days , 4 , days , 5 days , 6 days or 7 days . the following examples are illustrative in nature and are in no way intended to be limiting . formulations prepared as described in example 1 were tested in vitro for skin flux . the results are shown in fig1 - 4 . while a number of exemplary aspects and embodiments have been discussed above , those of skill in the art will recognize certain modifications , permutations , additions and sub - combinations thereof . it is therefore intended that the following appended claims and claims hereafter introduced are interpreted to include all such modifications , permutations , additions and sub - combinations as are within their true spirit and scope .

US-201615176080-A

disclosed is a dual access - point system for holding an item . the dual access - point system allows a traveler to easily store and retrieve one or more items through two sides of a backpack . additionally , the backpack can be quickly converted into a suitcase ; for example , by hiding the straps in the pockets on the backpack . the dual access - point system may be used as a standalone system . alternatively , the dual access - point system may be integrated with a backpack . the disclosed dual access - point system saves time and money for its users , making their lives easier while making them look good and professional .

as a preliminary matter , it will readily be understood by one having ordinary skill in the relevant art that the present disclosure has broad utility and application . as should be understood , any embodiment may incorporate only one or a plurality of the above - disclosed aspects of the disclosure and may further incorporate only one or a plurality of the above - disclosed features . furthermore , any embodiment discussed and identified as being “ preferred ” is considered to be part of a best mode contemplated for carrying out the embodiments of the present disclosure . other embodiments also may be discussed for additional illustrative purposes in providing a full and enabling disclosure . moreover , many embodiments , such as adaptations , variations , modifications , and equivalent arrangements , will be implicitly disclosed by the embodiments described herein and fall within the scope of the present disclosure . accordingly , while embodiments are described herein in detail in relation to one or more embodiments , it is to be understood that this disclosure is illustrative and exemplary of the present disclosure , and are made merely for the purposes of providing a full and enabling disclosure . the detailed disclosure herein of one or more embodiments is not intended , nor is to be construed , to limit the scope of patent protection afforded in any claim of a patent issuing here from , which scope is to be defined by the claims and the equivalents thereof . it is not intended that the scope of patent protection be defined by reading into any claim a limitation found herein that does not explicitly appear in the claim itself . thus , for example , any sequence ( s ) and / or temporal order of steps of various processes or methods that are described herein are illustrative and not restrictive . accordingly , it should be understood that , although steps of various processes or methods may be shown and described as being in a sequence or temporal order , the steps of any such processes or methods are not limited to being carried out in any particular sequence or order , absent an indication otherwise . indeed , the steps in such processes or methods generally may be carried out in various different sequences and orders while still falling within the scope of the present invention . accordingly , it is intended that the scope of patent protection is to be defined by the issued claim ( s ) rather than the description set forth herein . additionally , it is important to note that each term used herein refers to that which an ordinary artisan would understand such term to mean based on the contextual use of such term herein . to the extent that the meaning of a term used herein — as understood by the ordinary artisan based on the contextual use of such term — differs in any way from any particular dictionary definition of such term , it is intended that the meaning of the term as understood by the ordinary artisan should prevail . regarding applicability of 35 u . s . c . § 112 , ¶ 6 , no claim element is intended to be read in accordance with this statutory provision unless the explicit phrase “ means for ” or “ step for ” is actually used in such claim element , whereupon this statutory provision is intended to apply in the interpretation of such claim element . furthermore , it is important to note that , as used herein , “ a ” and “ an ” each generally denotes “ at least one ,” but does not exclude a plurality unless the contextual use dictates otherwise . when used herein to join a list of items , “ or ” denotes “ at least one of the items ,” but does not exclude a plurality of items of the list . finally , when used herein to join a list of items , “ and ” denotes “ all of the items of the list .” the following detailed description refers to the accompanying drawings . wherever possible , the same reference numbers are used in the drawings and the following description to refer to the same or similar elements . while many embodiments of the disclosure may be described , modifications , adaptations , and other implementations are possible . for example , substitutions , additions , or modifications may be made to the elements illustrated in the drawings , and the methods described herein may be modified by substituting , reordering , or adding stages to the disclosed methods . accordingly , the following detailed description does not limit the disclosure . instead , the proper scope of the disclosure is defined by the appended claims . the present disclosure contains headers . it should be understood that these headers are used as references and are not to be construed as limiting upon the subjected matter disclosed under the header . the present disclosure includes many aspects and features . moreover , while many aspects and features relate to , and are described in , the context of a dual access - point system for holding an item , embodiments of the present disclosure are not limited to use only in this context . according to some embodiments , the present disclosure relates to a dual access - point system for holding an item securely inside a bag . fig1 illustrates a front view of a dual access - point system 100 for holding an item securely inside a bag . as shown , the dual access - point system 100 includes a first sleeve 102 , a second sleeve 104 , a top fastener 106 , a side fastener 108 , a top ladder formation 110 , a side ladder formation 112 , a first sleeve connector 114 and a second sleeve connector 116 . the dual access - point system 100 may also include a back cover 118 . the back cover 118 may be one of the interior walls of a host bag 300 ( shown in fig3 - 4 ), when the dual access - point system 100 is integrated within the bag 300 . in some embodiments , a detachable mechanism may be used to connect back cover 118 with the host bag 300 . the first sleeve 102 may be attached to the back cover 118 on two sides meeting on a corner 120 . for example , the first sleeve 102 may be sewn to the back cover 118 on two sides meeting on the corner 120 . alternatively , the first sleeve 102 may be attached to the back cover 118 using an adhesive on two sides meeting on the corner 120 . yet further , the first sleeve connector 114 attaches an opposite corner 122 of the first sleeve 102 to the corner 124 of the back cover 118 . for example , the first sleeve connector 114 may be a strap with two ends , such that each end of the first sleeve connector 114 may be sewn to the opposite corner 122 of the first sleeve 102 and the corner 124 of the back cover 118 respectively . similarly , the second sleeve 104 may be attached to the first sleeve 102 on two sides meeting on a corner 126 . for example , the second sleeve 104 may be sewn to the first sleeve 102 on two sides meeting on the corner 126 . alternatively , the second sleeve 104 may be attached to the first sleeve 102 using an adhesive on two sides meeting on the corner 126 . further , the second sleeve connector 116 attaches an opposite corner 128 of the second sleeve 104 to the corner 124 of the back cover 118 . for example , the second sleeve connector 116 may be a strap with two ends , such that each end of the second sleeve connector 116 may be sewn to the opposite corner 128 of the second sleeve 104 and the corner 124 of the back cover 118 respectively . one or more items may be securely placed in the first sleeve 102 and the second sleeve 104 . the one or more items may include an electronic item such as a laptop , a tablet , a smartphone and a net book . further , the one or more items may include a notebook and book . in an embodiment , a bigger item may be placed in the first sleeve 102 and a smaller item may be placed in the second sleeve 104 . further , the top fastener 106 may be a strap , such that one end of the top fastener 106 may be attached to a top edge 130 of the back cover 118 . for example , the one end of the top fastener 106 may be sewn to the top edge 130 . the other end of the top fastener 106 may include attachment means to temporarily attach the other end of the top fastener 106 to the second sleeve 104 . the top fastener 106 may be a strap made of elastic material . further , the top fastener 106 may be fed through the top ladder formation 110 . a traveler may use the top ladder formation 110 to tighten the top fastener 106 based on the size of an item placed in one or more of the first sleeve 102 and the second sleeve 104 . further , the side fastener 108 may be a strap , such that one end of the side fastener 108 may be attached to a side edge 132 of the back cover 118 . for example , the one end of the side fastener 108 may be sewn to the side edge 132 . the other end of the side fastener 108 may include attachment means to temporarily attach the other end of the side fastener 108 to the second sleeve 104 . the side fastener 108 may be a strap made of elastic material . further , the side fastener 108 may be fed through the side ladder formation 112 . a traveler may use the side ladder formation 112 to tighten the side fastener 108 based on the size of an item placed in one or more of the first sleeve 102 and the second sleeve 104 . the attachment means to temporarily attach the top fastener 106 or the side fastener 108 to the second sleeve 104 may include one or more of a button , a zipper , a magnetic button , a securing pin , a snap , a clasp and velcro . a traveler may place an item into either the first sleeve 102 or the second sleeve 104 from the top edge or the side edge of the dual access - point system 100 . in one possible embodiment , a traveler may temporarily disengage the top fastener 106 from the second sleeve 104 . then , the traveler may place an item in one of the first sleeve 102 and the second sleeve 104 . once the item is placed in one of the first sleeve 102 and the second sleeve 104 , the traveler may thread the top fastener 106 through the top ladder formation 110 based on the size of the largest item in the first sleeve 102 and the second sleeve 104 . thereafter , the traveler may temporarily engage the top fastener 106 to the second sleeve 104 to securely hold the item in place inside the dual access - point system 100 . in another exemplary embodiment , a traveler may temporarily disengage the side fastener 108 from the second sleeve 104 . then , the traveler may place an item in one of the first sleeve 102 and the second sleeve 104 . once the item is placed in one of the first sleeve 102 and the second sleeve 104 , the traveler may thread the side fastener 108 through the side ladder formation 112 based on the size of the largest item in the first sleeve 102 and the second sleeve 104 . thereafter , the traveler may temporarily engage the side fastener 108 to the second sleeve 104 to securely hold the item in place inside the dual access - point system 100 . top fastener 106 and side fastener 108 may be disengaged via a detachable means ( e . g ., velcro , snaps , magnetics , buttons , clasps ) attached to , for example , back cover 118 and located , for example , behind the second sleeve 102 . fig1 illustrates the ladder formations 110 - 112 threaded for a smaller 13 - inch laptop . fig2 illustrates the ladder formations 110 - 112 threaded for a larger 15 - inch laptop in an embodiment , one or both the top fastener 106 and the side fastener 108 may be attached to the back cover 118 from underneath the first sleeve 102 rather than the edge of the back cover 118 . in various embodiments , the dual access - point system 100 may be used as a standalone unit . alternatively , the dual access - point system 100 may be a part of a bag 300 . in various embodiments , one or more components of the dual access - point system 100 may be attached by methods other than sewing , such as , adhesion , and nailing . in various embodiments , the bag 300 may include a zipper that goes around three sides of the bag 300 . therefore , the bag 300 may open like a suitcase as shown in fig3 a - 3b . in open position , the bag 300 may include two sides 302 - 304 . as shown , the dual access - point system 100 may be integrated with the side 302 . although , fig3 a shows dual access - point system 100 within an internal compartment of bag 300 . it should be understood that such placement is only one possible placement of dual access - point system 100 . other locations within the bag , both external and internal , are contemplated to be within the scope of dual access - point system 100 &# 39 ; s integration with bag 300 . in various embodiments , the bag 300 may include two sets of positioning straps including one or more waist straps and shoulder straps . in a further embodiment , the positioning straps may be quickly hidden in pockets arranged in the bag 300 . for example , the positioning straps may be hidden in less than 10 seconds . the positioning straps may also include pullers to tighten the waist straps and shoulder straps , while carrying the bag 300 . the pullers may be suitable for both the right - handed and the left - handed people . in various embodiments , the bag 300 is a backpack that packs like a suitcase . fig4 a - 4b illustrate the bag 300 in closed position . the bag 300 may be quickly converted from a backpack configuration to a suitcase configuration . for example , the positioning straps may be hidden in the pockets . further , the bag 300 may include a side handle that may be used to carry the bag 300 sideways in the suitcase configuration . in various embodiments , the bag 300 may include a seam - sealed rain cover that is easy to pull out ( of a pocket in the bag 300 ), then pull on the bag 300 , and then pack into the pocket and may be removed permanently , if unnecessary . for example , underside of the bag 300 may include a tiny zip on the pocket to pack the rain cover inside . in various embodiments , an outer cover ( for example , a back panel ) of the bag 300 includes high - quality custom - molded foam , which makes it easy for the traveler to carry the bag 300 on the back . in an exemplary embodiment , the interior of the bag 300 may include one or more of a soft - lined phone pocket , document sleeve , a passport pocket , penholders , three card sleeves , a key clip inside an internal zip pocket and a drink holder . the phone pocket may be soft - lined . in various embodiments , the bag 300 may save time and money , may make travelers &# 39 ; life easier and may help them look good and professional . further , the bag 300 may keep items safe and easily accessible via the top and the side . the first sleeve 102 and the second sleeve 104 may be made using neoprene . therefore , an item may be suspended in a neoprene sleeve , such that if the bag 300 falls down the items do not hit the ground . the design of the bag makes it is easy to pack , carry and use it . in various embodiments , the bag 300 may fit inside almost all current major airline carry - on dimensions . for example , the net weight of the bag may be 1 . 415 kg ; the size of the bag may be 55 cm ( length ), 35 cm ( width ) and 20 cm ( height ) when fully packed . the depth of main compartment may be 20 cm . the weight of a carry - on rain cover may be 0 . 07 kg . in various embodiments , the bag 300 may have an ergonomic design . for example , the bag may include a 4 - point load balancing system and an adjustable chest strap . fig5 a illustrates yet another bag in closed position according to some embodiments . fig5 b illustrates yet another embodiment of the dual - access point system installed in a bag according to some embodiments . fig6 illustrates a bag with hidden straps in closed position according to some embodiments . fig7 illustrates the bag with adjustable straps in closed position according to some embodiments . fig8 illustrates the bag with a chest strap in closed position according to some embodiments .\ embodiments of the present disclosure , for example , are described above with reference to block diagrams and / or operational illustrations of methods and apparatus , according to embodiments of the disclosure . the functions / acts noted in the blocks may occur out of the order illustrated or in various combinations . for example , two blocks shown in succession may in fact be executed substantially concurrently or the blocks may sometimes be executed in the reverse order , depending upon the functionality / acts involved .

US-201615337273-A

a pad for a forehead support includes an outer wall having a first side configured to engage a user &# 39 ; s forehead and a second side having engaged surfaces configured to rest against engaging surfaces of the forehead support ; at least one retaining wall provided between the first side and the second side ; and at least one retained portion configured to be retained by a retainer formed on the forehead support , wherein a space is defined between the outer wall and the engaged surfaces . the space has a substantially constant cross sectional profile , and the outer wall , the at least one retaining wall , and the engaged surfaces are formed of a deformable elastomeric material . deformation of the pad occurs by deflection of at least the outer wall and the at least one retaining wall .

fig1 shows a general perspective view of the forehead support 10 of the present invention . the forehead rest or support 10 is attached to an extending airflow tube 12 from the mask 14 . the mask 14 and forehead support 10 are shown with headgear 16 which secures the mask 14 to the head of a patient . the headgear 16 may take a variety of forms , with one example being shown as 16 . as can be seen in fig1 , preferably the headgear 16 loops through the forehead support 10 at 18 and 20 . this pulls the forehead support 10 against the forehead , thus creating a snugly fitted mask 14 and also provides a stabilizing member for the mask 14 . the mask 14 , shown in fig1 is merely one example of a mask which can be used with a forehead support , but any respiratory mask could be used . a fill face mask which may cover the entire face or just both the nose and mouth could be used , for example . additionally , the airflow tube 12 could be extending from the bottom of the mask 14 , thus the tube 12 supporting the forehead support 10 would terminate above forehead support 10 . if the airflow tube 12 extended in a downward or other direction from the mask 14 , then preferably a post would extend up from the mask 14 ( this post position is referenced as 22 ). this post 22 would terminate slightly above where forehead support 10 is shown secured to tube 12 . thus the forehead support 10 would be secured to the post in this alternative embodiment . fig2 discloses the preferred construction of the forehead support 10 of the present invention . the forehead support 10 has pads 24 and 26 . these pads 24 and 26 are the actual contact points of the forehead support 10 to the forehead . pads 24 and 26 are preferably made of a deformable elastomeric material which retains its original shape upon release of pressure and provides the wearer with increased comfort and stability . as can be seen in the preferred embodiment , the forehead pads 24 and 26 have an annular interior construction with two retaining walls 28 and 30 . the retaining walls 28 and 30 provide structural - integrity to the forehead contact support pads yet allow the pads to be deformed . the deformation preferably occurs by deflection of the pad walls . the pads also may be solid pads . the support pads 24 and 26 are mounted to the bridge 32 . the bridge 32 provides basically three purposes to the forehead 10 support 10 . first off , it acts as a securing means for forehead pads or cushions 24 and 26 . second of all , it has annular spaces 18 and 20 which receive the optional headgear 16 shown in fig1 . finally , it receives arms 34 and 36 , which may be adjusted , as described below . the bridge 32 and arms 34 and 36 operate in a cantilever fashion and are preferably made of a polymeric material , which may be easily molded , preferably injection molded . arms 34 and 36 are secured to bridge 32 by an adjustable locking mechanism which is better illustrated in the figures below . additionally , arms 34 and 36 join together to create an annular space 38 which may receive airflow tube 12 which is preferably connected to a flow generator to generate breathable air or some type of therapeutic gas . arms 34 and 36 preferably create an operational hinge . the tube 12 may be an axis of this hinge . the hinge could also be a flexible membrane and not a rotational or axial hinge . alternatively , the tube may extend through annular space 38 and terminate as described above ( in the “ post ” embodiment ) if the air flow tube is connected to another port on the mask . fig3 is an exploded view of fig2 and shows the forehead support 10 in greater detail . fig3 discloses how bridge 32 is configured such that forehead pads 24 and 26 may be secured thereto . in particular , tongues 40 , 42 , 44 and 46 all engage forehead pads 24 and 26 by entering the interior space of the pads . this is shown in fig2 wherein tongues 42 and 46 are shown securing pads 24 and 26 respectively by entering the annular space of the pads 24 and 26 . additionally , there may be engaging surfaces such as 48 , 50 , 52 and 54 , as shown in fig3 , which engage an inner side wall of forehead pads 24 and 26 . the means by which the forehead pads are secured to the bridge 32 can be done in many manners , and one skilled in the art can come up with numerous methods of achieving this securement . two sided tape may be used , protruding pegs and apertures on the forehead pad may be used or many other methods . what is desirable is that the forehead pad ( s ) may be replaced after extended use or , in a clinical setting , with each new patient . the method of securement of the pad ( s ) to the support is not a limiting feature of the present invention . the type of forehead pad may also vary , it may include a solid foam 15 sponge , a stuffed pad , a dual durometer foam which may be a single pad or multiple pads attached together , or many other known pads which would impart comfort when placed directly on the forehead . finally , a single pad which extends all the way across bridge 32 may be used or more than two pads may be used . bridge engaging pins 56 , 58 , 60 and 62 are shown in fig3 . as will be 20 more apparent in the figures below , these engaging pins provide for the adjustability of the forehead support 10 of the present invention . there are pin receiving means located on the bridge 32 which receive pins 56 , 58 , 60 and 62 . the pins 56 , 58 , 60 and 62 are merely one example of how the arms 34 and 36 may be secured to bridge 32 . there are other designs which would work just as well as the pin designs . such designs are known to those skilled in the art . additionally , there is a space or recess at arms 34 and 36 shown clearly on arm 34 as 64 . the purpose of this space 64 is so that the user may compress arm 34 and thus press 56 and 58 together by pressing on surfaces 66 and 68 . the purpose of the compression is such that the distance between prongs 56 and 58 is decreased and thereby they may be inserted and locked into bridge 32 . the structure and method of this insertion will be described in further detail below . fig4 is a side view of the mask 14 and forehead support 10 of the present invention . the mask is shown as 14 with a dotted line showing the nose of a wearer 70 and the dotted line showing the forehead 72 of the wearer . pad 26 is shown compressed by the forehead of the individual wearing the mask . fig5 is a top view of the forehead support 10 of the present invention taken along lines s of fig4 . also , the mask 14 is not shown in fig5 . this figure illustrates the forehead support 10 in a position wherein the forehead support is the closest to the tube 12 ( shown as merely a space in fig5 - 8 ). the bridge 32 is shown essentially in contact with tube 12 . the pins 56 , 58 , 60 and 62 are shown in their furthest position from the center of the bridge 32 . this position may be utilized by someone with a large , protruding or bulbous forehead , or a high nasal bridge , or someone who prefers the airflow tube to be snug against their forehead . fig6 shows the same forehead support in the next position , wherein the bridge 32 is moved away from tube 12 such that there is a gap 74 between bridge 32 and tube 12 . as is visible from the figure , the forehead support 10 is now moved further away from tube 12 , and is positioned differently than in fig5 . this may be configured to fit someone with a less protruding forehead , or someone who wants the flexible tube further from their head than is possible in fig5 . fig7 and s show the third and fourth position for the forehead support of the present invention . although the present embodiment shows a four - positioned forehead support , the number of slots , shown as 76 , 78 , 80 , 82 . 84 86 , 88 and 90 may be varied . there may be more or fewer slots , or there may just be one single slot wherein pins 56 and 58 slides transversely across bridge 32 and has locking recesses located along the slide . additionally , the adjustments do not have to be uniform . in other words , the right side may be adjusted to slot 88 where the left side may be adjusted to slot 84 for some particular patient . there may also be more slots or adjustments on one side of the bridge as compared to the other side of the bridge . finally , the arms may be coupled such that movement of just one arm moves the other arm in a likewise manner . fig9 shows an isolated view of bridge 32 . the slots 76 , 78 , 82 , 84 , 86 , 15 88 and 90 are visible from this view . the slots are configured such that prongs 56 , 58 , 60 and 62 may be inserted therein . there is a mirror set of slots on the upper portion of bridge 32 which are not visible in fig9 . again , there can be additional slots , fewer slots , or different methods of locking the arms 34 and 36 to various positions along the bridge 32 . what is important to the present invention is that the bridge 32 with the accompanying pads 24 and 26 may be positioned to a variety of distances between the tube 12 and the pads 24 and 26 . additionally , the pad may be one continuous pad , three pads , five pads , four pads , etc . there also may a double bridge used , wherein there could be a total of two or more pads with two bridges . fig1 is a perspective view of the preferred forehead pad of the present invention . as indicated above , there could be many shapes or variations of a forehead pad and type of forehead pad or the shape of forehead pad is not limited in the present invention . it is to be understood that while the invention has been described above in conjunction with preferred specific embodiments , the description and examples are intended to illustrate and not limit the scope of the invention , which is defined by the scope of the appended claims . while the invention has been described in connection with what is presently considered to be the most practical and preferred embodiment , it is to be understood that the invention is not to be limited to the disclosed embodiment , but on the contrary , is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims .

US-201514943360-A

a biopsy device for obtaining tissue samples from human or animal tissue is optimized for the sampling of tissues that are resilient and difficult to cut using conventional approaches . the biopsy device includes a cutting cannula , an inner member including a toothed rack having a sharpened distal tip configured to be introduced into the body and a sample notch for receiving the at least one severed tissue sample , the inner member receivable in the cutting cannula , and a cutting mechanism configured for causing the cutting cannula to be longitudinally displaced in a distal direction from a first position at the proximal end of the sample notch exposing the sample notch , to a second position at the distal end of the sample notch , so as to sever said tissue sample from remaining body tissue at the harvesting site . the toothed rack may be a rotatable and may be rigid .

the drawings illustrate exemplary biopsy devices which are provided with a needle portion comprising a cutting cannula 1 , 1 ′ and a sample notch 3 with a sharpened distal tip 4 for piercing tissue . the cutting cannula 1 is provided with a slanted cutting profiled as illustrated e . g . in fig2 and 6 , whereas the cutting cannula 1 ′ is provided with a straight cutting profile 24 as illustrated e . g . in fig5 and 9 . the sample notch 3 is part of a rigid toothed rack 2 , and is movable between a first advanced and a second retracted position when actuated by a suitable source of mechanical motion . the source of mechanical motion may be a motor that may be powered by a battery and operatively connected to the rigid toothed rack 2 by means of one or more gear wheels 11 . the operative connection between the rigid toothed rack 2 and the gear wheels 11 is configured to permit full 360 degree rotation of the toothed rack 2 , including the sample notch 3 , about its longitudinal axis . such rotation may for instance be permitted by providing a proximal rotation zone 12 with a series of cut - outs that run around the entire circumference of the toothed rack . a rotation control gear 9 , that is in operative connection with the rigid toothed rack , is engaged by a rotation driver gear 10 to support the rotation of the rigid toothed rack 2 about its longitudinal axis . another set of gearwheels may be in operative engagement with the cutting cannula 1 to provide full 360 - degree rotation of the cutting cannula 1 either independently or in step with the rotation of the rigid toothed rack 2 . the cutting cannula 1 , 1 ′ may be retracted when actuated by a suitable source of mechanical motion . in the first embodiment , the source of mechanical motion may be a second motor that is powered by a battery and operatively connected to the cutting cannula 1 , 1 ′ by means of a series of gears driving an actuator rod . retraction of the cutting cannula 1 , 1 ′ exposes the sample notch 3 , 3 ′, and permits tissue to prolapse into the lateral opening of the sample notch 3 , 3 ′. during or after retraction of the cutting cannula 1 , 1 ′, a vacuum may be switched on to support the prolapsing of tissue into the sample notch 3 , 3 ′. vacuum is communicated from a vacuum pump and a hose through a vacuum gasket 7 that is in operative connection with the cutting cannula 1 , 1 ′ and into the inner lumen of cutting cannula 1 , 1 ′. the rigid toothed rack 2 is provided with at least one vacuum cut - out 16 that run along the length of the rigid toothed rack 2 , and end in sample notch 3 , and the vacuum from the vacuum pump is communicated through these vacuum cut - outs 16 to the sample notch 3 as soon as the pump is turned on . a vacuum accumulator / reservoir may be configured to build and store a vacuum , is also in fluid communication with the sample notch 3 , 3 ′, and may provide a transient boost to the vacuum strength immediately prior to firing of the cutting cannula 1 , 1 ′ to increase sample size . retraction of the cutting cannula 1 , 1 ′ cocks a spring - loaded firing mechanism that is capable of powering the cutting cannula forward ( i . e . in a distal direction ) at high speed . as the cutting cannula 1 , 1 ′ moves forward at high speed , the sharpened distal end of the cannula 1 , 1 ′ makes contact with the tissue that has prolapsed into the sample notch 3 , 3 ′ and severs it from the surrounding connecting tissue . as illustrated in fig5 the cutting cannula 1 ′ may be permitted to continue its travel by a damper spring 13 that is placed in a damper spring housing 14 and is in operative connection with a rear flange 15 of the cutting cannula 1 ′. the inertia of the cutting cannula 1 ′ will allow it to proceed 1 - 2 mm beyond the permissible traveling distance of the spring - loaded firing mechanism , and will ensure that the sharpened distal end of the cutting cannula 1 ′ has achieved a suitable overlap with the distal section of the sample notch 3 ′. following the overthrow , the damper spring 13 ensures that the cutting cannula 1 ′ is returned to its neutral position in preparation for the next tissue sample . as illustrated in fig6 the user of the biopsy device has the option of rotating the toothed rack 2 with the sample notch 3 relative to the stationary cutting cannula 1 to sever any connective tissue that has not been completely severed by the cutting cannula 1 . connective tissue that has not been completely severed may restrict retraction of the tissue sample and cause pain to the patient . the rotation causes connective tissue that has not been completely severed to saw against the sharpened distal end of cutting cannula 1 for as long as needed to complete the severing . rotation may be step - wise and may interchange between a clockwise and a counter - clockwise direction and take place over a rotation angle of e . g . +/− 20 degrees relative to a neutral position . furthermore the cutting cannula 1 may be retracted and advanced in steps of 1 - 2 mm during rotation to further support the severing of tissue . when unrestricted movement of the sample notch 3 has been restored , the toothed rack 2 may continue its motion from the first advanced to the second retracted position to transport the tissue sample in sample notch 3 out of the body of the patient . the tissue sample may be collected in a tissue collection tank 8 comprising a vacuum spout 21 through which a vacuum from a vacuum pump or vacuum accumulator may be communicated into a collection tank chamber 22 . from the collection tank chamber , the vacuum may be communicated through a tissue collection spout 23 for enhanced collection of the tissue sample . as illustrated in fig8 b the collection spout 23 forms a collection tube 23 ′ inside the collection tank 22 extending with a certain length from the bottom of the tank 22 . following collection of the tissue sample from the sample notch 3 , said sample notch 3 may be returned to the sampling site for collection of the next tissue sample . as illustrated in fig7 and 9 the cutting cannula may have an inner tube 17 and an outer tube 18 forming between them a longitudinal air channel 19 that is at a proximal end in fluid communication with a first vacuum pump through a two - way valve that may be switched between a vacuum position and a position that permits entry of atmospheric air into the air channel . at the distal end the air channel 19 is in fluid communication with the lateral opening of the sample notch 3 through at least one vent hole 20 that is formed in the inner tube 17 . as illustrated in fig9 a plurality of the vent holes 20 may be distributed circumferentially around the inside of the inner tube 17 . as illustrated in fig9 a protrusion 25 formed as a collar may be provided adjacent to the sharpened distal end 4 ′. the interface 26 between the protrusion 25 and the cutting cannula 1 ′ forms a cutting board to ensure that connective tissue is cut properly during severing . a frequently encountered complication in the harvesting of tissue samples is the presence of fibrous or connective tissue . such tissue is characterized by being highly resilient and difficult to cut . the typical manifestation of malfunctions related to connective tissue is that the biopsy device gets stuck in the body of the patient and has to be removed by force or surgical intervention . this may be stressful to both physician and patient and may additionally be very painful for the patient . inadequately severed connective tissue is a known problem for all kinds of biopsy devices and the problem is highly undesirable . the use of a linear cutter requires a very precise interplay between the sharpened distal end of the cutting cannula and the distal section of the sample notch if appropriate severing of connective tissue is to occur . for this reason it is important that the position of the sample notch is very precisely controlled relative to the position of the cutting cannula . sims devices featuring a linear , spring - loaded cutting cannula typically employ a sample notch that is attached to a flexible bendable elongate member ( e . g . a non - rigid toothed rack ), and this toothed rack may not always produce the desired control of position of the sample notch due to the flexibility , design and material chosen . some prior art devices employ toothed racks made of thermoplastic elastomers with significant longitudinal elasticity . by having the sample notch in a rigid toothed rack , which is longitudinally inelastic , a better control of position is provided . thereby an appropriate overlap of the sharpened end of the cutting cannula with the distal section of the sample notch can be provided . failure to establish a precise position of the sample notch may result in the incomplete closing of the sample notch opening . a rigid toothed rack provides the necessary lateral inelasticity and stability to ensure that the sharpened distal end of the cutting cannula completely closes the opening of the sample notch . employing a rigid toothed rack therefore provides an improved control of the longitudinal and lateral position of the distal sharpened end of the cutting cannula relative to the distal section of a sample notch . in one embodiment the proximal end of the rigid toothed rack is configured to operatively connect with a retraction gear wheel , and is furthermore configured to permit 360 degree rotation of the toothed rack about its longitudinal axis without requiring that the operative connection with the retraction gearwheel is interrupted . this may be provided by means of a rotation mechanism . in a further embodiment of the invention the rigid toothed rack comprises a rotation zone in the proximal end with circumferential teeth , e . g . in the form of a series of cut - outs that run around the entire circumference of the toothed rack , thereby permitting rotation of the rigid toothed rack . the rigid toothed rack may be rotatable within the cutting cannula and / or the rigid toothed rack and the cutting cannula are rotatable simultaneously relative to the biopsy device . the permitted rotation may be 360 degrees . the biopsy device may further comprise a rotation control gear attached to the rigid toothed rack . a rotation driver gear may be provided and configured to engage with the rotation control gear for rotation of the rigid toothed rack . the cutting cannula may also be configured to rotate , such as 360 degrees , about its longitudinal axis . in a further embodiment of the invention the rigid toothed rack is configured such that longitudinal displacement of the rigid toothed rack to the second retracted position can only be provided in a predefined rotational orientation of the rigid toothed rack . thus , the rigid toothed rack may be rotatable within the cutting cannula only in the first advanced position , and / or the rigid toothed rack and the cutting cannula are rotatable simultaneously relative to the biopsy device only in the first advanced position . whether the rigid toothed rack and / or the cutting cannula is rotated simultaneously or independently may at least partly be controlled by means of an interlock mechanism configured for fixing the rigid toothed rack and the cutting cannula relative to each other . e . g . the interlock mechanism may have two states , one state that allows free movement of the cutting cannula and the toothed rack relative to each other and one state that fixes the two to each other . this may help to ensure that the sample notch is always oriented correctly with respect to a tissue collection tank when a tissue sample is transferred to the tank . this may be provided if the toothing of the toothed rack is only located at one side of the rigid toothed rack . if there is a proximal rotation zone of the toothed rack as mentioned above , the toothing that extends in the distal direction beyond the rotation zone is only located at one side of said rigid toothed rack . a control system may help to ensure that the rigid toothed rack has the correct rotational orientation before retracting to the retracted position . rotation of the rigid toothed rack relative to the cutting cannula ( or vice versa ) may be advantageous during severing of a tissue sample and may thereby be an improvement of the cutting mechanism . rotation of the toothed rack , and thereby the sample notch , relative to the cutting cannula with the sharpened distal end , may result in a “ sawing ” motion that may complete the severing of incompletely severed connective tissue . counter - rotation of the cutting cannula and the rigid toothed rack may further be provided during cutting which allows for enhanced cutting of e . g . connective tissue . thus , in one embodiment of the invention the rigid toothed rack is rotatable within the cutting cannula during severing of the at least one tissue sample . the cutting mechanism may be configured to rotate the rigid toothed rack within the cutting cannula during severing of the at least one tissue sample . the rotation may be either stepwise or continuous . the rigid toothed rack and / or the cutting cannula may be rotatable in clockwise and / or in counter - clockwise directions . during severing the rotation angle of the rigid toothed rack relative to the cutting cannula may oscillate between − 5 and + 5 degrees during severing , more preferably between − 10 and + 10 degrees , more preferably between − 15 and + 15 degrees , more preferably between − 20 and + 20 degrees , more preferably between − 25 and + 25 degrees , more preferably between − 30 and + 30 degrees , i . e . like a sawing motion oscillating between clock - wise and counter clock - wise directions . when taking a biopsy it is often necessary to rotate the entire biopsy device inside the patient in order to position the sample notch against the suspect tissue mass . this may lead to awkward handling situations during harvesting of tissue samples . a further advantage of rotational capability is therefore that the rigid toothed rack and the cutting cannula can be rotated simultaneously , preferably controlled by the user , about their longitudinal axis relative to the biopsy device in order to orientate the sample notch towards the suspect tissue mass , e . g . prior to activation of the firing mechanism . thus , the biopsy device can be held in a steady position while the rigid toothed rack and the cutting cannula are rotated into the correct angular orientation relative to the suspect tissue mass . another way to enhance the correct severing of tissue is if the cutting mechanism is configured to interchangeably retract and advance the cutting cannula in small longitudinal steps during severing of a tissue sample . the size of the steps may between 0 and 3 mm , or between 0 and 1 mm , or between 1 and 2 mm or between 2 and 3 mm . this corresponds to a sawing motion in the longitudinal direction . the cutting mechanism may also be improved if it is configured to provide a predefined overlap and / or overshoot during severing of a tissue sample such that the distal end of the cutting cannula passes beyond the distal end of the sample notch temporarily before returning to said second position . the length of said overshoot may be between 0 . 5 and 5 mm , or between 0 . 5 and 1 mm , or between 1 and 2 mm , or between 2 and 3 mm , or between 3 and 4 mm , or between 4 and 5 mm . this overshoot of the cutting cannula may help to apply further stress to incompletely severed tissue . the overshoot may be provided by means of an elastic element provided in connection with the cutting cannula . one solution could be in the form of at least one damper spring mounted in a damper spring housing . the damping may also be provided by using a damping element formed in rubber . the elastic element may be configured to work along with a firing mechanism of the cutting cannula effected during severing of a tissue sample . if the firing mechanism is stopped by the elastic element the inertia of the cutting cannula and the elasticity of the elastic element will allow the sharpened end of the cutting cannula to proceed a certain length beyond the traveling distance of the spring - loaded firing mechanism , and thereby ensure that the sharpened distal end of the cutting cannula achieves a suitable overlap with the distal section of the sample notch . subsequent to this overshoot , the elastic element ensures that the cutting cannula can be returned to its neutral position in preparation for the next tissue sample . as an alternative , or supplement to , an overlap or overshoot between the distal sharpened end of the cutting cannula and the distal section of the sample notch , the inner member may further comprise a circumferential protrusion and / or collar located between the sharpened distal end and the sample notch , said circumferential protrusion formed to match the distal end of the cutting cannula . the circumferential protrusion may thus be configured to form a cutting surface for the cutting cannula during severing of a tissue sample . the cutting board ( protrusion ) may be disposed about the outer periphery of the sample notch and serve the purpose of ensuring that the tissue sample is completely and cleanly severed by the cutting cannula . the cutting mechanism may be configured such that the cutting cannula and the circumferential protrusion encounter during severing of a tissue sample . the protrusion is then preferentially formed in a material that is softer than the cutting cannula in order not to blunt the cutting cannula and preserve the sharpness of the cutting cannula . the cutting mechanism may alternatively be configured such that the cutting cannula and the circumferential protrusion does not encounter during severing of a tissue sample . thus , the circumferential protrusion may be brought into close proximity without encountering during severing of a tissue sample . i . e . direct physical contact between the protrusion and the sharpened distal end of the cutting cannula is avoided but established at the material surface in close proximity to said sharpened distal end . with such a protrusion the transport of the tissue sample must be provided through the inside of the inner member , typically by means of vacuum , if sims functionality is desired . in a further embodiment of the invention the cutting cannula comprises at least one longitudinal vacuum channel ( aka longitudinal air channel or passage ) formed inside the external shell / wall of the cutting cannula . the longitudinal vacuum channel may be circumferential . this air channel may be provided by forming the cutting cannula as an inner and an outer tube forming between them an air passage that runs longitudinally along the length of the inner and outer tube . fluid communication from this air channel and into the inner lumen of the cutting cannula may be provided by one or more lateral vent holes extending from the inside of the cutting cannula to the longitudinal air channel . a plurality of said lateral vent holes may be distributed circumferentially in the cutting cannula . the longitudinal vacuum channel may then , in its distal end , be in fluid communication with the sample notch when the rigid toothed rack is in its first advanced position . thereby the cutting cannula may be configured such that a vacuum or air flow can be provided and / or established inside the cutting cannula , e . g . an airflow from the air channel and into the inner lumen of the cutting cannula . fluid communication from this air channel and to the external of the cutting cannula may be provided by at least one vacuum spout and may be controlled by at least one vacuum valve . a vacuum pump may then be connected to the air channel via this vacuum valve , in which case a vacuum may be communicated through the air channel and the air vent holes and into the inner lumen of the cutting cannula . thus , air may be sucked out of the inner lumen of the cutting cannula . such evacuation may be useful for reducing or eliminating problems with air that has been accidentally introduced in the biopsy cavity and disturbs image quality in an ultrasound - guided biopsy procedure . unwanted air may be introduced in the biopsy cavity when the rigid toothed rack is being advanced from the second retracted position and to the first advanced position . this advancement of the rigid toothed rack inside the cutting cannula may function as a piston that compresses the air inside the cutting cannula and this air is consequently blown into the biopsy cavity disturbing the ultrasound picture . if air is evacuated from the cutting cannula through the longitudinal vacuum channel inside the sidewall of the cutting cannula during advancement of the rigid toothed rack this problem can be addressed and solved . a further embodiment of the invention comprises a tissue collection tank for collecting the at least one tissue sample transferred from the sample notch . the tank may comprise a tissue - collecting spout that may be configured to slide into the sample notch chamber and scoop the tissue sample into a sample tank . to enhance the collection of the tissue sample the tissue collection tank may be configured to be vacuumized , e . g . by connection to a vacuum pump via a vacuum port at the tank . the collecting spout may be elongated to form a pipe ( aka collection pipe ) to enhance the vacuum assisted collection of a tissue sample into the tank . at the outside the collection spout / pipe forms a small spout but at the inside of the tissue collection tank the collection pipe extends and / or protrudes into the tissue collection tank , i . e . the collection pipe may protrude from the bottom or side of the inside of the tissue collection tank . thus , the collection pipe has a certain length inside the tissue collection tank . this length of the collection pipe may be at least 2 mm , or at least 4 mm , or at least 6 mm , or at least 8 mm , or at least 10 mm , or at least 12 mm , or at least 14 mm , or at least 16 mm , or at least 18 mm , or at least 20 mm , or at least 22 mm , or at least 24 mm , or at least 26 mm , or at least 28 mm , or at least 30 mm , or at least 32 mm , or at least 34 mm , or at least 36 mm , or at least 38 mm , or at least 40 mm . some biopsy devices are constantly connected to external vacuum pumps via external vacuum hoses . these pumps can deliver a powerful and constant vacuum to the biopsy device but the necessary vacuum hoses reduce the manageability of the biopsy device for the user . a solution to that problem has until now been to provide one or more local battery driven small vacuum pumps integrated in the biopsy device . however , such small vacuum pumps can only provide a limited airflow which sometimes is not sufficient to maintain a constant vacuum level . a solution to that problem can be a vacuum reservoir integrated in the biopsy device that can deliver a boost to the ( negative ) airflow for one or more short periods of time , this additional airflow provided by the vacuum reservoir can thereby maintain a certain vacuum level . the biopsy device can thereby be provided with one or more small vacuum pumps supplied by the vacuum reservoir when necessary . a further embodiment of the invention therefore comprises a vacuum reservoir ( aka vacuum accumulator ) configured for accumulating a volume of vacuum that can be delivered as a transient boost in the airflow so as to maintain a level of vacuum present in the system . such a vacuum reservoir can for instance be powered by a battery . the vacuum reservoir may be in fluid communication with the sample notch and configured to provide an increased suction to maintain the vacuum level in the sample notch during severing of a tissue sample , e g immediately before release of the cutting cannula in order to increase the amount of tissue that prolapses into the sample chamber and thereby maximize the size of the severed tissue sample . the vacuum reservoir may also be in fluid communication with the inside of the hollow inner member and configured to provide a transient boost of airflow when a tissue sample is being sucked through the inner member . furthermore , the vacuum reservoir may be in fluid communication with the tissue collection tank and configured to provide a vacuum to or an increased suction in the tissue collection tank to main a vacuum level when a tissue sample is transferred from the sample notch and into the tissue collection tank . the vacuum reservoir may have a volume of 5 - 100 ml , or 5 - 10 ml , or 10 - 20 ml , or 20 - 30 ml , or 30 - 40 ml , or 50 - 100 ml . retraction of the cutting cannula to expose the sample notch may for instance be actuated by a motor that is powered by a battery and connected to one or more gearwheels , but other power sources and means of mechanical actuation are also envisioned . this retraction of the cutting cannula may facilitate the cocking of a firing mechanism that may for instance be spring - loaded . other firing mechanisms , including electric , pneumatic and chemical , may also be provided . the cutting movement of the cutting cannula during the actual severing of tissue may be powered by the energy that is stored in a firing mechanism and happens as a high - speed linear passage across the laterally facing opening of the sample notch . during this passage , the sharpened distal end of the cutting cannula makes contact with the tissue that has prolapsed into the sample notch chamber and severs it from the surrounding tissue , thus creating a tissue sample in the sample notch . the firing mechanism may be replaced with a linear actuator that allows the controlled advancement of the cutting cannula during severing . in this case advancement of the cutting cannula is more controlled and it may be desirable to rotate the cutting cannula during advancement to adequately sever the tissue as described previously . to provide for sims functionality retraction of the sample notch may be provided by means of a motor that is operatively connected to the rigid toothed rack by means of one or more gearwheels . when activated , this motor causes the rigid toothed rack and the sample notch to travel from the first advanced position to the second retracted position , where the sample may be retrieved , e . g . by means of a tissue collection tank , but other means of retrieval — including manual retrieval — may also be envisioned . after completion of sample retrieval , the sample notch may be returned to the sampling site by reversing the direction of rotation of the motor . the firing mechanism may be configured for causing the cutting cannula and the inner member to be longitudinally displaced in a distal direction , so as to penetrate body tissue at or near the suspect tissue mass prior to the cutting operation when harvesting a sample . in one embodiment of the invention the inner member comprises a vacuum port in fluid communication with the sample notch . the inner member may thus be configured such that the sample notch can be vacuumized . a vacuum pump may be provided for generating a suction effect in the sample notch to increase the size of the tissue sample that prolapses into the sample notch , the vacuum pump being in fluid communication with the sample notch through a longitudinally extending passage in the inner member . a further embodiment of the invention comprises a handle unit with a power source and at least one motor for driving the cutting mechanism and the displacement of the inner member and wherein at least the cutting cannula and the inner member are comprised in a disposable unit , which is releasably secured to the handle unit . to ensure that the cutting cannula and the sample notch achieve an overlap that is sufficient to cleanly sever the tissue to be sampled , the cutting cannula is preferably characterized by very tight length tolerances . such tolerances may be achieved by the use of materials with low creep that are processed using high - precision milling or molding , and possibly result in total length variations of no more than +/− 0 . 5 mm depending on the overall total length of the cutting cannula . a preferred material for the cutting cannula is stainless steel which is made into tubes . these tubes are typically made by rolling and welding sheet metal to form a tubular structure which is then drawn through a tool with a diamond insert to achieve the desired diameter . multiple drawings may be employed to achieve high precision . by utilizing stainless steel low creep for the cutting cannula , none or minimal elongation and achievable manufacturing tolerances are possible . other materials , including titanium , are also envisioned for the making of the cutting cannula . to further support appropriate overlap between cutting cannula and sample notch , also the rigid toothed rack may be characterized by very tight length tolerances . such tolerances may in some embodiments be achieved by the use of materials with low creep that are processed using high - precision milling or molding , and possibly result in total length variations of no more than +/− 0 . 5 mm depending on the overall total length of the rigid toothed rack . a preferred material for the rigid toothed rack is stainless steel . the rigid tooted rack would typically be made by milling a turned stainless steel metal rod in order to achieve the desired geometry . other materials suited for the rigid tooted rack are titanium or similar metals with a high modulus of elasticity . alternative materials include thermoplastic elastomers with suitable fillers for increased modulus of elasticity . suitable types for a rigid toothed rack would be lcp ( liquid crystal polymer ), peek ( polyetheretherketone ) in any grade . thermoplastic elastomers have the benefit of being relatively easy to process and manufacture , but they are less rigid and will also tend to creep and shrink more than metal . while this invention has been described with respect to at least one embodiment , the present invention can be further modified within the spirit and scope of this disclosure . this application is therefore intended to cover any variations , uses , or adaptations of the invention using its general principles . further , this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims .

US-201414772994-A

a turf aerating machine including a plurality of tyne arms , having tynes attached to their lower ends , and extending substantially vertically downwardly from the cranks of a crankshaft located transversely of the direction of travel of the aerator . a drive linkage connects the crankshaft to the power take - off of the tractor or other power source and is driven such that , as the aerator is moved forward , the crankshaft moves with the lower arc of its rotation in the rearward direction . the tyne arms are projected into the ground as the respective crank moves through its lower arc and they are lifted clear of the ground as the crank moves through the upper arc of its travel . while the tynes are engaged with the ground , the tyne arm is maintained in a substantially vertical orientation by the rearward motion of the respective crank through the lower arc of its rotation . the lower end of each tyne arm extends through a slot running longitudinally of the aerator such that lateral movement of the tyne arm is prevented . each tyne arm is biased toward the forward end of its slot when the tyne is engaged in the ground due to the forward motion of the aerator over the ground . when the tyne is retracted from the ground by the crankshaft the tyne arm is returned to the forward end of its slot by the spring .

referring to fig1 and 2 an aerator 10 in accordance with the present invention has a frame 11 to which are mounted at least two ground engaging wheels 12 . these wheels are mounted for rotation about an axle 13 extending tranversely of the aerator and the wheels may function as depth wheels to provide for adjustability of the height at which the aerator travels over the ground . in one form the axle 13 may have a cranked portion and the position of this portion relative to the frame may be adjusted to provide for this height adjustment . this adjustment enables the height of the aerator to be varied to achieve varying depth of penetration of the tynes during operation of the aerator . when the aerator is to be transported from one site to another , it is raised from the ground on the three point linkage of the tractor to which it is connected . the aerator 10 has a crankshaft 14 extending transversely of the frame 11 . the crankshaft is supported by main bearings 15 , 16 and 17 and carried by support members or bearing mounts 18 integral with the frame 11 . whilst only one crankshaft 14 is illustrated , where a wider aerator is required two crankshafts 14 may be coupled end to end . the aerator includes drive means for rotating the crankshaft . the drive means illustrated comprises a gearbox 20 having an input shaft 21 and an output shaft 22 , the input shaft 21 being capable of being coupled to a power take off of the towing vehicle . the gearbox is fixed relative to mount 23 secured to a member of the frame 11 and the crankshaft 14 may be suitably driven from the gearbox via a drive chain 24 extending over drive sprockets 25 , 26 . where there are two crankshafts they may be driven by respective drive chains from the output shaft of the gearbox or alternatively by a duplex chain meshing with respective single sprockets on adjacent ends of the crankshafts . alternatively the shafts may be driven from their remote ends via suitable drives from spaced take off means on a common shaft or from the opposite ends of a conventional vehicle rigid rear driving axle assembly . a chain connection is convenient since it permits the respective crankshafts 14 to be timed with respect to one another to place the throws of one shaft out of phase with the throws of the adjacent shaft . this has the advantage of staggering tyne arms 30 and hence tynes 31 engage the ground in a staggered fashion resulting in smoother operation of the aerator . by using a crankshaft on which the respective cranks are offset with respect to one another , the energy required to drive the tynes into the ground is spread more evenly over the rotational cycle of the crankshaft , thereby reducing peak power requirements and reducing the forces applied to the mechanical drive components of the aerator . tyne arms 30 are mounted relative to the crankshaft with a bearing 32 located between the upper end of each arm 30 and the crankshaft . the frame has a transverse frame member 33 formed with a plurality of slots 34 within which the arms 30 are located and travel . the arms are biased towards the front of the slots by respective springs 35 and these slots act as guides for fore and aft movement of the arms . mounted at the lower end of each arm 30 is a tyne foot 36 which carries at least one tyne , however , two or more tynes can be carried by the foot to provide different core patterns or to increase operating speed . the foot may be formed integral with the arm 30 althought it is preferred that it be detachable , and to this end the foot may have a sleeve 37 which may be mounted about the lower end of the arm 30 and secured thereto by a clamp 38 . the lower end of one of the tyne arms 30 is illustrated in elevation and section plan in fig3 and 4 . the tyne arm 30 is substantially formed from square section tube . a rod 41 is inserted into the lower end of the tyne arm 30 and a flange 42 locates the rod relative to the tyne arm . the rod 41 is then welded to the tyne arm to form a rigid assembly . the lower portion 43 of the rod 41 which projects from the tyne arm 30 provides a stub to which the tyne feet 36 are clamped . embodiments of the foot 36 are shown in fig5 to 8 , and referring to fig5 and 6 , a first foot 36a comprises a central tube 37 to which are welded a pair of tyne holding tubes 44 into which tynes 31 may be clamped by tightening the respective allen screw 110 which extends through an unthreaded lug 111 and a threaded lug 112 located either side of a slit 113 in the tube 43 . the tyne holding tubes 44 are sized to closely co - operate with the tynes located therein and have an internal lip 114 at their upper end to prevent slippage of the tyne while it is being inserted into the ground . similarly , the socket tube 37 is sized to closely cooperate with the stub 43 of the tyne arm to which it is clamped , an allen screw 115 which extends through an unthreaded lug 116 and a threaded lug 117 located either side of a slot 118 in the socket 37 . the transverse spacing s between the tynes will typically be about 50 mm . fig7 and 8 show a foot 36b having four tynes . this foot also has a central socket 37 adapted to be clamped to the stub 43 of a tyne arm 30 . the four tyne holding tubes 44 are joined to the socket 37 by four webs 46 extending radially from the socket 37 . the transverse spacing s between the tynes of fig4 is also typically about 50 mm as is the longitudinal pitch p . the tynes may either be solid or hollow . each of the tyne holding tubes 44 is preferably provided with a bevelled lower edge 119 such that the &# 34 ; foot print &# 34 ; of the tyne holder is minimized . this has the effect of reducing the amount of soil which builds up on the lower surfaces of the tyne holder . similarly the socket 37 preferably has an internally bevelled lower edge 120 and webs 46 of the four tyre holder of fig7 and 8 are also bevelled on their lower edges ( not shown ). with the square grid pattern of tynes shown in fig4 the foot can be moved forward after each stroke by a distance equal to the number of rows of tynes multiplied by their pitch p , that is , by twice the longitudinal spacing of the tynes in the foot , thereby providing a square grid pattern for aeration . thus , for a given crankshaft speed , when using the arrangement of fig4 the forward speed may be doubled compared to that of a single row tyne arrangement of fig3 while still providing a square grid aeration pattern . if a square grid pattern is not required the arms can be moved forward by any selected distance between operations . referring to fig9 mounted at spaced intervals transversely of the aerator are a series of buffers 50 , the number of buffers corresponding to the number of tyne arms 30 . the buffers are mounted on a transverse frame member 51 and each comprises a roller 52 rotatably mounted on support 53 by axle 54 . as the arms 30 are brought forward in the slots 34 by springs 35 the buffers ensure that there is no jarring metal to metal contact during motion . if desired the rear of the slot may also be cushioned in some suitable fashion . it will be seen that each time the arm 30 strikes the buffer 50 the roller 52 presents a different part of its periphery for the next buffering action , thereby increasing the life of the roller . the rate of the return spring 35 is selected such that during high speed operation the tyne 31 will be brought back into engagement with the ground just before the arm reaches the buffer roller 52 , while when the tynes are not engaging the ground , such as when the aerator is lifted clear of the ground during transport , the tyne arms move vertically in one position and roll past the rollers 52 . to ensure that turf is not lifted from the ground when the tynes are withdrawn , the aerator is provided with a guard 60 . the guard 60 is secured to a member of the frame and extends from this member past the area over which the tynes operate . the guard , during use , is in contact with the ground and may be biased against it . the guard has a forward inclined portion 61 attached to the frame and a rear ground engaging portion 62 , the free end of which has a turned up end 63 , which enables the aerator to be reversed without the guard prohibiting such movement . the rear portion is formed with a series of arms which when viewed in plan appear as a comb ( not shown ). the respective arms of this portion extend between adjacent tynes of each foot and between the tynes of adjacent feet to ensure that withdrawal of the tynes does not result in lifting of the turf . the operation of the aerator described with reference to fig1 to 9 is as follows . the crankshaft is caused to rotate in the direction of arrow a , such that each tyne arm bearing 32 will sequentially move towards bottom dead centre to engage its respective tynes in the ground . as the aerator advances , the bearing mount for each tyne arm bearing 32 will move rearwardly relative to the rest of the aerator due to rotation of the crankshaft and at the same time the tyne arm moves along the slots 34 against the action of springs 35 due to its engagement with the ground . this action results in the tyne arms being maintained substantially vertical whilst the tynes are engaged in the ground . when each tyne is retracted from the ground by continued rotation of the crankshaft the springs 35 return the tyne arms to the forward end of the slots 34 ready for the next downward thrust . although the tyne arms are maintained substantially vertically while the tynes are engaged with the ground a small amount of rocking motion of the tyne arm occurs , with the result that the core is effectively snapped off at the bottom of the stroke of the tyne arm , ensuring that practically all of the core is removed with the tyne . without this snapping action , it is possible for cores to break off partway along their length as the tyne is withdrawn from the ground , such that part of the core is left in the core hole . the rocking motion of the tyne arm also tends to elongate the base of the core hole , thereby providing better penetration of air and nutrients . the frame 11 may be adapted to be supported by a three point linkage with the crankshaft connected to a power take off of a towing vehicle such as a tractor . the drive for the crankshaft could be mechanical as illustrated or could be any other suitable drive such as hydraulic . referring now to fig1 and 11 , a second embodiment of the invention is schematically illustrated wherein means are provided for self propulsion of the aerator . the aerator of the second embodiment has a chassis 71 to which are pivotally connected a pair of rearwardly extending arms 72 . a rear axle 73 is rotatably mounted between the arms 72 and a pair of rear wheels 74 , are mounted at the extremities of the axle , outboard of the arms 72 . a pair of dolly wheels 75 are located centrally of the chassis 71 at the front end thereof . the dolly wheels are mounted on the lower end of a vertical steering shaft 76 which is rotatably connected to the chassis 71 and is provided with a tiller 77 pivotably connected to the top end thereof such that the tiller can be folded out of the way when not in use . a sprocket 78 on the steering shaft 76 is provided to communicate rotation of a steering wheel 79 to the steering shaft 76 , the sprocket 78 being connected to a sprocket 81 fixedly coupled to the steering wheel 79 by a chain 82 . the steering wheel 79 is located adjacent to a seat 83 which is provided for &# 34 ; ride on &# 34 ; operation , whereas the tiller 77 is provided for &# 34 ; pedestrian &# 34 ; operation . the self propelled aerator is also provided with an additional retractable wheel 84 mounted on a pivotable arm 85 and located inboard of the outermost tyne arm such that , with the retractable wheel in its lowered position , the aerator can core right up to the edge of depressions such as sand traps on golf courses and bowling green ditches . this feature is not required on the towed embodiment as it can be supported by the three point linkage of the tractor to which it is fitted if one wheel is suspended over the edge of a ditch or sand trap . the height of the rear of the self propelled aerator , and therefore the penetration depth of the tynes , is adjusted using hydraulic rams 86 connected between the chassis 71 and respective arms 72 , while the retractable wheel 84 can be lowered using a hydraulic ram 87 or alternatively it can be lowered by rotation of a threaded rod . power to drive the aerator is provided by an internal combustion engine 88 which would typically provide in the order of eight horsepower . a small fuel tank 89 is provided to supply fuel to the engine 88 . transmission of power from the engine 88 to the rear wheels 74 is by chain drive , a first part of which comprises a sprocket 91 on the engine drive shaft , a chain 92 , and a sprocket 93 mounted co - axially with the pivotal mounting point for the arms 72 . a sprocket 94 connected to sprocket 93 drives a chain 95 which in turn drives a sprocket 96 on the rear axle 73 . the connection between the sprockets 93 and 94 may be fixed , in which case only one forward speed will be possible , or alternatively the sprockets 93 and 94 may be connected through a gearbox in which case several forward speeds will be possible plus reverse . multiple speeds can also be provided by providing a plurality of parallel chain drives each having a different sprocket ratio and each being provided with a clutch to allow selective engagement of one chain drive . it will be recognised that when reference is made to a drive speed of the aerator it is actually the ratio of forward speed to tyne operating speed which is referred to , and it is this ratio which determines the core pattern achieved by the machine . absolute forward speed can be controlled by controlling the throttle of the engine 88 and a differential may also be provided on the rear axle or in the hub of one of the rear wheels to simplify turning of the aerator . the pressure to operate the hydraulic cylinders 86 and 87 is provided by a hydraulic pump 96 which is driven from engine 88 through a v - belt 98 and a pair of pulleys 99 , 100 . the tyne arm drive of fig3 and 11 is essentially identical to that described with reference to fig1 to 9 and will not be described in detail . the crankshaft 14 of the tyne arm drive is driven via a chain 101 which drives sprocket 25 and is driven by sprocket 102 mounted on a transverse shaft 103 having a sprocket 104 fitted to its other end . the sprocket 104 is in turn driven by chain 105 and sprocket 106 fitted to the drive shaft of engine 88 .

US-71546385-A

a medical device includes an elongated member and a reinforced retention structure . the device can be used for draining substances from organs or abscessed areas within a body of a patient . the elongated member is made of a flexible material . the reinforced retention structure extends from or is formed integrally with the elongated member and comprises an elastic member and the flexible material . the reinforced retention structure provides retention strength while providing flexibility and patient comfort . the use of the reinforced retention structure also provides increased stability to the device within the patient &# 39 ; s body and combats migration and / or expulsion of the device . the nature of the reinforcement in the retention structure may extend into the elongated member , which allows for larger drainage openings in the device and increases the radiopacity of the device .

medical devices of the present invention are generally constructed of an elongated member and a reinforced retention structure . the elongated member includes a flexible material and the reinforced retention structure includes the same or a different flexible material with an elastic member embedded within or bound to a surface or groove of the flexible material . preferred materials for the flexible material include , but are not limited to plastic , silicone , teflon ®, and other ptfe polymers , polyurethane polymers and the like . these materials may also be provided with radiopaque portions to assist in the implantation of the devices in a body of a patient under fluoroscopic monitoring . the elongated member may be tubular or conical or a combination of both . generally , the elongated member comprises a lumen extending through the entire length of the elongated member to provide drainage of fluid from a body cavity . alternatively or additionally , drainage may be provided or enhanced by grooves located on the external surface of the retention structure and / or elongated member . the reinforced retention structure is designed to anchor the medical device in place notwithstanding certain forces such as internal forces from involuntary bodily functions such as peristalsis and other secretory forces , or patient movement . the reinforced retention structure may be formed as an extension of the elongated member . under this construction , an elongated member is molded into a predetermined shape to form a reinforced retention structure such that it can extend from the elongated member . alternatively , a reinforced retention structure may be fixedly mounted to the elongated member in that both the elongated member and retention structures are pre - formed and thereafter attached to one another . the reinforced retention structure may adopt any geometry that protrudes laterally or radially from the elongated member to provide adequate anchoring . examples of retention structure geometry include , but are not limited to , a retention coil including one turn , a retention coil including two or more turns , a j curl , an inward spiral coil , a barb , a malecot , and a protruding ring . the retention structure and / or the elongated member itself can have a number of drainage holes disposed along its length . the holes provide drainage areas to allow fluids to drain into the lumen of the elongated member . alternatively or additionally , a large drain hole slot ( fig1 b ) may be cut into the retention structure and / or the elongated member to further facilitate drainage . retention structures according to the invention may be reinforced by a segment made of an elastic member embedded within the flexible material or bound to a surface or groove of the retention structure ( such as the inner or outer wall of the retention structure ). the elastic member may have a cross - section that can be round , flat , square , crescent or d - shaped . certain examples of these cross - sectional shapes are illustrated in fig3 a - c and 4 a - c . the elastic member may be fabricated from a material having “ superelastic ” properties . materials with superelastic properties , make it possible to configure a segment into a particular advantageous shape of a retention structure , such as a pigtail , a malecot arm , a coil , a barb or a ring and then modify reversibly the geometry of the retention structure by straightening the retention structure through use of guidewires , outer sheaths and the like for easy implantation in the body . for example , the pigtail , malecot , and coil retention structures assume straightened geometries when placed over or within the length of a cannula . after the device is straightened , placement into a body with conventional insertion techniques may occur . after insertion and removal of the straightening device , the elastic member reverts spontaneously to its predetermined configuration thereby regaining its deployed geometry and reforming the retention structure . the superelastic material may comprise an alloy of in — ti , fe — mn , ni — ti , ag — cd , au — cd , au — cu , cu — al — ni , cu — au — zn , cu — zn , cu — zn — al , cu — zn — sn , cu — zn — xe , fe 3 be , fe 3 pt , ni — ti — v , fe — ni — ti — co , and cu — sn . preferably , the superelastic material comprises a nickel and titanium alloy , known commonly as nitinol available from memry corp of brookfield , ct or sma inc . of san jose , calif . the ratio of nickel and titanium in nitinol may be varied . examples include a ratio of about 50 % to about 52 % nickel by weight or a ratio of about 47 % to about 49 % nickel by weight . nitinol has shape retention properties in its superelastic phase . in other embodiments , the elastic member comprises any suitable material that has sufficient elastic properties to allow for straightening of the retention structure during insertion into the body , but provides desired reinforcement strength to the retention structure during use . such materials include , for example , stainless steel or suitable polymeric materials . the elastic member disposed within the retention structure may have a one - dimensional shape , such as a linear wire , a two - dimensional shape , such as a curled wire to form a loop or an inward coil , or a three - dimensional shape , such as a helical coil or a pigtail coil . in two - dimensional embodiments , the wire may be bent along a second axis such that the wire occupies a plane . in three - dimensional embodiments , the wire may be coiled tightly about itself within the retention structure . an embodiment of a medical device 10 according to the present invention is shown in fig1 . the medical device comprises an elongated member 12 and a reinforced retention structure 14 . the elongated member may be viewed as extending along a first axis 16 . in fig1 the first axis 16 extends in a longitudinal direction . the retention structure 14 extends along the first axis 16 and a second axis 18 . as seen in fig1 , the second axis 18 extends laterally from the first axis 16 . the elongated member 12 defines an internal lumen 20 . the internal lumen 20 also extends into and through the retention structure 14 . in fig1 , the retention structure 14 is shaped into a coil including a single turn . the retention structure comprises a reinforcing structure made of an elastic member 22 embedded within a flexible material 24 . fig1 a is an enlarged cross sectional view of an portion of the single loop retention structure of fig1 , and depicts the elastic member embedded within the flexible material . alternatively , the reinforcing elastic member 22 may be bound to an inner or outer wall of the flexible material 24 . the stability provided by the elastic member 22 to the retention structure 14 allows for a large drain hole slot 26 to be cut into the retention structure 14 alongside the reinforcing material 22 . optionally , the elastic member 22 can extend into the elongated member 12 . a large drain hole slot 28 may be cut into a portion of a wall of the elongated member 12 for increased drainage . to facilitate drainage , both the retention structure 14 and / or the elongated member 12 may , alternatively or additionally , incorporate a plurality of drainage holes 30 disposed along their lengths to permit drainage of fluid into the lumen 20 . insertion of the device 10 into a body of a patient can be accomplished by straightening the retention structure 14 with a rigid elongated member along the first axis 16 , such as inserting a stylet or guidewire within the lumen 20 or a cannula or sheath over the elongated member , inserting the device 10 with the rigid member into the body and removing the rigid member from the device to deploy the retention structure once the device has been inserted and properly positioned within a body cavity . removal of the rigid member from the device 10 releases the constraint on the elastic member and allows the retention structure to regain its shape . for example , referring to fig2 a - b , a catheter includes a rigid member 13 connected to a handle 17 manually inserted into the lumen of the device 10 . the catheter 15 comprises an adapter 19 for attaching the medical device 10 to the handle 17 , another catheter , or a collection bag . when the rigid member 13 extends throughout the entire device 10 as in fig2 b , the single coil retention structure 14 is straightened along the longitudinal axis 16 . the insertion catheter 15 is then inserted into a body of a patient , and the rigid member 13 is removed from the body proximally . the elastic member allows the retention structure 14 to regain its coiled shape in the body upon removal of the rigid member 13 as in fig2 a . the elastic member may have a variety of shapes and arrangements within the wall of the flexible material 24 forming the retention structure . for example , fig3 a - c represent cross - sectional views of retention structures 14 of the present invention , and show a wire made of a elastic core 22 disposed within the wall of the retention structure 14 . this configuration and these shapes may be suitable for coiled reinforced retention structures ( e . g . fig1 , and 10 ) or barbed retention structures ( e . g . fig8 ). in cross - section , the inner lumen 20 is surrounded by the walls of the retention structure 14 with the elastic member 22 embedded within the flexible material 24 . the elastic member 22 embedded within the flexible material 24 may be d - shaped as shown in fig3 a , round as in fig3 b or flat , rectangular , or ribbonlike as in fig3 c . the elastic member may also have more complex shapes such as wires with enlarged or thinner segments along their length , or more intricate shapes such as an arrow head for a barb or the like . alternatively , the retention structure may have more than one elastic core disposed at various intervals ( regular or irregular ) within the wall of the flexible material . for example , fig4 a - c show four superelastic cores 22 having various shapes disposed within the wall of the retention structure 14 . in cross - section , within the retention structure 14 , an inner lumen 20 , is surrounded by the flexible material 24 . elastic member 22 is disposed within the flexible material 24 of the retention structure 14 . in the cross - sectional views of the embodiments displayed in fig4 a - c , the elastic member 22 is disposed at four different locations within the flexible material 24 . these four locations lie at 0 °, 90 °, 180 °, and 270 ° angles along the radius of the retention structure 14 . the elastic member may , however , lie at any combination of angles along the radius of the retention structure 14 . these configurations may be suitable to a coil ( e . g . fig1 , and 10 ) multiple barbs ( e . g . fig8 ) or multiple arms of a malecot retention structure ( e . g . fig6 ). the elastic member 22 within the flexible material 24 may be d - shaped as in fig4 a , round as in fig4 b , or flat , rectangular , or ribbonlike as in fig4 c . referring now to fig5 , another embodiment of a medical device 10 a according to the invention is shown . the device 10 a is suitable for use as a ureteral stent , and is made of a flexible material forming an elongated member 12 a . the elongated member 12 a extends along a longitudinal axis 16 a and forms two retention structures 32 and 34 at its proximal and distal ends defining a longitudinal portion 11 therebetween . the retention structures extend along lateral axes 18 a and 18 a ′ relative to the longitudinal axis 16 a . here , both retention structures 32 and 34 occupy the same plane . but the retention structures 32 and 34 may occupy different planes . the use of dual retention structures provides increased stability to the device within a patient &# 39 ; s body and combats migration and / or expulsion of the device 10 a . the two or more retention structures 32 and 34 may also be positioned anywhere along the length of the elongated member 12 a . the elastic member 22 a embedded within the flexible material 24 a may be positioned in one or both of these retention structures 32 and 34 and may extend along a short segment of the wall in the longitudinal portion 11 . the enhanced stability provided to the device 10 a by the elastic member 22 a in the flexible material 24 a allows for a large drain hole slot 26 a or slots to be cut into the side of one or both of the retention structures 32 and 34 . alternatively or additionally , a large drain hole slot 28 a may be cut into the side of the longitudinal portion of the elongated member 12 a that contains the extension of the elastic member 22 a in the flexible material 24 a . a plurality of drain holes 30 a may be disposed along the elongated member 12 a and / or the retention structures 32 and 34 to permit drainage of fluid into the lumen . fig6 depicts a retention structure 35 , known as a malecot , with two or more laterally bulging arms formed along a portion of a length of an elongated member 12 b . the elongated member 12 b extends along a longitudinal axis 16 b . two arms 33 and 36 of the retention structure 35 extend along a lateral axis 18 b relative to the longitudinal axis 16 b . the malecot 35 may also comprise a plurality of collapsible bulging arms including , but not limited to , any number of arms from two arms to eight arms , for example , with three to six arms typical . as with other retention structure constructions , the malecot 35 comprises an elastic member 22 b embedded within the flexible material 24 b in each of the malecot &# 39 ; s arms . in their deployed shape , the arms may have a symmetrical omega ( ω ) shape or an omega shape tilted proximally or distally as shown in fig6 . formation of the malecot 35 can be a multi - step process . a piece of tubing may be first extruded , molded or otherwise shaped into an elongated member 12 b to have a central lumen 20 b surrounded by a series of smaller outer lumens disposed into the wall of the elongated member 12 b and surrounding the lumen 20 b . lengths of elastic material are shaped into curved geometries formed by a sequence of alternating convex and concave curves of varied length and radii that shape the arms of the malecot . these pre - formed lengths of elastic material 22 b are then placed into the outer lumens of the flexible material 24 b . the multi - lumen tubing is then cut longitudinally between each of the pieces of elastic material 22 b to separate the arms of the malecot from each other . the elastic member 22 b allows the arms of the malecot 35 to protrude laterally from the elongated member 12 b in a natural state , and collapse to lie flat along the length of the elongated member 12 b for insertion of the device 10 b as seen in fig7 a - b . an insertion catheter 21 comprising a rotatable handle 23 having internal threads , a threaded element 25 that interlocks with the rotatable handle 23 , a molded hub 27 , a rigid member 29 , and a malecot in an expanded state is shown in fig7 a . to collapse the malecot 35 , the device 10 b is disposed on the rigid member 29 while holding the molded hub 27 steady . longitudinal tension exerted on device 10 b by opposing tugs exerted on the hub 27 and distal end of the rigid member 29 pulls opposite ends of the device 10 b apart and collapses the malecot 35 . fig7 b shows the malecot 35 in its collapsed state . after the malecot has been collapsed , the insertion catheter 21 may be directly inserted into a body of a patient . the rigid member 29 is released from the device 10 b by rotating handle 23 to release it from the hub 27 . removal of the rigid member 29 releases tension on the device 10 b and allows the elastic member to resume its expanded shape deploying the malecot and securing the device 10 b within the body . fig8 depicts a retention structure 38 as a barb having two ends . one end 37 of the barb is formed integrally with the elongated member 12 c . the other end 39 of the barb extends laterally from the elongated member 12 c . the elongated member 12 c extends along a longitudinal axis 16 c . the retention structure 38 extends along a lateral axis 18 c relative to the longitudinal axis 16 c . the barb 38 may be disposed anywhere along the length of the elongated member 12 c . the barb comprises a curved elastic member 22 c embedded within a flexible material 24 c . the barb 38 mayor may not create an opening in the elongated member 12 c depending on the depth of the cut made in the elongated member 12 c . in the embodiment depicted in fig6 , the barbed portion 38 forms an opening 40 . to form the barbed retention structure 38 a piece of tubing is extruded to have a central lumen surrounded by a smaller outer lumen in a wall of the elongated member 12 c . two angled cuts are made into the wall of the elongated member 12 c intersecting to form end 39 . the end 39 or the barb extending laterally from the elongated member 12 c exposes the small lumen . an elastic member 22 c is shaped into a curved geometry that will form to the shape of the barb 38 . the curved length of elastic member is then inserted into the small lumen through end 39 . referring to fig9 , insertion of the device 10 c into a body of a patient can be accomplished by placing the device 10 c in a conventional delivery system 41 and inserting the delivery system 41 into a body of a patient . in fig9 , the device 10 c is disposed over a rigid member 43 on the delivery system 41 . the delivery system 41 comprises a handle 45 , a threaded hub 47 , the rigid member 43 , and an adapter 51 designed to attach the medical device 10 c . when the device 10 c is disposed over the rigid member 43 , the end 37 of the barb 38 formed integrally with the elongated member 12 c is preferably inserted into the body first so that the barb 38 folds into the opening 40 created in the elongated member 12 c . for applications where end 39 of the barb is to be inserted first , a cannula 53 may be inserted over the elongated member 12 c to cover and collapse the barb 38 therein . once the device is positioned into the body , the cannula is withdrawn deploying the barb within a body cavity thereby anchoring the device 10 c in the body . fig1 shows a reinforced inward spiral coil retention structure 42 . the inward spiral retention structure may be disposed at either end or at both ends of the elongated member 12 d . the elongated member 12 d extends along a longitudinal axis 16 d . the spiral coil 42 extends along a lateral axis 18 d relative to the longitudinal axis 16 d . the spiral coil 42 anchors the medical device 10 d in place to prevent migration . as with the single and double retention coils ( fig1 and 5 ), the elastic member 22 d embedded within the flexible material 24 d in the spiral coil retention structure 42 may be disposed along its inner perimeter . alternatively , the elastic member may be disposed along the outer perimeter of the coil or along its flanks . it may optionally also extend within a portion of the elongated member 12 d itself . the lumen 20 d extends through at least a portion of the spiral coil 42 to facilitate drainage of fluid and other substances and may extend all the way through the spiral coil 42 . the elongated member 12 d and the retention structure 42 may incorporate a plurality of holes 30 d and / or a large drain hole slot 28 d to further facilitate drainage . insertion of the device 10 d into a body of a patient can be accomplished through use of the insertion catheter shown in fig2 . to form a j curl retention structure , a single cut between approximately ⅜ and ¾ or a turn along the spiral coil retention structure may be made . as shown in fig1 , two examples of suitable cuts 55 and 56 made in the spiral coil retention structure at approximately ⅜ and ¾ of a turn respectively form the j curl retention structure . after the cut is made , the open end of the retention structure may then be tapered on both sides to form a small opening at the distal tip of the device . to form the inward spiral retention structure , a dual lumen elongated member of flexible material is provided . an elastic member pre - formed into an inward coil may be inserted into one of the lumens , and the elongated member wound about itself to form the designated structure . alternatively , the pre - formed elastic member 22 may be bound to an outer wall of the flexible material 24 , and the distal end of the elongated member of flexible material wound about itself . referring to fig1 , a reinforced retention structure of the invention can be an elastic ring 44 containing an elastic member 22 e embedded within a flexible material 24 e . the elongated member 12 e extends along a longitudinal axis 16 e . the retention structure 44 extends along a lateral axis 18 e relative to the longitudinal axis 16 e . the reinforced ring may be at a 90 ° angle transverse from the longitudinal axis 16 e or at a lesser angle designed to adapt to various internal body openings . the elastic ring or rings 44 protrude from the external surface of the elongated member 12 e . the elastic rings 44 are designed to provide rigidity to the device and prevent migration of the device 10 e . drainage holes or apertures 30 e are disposed along the length of the elongated member 12 e to provide for fluid communication with the lumen 20 e and to facilitate urinary drainage . fig1 a - b show retention structures of the present invention in a straightened configuration . in fig1 a , a plurality of holes 46 are cut into a retention structure to increase the drainage rate of fluid passing through the lumen 20 f . in fig1 b , use of an elastic member provides stability to the retention structure 14 f to support a large continuous drain hole slot 48 in the surface of the retention structure 14 f . the drain hole slot 48 may also appear in the elongated member ( not shown ) if the elastic member extends out of the retention structure 14 f into the elongated member . the length and width of the drain hole slot can vary depending on the needs of the particular patient . the width of the drain hole slot can be very narrow to prevent tissue in - growth . one medical device of the present invention 10 g placed into a body of a patient is illustrated in fig1 . the medical device 10 g comprises an elongated member made of a flexible material and a reinforced retention structure 14 g including an elastic member in the flexible material . the retention structure 14 g featured in fig1 has the geometry of an inward spiral coil , but other retention structures described above may also adequately be employed . the device 10 g is easily inserted into the body through the ureter 50 and into the kidney 52 of the patient , as pictured herein . insertion is accomplished in any conventional manner , such as collapsing the retention structure of the device 14 g using a guidewire , stylet or cannula and then inserting the device 10 g through the urethra . after insertion and removal of the straightening device , the retention structure 14 g of the medical device reverts to a pre - determined geometry . a method of manufacturing the medical devices of the present invention ( fig1 , 6 , 8 , 10 , 11 ) comprises providing an elongated member made of a flexible material and affixing an elastic member to the flexible material to form a reinforced retention structure . the elastic member is first shaped by mechanical operation at elevated temperatures , for example 500 ° c . the elastic member may be shaped into a curl , a coil , a malecot , a ring or a barb . next , the elastic member may be positioned in the flexible material in a number of ways . for example , the pre - shaped elastic member may be introduced into a lumen of a multi - lumen extrusion tube of flexible material . the elastic member may be fed through one of the lumens of the multi - lumen extrusion by hand or by mechanical operation . the elastic member may also be molded in a thermosetting material , in that the pre - shaped elastic member is placed in a mold cavity and a flexible material poured around it such that it may ultimately bind to an external or internal surface of the flexible material . also , the elastic member may be bound to an external or internal surface of the flexible material with glue or tape . variations , modifications , and other implementations of what is described herein will occur to those of ordinary skill in the art without departing from the spirit and scope of the invention . accordingly , the invention is to be defined not only by the preceding illustrative description .

US-62722507-A

a method for implementing a sensor measurement system is disclosed herein . the method includes providing a plurality of generally identical modular sensor arrays each having a single array connector , applying two of the plurality of modular sensor arrays to a patient such that the two modular sensor arrays can receive biopotential signals from the patient , and coupling the array connector of each of the two modular sensor arrays with a monitor such that the two modular sensor arrays can transmit the biopotential signals to the monitor and the monitor can convey information pertaining to the biopotential signals in a selectable form . a corresponding sensor measurement system is also provided .

in the following detailed description , reference is made to the accompanying drawings that form a part hereof , and in which is shown by way of illustration specific embodiments that may be practiced . these embodiments are described in sufficient detail to enable those skilled in the art to practice the embodiments , and it is to be understood that other embodiments may be utilized and that logical , mechanical , electrical and other changes may be made without departing from the scope of the embodiments . the following detailed description is , therefore , not to be taken as limiting the scope of the invention . referring to fig1 , a modular sensor array 10 is shown in accordance with an embodiment . the modular sensor array 10 is referred to as being “ modular ” because it defines a standardized unit that may be implemented individually or in combination with other generally identical devices . the modular sensor array 10 is referred to as being an “ array ” because it comprises multiple sensors ( e . g ., the electrodes 12 ). the modular sensor array 10 is depicted as including three electrodes 12 , however it should be appreciate that alternate embodiments may include other types of sensors and / or additional sensors . each electrode 12 is operatively connected to a conductor 14 . the conductors 14 are each configured to transmit biopotential signals from a respective electrode 12 . the electrodes 12 and conductors 14 may be formed of a conductive material suitable for receiving and transmitting signals such as , for example , metallic foil or wire , vapor deposited or printed metallic layers , etc . the conductors 14 each include a first end that is connected to a respective electrode 12 , and a second end that is connected to an array connector 16 . an adhesive material 18 is generally disposed around the periphery of each electrode 12 in order to secure the electrodes 12 to a patient . referring to fig2 , a sensor measurement system 20 is shown . the sensor measurement system 20 will hereinafter be described in accordance with an embodiment having two modular sensor arrays , however , it should be appreciated that alternate embodiments may incorporate additional or fewer modular sensor arrays . the two modular sensor arrays shown in fig2 are generally identical to the modular sensor array 10 ( shown in fig1 ) and will therefore be identified using base reference numbers consistent with those of fig1 and a unique alphanumeric suffix . the sensor measurement system 20 includes a first modular sensor array 10 a and a generally identical second modular sensor array 10 b . an array connector 16 a of the first modular sensor array 10 a is coupled with a first monitor connector 22 , and an array connector 16 b of the second modular sensor array 10 b is coupled with a second monitor connector 24 . according to the illustrated embodiment , the array connectors 16 a , 16 b are male type connectors that are insertably coupled with female type monitor connectors 22 , 24 . it should , however , be appreciated that the connectors 16 a , 16 b , 22 and 24 may include any known device configured to establish an electrical connection . the first and second monitor connectors 22 , 24 are respectively coupled with a first and second monitor cable 26 , 28 , and the first and second monitor cables 26 , 28 are coupled with a monitor 30 . accordingly , the first and second modular sensor arrays 10 a , 10 b transmit boipotential signals from a patient through the cables 26 , 28 , respectively , and to the monitor 30 which is configured to display electroencephalogram ( eeg ) data in a desired form . according to an embodiment shown in fig3 , a sensor measurement system 32 includes a single monitor cable 34 having a dual input monitor connector 36 configured to couple the modular sensor arrays 10 a , 10 b with a monitor 38 . the dual input monitor connector 36 includes a first input port 40 adapted to accommodate the array connector 16 a , and a second input port 42 adapted to accommodate the array connector 16 b . in all other respects , the sensor measurement system 32 is similar to the sensor measurement system 20 ( shown in fig2 ). referring to fig4 and 5 , it can be seen that a single modular sensor array 10 may be implemented for applications requiring less detailed information , and multiple modular sensor arrays 10 can be implemented for applications requiring more detailed information . therefore , the modular sensor array 10 provides a single device that is flexible enough to accommodate a variety of different applications in a convenient and efficient manner . as an example , the modular sensor arrays 10 can be sterilized and pre - packaged , and thereafter stored in a common location and identified by a common part number . accordingly , a user can conveniently obtain one or more modular sensor arrays 10 from a single location whereas it may have previously been necessary to acquire a plurality of different components ( e . g ., electrodes , conductors , connectors , adhesive ) from a plurality of different locations . additionally , by using a common part number , it is less burdensome for a hospital to inventory and track the modular sensor arrays 10 . referring to fig4 , an electrode placement for a single modular sensor array embodiment is illustrated . when only one modular sensor array 10 is implemented , the electrodes 12 may be attached to the forehead 44 of a patient 46 in the manner shown . the array connector 16 can then be connected to one of the monitor connectors 22 , 24 ( shown in fig2 ) or inserted into one of the ports 40 , 42 of a dual input monitor connector 36 ( shown in fig3 ) to couple the modular sensor array 10 with a monitor . referring to fig5 , an electrode placement for a dual modular sensor array embodiment is illustrated . the electrode placement depicted in fig5 is sometimes referred to as a “ sub - hairline montage ” because the electrodes 12 are all applied below the patient &# 39 ; s hairline . advantageously , the sub - hairline montage requires minimal skin preparation , it obviates the need for hair removal , and it prevents the patient &# 39 ; s hair from interfering with biopotential signal reception . it should , however , be appreciated that the , electrode placement shown in fig5 and described hereinafter is provided for illustrative purposes , and that alternate electrode placements may be envisioned . when two modular sensor arrays 10 are implemented , four of the electrodes 12 can be attached to the patient &# 39 ; s forehead 48 in a spaced apart manner and the remaining two electrodes 12 can be attached to opposing sides of the patient &# 39 ; s neck 50 below and in close proximity to the patient &# 39 ; s ears 52 . advantageously , the implementation of two generally identical modular sensor arrays 10 on a single patient 54 can provide more detailed information than a system incorporating only three electrodes . additionally , a sensor measurement system incorporating the modular sensor arrays 10 is easily applied to a patient ( ease of application ), and less prone to application error ( correctness of application ). the ease of application and the correctness of application of the modular sensor arrays 10 will hereinafter be described in detail . the modular sensor array &# 39 ; s ease of application can be illustrated by the following example and with reference to fig5 . a user can obtain two pre - packaged modular sensor arrays 10 from a common location . thereafter , each pre - packaged modular sensor array 10 can be individually opened and applied to the patient 54 in the manner described hereinabove . the array connectors 16 of the two pre - packaged modular sensor arrays 10 can then be coupled with a complementary monitor connection device such as the monitor connectors 22 , 24 ( shown in fig2 ) or the dual input monitor connector 36 ( shown in fig3 ). this example shows that a system incorporating the modular sensor arrays 10 may be more easily applied than a conventional system wherein a user obtains a plurality of different components ( e . g ., electrodes , conductors , connectors , adhesive ) from a plurality of different locations , applies six electrodes to a patient , and then individually couples each of the six electrodes with a monitor . the modular sensor array &# 39 ; s correctness of application is related in part to the fact that each modular sensor array 10 can be coupled to a monitor using a single array connector 16 . therefore , a system incorporating two modular sensor arrays 10 only requires the formation of two electrical connections in order to couple all six electrodes 12 with a monitor . it should be appreciated that a user is less likely to improperly form one of the two electrical connections required for a system incorporating the modular sensor arrays 10 than to improperly form one of the six electrical connections of a conventional system . in other words , the likelihood that a user will improperly form an electrical connection is directly proportional to the number of electrical connections the user must form . while the invention has been described with reference to preferred embodiments , those skilled in the art will appreciate that certain substitutions , alterations and omissions may be made to the embodiments without departing from the spirit of the invention . accordingly , the foregoing description is meant to be exemplary only , and should not limit the scope of the invention as set forth in the following claims .

US-68351407-A

a system for distracting two tissue surfaces away from one another within a spine , involving a plurality of biocompatible and generally rectangular spinal inserts configured to be successively stacked within a spine to distract the two tissues surfaces away from one another . each spinal insert has a generally planar top surface having a leading edge and a trailing edge , a generally planar bottom surface disposed generally parallel to the top surface and including a leading edge and a trailing edge , and a beveled surface extending from at least one of the leading edge of the planar top surface and the leading edge of the planar bottom surface . the beveled surface is configured to allow a currently inserted spinal insert to be positioned at least one of above and below a previously introduced spinal insert to distract the two tissue surfaces .

illustrative embodiments of the invention are described below . in the interest of clarity , not all features of an actual implementation are described in this specification . it will of course be appreciated that in the development of any such actual embodiment , numerous implementation - specific decisions must be made to achieve the developers &# 39 ; specific goals , such as compliance with system - related and business - related constraints , which will vary from one implementation to another . moreover , it will be appreciated that such a development effort might be complex and time - consuming , but would nevertheless be a routine undertaking for those of ordinary skill in the art having the benefit of this disclosure . the stackable interlocking intervertebral support system disclosed herein boasts a variety of inventive features and components that warrant patent protection , both individually and in combination . referring first to fig1 , an exploded front side perspective view of the present stackable interlocking intervertebral support system 5 is provided . in one preferred arrangement , system 5 comprises a center portion 10 , a bottom portion 20 a and a top portion 20 b . ( as will be explained , other arrangements are possible ). as can be seen throughout the attached figs ., portions 20 a and 20 b may preferably be identical in shape and size . accordingly , the present system 5 may actually comprise one center portion 10 and two top / bottom portions 20 . fig2 and 3 show respective top and bottom perspective views of the present system , in an assembled format . as will be explained , an advantage of the present system is that it provides support between adjacent vertebrae without requiring any mechanical fastening systems between the top , center and bottom portions of the assembly . rather , center portion 10 , bottom portion 20 a and top portion 20 b are all assembled together with their novel shapes assisting in keeping them together . referring to the attached figs ., ( and to fig7 a to 10 in particular ), center portion 10 is provided with bottom recess 11 a and top recess 11 b , passing thereacross , as shown . also referring to the attached figs ., ( and to fig1 to 16 in particular ), bottom portion 20 a is also proved with a top recess 21 a . ( conversely , being identically shaped to bottom portion 20 a , top portion 20 b is also provided with a bottom recess 21 b ). an important aspect of the present invention is that , when bottom portion 20 a is positioned below center portion 10 , recess 21 a will engage and interlock with recess 11 a . conversely , when top portion 20 b is positioned on top of center portion 10 , recess 21 b will engage and interlock with recess 11 b . accordingly , when center portion 10 , bottom portion 20 a and top portion 20 b are stacked together , recesses 11 will engage recesses 21 , such that assembly 5 forms an “ x ” or “ cross ” shape . as can be seen , recesses 11 and 21 are preferably positioned mid - way ( ie : centrally ) along the respective lengths of portions 10 and 20 . as illustrated , assembly 5 will have an “ x ” shape with each of the four branches of the “ x ” being relatively equal in length . within the scope of the present invention , however , recesses 11 and 21 may instead be positioned closer to one end of their respective portions than another , such that the “ x ” shape of the present assembly will instead have two of its branches longer than another two of its branches ( and may even approach a “ v ” shape assembly ). moreover , the angles at which recesses 11 and 21 cut laterally across portions 10 and 20 can be angled as denoted by angle “ α ” in fig9 b ( for center portion 10 ). as such , when stacked together , the angles between each of the 4 “ arms ” of the “ x ” of the present assembly need not be perpendicular to one another . ( for example , 2 pairs of arms may be 60 ° apart , with the other 2 pairs of arms being 120 ° apart ). as can be seen throughout the attached figs ., center portion 10 has a bottom surface 12 and a top surface 14 . bottom portion 20 a has a bottom surface 22 a , and top portion 20 b has a top surface 22 b . when the three portions of the present assembly are assembled , surface 14 is coplanar with surface 22 b and surface 12 is coplanar with surface 22 a . as shown in fig5 , surfaces 12 and 22 a together support ( ie : buttress against ) vertebra 50 and surfaces 14 and 22 b together support ( ie : buttress against ) an opposite adjacent vertebra 52 . ( for illustration purposes only , opposite adjacent vertebrae 50 and 52 are shown in an exploded view ). it is to be understood that after distraction vertebrae 50 and 52 will tend to move toward one another , applying pressure to the top and bottom of assembly 5 , keeping assembly 5 together . as can be seen , surfaces 12 , 14 , 22 a , and 22 b may all have a plurality of small groves 23 ( or other surface irregularities ) which increases sliding friction across these surfaces . a further advantage of the novel shape of center portion 10 is that it has a tapered front end 13 . in a preferred method of assembling the present support assembly 5 , as illustrated in fig1 and 19 , center portion 10 is advanced minimally invasively into patient p in a posterolateral approach through cannula 60 and positioned between opposite adjacent vertebrae 50 and 52 ( shown here as being on top of vertebra 50 ). tapered end 13 will tend to pry apart adjacent vertebrae 50 and 52 , providing the surgeon with a “ self - distracting ” vertebral support system . bottom portions 20 a and top portions 20 b are advanced through minimally invasive cannula 62 in an opposite posterolateral approach . typically , bottom portion 20 a is positioned first , followed by center portion 10 and top portion 20 b stacked sequentially thereover . each of center portion 10 and top portion 20 b also have tapered front ends 13 and 25 which ( as center portion 10 and top portion 20 b are sequentially slipped over bottom portion 10 and center portion 10 ), will engage ramp structures 17 disposed within recesses 21 a and 11 a in respective bottom portion 20 a and center portion 10 , such that center portion 10 and top portion 20 b are “ snap - fitted ” over bottom portion 20 a . more specifically , during insertion , vertebrae 50 and 52 will tend to rest against surfaces 12 and 14 of center portion 10 . as center portion ( s ) 10 and top portion 20 b are “ snap - fitted ” over bottom portion 20 a and center portion 10 , their respective tapered ends 13 and 25 will assist in urging vertebrae 50 and 52 apart . when assembled , ramp structures 27 disposed within recesses 21 a and 21 b will interlock with engage ramp structures 17 in center portion 10 , such that assembly 5 will be held together , by intervertebral pressure ( on surfaces 14 and 22 b , and surfaces 12 and 22 a ) urging vertebrae 50 and 52 together . portions 10 and 20 of the present invention may preferably each have a narrow elongated shape , as shown . accordingly , they may be dimensioned to be small enough to pass through an operating cannula , for example , an operating cannula having an interior diameter equal to , or less than , 8 mm or 6 mm . in preferred aspects of the invention , portions 10 and 20 are preferably made of bone allograft material , offering the advantages of promoting healing and eventual absorption of system 5 . alternatively , portions 10 and 20 may be made of metal , or any other suitable bio - implantable material . each of center portion 10 , and top / bottom portion 20 may optionally have side grooves 15 and 25 in which opposite prongs 42 of a two prong inserter 40 ( such as a “ pinching ” inserter as shown in fig7 a and 13 ) which may be used when inserting each of center portion 10 and top / bottom portions 20 through respective surgical cannulae 60 and 62 . if desired , the vertical height of the present system can be increased by stacking more than one center portion 10 ( as shown in fig2 in which an assembly 5 a is shown having two center portions 10 ). it is to be understood that more than two center portions 10 may be used in assembling the present intervertebral support system , as desired . in yet another optional aspect of the invention , assemblies 5 may be made small enough such that more than one can be positioned side by side in a patient &# 39 ; s intervertebral space . as is seen in fig2 , a two portion intervertebral support assembly sb is also contemplated . in this aspect of the invention , top portion 20 b is positioned directly on top of bottom portion 20 a , with recesses 21 a and 21 b interlocking together . many other system arrangements are possible . for example , two , or more than two portions 10 can be stacked on top of one another ( similar to the stacking of portions 20 in fig2 ).

US-98185807-A

the present invention relates to a biodegradable dual density cigarette . the invention provides for a cost - effective process that ensures that the non - filter cigarette has smoke delivery quality comparable to that of a conventional filter cigarette . the invention also substantially reduces the tar and nicotine contents . the dual density cigarette is biodegradable and therefore environment friendly .

the present invention provides for enhancement of smoke delivery profile comparable to normal synthetic filter cigarette as well as results in substantial lo reduction of tar and nicotine . due to the high density tobacco at the mouth end the sogginess of tobacco when put into the mouth and the entrance of loose tobacco particles entering into the mouth is also avoided the cigarette is 100 % biodegradable and is cost effective since the conventional machines can be used . this cigarette is to be smoked through high - density end and this high density tobacco portion is tipped with porous cork tipping paper of different colour for identification to enable the consumer to know that tipped portion of the cigarette is to be put in the mouth . high - density tobacco rods can be manufactured using tobacco material such as cut and rolled stem , graded tobacco , reconstituted tobacco , tobacco dust with binders as well as various combination of above or natural materials . density of such rod may be selected as per individual product need . normally the density selected are at least 280 mg / cc . fig1 shows that the tobacco or filler rod ( 1 ) is a blend of tobacco wrapped in a cigarette paper at a pressure drop of 22 to 50 mm of water column . the filler rod ( 1 ) is filled with blend of tobacco comprising 75 to 85 % of lamina and 15 to 25 % of the expanded stem fibres or cut - roll stem . the lamina is normal density tobacco of 4 - 6 cc / gm at the rate of 12 . 5 % oven volatile preferably 5 - 6 cc / gm at the rate of 12 . 5 % oven volatile . the butt portion ( 2 ) comprising cut - roll stem particles of expanded fibres of the density of at least 0 . 28 / cc wrapped in a porous paper of at least 100 mm of water gauge . the expanded stem is 4 - 7 cc / gm at the rate of 12 . 5 % oven volatile , preferably 6 - 7 cc / gm at the rate of 12 . 5 % oven volatile . the pressure drop in the tobacco rod is 5 - 9 water column per mm . of filler end while the pressure drop in the butt end is 3 - 4 water column per mm . the stem portion is the mid rib of tobacco plant leaf having lower nicotinic content and higher chloride content . normal and high - density tobacco rods are manufactured on cigarette making machine using normal cigarette paper as wrapper for the rod . the stem of the tobacco leaf is subjected to a conventional conditioning process for 10 to 20 minutes at 30 - 40 ° c . to quench the moisture uniformly . the quenched stem is passed through conditioning tunnel or through a flattner or a roller to flatten the stem . the stem is then cut into small particles of the size 30 to 180 cpi . the small particles are cut through an expansion heated tunnel at a temperature of 100 to 103 ° c . for a period of 20 to 30 seconds . the particles are passed through a drier and a classifier to obtain a cut roll stem ( crs ). the crs are cooled at room temperature by storing in boxes rolled humidifier . the cooled cut rolled stem are encapsulated in a filter wrapping paper to obtain the filter butt ;. the filler or tobacco rods are made to required length and then supplied to assembler , the purpose of this unit to assemble the normal and high density tobacco filter butts in the ratio of 5 : 1 . the assembler further cuts the high - density rods in suitable pieces normally 4 to 6 pieces called “ plugs ” but other combination are also possible . this is followed by assembly of these “ plugs ” with the normal tobacco rod and over tipping with the tipping paper of suitable width , size and colour . the tipping paper or plug wrap can either be normal or relatively high porous to give required smoke delivery values . this specially made dual density cigarette is capable of delivery of smoke profile comparable to any other conventional filters as is evident from the test results . while particular embodiments of the present invention have been illustrated and described , it would be obvious to those skilled in art that various other changes and modifications can be made without departing from the sprit and scope of the invention . it is therefore intended to cover in the appended claims all such changes and modifications that are with in the scope of the invention . the following table shows the typical example of the property of the butt end : average minimum maximum moisture 10 . 03 9 . 10 10 . 80 nicotine 0 . 73 0 . 22 1 . 34 trs 10 . 87 2 . 61 20 . 21 chloride 2 . 70 1 . 28 3 . 59 the following table shows the property of the filler or tobacco rod : average minimum maximum moisture 11 . 79 11 . 00 12 . 50 nicotine 1 . 82 1 . 63 2 . 00 trs 14 . 60 12 . 15 17 . 12 chloride 0 . 72 0 . 49 0 . 96 it is clear that the moisture nicotinic content are less in the butt end while trs and chloride content are more in the but end as compared to the filler end . a number of analytical tests were conducted to compare the tar and nicotine content of the non - filter cigarettes , filter cigarettes and dual density cigarettes . the three analytical tables are as given below : table 1 comprises of 3 sub - tables showing the density trend of micro plain cigarettes ( table 1a ), plain and regular filter type cigarettes ( table 1b ) and king size brands ( table 1c ). the tables 1a , 1b and 1c show the comparative tobacco density that exists in different brands of cigarette having a standard length of 59 mm . the data is taken for two years i . e . for the years 2000 and 2001 . the figures show that the average density of tobacco in micro plain brands ( table 1a ), filter size brands ( table 1b ) and the king size brands ( table 1c ) ranges between 232 mg / cc and 264 mg / cc . the table 2 features the analytical data showing the comparison of tar and nicotine in the non - filter and dual density cigarettes . the analytical data reveals that the dual density cigarettes shows lesser value of the tar & amp ; nicotine as compared with the non - filter cigarettes of same lengths . table 3 shows the comparison of “ tar ” and “ nicotine ” yield obtained from the conventional filter tipped cigarettes , the dual density cigarettes fitted with present invention and the non - filter plain cigarette . the table reveals that the quality of smoke delivery of dual density cigarette is comparable with the filter cigarette . the tar content of the smoke from the dual density cigarette with a circumference of 24 . 44 mm is slightly higher than the tar content in the filter cigarette with the circumference of 24 . 46 mm . table 1a density trend of micro plain brands brands 59 mm month brands year jan feb mar apr may jun jul aug sep oct nov dec avg min max cav super 2001 259 261 254 253 251 252 256 244 266 2000 256 259 257 250 251 266 254 244 260 fs super 2001 245 272 257 252 255 250 258 250 250 254 245 272 2000 250 256 rw super 2001 255 254 264 260 246 253 233 249 248 255 271 253 233 278 2000 258 241 254 278 251 266 262 243 245 245 247 242 bristol std 2001 274 271 246 264 246 274 2000 capstan 2001 246 233 240 233 246 super 2000 scissors 2001 268 260 258 247 268 standard 2000 247 [ 0056 ] table 1b density trend of plain & amp ; regular filter size brands month brands year jan feb mar apr may jun jul aug sep oct nov dec avg min max cvgl - 69 mm 2001 261 267 253 257 260 267 255 263 263 263 260 247 267 2000 263 247 265 257 261 250 261 265 rw plain - 2001 270 273 245 272 249 249 251 252 242 273 67 mm 2000 245 243 247 244 251 245 253 255 255 244 242 scissors 2001 245 248 238 247 245 238 248 plain - 68 mm 2000 fs special 2001 254 259 254 257 255 263 267 278 262 260 262 266 260 254 278 2000 254 255 254 257 255 262 255 267 264 255 270 258 fs premier 2001 260 260 257 259 256 258 256 271 260 261 264 262 260 249 271 2000 254 261 257 260 249 265 257 264 267 252 rw flake 2001 257 253 254 261 261 265 265 266 252 258 267 258 244 267 2000 251 255 244 258 255 264 250 255 265 257 265 263 gf premium 2001 250 263 254 254 255 256 261 257 258 250 266 2000 256 263 266 261 257 262 wills flake 2001 256 255 262 265 261 255 274 2000 256 264 274 256 [ 0057 ] table 1c density trend of king size brands month brands year jan feb mar apr may jun jul aug sep oct nov dec avg min max fs kings 2001 248 246 242 255 251 251 255 266 257 253 252 255 252 242 266 2000 250 247 254 248 246 252 255 255 257 249 257 248 gf kings 2001 251 249 247 249 249 253 260 251 244 264 2000 252 257 252 244 244 248 251 classic kings 2001 264 244 252 249 244 255 2000 247 255 244 251 bh sp 2001 242 233 236 242 233 249 2000 249 246 245 555 kings 2001 244 244 243 245 2000 243 245 marlboro 2001 225 233 235 232 225 235 lights 2000 235 [ 0058 ] table 2 14 . 2 . 2002 analytical report dual density cigt . plain 59 × 24 . 50 × 11 mm crs ( den . sample type 59 × 24 . 50 pl ( den . 262 mg / cc 262 mg / cc ) test 59 mm 1 2 3 4 avg 1 2 avg iso tar mg / cig 16 . 9 17 . 4 16 . 3 15 . 9 16 . 6 15 . 5 15 . 2 15 . 4 nicotine mg / cig 1 . 43 1 . 57 1 . 47 1 . 48 1 . 49 1 . 26 1 . 27 1 . 27 cigt . length mm 59 59 59 59 59 59 59 59 ft length / type mm — — — — — 11 / crs 11 / crs 11 / crs circumference mm 24 . 57 24 . 57 24 . 57 24 . 57 24 . 44 24 . 43 24 . 44 density a mg / cc 259 261 263 261 259 263 261 12 . 5 % o . v . dual density cigt . plain 69 × 24 . 50 × 11 mm crs ( den . 262 sample type 69 × 24 . 50 pl ( den . 262 mg / cc mg / cc ) test 69 mm 1 2 3 4 avg 1 2 3 avg iso tar mg / cig 21 . 2 19 . 8 22 . 1 21 . 1 21 . 1 19 . 9 20 . 1 19 . 8 19 . 9 nicotine mg / cig 1 . 81 1 . 88 1 . 85 1 . 87 1 . 85 1 . 68 1 . 62 1 . 59 1 . 63 cigt . length mm 69 69 69 69 69 69 69 69 69 ft . length / type mm — — — — — 11 / cr 11 / cr 11 / cr 11 / cr s s s s circumference mm 24 . 59 24 . 59 24 . 58 24 . 59 24 . 42 24 . 42 24 . 42 density a mg / cc 262 262 268 264 269 264 267 12 . 5 % o . v . [ 0059 ] table 3 smoke 69 × 24 . 5 × 11 59 × 24 . 5 × 11 parameters 59 × 24 . 5 pi . mm crs mm ca iso tar 16 . 6 15 . 4 14 . 9 nicotine 1 . 49 1 . 27 1 . 27 circum - 24 . 57 24 . 44 24 . 46 ference

US-39612803-A

the current invention discloses a fluid reservoir module for holding a fluid that may be used in a fluid dispenser . the fluid reservoir has a base , a reservoir body enclosing an internal void , and at least one removable tab attached to the reservoir body . the reservoir body is disposed on the base and the removable tab blocks inserting the reservoir body into a dispenser body . by detaching the removable tab , the reservoir body may be inserted into the dispenser body . simultaneously , a fluid transfer structure , preferably a hollow spike , may penetrate a frangible part of the reservoir so that fluid in the reservoir may be extracted . the fluid in the reservoir is preferably pre - loaded . the current invention is particularly useful for dispensing small amounts of fluid , such as eye drops , but it may also be scaled up for larger volumes .

the preferred embodiments of the present invention will now be described with reference to the drawings . identical elements in the various figures are identified , as far as possible , with the same reference numerals . reference will now be made in detail to embodiments of the present invention . such embodiments are provided by way of explanation of the present invention , which is not intended to be limited thereto . in fact , those of ordinary skill in the art may appreciate upon reading the present specification and viewing the present drawings that various modifications and variations can be made thereto without deviating from the innovative concepts of the invention . fig1 shows a perspective view of the preferred embodiment of a fluid dispenser 1 having a reservoir module 5 , with the reservoir module 5 shown in its “ pre - loaded ” state and prior to initial use . shown in fig1 is the fluid dispenser 1 having a dispenser body 10 and a reservoir module 5 , the reservoir module including a base 12 and a reservoir body 11 having weld - seam protrusions 14 . as shown in fig1 , the reservoir body 11 is disposed beneath the dispenser body 10 , and held in place by two removable tabs 15 . the base 12 is positioned under the reservoir body 11 and attaches to the reservoir body 11 by means of ribs 13 . upon removal of the removable tabs 15 , the reservoir body 11 may be fully inserted into dispenser body 10 . in addition , snapping tongue 16 resides on base 12 and snaps into a snapping tongue receiver ( not shown ) within dispenser body 10 when the reservoir body 11 is fully inserted . the fluid dispenser 1 may be used for various purposes . the preferred use of the fluid dispenser 1 is to deliver eye drops to a human eye . the fluid dispenser 1 may be used in an up - right position , or it may be leaned forward to deliver a dose to a person whose eye is directly below the dispenser , as is typical with the use of dropper bottles , and the fluids discharged from the fluid dispenser 1 may be applied in a trajectory that ends up on a target , such as an eye . the fluid dispensed may be any fluid or liquid . the fluid may be a pharmaceutical formulation , solution , gel , or suspension . the fluid may be delivered to the eye , ear , or any other targets . fig2 shows a side view of the preferred embodiment of the fluid dispenser 1 having a reservoir module 5 , with the reservoir module 5 shown in its “ pre - loaded ” state and prior to initial use . shown in fig2 is the fluid dispenser 1 having a dispenser body 10 and a reservoir module 5 , the reservoir module including a reservoir body 11 and a base 12 . as shown in fig2 , the reservoir body 11 is disposed beneath the dispenser body 10 , and held in place by two removable tabs 15 . the base 12 is positioned under the bottom portion 45 of the reservoir body 11 and attaches to the bottom portion 45 by means of ribs 13 , the ribs 13 having a profiled inner form 17 which conforms with profiled surfaces 18 on the bottom portion 45 of the reservoir body 11 . markers a and a ′ serve as indicators for sectional views of the dispenser and / or the reservoir module shown in fig6 . it should be noted that the base 12 is not an indispensible structure for the reservoir module though it is preferred that base 12 is included . base 12 provides a foundation onto which the reservoir body 11 and other structures such as the snapping tongue 16 may be positioned . without the base 12 , the reservoir body 11 may be the structure at the bottom . in that case , it is preferred that the bottom portion 45 of the reservoir body 11 is enlarged so that it is not completely inserted into the dispenser body and serves as the supporting structure . fig3 shows a top view of the preferred embodiment of the fluid dispenser 1 having reservoir module , with the reservoir module shown in its “ pre - loaded ” state and prior to initial use . shown in fig3 are the dispenser body 10 and the removable tabs 15 of the reservoir module . markers b and b ′ serve as indicators for sectional views of the dispenser and reservoir module shown in fig4 - 5 . fig4 shows a side sectional view of the preferred embodiment of the fluid dispenser 1 having a reservoir module 5 , with the reservoir module 5 shown in its “ pre - loaded ” state and prior to initial use . the section is indicated in fig3 by markers b and b ′. shown in fig4 is the fluid dispenser 1 having a dispenser body 10 and a reservoir module 5 , the reservoir module 5 including a reservoir body 11 , a base 12 , and ribs 13 . the reservoir body 11 encloses an internal void 33 . the dispenser body encloses an interior , which is divided by a bulkhead 27 into an upper chamber 30 and a lower chamber 40 . as shown in fig4 , the reservoir body 11 has weld - seam protrusions 14 . these protrusions may be omitted if the reservoir body is not made from the bfs process or if proper steps are taken to eliminate such welding features . for the embodiment shown in fig4 , the weld - seam protrusions are connected to projecting arms 22 . the projecting arms 22 are spring - loaded such that they maintain sliding contact with two pairs of retaining beads 23 residing in the dispenser body 10 . the removable tabs 15 have a notch 20 that engages with a block tip 21 on the dispenser body 10 . prior to use , tabs 15 are removed from the reservoir body 10 by a twisting action , and are then detached . the removal of tabs 15 permits the projecting arms 22 to slide upwards between retaining beads 23 to guide the reservoir body 11 into the lower chamber 40 . after the reservoir body 11 is completely inserted , the base 12 engages the dispenser body 10 and the reservoir body 11 resides in the lower chamber . during the sliding engagement of the reservoir body 11 and dispenser body 10 the lower portion of the weld - seam protrusion 14 also enters the gap between the retaining beads 23 to provide further alignment . the removable tabs 15 are used to block the insertion of the reservoir body 11 into the dispenser body 10 . however , it should be noted that the removable tab is not an indispensible structure , nor is the number of removable tabs fixed . when there is no removable tab 15 included in the reservoir module , other structures may serve as the blocking mechanism . for example , without the removable tabs 15 , the projecting arm 22 shown in fig4 may be made from roughened materials or may have roughened surfaces facing the inner walls of the dispenser body 10 . the substantial friction between the projecting arm 22 and the dispenser body wall may prevent the unwanted insertion of the reservoir body . alternatively , there may be engaging mechanisms present on the projecting arm 22 and the dispenser body wall . for example , there may be semi - spherical protrusions on the projecting arm and corresponding sockets on the dispenser body wall . the protrusion - socket engagement may block the insertion of the reservoir body , while pushing forces exceeding a certain threshold may disengage the attachment and allow the insertion . as shown in fig4 , a hollow spike 24 having a through hole 25 extends downward from the bulkhead 27 . the upper end of the through hole 25 in the hollow spike 24 levels with the top of bulkhead 27 . the upper portion 29 of the hollow spike 24 is positioned close to the bottom of the bulkhead 27 , the upper portion having a bigger diameter than the other parts of the hollow spike 24 . through the bulkhead 27 and adjacent to the through hole 25 is a second hole 26 , which continues downwards as a partial hole along the upper portion 29 of the hollow spike 24 . the upper chamber 30 above the bulkhead 27 may be used to accommodate a pump mechanism ( not shown ) which connects to the through hole 25 in the hollow spike 24 . the through hole 25 may serve as an inlet for the fluid held in the internal void 33 to be supplied to any suitable form of pump , which provides the propelling forces to dispense the fluid through an outlet . fig5 shows a side sectional view of the reservoir module 5 , with the reservoir module shown in its “ pre - loaded ” state and prior to initial use . the section is indicated in fig3 by markers b and b ′. shown in fig5 is part of the fluid dispenser 1 having a dispenser body 10 and a reservoir module 5 , the reservoir module 5 including a reservoir body 11 , removable tabs 15 , a base 12 , and ribs 13 . the reservoir body 11 encloses an internal void 33 , which defines the reservoir module &# 39 ; s volumetric capacity . as shown in fig5 , the top portion of the reservoir body 11 has an upper neck 31 encircling a neck hole 32 . the neck hole 32 is covered by a thin frangible membrane 34 . when the frangible membrane 34 is intact , the internal void 33 is hermetically sealed . the hollow spike 24 is retained in position closely above the frangible membrane 34 in the pre - loaded state . fig6 shows a sectional view of the reservoir module 5 , with the reservoir module shown in its fully loaded state , and ready for use . the section is indicated in fig2 by markers a and a ′. shown in fig6 is part of the fluid dispenser 1 having a dispenser body 10 and a reservoir module 5 , the reservoir module 5 including a reservoir body 11 and a base 12 . the reservoir body 11 encloses an internal void 33 . the hollow spike 24 protrudes from the bottom side of the bulkhead 27 , which separates the interior of the dispenser body 10 into a lower chamber 40 and an upper chamber 30 ( not shown in fig6 ). in the fully loaded state , as shown in fig6 , the reservoir body 11 is accommodated in the lower chamber 40 , the base 12 is engaged with the lower end of the dispenser body 10 , and in particular the blocking tip 21 , and hollow spike 24 is inserted into the internal void 33 of the reservoir module 5 . during the insertion of the reservoir body 11 into the lower chamber 40 , the frangible membrane 34 is pierced by the hollow spike 24 . as shown in fig6 , once the lower tip 28 of the hollow spike 24 reaches the bottom of the internal void 33 of the reservoir body 11 , the fluid in the internal void 33 may be extracted by pump mechanisms through the through hole 25 of the hollow spike 24 . simultaneous with the lower tip 28 of the hollow spike 24 reaching the bottom of the internal void 33 of the reservoir body 11 , a vent path 36 is established through neck hole 32 and the second hole 26 on the bulkhead . the vent path 36 allows the internal void 33 of the reservoir body 11 to prevent a vacuum from forming within the internal void 33 as fluid is drawn from it by the pump mechanism . any suitable form of pump ( not shown ), and as housed within the upper chamber 30 , may connect with hole 26 to provide atmospheric venting to reservoir body 11 . fig7 shows a perspective view of the preferred embodiment of the fluid dispenser 1 having a reservoir module 5 , with the reservoir module in its fully loaded state and the base part secured . shown in fig7 are the dispenser body 10 and the base 12 of the reservoir module . in this state , the dispenser is fully assembled ( loaded ) and ready to be used . the dispenser body 10 and the reservoir body 11 may be made from the same or different materials including but not limited to metal , wood , and plastics such as but not limited to , polyethylene terephthalate ( pet ), polyethylene ( pe ), high - density polyethylene ( hdpe ), polyvinyl chloride ( pvc ), polyvinylidene chloride ( pvdc ), low - density polyethylene ( ldpe ), polypropylene ( pp ), polystyrene ( ps ), high impact polystyrene ( hips ) and polycarbonate ( pc ), or paperboard coated with a suitable waterproof coating , or some combination thereof . the preferred materials for the dispenser body 10 and the reservoir body 11 are plastics , including but not limited to : acrylics , polypropylene , polyethylene , and most other families of thermoplastic resins or co - polymers . similarly , the various components of the fluid dispenser 1 , including the components of the reservoir module 5 , may be made from the same or different materials as the dispenser body 10 and reservoir body 11 . some components may have special requirements as to the property of the materials . for example , the frangible membrane may be made from a thin flexible plastic , such as cellophane . as indicated above , the current reservoir module and dispenser incorporating the module may be used for many purposes and the embodiments may be any dimension that is suitable for the use of the dispenser . preferably , the reservoir and dispenser are used for the delivery of ophthalmic fluids in small doses , such as 1 to 100 microliters per dose . the reservoir module may hold multiple doses of the fluid to be dispensed , with a preferred overall volume to be 100 microliters to 500 milliliters . nevertheless , the reservoir module and the dispenser may be scaled up for dispensing large quantities of liquid . preferably , the reservoir module is pre - filled with the fluid to be dispensed and the dispenser , including the reservoir module , is provided to a user in a pre - loaded state . the user then may detach the removable tab 15 , insert the reservoir module , and start using the dispenser . however , the dispenser may be provided to the user with the reservoir module already in a fully loaded condition . the reservoir module may also be coupled with different kinds of pump mechanisms , as indicated above . although this invention has been described with a certain degree of particularity , it is to be understood that the present disclosure has been made only by way of illustration and that numerous changes in the details of construction and arrangement of parts may be resorted to without departing from the spirit and the scope of the invention .

US-201214235212-A

a sitting group that can be used for sitting purposes , as well as advertisement media in gardens , green fields , shopping centers , etc .

the product of the invention is complete with the main body ( 1 ) as the frame . the backrest body ( 2 ) and sitting body ( 3 ) are installed on the main body ( 1 ). the backrest body and sitting body ( 2 and 3 ) are fixed onto the main body ( 1 ) via robust fasteners like bolts and nuts , etc . there are information zones ( 4 ) on the back surfaces of backrest body and sitting body ( 2 and 3 ). there is information zones ( 4 ) are suitable for accommodating the advertisements , promotions , warning , as similar inscriptions / visuals , as necessary . thanks to the pivoting spindles ( 5 ) incorporated on the sitting body ( 3 ); it is rotational along the spindle grooves ( 6 ) on the main body ( 1 ) around its own axis . the center of gravity of the product of the invention is located at the back of the sitting body ( 3 ). by this way , it is possible to fold the sitting body ( 3 ) toward to the backrest body ( 2 ) when the sitting body ( 3 ) is not in use and this exposes the information zones ( 4 ) located on the bottom surface . the option is also provided to incorporate the motion pistons ( 7 ) to the product of the invention . the motion pistons ( 7 ) ensure progressive folding of the sitting body ( 3 ). by this way , instant folding of the sitting body ( 7 ) onto the main body ( 1 ) or hitting to the backrest body ( 2 ) and thus any deformation is prevented and the service life of the product of the invention is increased . the product of the invention will be preferred and have a competitive stand in the market , since it saves the available area and be used in confined areas for the advertisement and promotion .

US-201114350633-A

board - based machines assembled from components including crank and winch attributes which allow for coupling between the components , and which allows the user to position various elements into desired positions . a kit of components including coupling attributes which allow for assembly into a large number of different types of machines and structures of different types and shapes . a book adapted to teach children about mechanical aspects of design in concert with a kit of components adapted to be used to create board based machines .

in some embodiments of the present invention , a kit of pieces adapted to be constructed into a variety of shapes , and into a variety of configurations , allows for the construction of machines which may illustrate for the user , especially a child , aspects of mechanical relationships . the kit of pieces may be used in conjunction with a book which may act as an instruction book on how to assemble various configurations which incorporate mechanical relationships . the kit may include ornamental pieces which may be incorporated into the mechanical design pieces and which may further enhance the experience for a young child . it will be appreciated , as the following description of the various pieces proceeds , that a kit made according to the teachings of the present invention can include any number and variety of the pieces described herein . fig1 illustrates a mounting board 101 adapted to act as the base for the building of a variety of types of mechanisms with the use of a kit of piece part elements . the mounting board 101 has a plurality of top holes 112 spaced in a pattern which allow a variety of insertion points into the top holes 112 , which have an axis perpendicular to the main plane of the mounting board 101 . the mounting board has a plurality of side holes 111 space along the edge of the mounting board 101 . the side holes have an axis parallel to the main plane of the mounting board 101 , and allow for insertion into the sides of the mounting board 101 . fig2 illustrates a shaft 102 adapted to be used for a variety of purposes . the shaft 102 may be a long , narrow cylinder . the shaft 102 is adapted to be inserted in the top holes 112 or the side holes 111 and may be retained with some gripping force due to a minor interference fit , or through other gripping means . in some aspects , the shaft 102 may be used to support a wheel as an axle . in some aspects , shafts 102 may be used to join mounting boards 101 together . fig3 illustrates a wheel 103 adapted to be used for a variety of purposes . the wheel 103 has a hole 117 which may allow for the placement of the wheel 103 over a shaft 102 in some aspects . the wheel 103 has a wheel fitting 114 adapted to interlock with a crank handle to allow for manual cranking of the wheel 103 . the wheel 103 may also have holes 113 which may allow for insertion of one or more shafts 102 through the wheel . the wheel 103 may also have holes 121 which may allow for insertion of shaft 102 with some gripping force due to a minor interference fit . in some embodiments , the wheel 103 may have a surface along its exterior radial periphery adapted to allow for the application of mechanical advantage . this surface may be part of a hook and loop fastening system , allowing rotation of the wheel 103 to be translated into linear motion of a ribbon 106 which has the mating part of the hook and loop fastening system thereon . in some aspects , character figures may have a mating interface for the wheel fitting such that the character figure may mount on the wheel . fig4 illustrates a crank arm 104 adapted to be used in conjunction with a wheel 103 . the crank arm 104 has a crank fitting 115 adapted to mate with a wheel fitting 103 in order to allow a user to rotate a wheel 103 by cranking the crank handle 116 of the crank arm 104 . in cases wherein the wheel 103 has a loop or hook surface , the cranking of the wheel translates rotary motion of the crank arm 104 into a linear motion of the ribbon 106 . in some aspects , a plurality of wheels may be interlinked with a ribbon , or other flexible element , and all of the wheels may be rotated with the cranking of a single crank arm engaged with the ribbon . in some aspects , wheels other than the wheel with the crank arm may have character figures mounted thereon , allowing for rotation of the character figures on the wheels engaged on the ribbon with the rotation of the crank arm . the use of a ribbon may enhance a playful aspect of the use of the kit by children , while simultaneously allowing the child to learn about mechanical relationships . fig5 is an exploded perspective view illustrating the use of a mounting board 101 as a base for a wheel assembly . a shaft 102 is inserted into a top hole 112 of the mounting board 101 . a wheel 103 is placed over the shaft 102 . the wheel 103 is then able to spin freely around a vertical axis . a crank arm 104 is placed onto the top of the wheel 103 through the interlocking of the wheel fitting 114 and the crank fitting 115 . when assembled in this manner , the crank arm allows for the rotation of the wheel 103 by the user . fig6 illustrates an exemplary machine assembly 120 according to some embodiments of the present invention . a mounting board 101 is seen with a plurality of wheels 103 mounted thereon . the wheels 103 are placed on shafts 102 inserted into top holes 112 in the mounting board 101 . a ribbon 106 is threaded in a serpentine pattern around the wheels 103 . other shafts 102 are mounted into top holes 112 and are used as guide posts for the serpentine ribbon path . the shafts used as guide posts have caps 105 mounted onto their top ends . with the engagement of the hook and loop portion on the ribbon with the portion on the wheels , the pulling of the ribbon 106 , whether by hand or with the use of a wheel with a crank mounted thereon , will cause the rotation of all of the wheels 103 . for example , the hooks may be on the central engagement portion of the wheels , and the loops may be integral to one or both sides of the ribbon . when character figures are mounted on the wheels 103 , the rotation of the wheels 103 will cause the rotation of the character figures . with a kit of pieces , which may include a plurality of shafts , wheels , and caps , the user may create numerous configurations of integrated machines which may move in a synchronous manner . fig7 illustrates an exemplary machine assembly 130 according to some embodiments of the present invention . a plurality of mounting boards 101 are seen with a plurality of wheels 103 mounted thereon . the wheels 103 are placed on shafts 102 mounted horizontally between caps 105 on shafts 102 inserted into top holes 112 in the mounting board 101 . a ribbon 106 is threaded in a linear pattern around the wheels 103 . in embodiments such as this , two boards 101 are attached at right angles to each other . shafts 102 are linked with caps 105 to effect a right angle attachment between two of the mounting boards 101 . with the engagement of the hook and loop portion on the ribbon with the portion on the wheels , the pulling of the ribbon 106 , whether by hand or with the use of a wheel with a crank mounted thereon , will cause the rotation of all of the wheels 103 . with a kit of pieces , which may include a plurality of shafts , wheels , and caps , the user may create numerous configurations of integrated machines which may move in a synchronous manner . fig8 illustrates an exemplary machine assembly 140 according to some embodiments of the present invention . a mounting board 101 is seen with a plurality of shafts 102 mounted thereon . wheels 103 are placed on shafts 102 mounted horizontally between caps 105 on shafts 102 inserted into side holes 111 in the mounting board 101 . a ribbon 106 is threaded in a linear pattern around the wheels 103 . the ribbon finds friction with the wheel with hook and loop features , and then may be threaded around another wheel to create a pulley mechanism . where the ribbon is pulled , the wheel / shaft / cap combination may lift upward off the mounting surface . in embodiments such as this , shafts are used as supports of the mounting board to raise it off of the mounting surface . shafts 102 are linked with caps 105 to effect a right angle or continuation attachments between two or more of the shafts . longer shafts may be part of the kit of pieces available to the user in some embodiments . fig9 and 10 illustrate using wheels mounted adjacently at right angles in order to create a driving effect from a first wheel to a second wheel . in addition to the driving of a wheel by the use of a ribbon , wheels mounted adjacently , and at right angles to each other , may drive one another through frictional engagement . in an exemplary embodiment , a mounting board may be 24 . 5 cm square and 1 . 5 cm thick , with 0 . 7 cm holes on 3 . 65 cm spacings , offset . the shaft may be 6 . 5 cm long and 0 . 6 cm in diameter , with longer shaft pieces at 13 cm long . the wheels may be 5 cm in height and 3 . 5 cm in diameter , with the 1 . 4 cm loop side of the hook and loop fasteners affixed thereon . the ribbon / tape may be 3 cm wide with different lengths ( for example 4 feet long ) with a 3 cm × 1 . 5 cm hook side of the hook and loop fasteners affixed thereon . as evident from the above description , a wide variety of embodiments may be configured from the description given herein and additional advantages and modifications will readily occur to those skilled in the art . the invention in its broader aspects is , therefore , not limited to the specific details and illustrative examples shown and described . accordingly , departures from such details may be made without departing from the spirit or scope of the applicant &# 39 ; s general invention .

US-201313831776-A

a medical instrument is provided with enhanced ultrasonic visibility . the medical instrument includes an elongate probe or needle for insertion into a patient . selected locations along the instrument are provided with deposits of a material exhibiting a high degree of ultrasonic reflectivity . the material includes a matrix of gas bubbles contained in a polymeric material . the gas bubbles exhibit high reflectivity of ultrasonar energy .

a needle assembly in accordance with the subject invention identified generally by the numeral 10 , is depicted 10 in fig3 - 5 . needle assembly 10 includes a biopsy needle 12 having an elongate needle cannula 14 . needle cannula 14 has a proximal end 16 , an opposed sharply pointed distal end 18 and a cylindrical lumen 20 extending therebetween as shown in fig4 and 5 . needle cannula 14 also includes a substantially smooth cylindrical exterior surface 22 . as shown in fig5 needle cannula 14 typically will define an outside diameter &# 34 ; a &# 34 ; of about 0 . 020 - 0 . 080 inch and a wall thickness b of about 0 . 003 - 0 . 010 inch . biopsy needle 12 further includes a mounting hub 24 securely affixed to proximal end 16 of needle cannula 14 . mounting hub 24 is threadedly engageable with a luer collar of hypodermic syringe ( not shown ). biopsy needle assembly 10 includes a stylet 26 slidably and removably disposed within lumen 20 of needle cannula 14 . stylet 26 substantially blocks lumen 20 to prevent distal end 18 of needle cannula 14 from butting a core of tissue during insertion of needle cannula 14 into a patient . stylet 26 typically will be retained in needle cannula 14 during insertion of needle cannula 14 into a patient . however , stylet 26 may be slidably removed from needle cannula 14 after distal end 18 of needle cannula 14 is properly positioned in the patient . mounting hub 24 may then be threadedly engaged with a luer collar of a hypodermic syringe . biopsy needle 12 is characterized by one or more ultrasonic reflectors 28 - 32 at axial spaced positions along needle cannula 14 . ultrasonic reflector 28 functions to locate distal end 18 of needle cannula 14 in the video image produced by an ultrasonic imaging apparatus . as a result , ultrasonic reflector 28 is desirably close to distal end 18 and a known distance &# 34 ; c &# 34 ; therefrom . ultrasonic reflectors 30 and 32 are used to define the alignment of needle cannula 14 on the video monitor of the ultrasonic imaging apparatus . as a result , the precise location and spacing between ultrasonic reflectors 28 - 32 normally is less critical than the distance &# 34 ; c &# 34 ; between ultrasonic reflector 28 and distal end 18 . as shown most clearly in fig4 and 5 , the ultrasonic reflectors define annular deposits of ultrasonically reflectable material securely disposed on outer circumferential surface 20 of needle cannula 14 . each ultrasonic reflector is preferably a polymeric foam having a matrix of gas bubbles contained therein and sized to maximize the number of reflecting surfaces in the space available . as noted above , air is a good reflector of ultrasonic energy . furthermore , the large number of spherical air bubbles entrained in each reflector 28 - 32 provide a large number of surfaces from which the ultrasonic energy may be reflected . spherically shaped air bubbles are desirable because the spherical surface always presents a reflective facet or surface portion to the observer . although some of the ultrasonic energy will be reflected away from the transducer of the ultrasonic imaging apparatus , each spherical air bubble significant percentage will be reflected along alignments that will enable detection by the transducer . smaller bubbles , even microscopic in size , are desirable . regardless of the angle of incidence , virtually all spherical bubbles impinged upon by ultrasonic energy will reflect some of the ultrasonic energy impinging thereon back toward transducer 100 , as illustrated schematically in fig6 and 7 . this will result in a circumferentially much wider and axially much longer reflective area than had been available in the prior art . additionally , ultrasonic energy that is not reflected by the air bubbles will pass through the ultrasonic reflector 28 - 32 and may be reflected by the underlying needle cannula 14 . thus , ultrasonic reflectors 28 - 32 effectively add to any ultrasonic reflectivity that may be provided by the underlying portions of the needle cannula 14 . the preferred embodiment depicted in fig4 and 5 includes the polymeric foam material with the matrix of entrained air bubbles deposited directly on the exterior surface 22 of the cylindrical needle cannula 14 . this construction will provide a slight cross - sectional discontinuity at axial locations along the needle cannula 14 coinciding with each ultrasonic reflector 28 - 32 . the cross - sectional discontinuity will provide no functional disadvantages for most applications . in this regard , cross - sectional discontinuities are defined by the above described prior art biopsy needles with annular grooves . applications may exist where a more uniform cross - section is desired . for these applications , as shown in fig8 undercuts 34 are provided in the needle cannula 14 &# 39 ; at selected locations . the polymeric foam with the matrix of entrained air bubbles is then deposited in the undercut 34 to define an ultrasonic reflector 36 having an outside diameter approximately equal to the outside diameter &# 34 ; a &# 34 ; of needle cannula 14 &# 39 ;. undercut 34 also defines a region along needle cannula 14 &# 39 ; for mechanically anchoring the annular band of polymeric foam which defines the ultrasonic reflector 36 . the technology of making plastic materials having air bubbles , such as foam , is known in the art . several different methods are used to produce foam parts , these methods or systems disburse a gas into the polymer melt during processing . this is done either by adding a chemical blowing agent to the compound or by inducing a gas directly into the melt . the gas creates the cellular core structure in the part during the molding process . one way of making the medical instrument of the present invention is to insert mold the ultrasonically reflectable material around the probe or needle cannula . curable resin , containing gas bubbles , may also be applied to the exterior of the probe or needle cannula .

US-6291793-A

a novel inbred corn line , designated lh283 , is disclosed . the invention relates to the seeds of inbred corn line lh283 , to the plants of inbred corn line lh283 and to methods for producing a corn plant produced by crossing the inbred line lh283 with itself or another corn line . the invention further relates to hybrid corn seeds and plants produced by crossing the inbred line lh283 with another corn line .

inbred corn line lh283 is a yellow dent corn with superior characteristics , and provides an excellent parental line in crosses for producing first generation ( f 1 ) hybrid corn . this inbred is best adapted for the northcentral region of the united states . inbred corn line lh283 was developed from the cross va99 × lh82 by selfing and using the ear - row pedigree method of breeding . yield , stalk quality , root quality , ear retention , disease tolerance , late plant greenness , late plant intactness , ear retention , pollen shedding ability , silking ability and corn borer tolerance were the criteria used to determine the rows from which ears were selected . selfing and selection were practiced within the above f 1 cross for seven generations in the development of lh283 . during the development of the line , crosses were made to inbred testers for the purpose of estimating the line &# 39 ; s general and specific combining ability , and evaluations were run by the williamsburg , iowa research station . the inbred was evaluated further as a line and in numerous crosses by the willaimsburg , iowa research station and other research stations across the corn belt . the inbred has proven to have a very good combining ability in hybrid combinations and to produce hybrids which are better adapted for several environments within the corn belt . the inbred has shown uniformity and stability for all traits , as described in the following variety description information . it has been self - pollinated and ear - rowed a sufficient number of generations , with careful attention to uniformity of plant type to ensure homozygosity and phenotypic stability . the line has been increased both by hand and sibbed in isolated fields with continued observation for uniformity . no variant traits have been observed or are expected in lh283 . inbred corn line lh283 , being substantially homozygous , can be reproduced by planting seeds of the line , growing the resultant corn plants under self - pollinating or sib - pollinating conditions with adequate isolation and harvesting the resultant seed , using techniques familiar to the agricultural arts . inbred corn line lh283 has the following morphologic and other characteristics ( based primarily on data collected at williamsburg , iowa ). the number in each parenthesis corresponds to the standard deviation in a sample size of 50 , unless marked by an asterisk for which case the sample size is 15 . leaf angle : 21 ° ( 5 . 54 ) ( measured from 2nd leaf above ear at anthesis to stalk above leaf ) leaf sheath pubescence : 3 ( rated on scale from 1 = none to 9 = like peach fuzz ) tassel length ( from top leaf collar to tassel tip ): 39 . 3 cm ( 3 . 50 ) pollen shed : 7 ( rated on scale from 0 = male sterile to 9 = heavy shed ) silk color ( 3 days after emergence ): light green ( munsell code : 2 . 5gy 8 / 4 ) fresh husk color ( 25 days after 50 % silking ): light green ( munsell code : 2 . 5gy 8 / 6 ) dry husk color ( 65 days after 50 % silking ): buff ( munsell code : 7 . 5yr 7 / 4 ) husk tightness : 6 ( rated on scale from , 1 = very loose to 9 = very tight ) stay green ( at 65 days after anthesis ): 8 ( rated on scale from 1 = worst to 9 = excellent ) this invention is also directed to methods for producing a corn plant by crossing a first parent corn plant with a second parent corn plant , wherein the first or second corn plant is the inbred corn plant from the line lh283 . further , both first and second parent corn plants may be from the inbred line lh283 . therefore , any methods using the inbred corn line lh283 are part of this invention : selfing , backcrosses , hybrid breeding , and crosses to populations . any plants produced using inbred corn line lh283 as a parent are within the scope of this invention . advantageously , the inbred corn line is used in crosses with other corn varieties to produce first generation ( f 1 ) corn hybrid seed and plants with superior characteristics . as used herein , the term &# 34 ; plant &# 34 ; includes plant cells , plant protoplasts , plant cell of tissue culture from which corn plants can be regenerated , plant calli , plant clumps , and plant cells that are intact in plants or parts of plants , such as embryos , pollen , flowers , kernels , ears , cobs , leaves , husks , stalks , root , root tips , anthers , silk and the like . tissue culture of corn is described in u . s . pat . nos . 4 , 665 , 030 , 4 , 806 , 483 and 4 , 843 , 005 , incorporated herein by reference . corn tissue culture procedures are also described in green and rhodes , &# 34 ; plant regeneration in tissue culture of maize &# 34 ;, maize for biological research ( plant molecular biology association , charlottesville , va . 1982 ), at 367 - 372 . thus , another aspect of this invention is to provide for cells which upon growth and differentiation produce the inbred line lh283 . transformation of corn is described in u . s . pat . nos . 5 , 384 , 253 , 5 , 489 , 520 , 5 , 538 , 877 and 5 , 550 , 318 , incorporated herein by reference . corn transformation is also described in prioli and sondahl , &# 34 ; plant regeneration and recovery of fertile plants from protoplasts of maize ( zea mays l . )&# 34 ;, bio / technology 7 : 589 - 594 ( 1989 ); shillito et al ., &# 34 ; regeneration of fertile plants from protoplasts of elite inbred maize &# 34 ;, bio / technology 7 : 581 - 587 ( 1989 ). thus , another aspect of this invention is to provide inbred line lh283 which contains a heterologous gene . lh283 is most similar to parental line va99 . however the most distinguishing difference is silk color . the silk color of lh283 is green , while the silk color of va99 is red . when using the munsell color charts for plant tissues as a reference , the silk color of lh283 is classified as 2 . 5gy 8 / 6 and the silk color of va99 is classsified as 2 . 5r 4 / 6 . the tassel branch angle of lh283 is less and more upright than the tassel branch angle of va99 . the data for tassel branch angle for lh283 and va99 with 50 observations from two different planting dates during the 1996 growing season are as follows : ______________________________________a ) average : standard deviation : lh283 : 22 . 94 lh283 : 6 . 65 va99 : 62 . 10 va99 : 12 . 00 statistic : t = - 20 . 17 ( df = 76 ) probability value : 0 . 000b ) average : standard deviation : lh283 : 20 . 23 lh283 : 5 . 01 va99 : 51 . 03 va99 : 9 . 73 statistic : t = - 15 . 42 ( df = 43 ) probability value : 0 . 000______________________________________ in both cases , the data shuggests a significant difference at the 1 % probability level according to a paired t - test . the means show that on average the tassel branch angle of lh283 is less than the tassel branch angle of va99 . the embryo on a normal kernel of dent corn , when the kernel is still attached to the cob , faces toward the tip of the ear . however , some of the kernels of lh283 while still attached to the cob , exhibit a unique trait of facing the butt of the ear as well as the tip . lh283 is a medium season field corn inbred line that flowers similar to lh216 . it is an excellent pollinator , but is not suitable for use as a seed parent . in addition to high yield , lh283 contributes a number of other favorable characteristics to its hybrids : a long cylindrical ear , excellent staygreen , very good test weight and grain quality , favorable plant height and ear height and very good leaf disease tolerance especially to gray leaf spot . however , lh283 is susceptible to second brood corn borer which does cause some late season stalk lodging below the ear . lh283 contributes adequate root strength to its hybrids , but fall root strength can be weak at times . lh283 combines well with members of the stiff - stalk family and its hybrids are best adapted to the central and southern corn belt . when compared to lh172 crosses , lh283 hybrids are substantially higher yielding with 1 % higher moisture . in the tables that follow , the traits and characteristics of inbred corn line lh283 are given in hybrid combination . the data collected on inbred corn line lh283 is presented for the key characteristics and traits . the tables present yield test information about lh283 . lh283 was tested in several hybrid combinations at seven to thirteen locations , with two or three replications per location . information about these hybrids , as compared to several check hybrids , is presented . the first pedigree listed in the comparison group is the hybrid containing lh283 . information for the pedigree includes : 2 . a mean for the percentage moisture (% m ) for the hybrid across all locations . 3 . a mean of the yield divided by the percentage moisture ( y / m ) for the hybrid across all locations . 4 . a mean of the percentage of plants with stalk lodging (% sl ) across all locations . 5 . a mean of the percentage of plants with root lodging (% rl ) across all locations . 6 . a mean of the percentage of plants with dropped ears (% de ). 7 . the number of locations indicates the locations where these hybrids were tested together . the series of hybrids listed under the hybrid containing lh283 are considered check hybrids . the check hybrids are compared to hybrids containing the inbred lh283 . the (+) or (-) sign in front of each number in each of the columns indicates how the mean values across plots of the hybrid containing inbred lh283 compare to the check crosses . a (+) or (-) sign in front of the number indicates that the mean of the hybrid containing inbred lh283 was greater or lesser , respectively , than the mean of the check hybrid . for example , a + 5 in yield signifies that the hybrid containing inbred lh283 produced 5 bushels more corn than the check hybrid . if the value of the stalks has a (-) in front of the number 2 , for example , then the hybrid containing the inbred lh283 had 2 % less stalk lodging than the check hybrid . table 1__________________________________________________________________________overall comparisons of lh200 × lh283 hybrids vs . check hybridshybrid mean yield % m y / m % sl % rl % de plnt hgt . ear hgt__________________________________________________________________________lh200 × lh283 173 19 . 30 8 . 95 3 1 0 99 45 ( at 13 loc &# 39 ; s , 1995 ) as compared to : lh200 × lh262 - 2 - 1 . 57 +. 57 - 2 0 0 - 13 - 10lh200 × lh216 + 5 - 1 . 12 +. 71 + 2 0 0 - 7 - 2lh195 × lh212 + 4 + 0 . 58 -. 06 - 1 - 1 0 - 7 - 2lh200 × lh172 + 21 + 1 . 38 +. 49 + 1 0 0 + 5 + 2lh200 × lh59 + 6 + 2 . 06 -. 72 - 3 0 - 1 - 5 - 1__________________________________________________________________________ table 2__________________________________________________________________________overall comparisons of lh231 × lh283 hybrids vs . check hybridshybrid mean yield % m y / m % sl % rl % de plnt hgt . ear hgt__________________________________________________________________________lh231 × lh283 162 18 . 74 8 . 63 2 5 1 105 38 ( at 11 loc &# 39 ; s ; 1995 ) as compared to : lh192 × lh172 + 4 +. 15 +. 63 0 + 4 0 + 9 + 4lh231 × lh172 + 10 + 1 . 28 -. 06 + 1 + 5 0 + 8 + 4lh198 × lh172 + 3 + 1 . 58 -. 64 0 + 4 0 + 8 + 3__________________________________________________________________________ table 3__________________________________________________________________________overall comparisons of lh198 × lh283 hybrids vs . check hybridshybrid mean yield % m y / m % sl % rl % de plnt hgt . ear hgt__________________________________________________________________________lh198 × lh283 176 17 . 17 10 . 26 3 6 1 116 48 ( at 8 loc &# 39 ; s , 1995 ) as compared to : lh231 × lh172 0 -. 37 +. 19 + 1 + 3 0 + 11 + 4lh198 × lh172 - 2 -. 15 -. 03 + 1 0 + 1 + 15 + 9pioneer 3525 - 6 +. 12 -. 41 - 2 0 0 - 10 - 5lh197 × lh176 + 5 +. 72 -. 11 0 + 4 0 - 2 + 1lh202 × lh172 + 5 +. 93 -. 23 + 1 + 2 0 + 9 + 3__________________________________________________________________________ initial disease ratings of several inred lines were taken at williamsburg , iowa in 1995 and are as follows in which 0 = excellent and 9 = poor . ______________________________________disease lh283 lh51 lh59 lh168 lh172 lh212______________________________________carbonum 0 . 0 0 . 2 0 . 5 1 . 0 0 . 4 1 . 3northern ( race2 ) 1 . 0 1 . 1 1 . 6 3 . 8 4 . 0 2 . 3soutehrn 4 . 0 1 . 1 1 . 5 4 . 3 3 . 5 1 . 7______________________________________ inbred seeds of lh283 have been placed on deposit with the american type culture collection ( atcc ), rockville , md . 20852 , under deposit accession number 97820 on 6 dec . 1996 . the deposit of inbred lh283 consists of 2500 seeds . a plant variety protection certificate is being applied for with the united states department of agriculture . although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity and understanding , it will be obvious that certain changes and modifications may be practiced within the scope of the invention , as limited only by the scope of the appended claims .

US-76167396-A

the present invention comprises apparatus and methods for maintaining patency in body passages subject to occlusion by invasive tissue growth . the apparatus and methods of the present invention may be used to open and maintain patency in virtually any hollow body passage which may be subject to occlusion by invasive cellular growth or invasive solid tumor growth . suitable hollow body passages include ducts , orifices , lumens , and the like , with exemplary body passages including the coronary arteries . the present invention is particularly useful for reducing or eliminating the effects of restenosis in coronary arteries by selectively removing tissue ingrowth in or around stents anchored therein .

the present invention provides systems and methods for selectively applying electrical energy to a target location within or on a body lumen , particularly including atheromatous material which partially or fully occludes a blood vessel or other body lumen . in addition to blood vessels , body lumens that may be treated by the method and apparatus of the present invention include the urinary tract ( which for example may be occluded by an enlarged prostrate in males ), the fallopian tubes ( which may be occluded and cause infertility ), and the like . exemplary solid tissues include abdominal tissues , neurological tissues , benign and malignant solid tumors , myocardial tissue and the like . thus , the methods and apparatus may be used in a wide variety of procedures , including intravascular , urological , laparoscopic , arthroscopic , thoracoscopic , orthopedic , gynecologic , electrothermal , lithotripsy , spinal disc ablation , and the like . for convenience , the remaining disclosure will be directed specifically to the intravascular treatment of blood vessels but it should be appreciated that the apparatus and methods can be applied to other body lumens and passages as well as solid tissue sites for a variety of purposes . the stenotic material in blood vessels will be , by way of example but not limited to , atheroma or atheromatous plaque . it may be relatively soft ( fresh ) or it may be calcified and hardened . the invention applies heat selectively to the stenotic material while limiting unwanted heating of the blood , the surrounding vessel wall and the stent anchored therein . more particularly , the present invention confines the current flow paths between the return electrode and electrode terminals to the vicinity of the tissue ablating region . this confinement of current flow paths minimizes the undesired flow of current through portions or all of the stent , which may otherwise induce non - specific tissue injury beyond the site of recanalization of the occluded lumen . the present invention may use a single active electrode or an electrode array distributed over a distal contact surface of a catheter . the electrode array usually includes a plurality of independently current - limited and / or power - controlled electrode terminals to apply electrical energy selectively to the target tissue while limiting the unwanted application of electrical energy to the surrounding tissue and environment ( e . g ., the stent and the lumenal wall ). the electrode terminals may be independently current - limited by isolating the terminals from each other and connecting each terminal to a separate power source or current or power limiting element ( e . g ., inductor ) that is isolated from the other electrode terminals . alternatively , the electrode terminals may be connected to each other at either the proximal or distal ends of the probe to form a single wire that couples to a power source . the electrosurgical catheter will comprise a flexible body having a proximal end and a distal end which supports one or more electrode terminals . the electrode terminal ( s ) are preferably supported by an inorganic insulating support positioned near the distal end of the catheter body . the return electrode may be part of the catheter body , part of a separate movable guide wire or on another instrument . in the preferred embodiments , the return electrode comprises a separate movable guide wire positioned within an internal lumen of the catheter body . the proximal end of the catheter will include the appropriate electrical connections for coupling the return electrode and the electrode terminal ( s ) to a high frequency power supply , such as an electrosurgical generator . the catheter will also include other internal lumens for providing separate functions , such as delivering fluid and aspirating products of ablation from the target site . preferably , the catheter will have a fluid delivery lumen for delivering electrically conducting fluid to the target site , and an aspiration lumen coupled to a vacuum source for aspirating non - condensible gases and other products of ablation from the site . the catheter will also preferably include an isolation system for fluidly isolating the region around the target site . in one embodiment , the isolation system includes proximal and distal balloons that are movable to portions of the body passage proximal and distal to the region of the target site . the distal balloon , by way of example , may be formed on a hollow guide wire that is fluidly coupled to an inflation source , such as a syringe . the proximal balloon , for example , may be coupled to the catheter body proximal to the active and return electrodes . the invention typically includes guiding apparatus for guiding the catheter along a pathway approximating the central region of the occluded blood vessel . the guiding apparatus is usually an electrically conducting wire that may serve as the return electrode . the electrically conducting wire is extensible from the tip of the catheter and is located within and concentric to the catheter conveniently being in the form of a movable or fixed guidewire , usually being a movable guidewire . the electrode array may include only one electrode terminal , or it may include at least two isolated electrode terminals , sometimes at least four electrode terminals , sometimes at least six electrode terminals , and often 50 or more electrode terminals , disposed over the distal contact surfaces on the catheter . by bringing the electrode array ( s ) on the contact surface ( s ) in close proximity with the target tissue ( e . g ., occlusive media ) and applying high frequency voltage between the array ( s ) and an additional return electrode in direct or indirect contact with the patient &# 39 ; s body , the target tissue is selectively ablated or cut , permitting selective removal of portions of the target tissue while desirably minimizing the application of energy to the surrounding stent and lumenal wall . in an exemplary embodiment , each individual electrode terminal in the electrode array is electrically insulated from all other electrode terminals in the array and is connected to a power source which is isolated from each of the other electrodes in the array or to circuitry which limits or interrupts current flow to the electrode when low resistivity material ( e . g ., blood or electrically conductive saline irrigant ) causes a lower impedance path between the return electrode and the individual electrode terminal . the isolated power sources for each individual electrode may be separate power supply circuits having internal impedance characteristics which limit power to the associated electrode terminal when a low impedance return path is encountered , may be a single power source which is connected to each of the electrodes through independently actuatable switches or may be provided by independent current or power limiting elements , such as inductors , capacitors , resistors and / or combinations thereof . the current or power limiting elements may be provided in the probe , connectors , cable , controller or along the conductive path from the controller to the distal tip . a more complete description of a system and method for selectively limiting current and power to an array of isolated electrode terminals can be found in commonly assigned , copending application ser . no . 08 / 561 , 958 , filed nov . 22 , 1995 ( attorney docket no . 16238 - 000700 ), the complete disclosure of which is incorporated herein by reference for all purposes . in a preferred aspect , this invention takes advantage of the differences in electrical resistivity between the target occlusive media and the surrounding conductive liquid ( e . g ., isotonic saline irrigant , blood or the like ). by way of example , for any selected level of applied voltage , if the electrical conduction path between the return electrode and one of the individual electrode terminals within the electrode array is blood ( having a relatively low electrical impedance ), the current control means connected to the individual electrode will limit current flow so that the heating of intervening conductive fluid is minimized . on the other hand , if a portion of or all of the electrical conduction path between the common or return electrode and one of the individual electrode terminals within the electrode array is occlusive media ( having a relatively higher electrical impedance ), the current control circuitry or switch connected to the individual electrode will allow current flow sufficient for the deposition of electrical energy and associated ablation or electrical breakdown of the target tissue in the immediate vicinity of the electrode surface . it should be clearly understood that the invention is not limited to electrically isolated electrode terminals , or even to a plurality of electrode terminals . for example , the array of active electrode terminals may be connected to a single lead that extends through the catheter shaft to a power source of high frequency current . alternatively , the catheter may incorporate a single electrode that extends directly through the catheter shaft or is connected to a single lead that extends to the power source . in the case of a single electrode , the invention may also use current limiting means to apply electrical energy selectively to the target tissue while limiting the unwanted application of electrical energy to the surrounding tissue . in this embodiment , the electrode may be connected to current limiting elements or to circuitry which limits or interrupts current flow to the electrode when low resistivity material ( e . g ., blood or electrically conductive saline irrigant ) causes a lower impedance path between the return electrode and the electrode . the current limiting elements or circuitry may be configured to completely interrupt or modulate current flow to the electrode , for example , when a certain percentage of the electrode surface is in contact with low resistivity material . in one embodiment , the current flow will be modulated or completely interrupted when , for example , a large portion of the electrode surface is exposed to electrically conductive fluids and , therefore , not in sufficiently close proximity or contact with the target tissue . in this manner , current can be selectively applied to the target tissue , while minimizing current flow to surrounding fluids and adjacent non - target tissue structures . in addition to the above described methods , the applicant has discovered another mechanism for ablating tissue while minimizing the depth of necrosis . this mechanism involves applying a high frequency voltage between the active electrode surface and the return electrode to develop high electric field intensities in the vicinity of the target tissue site . in this embodiment , the active electrode ( s ) include at least one active portion having a surface geometry configured to promote substantially high electric field intensities between the active portion and the target site when a high frequency voltage is applied to the electrodes . these high electric field intensities are sufficient to break down the tissue by processes including molecular dissociation or disintegration . the high frequency voltage imparts energy to the target site to ablate a thin layer of tissue without causing substantial tissue necrosis beyond the boundary of the thin layer of tissue ablated . this ablative process can be precisely controlled to effect the volumetric removal of tissue with minimal heating of or damage to the surrounding stent and tissue structures , such as the lumenal wall . in an exemplary embodiment , the high electric field intensities at the active portion of the active electrode ( s ) may be generated by positioning the active electrode and target site within an electrically conducting fluid , such as isotonic saline or the naturally occurring body fluids in a blood vessel , such as blood , and applying a high frequency voltage that is sufficient to vaporize the electrically conducting fluid over at least a portion of the surface of the active electrode in the region between the active portion of the active electrode and the target tissue . since the vapor layer or vaporized region has a relatively high electrical impedance , it increases the voltage differential between the active electrode tip and the tissue and causes ionization within the vapor layer due to the presence of an ionizable species ( e . g ., sodium when isotonic saline is the electrically conducting fluid ). this ionization , under optimal conditions , induces the discharge of energetic electrons and photons from the vapor layer and to the surface of the target tissue . a more detailed description of this phenomena can be found in application ser . no . 08 / 561 , 958 , filed on nov . 22 , 1995 ( attorney docket 16238 - 000700 ), the complete disclosure of which has already been incorporated herein by reference . suitable electrode surface geometries for producing sufficiently high electric field intensities to reach the threshold conditions for vapor layer formation may be obtained by producing sharp edges , discontinuities , and / or corners at the active portion of the active electrode ( s ). alternatively , the electrode ( s ) may be specifically designed to increase the edge / surface area ratio of the active portion through the use of shaped wires ( e . g ., square or hexagonal wires ) or tubular electrodes offering high electric field intensities along the inside and outside perimeters of the tubular electrode . additionally or alternatively , the active electrode surface ( s ) may be modified through chemical , electrochemical or abrasive methods to create a multiplicity of surface aspirates on the electrode surface . suitable electrode designs for use with the present invention may be found in co - pending , commonly assigned application ser . no . 08 / 687 , 792 , filed jul . 19 , 1996 ( attorney docket no . 16238 - 16 ), the complete disclosure of which is incorporated herein by reference . the voltage applied between the return electrode and the electrode array will be at high or radio frequency , typically between about 5 khz and 20 mhz , usually being between about 30 khz and 2 . 5 mhz , and preferably being between about 50 khz and 1 mhz . the rms ( root mean square ) voltage applied will usually be in the range from about 5 volts to 1000 volts , preferably being in the range from about 50 volts to 800 volts , and more preferably being in the range from about 60 volts to 500 volts . these frequencies and voltages will result in peak - to - peak voltages and current that are sufficient to vaporize the electrically conductive fluid and , in turn , create the conditions within the vaporized region which result in high electric fields and emission of energetic photons and / or electrons to ablate tissue . typically , the peak - to - peak voltage will be in the range of 40 to 4000 volts and preferably in the range of 100 to 3200 volts and more preferably in the range of 300 to 2400 volts . as discussed above , the voltage is usually delivered in a waveform having a sufficiently high frequency ( e . g ., on the order of 5 khz to 20 mhz ) such that the voltage is effectively applied continuously ( as compared with e . g ., lasers claiming small depths of necrosis , which are generally delivered in brief pulses at a repetition rate of about 10 to 20 hz ). hence , the duty cycle ( i . e ., cumulative time in any one - second interval that energy is applied ) is on the order of about 50 % for the present invention , as compared with lasers which typically have a duty cycle of about 0 . 001 % to 0 . 0001 %. usually , the current level will be selectively limited or controlled and the voltage applied will be independently adjustable , frequently in response to the resistance of tissues and / or fluids in the pathway between an individual electrode and the return electrode . also , the applied voltage level may be in response to a temperature control means which maintains the target tissue temperature within desired limits at the interface between the electrode arrays and the target tissue . the desired tissue temperature along a propagating surface just beyond the region of ablation will usually be in the range from about 40 ° c . to 100 ° c ., and more usually from about 50 ° c . to 60 ° c . the tissue being ablated ( and hence removed from the operation site ) immediately adjacent the electrode array may reach even higher temperatures . a temperature sensor may be incorporated within the distal end of the electrosurgical device to measure a temperature indicative of the nearby tissue beyond the ablation boundary . referring to the drawings in detail , wherein like numerals indicate like elements , a lumen recanalization catheter system 2 is shown constructed according to the principles of the present invention . catheter system 2 generally comprises an electrosurgical catheter 6 connected to a power supply 80 by an interconnecting cable 86 for providing high frequency voltage to a target tissue and an irrigant reservoir or source 100 for providing electrically conducting fluid to the target site . catheter 6 generally comprises an elongate , flexible shaft body 12 including a tissue ablating region 8 at the distal end of body 12 , and a proximal balloon 40 positioned on body 12 proximal to region 8 . in a specific embodiment , a guide wire 28 ( which may also serve as a return electrode ) includes a distal balloon 18 which may be axially translated relative to region 8 and proximal balloon 40 , as discussed in further detail below . the proximal portion of catheter 6 includes a multi - lumen fitment 114 which provides for interconnections between lumens and electrical leads within catheter 6 and conduits and cables proximal to fitment 114 . by way of example , a catheter electrical connector 96 is removably connected to a distal cable connector 94 which , in turn , is removably connectable to generator 80 through connector 92 . one or more electrically conducting lead wires ( not shown ) within catheter 6 extend between one or more active electrodes at tissue ablating region 8 and one or more corresponding electrical terminals ( also not shown ) in catheter connector 96 via active electrode cable branch 87 . in the illustrative embodiment , hollow guide wire 28 functions as the return electrode , and is electrically attached within a contact housing 111 by a sliding electrical contact ( not shown ). a return electrode cable branch 89 couples the sliding electrical contact to catheter connector 96 . electrical leads within cable 86 allow connection between terminals corresponding to return electrode 28 and one or more active electrodes 32 in distal cable connector 94 and generator 80 . generator 80 is a high frequency generator operating at a frequency in the range of about 5 khz to 20 mhz , more preferably in the range of 30 khz to 2 . 5 mhz . the output voltage of generator 80 can be selectively applied between the return electrode and one or more active electrodes using footpedal 88 , which is coupled to generator 80 via a footpedal cable 90 and removable connector 91 . generator has a selector 84 to change the applied voltage level , and may also include a second pedal ( not shown ) for remotely adjusting the energy level applied to the electrodes . a more complete description of a suitable generator is described in commonly assigned copending patent application ser . no . 08 / 561 , 958 , filed nov . 22 , 1995 , ( attorney docket no . 16238 - 000700 ), the complete disclosure of which has previously been incorporated herein by reference . conductive fluid 30 is provided to tissue ablation region 8 of catheter 6 via a lumen ( not shown in fig1 ) within catheter 6 . fluid is supplied to lumen from the source along a conductive fluid supply line 102 and a conduit 103 , which is coupled to the inner catheter lumen at multi - lumen fitment 114 . the source of conductive fluid ( e . g ., isotonic saline ) may be an irrigant pump system ( not shown ) or a simple gravity - driven supply , such as an irrigant reservoir 100 positioned several feet above the level of the patient and tissue ablating region 8 . a control valve 104 may be positioned at the interface of fluid supply line 102 and conduit 103 to allow manual control of the flow rate of electrically conductive fluid 30 . alternatively , a metering pump or flow regulator may be used to precisely control the flow rate of the conductive fluid . system 2 further includes an aspiration or vacuum system ( not shown ) to aspirate liquids and gases from the target site , and syringes 106 , 108 for inflating distal and proximal balloons 18 , 40 , respectively . by way of example , as the plunger of syringe 108 is depressed , fluid in the syringe chamber is displaced such that it flows through a conduit 107 and an internal lumen 57 within catheter 6 ( not shown in fig1 ) to expand and inflate balloon 40 . likewise , syringe 106 is provided at the proximal end of guide wire 28 for inflating distal balloon 18 , as shown by translation vectors 116 , 118 . also , guidewire 28 can be advanced or retracted relative to tissue ablation region 8 of catheter 6 as shown by translation vectors 116 , 118 such that , for each increment of relative displacement 116 at the proximal end of catheter 6 , there is a corrresponding displacement 118 of the hollow guidewire 28 relative to the tissue ablating region 8 of catheter 6 . referring now to fig2 a - 2c , one embodiment of the method and apparatus of the present invention will be described in detail . as shown , tissue ablating region 8 of catheter 6 progresses through occlusive media 14 , such as athermateous media or thrombus within a body lumen 10 , e . g ., a blood vessel . the principles of the present invention are also applicable to any body lumen which becomes partially or totally occluded . the present invention is particularly useful in a lumen containing a lumenal prosthesis , such as a stent 16 , stent - graft or graft , which may be metallic , nonmetallic or a non - metallic coated metallic structure . a particular advantage of the present invention is the confinement of current flow paths ( not shown ) between the return electrode ( hollow guide wire 28 in the present example ) and one or more active electrodes 32 to the vicinity of tissue ablating region 8 . this confinement of current flow paths minimizes the undesired flow of current through portions or all of stent 16 , which may otherwise induce non - specific tissue injury beyond the site of recanalization of the occluded lumen 10 . referring to fig2 a , tissue ablating region 8 of catheter 6 is positioned proximal to the occlusive media 14 within lumen 10 . the distal region of hollow guide wire 28 is positioned distal to the occlusive media 14 either before or after the initial positioning of tissue ablation region 8 . once hollow guide wire 28 is positioned as shown in fig2 a , proximal balloon 40 ( not shown in fig2 a ) is inflated to effect a seal between catheter shaft 42 and interior wall 12 of lumen 10 to minimize the flow of bodily fluid 26 ( e . g ., blood ) from regions proximal to the tissue ablating region 8 of catheter 6 . electrically conductive and biologically compatible fluid 30 ( e . g ., isotonic saline ) is delivered into lumen 10 for a sufficient period of time to displace naturally occurring bodily fluid 26 in the region between the tissue ablating region and the distal tip of guide wire 28 . after the bodily fluid has been displaced , distal balloon 18 is inflated to effect a seal between balloon 18 and the interior wall 12 of lumen 10 . once the target site is isolated from the rest of the vasculature , the supply of electrically conductive fluid 30 is continuously delivered to region 8 and balanced with the aspiration of fluid from the site of intended recanalization . the active electrode ( s ) 32 is ( are ) then energized by applying a high frequency voltage between active electrode ( s ) 32 and return electrode or guide wire 28 . a high electric field is created at the surface of active electrode ( s ) 32 which causes the volumetric removal or ablation or target tissue in close proximity with active electrode ( s ) 32 . the flow of electrical current between return electrode 28 and active electrode ( s ) 32 is shown by current flux lines 62 in fig2 b . as the occlusive media 14 is ablated , gaseous products are generated ( not shown ) which are entrained in the electrically conducting fluid 30 and removed through aspiration lumen 58 ( not shown ). the current flux lines 62 are generally confined to the central portion of tissue ablation region 8 because they generally flow inward towards return electrode 28 and because the occlusive media 14 generally shields the outer region of lumen ( including stent 16 ) from flux lines 62 . this minimizes undesirable interaction between the electrical current and stent 16 . referring to fig2 c , this ablation procedure is continued until the desired length of the lumen containing occlusive media is recanalized . during the recanalization process , the products of ablation are confined between proximal balloon 40 and distal balloon 18 to minimize , for example , the injection of any non - condensible gaseous products of ablation into the blood stream which could otherwise lead to the formation of injurious or life - threatening emboli . once the occlusive media 14 has been volumetrically removed ( i . e ., ablated ), the energy application is suspended , the valve on the aspiration lumen is closed , control valve 104 is closed and balloons 18 , 40 are deflated . the time period from the initial inflation of balloons 18 , 40 to the deflation of these balloons is typically about 15 - 45 seconds , depending on the length and the extent of occlusion in the vessel . for longer occlusions , the above process may be repeated several times with intervals of no balloon inflation so that vital oxygen - bearing blood can be reperfused through the zone of intended recanalization to preserve the tissue distal to the recanalization zone . a first embodiment of tissue ablation region 8 of catheter 6 is shown in fig3 a and 3b . as shown , two active electrodes 50 a and 50 b are secured within an electrically insulating support member 34 . the electrodes 50 a , 50 b are preferably composed of a refractory , electrically conductive metal or alloy , such as platinum , titanium , tantalum , tungsten , stainless steel and the like . the support member 34 is secured to the distal end of catheter 6 with a biocompatible adhesive 60 between support member 34 and outer sleeve 36 . an inorganic electrically insulating sleeve 54 preferably extends above the distal plane of active electrodes 50 a , 50 b by a distance h s . a central lumen in support member 34 provides a passageway for guide wire 28 that permits axial displacement and rotation of tissue ablating region 8 relative to guide wire 28 . in an exemplary embodiment , the support member 34 will comprise an inorganic insulator , such as ceramic , glass , glass / ceramic or a high resistivity material , such as silicon or the like . an inorganic material is generally preferred for the construction of the support member 34 since organic or silicone based polymers are known to rapidly erode during sustained periods of the application of high voltages between electrodes 50 and the return electrode 28 during tissue ablation . however , for situations in which the total cumulative time of applied power is less than about one minute , organic or silicone based polymers may be used without significant erosion and loss of material of the support member 34 and , therefore , without significant reduction in ablation performance . as shown in fig3 a , an irrigation lumen 56 and an aspiration lumen 58 are provided to inject electrically conducting fluid 30 and remove gaseous products of ablation 48 from the site of recanalization . an additional fluid lumen 57 provides fluid communication between inflation syringe 108 and proximal balloon 40 . this fluid lumen 57 is filled with a sealant in those portions of the catheter distal to proximal balloon 40 . in use with the present invention , catheter 6 is rotated about 180 degrees clockwise and then about 180 degrees counter clockwise as the electrodes 50 are energized by generator 80 ( fig1 ) to effect ablation of the occlusive media . using a reciprocating rotational motion combined with a small pressure to advance tissue ablation region 8 through the longitudinal length of the occlusive media 14 allow recanalization of the occluded vessel as described with reference to fig2 a - 2c . the cross - sectional shape of the active electrodes may be round wires as shown in fig3 b , or they may have shaped surfaces to enhance the electric field intensity at the distal surfaces of the active electrodes 50 . suitable electrode designs for use with the present invention may be found in co - pending , commonly assigned application ser . no . 08 / 687 , 792 , filed jul . 19 , 1996 ( attorney docket no . 16238 - 001600 ), the complete disclosure of which is incorporated herein by reference for all purposes . return electrode 28 comprises an electrically conducting material , usually metal , which is selected from the group consisting of stainless steel alloys , platinum or its alloys , titanium or its alloys , molybdenum or its alloys , and nickel or its alloys . the return electrode 28 may be composed of the same metal or alloy which forms the active electrodes 50 to minimize any potential for corrosion or the generation of electrochemical potentials due to the presence of dissimilar metals contained within an electrically conductive fluid 30 , such as isotonic saline ( discussed in greater detail below ). referring now to fig4 a and 4b , a second embodiment of tissue ablation region 8 of catheter 6 will now be described . in this embodiment , four active electrodes 32 a , 32 b , 32 c , 32 d are secured within an inorganic electrically insulating support member 34 . similar to the previous embodiment , support member 34 is secured to the distal end of catheter 6 with a biocompatible adhesive 60 between support member 34 and outer sleeve 36 . an inorganic electrically insulating sleeve 54 preferably extends above the distal plane of active electrodes 50 a , 50 b by a distance hs . a central lumen in support member 34 provides a passageway for guide wire 28 that permits axial displacement and rotation of tissue ablating region 8 relative to guide wire 28 . as shown in fig4 a , an irrigation lumen 56 and an aspiration lumen 58 are provided to inject electrically conducting fluid 30 and remove gaseous products of ablation 48 from the site of recanalization . an additional fluid lumen 57 provides fluid communication between inflation syringe 108 and proximal balloon 40 . this fluid lumen 57 is filled with a sealant in those portions of the catheter distal to proximal balloon 40 . in use , catheter 6 is rotated about 180 degrees clockwise and then about 180 degrees counter clockwise as the electrodes 32 are energized by generator 80 ( fig1 ) to effect ablation of the occlusive media . using a reciprocating rotational motion combined with a small pressure to advance tissue ablation region 8 through the longitudinal length of the occlusive media 14 allow recanalization of the occluded vessel as described with reference to fig2 a - 2c . the cross - sectional shape of the active electrodes may be round wires as shown in fig4 b , or they may have shaped surfaces to enhance the electric field intensity at the distal surfaces of the active electrodes 32 as described co - pending , commonly assigned application ser . no . 08 / 687 , 792 , filed jul . 19 , 1996 ( attorney docket no . 16238 - 001600 ), the complete disclosure of which has previously been incorporated herein by reference . the second embodiment of fig4 a and 4b is illustrated in greater detail in fig5 a and 5b . as shown , electrically conductive fluid flows through irrigation lumen 56 of catheter 6 to and through irrigation port 44 and subsequently surrounds the target tissue site ( i . e ., occlusive media 14 ). when high frequency voltage is applied between the return electrode 28 and active electrodes 32 , a vapor layer 64 forms at and around active electrodes 32 with concomitant volumetric removal ( ablation ) of the occlusive media 14 . a more detailed description of this phenomena can be found in commonly assigned , co - pending application ser . no . 08 / 561 , 958 , filed on nov . 22 , 1995 ( attorney docket 16238 - 000700 ), the complete disclosure of which has previously been incorporated herein by reference . the occlusive media 14 is decomposes into gaseous products of ablation 48 which are entrained in electrically conducting fluid 30 and evacuated through aspiration port 46 and to the proximal end of catheter 6 via aspiration lumen 58 . a third embodiment of tissue ablation region 8 is illustrated in fig6 a and 6b . many of the elements of this embodiment are the same as previous embodiments , and therefore will not be repeated . as shown , a single active electrode 200 is secured within support member 34 . active electrode 200 preferably has an l - shaped distal end so that a distal portion 202 of electrode 200 extends radially outward along the distal surface of support member 34 . as before , electrode 200 is rotated in both directions , as the region 8 is advanced through the lumen to recanalize the lumen . a fourth embodiment of tissue ablation region 8 is illustrated in fig7 a and 7b . many of the elements of this embodiment are the same as previous embodiments , and therefore will not be repeated . as shown , six active electrodes 66 a - 66 f are secured within inorganic support member 34 . an annular irrigation lumen 55 and an aspiration lumen 59 are provided to inject electrically conducting fluid 30 and remove gaseous products of ablation 48 from the site of recanalization . when high frequency voltage is applied between the return electrode 28 and active electrodes 66 , a vapor layer 64 forms at and around active electrodes 66 with concomitant volumetric removal ( ablation ) of the occlusive media 14 . for this embodiment and that shown in fig8 a and 8b , rotation may be limited to +− 30 degrees due to the greater number and circumferential distribution of active electrodes . the power or current supplied to each electrode may be individually controlled by active or passive mechanisms as previously described in commonly assigned , co - pending application ser . no . 08 / 561 , 958 , filed on nov . 22 , 1995 ( attorney docket 16238 - 000700 ). the occlusive media 14 is decomposed into gaseous products of ablation 48 which are entrained in electrically conducting fluid 30 and evacuated through aspiration port 46 and onto the proximal end of catheter 6 via aspiration lumen 59 . as shown in fig7 b , the current flux lines 62 are confined to the central portions of tissue ablation region 8 . fig8 a and 8b illustrate a fifth embodiment of the present invention . this embodiment is similar to the fourth embodiment in that six active electrodes 66 a - 66 f are secured within inorganic support member 34 . a return electrode 70 ( e . g ., metal sleeve ) is positioned proximal to the active electrodes 66 a - 66 f by a distance h x . in this embodiment , current flux lines 62 travel proximally from the distal tips of electrodes 66 to the proximally spaced return electrode 70 . referring to fig9 a and 9b , a sixth embodiment of the invention will now be described . as shown , a single active electrode 72 is secured within inorganic support member 34 . in this embodiment , active electrode 72 comprises a coiled wire having a plurality of concentric coils tightly and helically wrapped and secured on support member 34 ( fig9 b ). preferably , the helical coil extends around return electrode 28 in concentric configuration , as shown in fig9 a . a seventh embodiment of the invention is shown in fig1 a and 10b . this embodiment is similar to the sixth embodiment except that the single active electrode 73 defines a series of concentric machined grooves 75 to form concentric circular electrodes 78 surrounding return electrode 28 . the distal edges of electrodes 78 generate regions of high electric field intensities when high frequency voltage is applied between return electrode 28 and concentric active electrodes 78 . a vapor layer 64 forms at and around active electrodes 78 with concomitant volumetric removal ( ablation ) of the occlusive media . the embodiments of fig9 and 10 are usually advanced through the occlusive media without rotation .

US-87417397-A

a buoyant motivational object used to play with a dog or child . while afloat , the motivational object comprises of an above - water section located above the surface of the water and an underwater section located below the surface of the water , and it is comprised of a base body with at least one biting or gripping area shaped for pick - up by a dog &# 39 ; s muzzle or a human hand , and the biting or gripping area is at least partially located in the above - water section while the balance or gravity point of the motivational object is located in the underwater section .

the implementation example in fig1 shows a buoyant motivational object ( 10 ) in side view which consists of a base body ( 11 ) shaped like a cylinder with a circular , elliptical or rounded polygonal profile . fig1 shows the motivational object in a floating , static state where it has completed any pendulum movements and , absent of any additional external interfering or displacing forces , has reached its equilibrium state . in this state , the underwater section ( 13 ) of the motivational object is below the surface of the water ( 12 ) while its above - water section ( 14 ) is above the surface of the water . the motivational object ( 10 ) only assumes its equilibrium state shown in fig1 because it incorporates a ballast body ( 16 ) embedded near the submerged end ( 15 ) of its base body ( 11 ). the ballast body ( 16 ) is also cylindrical and clamped into a cylindrical recess in the base body ( 11 ). while the base body ( 11 ) may consist of rubber which could further incorporate an inner air - cavity to ensure sufficiently low density , the ballast body would typically be made of metal such as lead , steel or zinc . due to the upright position of the base body ( 11 ) in the floating , static state , i . e ., with the orientation of its longitudinal axis ( 17 ) in a direction perpendicular to that of the surface of the water ( 12 ), the distance ( 18 ) of the base body &# 39 ; s high - point ( 19 ) above the surface of the water ( 12 ) is about three times larger than as if the base body ( 11 ) would not be equipped with the ballast body ( 16 ) which would result in the motivational object in fig1 floating flat on the surface of the water . in the present case , the distance ( 18 ) is approximately 12 cm and the total length of the motivational object is about 30 cm . this means that the entire area of the base body ( 11 ) which extends above the surface of the water ( 12 ) would provide a biting or gripping area ( b ) for a dog or a child . the embodiment of a buoyant motivational object according to fig2 also consists of a cylindrical base body ( 11 ) which incorporates a ballast body ( 16 ) on one end ( 15 ). this rubber based motivational object ( 20 ) however is integrally combined with a circular - shaped support body ( 21 ) located in perpendicular direction to the longitudinal axis ( 17 ) of the base body ( 11 ). the appropriate matching of material densities and geometries of the base body ( 11 ), the support body ( 21 ) and the ballast body ( 16 ) allows the motivational object to assume a position where its longitudinal axis ( 17 ) rests in direction perpendicular to that of the surface layer of the water ( 12 ) as shown in fig2 . the radially outward - extending support body ( 21 ) stabilizes extreme pendulum movements around the longitudinal axis ( 17 ) ( see arrow 23 ) and its additional flotation surface helps to lift the grasping area ( b ) further above the surface of the water . both the visibility and the flotation characteristic of the motivational device have improved . the above - water section of the device in fig2 has increased significantly when compared to the basic version shown in fig1 . the fig3 and 3 a show an alternative motivational object ( 30 ) implementation example , with a base body ( 11 ) that incorporates a concentrically running longitudinal bore ( 31 , not shown in detail for purposes of clarity ) which runs from the lower end ( 15 ) to the opposite end of the base body ( 11 ). a rope ( 32 ) with a knot ( 33 ) on each end is fitted through the bore ( 31 ) one from the lower end ( 15 ) of the base body ( 11 ) extending section ( 34 ) of the rope ( 32 ) is attached to a spherical body ( 35 ) through a bore where the rope ( 32 ) is mounted . the inside of the spherical body ( 35 ) contains a cylindrically shaped ballast body ( 16 ) that also contains a bore for the rope ( 32 ). the ballast body ( 16 ) could be made of steel which could be embedded in a spherical body ( 35 ) made of rubber . the motivational object ( 30 ) per fig3 is equipped with a disc - shaped support body ( 21 ) to achieve optimal flotation characteristics . while the implementations of the invention shown in fig2 and 3 are made of a base body ( 11 ) and support body ( 21 ) that are integrally combined , fig4 shows alternative implementation of a motivational object ( 40 ) where base body ( 11 ) and support body ( 21 ) are made of two separate components . the surface of the base body ( 11 ) is threaded ( 41 ) over its entire length . these threads are complementary to the threads in a centric bore in the support body ( 21 ) allowing base body ( 11 ) and support body ( 21 ) to be screwed together . the support body ( 21 ) shifts ( in direction of the double arrow , 43 ) along the longitudinal axis of the cylindrical base body ( 11 ) when it is turned in direction of the double arrow ( 42 ). at its lower end , the base body ( 11 ) is also equipped with a ballast body ( 16 ). by adjusting the position of the support body ( 21 ) relative to the base body ( 11 ), flotation characteristics of the motivational object can be modified , i . e ., to adjust the motivational object for use in fresh water or salt water ( which has higher density ). the separate support body ( 21 ) which , for example , could be manufactured from polyurethane foam with low density is designed like a clamping - nut that tightly fits onto the matching threads of the base body ( 11 ) to prevent unintended twisting or even loss of the support body ( 21 ). a circular - cylindrical support body ( 21 ′) shown in fig4 a and 4 b could be mounted onto the base body of a motivational object that has a smooth surface without threads . the support body ( 21 ′) in fig4 a consist of two semicircular parts ( 44 a and 44 b ) that incorporate a matching recess ( 46 ) and a ridge ( 45 ) on each of two opposing sides to allow for a better interconnection of the two parts . each ridge ( 45 ) tightly fits into its corresponding recess ( 46 ) on each of the facial sides of parts 44 a and 44 b . a connection of the two individual parts ( 44 a and 44 b ) in both the assembled and unassembled state of the support body ( 21 ′) is achieved by combining both semicircular parts ( 44 a and 44 b ) with a rubber band ( 47 ) that surrounds the support body ( 21 ′) on its outer surface ( 48 ) tightly fitted into a circular groove ( 49 ). in the assembled state of the two semicircular parts ( 44 a and 44 b ), the diameter of the center opening ( d ) in the support body ( 21 ′) is slightly smaller than the outer diameter of the associated base body ( 11 ) to ensure that the rubber band ( 47 ) always applies a certain amount of force that presses both semicircular parts ( 44 a and 44 b ) onto the outer surface of the base body ( 11 ) and thus holds the support body ( 21 ′) securely in the selected position . another embodiment of a motivational object ( 50 ) illustrated in fig5 shows the support body ( 21 ) as a single , disk - shaped component with a circular center opening . the outer surface ( 22 ) along its longitudinal axis rotationally symmetric base body ( 11 ) is wave - shaped with regular intervals of circular wave crests ( 52 ) and troughs ( 51 ). the inner diameter of the center opening of the support body ( 21 ) is in any case smaller than its outer diameter of the base body ( 11 ) at the tip of a wave crest ( 52 ), possibly even a bit smaller than the outer diameter at the bottom of a wave trough ( 51 ). the support body ( 21 ) possesses a certain degree of e . g ., material based elasticity to allow limited radial expansion which enables it to be pushed over the wave crests ( 52 ) and into wave troughs ( 51 ) where it “ locks ” itself into position . as in other embodiments , a ballast body ( 16 ) is included in underwater section ( 13 ). the water surface ( 12 ), above water section ( 14 ) and gripping area b are also shown . distance ( 18 ) of the above water section and height point ( 19 ) are also shown . in the design illustrated in fig6 , object ( 60 ) the base body ( 11 ) is shaped as a hollow ellipsoid with an optional , ring - shaped support body ( 21 ) which could be integrally combined with the base body ( 11 ). the lower end of the base body ( 11 ) incorporates a ballast body ( 16 ). apart from a bone - shaped base body ( 11 ) in another example of a motivational object ( 70 ) shown in fig7 , there are wide ranging similarities with the motivational object ( 60 ) shown in fig6 . the optional support body ( 21 ) is also ring - shaped and a ballast body ( 16 ) is integrated at the lower end of the base body ( 11 ). alternatively , the bottom area of the “ bone ” ( 71 ) could be thickened or made of higher density material to serve as a ballast body ( 16 ′) itself . other variants of motivational objects ( 80 , 90 and 100 ) as shown in fig8 , 9 , and 10 are designed in the shape of a hook ( fig8 and 9 ) or in the shape of a loop ( fig1 ). these base bodies ( 11 ), all of which provide a grasping area ( b ) in their above - water section , could be adapted for the most wide ranging requirements . finally , fig1 illustrates the reduced visibility of a swimming dog ( 111 ) whose eyes ( 112 ) are only a few centimeters above the surface of the water . a small wave ( 114 ) of a few centimeters in height causes the dog ( 111 ) to lose eye - contact with a motivational object or floating toy ( 113 ) even in close proximity which might result in the loss of the article . in contrast , the motivational object ( 30 ) according to the invention with its substantially elevated high - point ( 19 ) clearly remains visible ( see line of sight 115 ) even if the wave would be taller , or with the wave in even closer proximity to the dog &# 39 ; s head ( 111 ). the improved recognizability of the motivational object ( 30 ) for the dog ( 111 ) is even further enhanced as the above - water section of the base body ( 11 ) seesaws back and forth in the water which stimulates a dog &# 39 ; s motion - oriented vision .

US-40324109-A

an agricultural implement includes a frame having a pair of tool - carrying wings pivotally mounted thereon for pivotal movement between raised transport positions and lowered ground - working positions . each wing has a hydraulic wing actuator connected thereto which is extendable and retractible for effecting the pivotal motion . a hydraulic wing actuator circuit is connected to each of the wing actuators , which circuit , when connected to a tractor hydraulic system , enables the wing actuators to apply down pressure to said wings when the wings are in the lowered working positions . a hydraulic pressure control valve system controls the down pressure exerted by the wing actuators .

referring to fig1 a first embodiment of the implement has wing sections 10 and 12 pivotally attached via joints 14 and 16 to a frame middle section 18 for carrying suitable ground working tools ( not shown ), which joints each have an axis that is oriented generally horizontal in the working position so that the wing sections are allowed pivotal movement over uneven ground . in the headland position shown in fig1 the wing sections 10 and 12 are supported generally horizontally over the ground , suspended from the middle section 18 by their joints and by hydraulic wing actuators 20 . no other means is supporting the wings in this position . when lowered to a working position , gauge wheels 22 support each wing above the ground . the gauge wheels 22 can be adjusted to set the working height above the ground for each wing section . the wing can thereby float ( pivot freely ) to follow ground contours , or it may be biased toward the ground , and the gauge wheel 22 will limit the downward motion . downward biasing may be required in soil conditions in which ground engaging tools do not penetrate to the desired depth as set by the gauge wheel and the gauge wheel and wing section is suspended off the ground by the ground tools . points 24 and 26 for attachment to a three - point hitch are provided on the middle section 18 for towing and for controlling the height of the middle section . ( alternately the invention would work on implements having ground wheel means to support the middle section , with a floating or fixed hitch for towing ). the hitch of the implement shown is particularly suited for connection to the three - point hitch of an aircart having double acting lower link actuators . most three - point hitches on tractors or other implements provide only lifting action by the lower links and allow free upward movement of the links . the lower links of the aircart can be maintained in a fixed position . the implement middle section 18 is pivotally attached to the aircart lower links by connections at points 24 and 26 allowing the implement movement about a horizontal transverse axis 28 . a hydraulic top link 30 is pivotally connected at one end to the aircart ( offset from the axis of the lower links ), and at the second end is pivotally connected to the implement middle section 18 at a point offset from the horizontal axis 28 . an intermediate link 32 , is connected between the second end of the top link and the implement middle section by pivotal connections on both ends . the implement is allowed free downward pivotal movement about the horizontal axis 28 ( limited by the length of the actuator and link 32 , and by rear support assembly 40 ) but upward pivotal movement is limited by an abutment 36 along the intermediate link 32 . the implement middle section 18 abuts the intermediate link at abutment 36 and the top link 30 reacts to the upward pivotal movement . [ 0024 ] fig1 a and 1b help to illustrate the above and they show the implement connected to an aircart by the preferred 3 point hitch with hydraulic top link 30 and intermediate link 32 in both working and raised positions . this shows how there is freedom of pivoting in the raised position , even though the top link 30 may be locked out , and therefore rigid . the intermediate link 32 is drawn away from the abutment 36 , not by the top link but by the system geometry and during the raising action from the lower links 38 and rear support assembly 40 . rear support assembly 40 is well known per se and each includes a castored ground wheel 42 connected by linkages 44 to frame middle section 18 . actuator 46 effects movement of the linkages 44 during raising and lowering in a well known fashion . alternately a rigid top link ( not shown ) may be connected directly between the aircart and the implement , as in a conventional three point hitch . this is used on implements not having rear support assembly 40 , so the rotation of the frame middle section 18 about the horizontal axis 28 is controlled , maintaining a generally constant relative orientation between the implement and the aircart as the implement is raised or lowered . when a rear lift support assembly 40 is provided on the implement , a compressible top link is required so that the implement is allowed pivotal movement about axis 28 . this may be a spring connected directly to the implement or via an abutting intermediate link 32 . in the preferred embodiment the required compressible link is a hydraulic top link operated by a biasing pressure and an intermediate link is also provided to create freedom to pivot in the transport position when hydraulic flow to the top link is blocked . the top link 30 is locked out of the circuit by valve 48 ( fig4 ) when the implement is raised ( by rear lift means and lower arms of hitch ) and the link 32 pivots away from the frame middle section so it no longer abuts the frame . the geometry between the lower links 38 and top link 30 causes this action . this allows pivoting of the implement relative to the aircart about horizontal axis 28 when in transit over uneven ground . referring further to the embodiment of fig1 the headland actuator system includes a headlands cylinder 50 , having its opposite ends pivotally attached to elongated center links 52 and 54 . the outer ends of links 52 and 54 are secured by pins 56 , 58 to the inner ends of the wing actuators 20 and these pins are disposed for movement in slots 60 and 62 formed in the upper ends of spaced towers 64 , 66 fixed to the frame middle section 18 . the headlands cylinder 50 is stabilized by means of stabilizing links 68 , 70 having upper ends connected at opposing ends of the cylinder 50 and their lower ends pivoted to the middle section 18 of the implement frame . thus , as cylinder 50 is extended and retracted , the inner ends of the wing actuators 20 are caused to travel along the paths defined by slots 60 , 62 between the inner and outer extremities of these slots . ( in an alternative arrangement an extra long headlands actuator could be used with its opposing ends being directly connected to the inner ends of the wing actuators 20 and eliminating the need for links 52 to 70 described above ). in operation without down pressure , ( fig2 ) the wing lift circuit cd can be set to float mode in the tractor when the implement wings 10 and 12 have been lowered from their transport position . after the implement is lowered to the ground , continued flow into line b builds pressure to further operate the implement lift actuators until the depth stop ( not shown ) is reached . during this period pressure in line b causes pilot - to - open check valve 72 to open to allow flow from the rod end of the cylinder 50 , and the headlands system is extended by pressure in line b . this forces the ends of the wing actuators 20 to the outer ends of slots 60 and 62 for extra downward pivotal range of the wings 10 and 12 . the actuators 20 are held at the outer ends of slots 60 and 62 during operation in the working position . when raising the implement at headlands the cylinder 50 is retracted . this limits droop of the wings when the middle section 18 is raised by applying pressure to line a . the implement is typically raised just enough for working tools to clear the ground for turning at the field headlands . the pilot - to - open check 72 prevents fluid from escaping from the cylinder 50 to the rear or front lift actuators which may be extended only to an intermediate position at headlands . the check valve 72 also limits the droop of the wings 10 and 12 until the implement is lowered to the ground and line b is pressurized , repeating the cycle above . to raise the wings to transport position , the implement is first raised . pressure is applied to line a , retracting the cylinder 50 and at the same time operating the three point hitch actuators ( and rear lift actuators if present ) which raise the middle section 18 . after the middle section 18 is raised , pressure is applied to line d and the wing actuators 20 rotate wings 10 and 12 to a generally vertical position for transport . the ends of the wing actuators 20 are held at the inner ends of slots 60 and 62 by the cylinder 50 . in this held position the headlands actuator motion is completely restricted so that motion of one wing may not be transmitted to the opposite wing through the linkage system when the wings are being raised . otherwise the wings could freely toggle side to side in the vertical position until they came to rest against some other abutment . alternately the slots 60 and 62 could be replaced by links pivotally connected to the middle section 18 and end of the wing actuator providing the link &# 39 ; s rotation is limited by stops corresponding to the inner ends of the slots of the present embodiment . in operation with down pressure , ( see the hydraulic circuits of fig3 or 4 ) the operation of the headlands system is the same . the wing lift circuit may be set to down pressure mode by setting the valve in the tractor to pressurize line c . the down pressure circuit to the wings may be connected in combination with the hydraulic top link 30 , or may act alone as in the case of a rigid top link . a hydraulic top link not connected to a down pressure circuit is known in the prior art for adjusting the angle of an implement relative to a tractor , and remains fixed as a rigid link during operation . ball valve 74 ( fig3 or 4 ) is closed when wings 10 and 12 are raised to the transport position . this allows full tractor pressure to be applied to wing actuators 20 to lower the wings which generally rest past an overcenter position in transport ( generally vertical ). the ball valve 74 is controlled by a cam or link mechanism so that it is open when the wing position is lower than about 15 degrees up from horizontal as described in the above - noted u . s . patent . referring to fig3 and 4 , wing down pressure is controlled by relief valve 76 , which limits the pressure in line c 2 . this relief valve allows fluid to return through line d when pressure in line c 2 exceeds the setting . an optional top link actuator may also be connected to line c 2 via line c ′, and pressure to both the wing actuators and the top link actuator may be controlled by valve 76 . with particular reference to fig4 valve 80 is provided when connecting a hydraulic biasing top link to lockout the top link biasing function when the implement is being raised . when the implement is lowered to the set working height there is no pressure in line a or to pilot a ′, and valve 80 will open with any pressure at c 4 or c 1 to allow the top link to extend or retract with the biasing function . a second relief valve 82 ( fig4 ) may be added to the circuit to control the top link pressure separately . this valve may be set at pressures greater than that of relief valve 76 to create a differential pressure between lines c 2 and c ′. the valve 82 allows pressure in c ′ to build higher , before continuing into line c 2 , where relief valve 76 will control the pressure in that part of the circuit . this type of down pressure circuit described above which uses relief valves or pressure regulating valves rather than prrv ( pressure reducing - relieving valve ) controls is preferred when connecting to tractors having ccls ( closed center - load sensing ) controls . the tractor valve controlling this circuit is preferably set to deliver 3 gpm , which generally satisfies the rate at which the various actuators respond to uneven ground . this set flow will continuously pass through circuit cd during operation of down pressure , and be used as required by the actuators when they extend or retract as they provide bias to force the middle section 18 and / or wing sections 10 and 12 toward the ground . a flow divider 84 can be used to separate equal portions of flow when a second circuit is connected to the same control valve . in this case the tractor valve may be set to 6 gpm . a 50 / 50 divider will split 3 gpm to each circuit regardless of the pressure at which either circuit is operation . in the embodiment shown in fig4 the second circuit operates hydraulic drives for metering seed or other materials for planting . a check valve 86 in the second circuit blocks reverse flow to the second circuit so that full pressure may be applied to the wing actuators when raising the wings . depending on the ratio of flow required by the branch circuits , a flow divider with a different split ratio could be used . or a priority flow divider could be used which sets a fixed flow to one branch and delivers any excess flow to the other . other multiple number of branch circuits is conceivable by using primary and secondary flow dividers and so on . preferred embodiments of the invention have been described and illustrated by way of example . those skilled in the art will realize that various modifications and changes may be made while still remaining within the spirit and scope of the invention . hence the invention is not to be limited to the embodiments as described but , rather , the invention encompasses the full range of equivalencies as defined by the appended claims .

US-89787401-A

an apparatus and method for depositing flowable solids onto articles located on a moving conveyor . a flowable solid is placed on a vibrating trough and dispensed to an article on the moving conveyor through a slot in the trough . a third planar surface placed beneath the slot receives the flowable solid from the slot and provides an even dispersing pattern of the flowable solid onto the articles .

the present invention is generally related to a flowable solids dispensing apparatus that has a first surface and a second surface disposed about a central axis . the first surface and the second surface are generally disposed about the central axis to form an angle therein . the second surface is generally disposed below the first surface and forms a slot with the first surface so that a flowable solid material will progress from the first surface to the second surface through the slot . the purpose for progressing a flowable solid material from a first surface to a second surface is not limited to , but includes , the ability to provide an even distribution of a flowable solid onto a product positioned beneath the flowable solids dispensing apparatus . providing an even distribution of a flowable solid material , such as a seasoning , to a snack food product can provide a snack food product that is more evenly coated , and thereby more evenly seasoned , thus providing a more consistently coated and / or flavored snack food . a more consistently flavored snack food can provide the snack food consumer with a more flavorful and enjoyable snack food consumption experience . referring to fig1 and 2 , an exemplary flowable solids dispensing apparatus 10 generally comprises a first surface 14 and a second surface 15 . first surface 14 and second surface 15 are generally arranged about an axis . preferably , surface 14 and surface 15 are parallel to the axis and surface 15 is disposed below surface 14 to form slot 18 so that a flowable sold material 19 can traverse surface 14 , pass through slot 18 onto surface 15 . the flowable solid material 19 can then traverse surface 15 and then be disposed upon an object passing or disposed thereunder upon leaving surface 15 . surface 14 and / or surface 15 can be provided as planar surfaces , substantially planar surfaces , inward or outward frustoconical surfaces , inward or outward substantially frustoconical surfaces , corrugated surfaces , inward or outward vortically - shaped surfaces , “ v ”- shaped surfaces , concave surfaces , convex surfaces , and combinations thereof . in any regard , it is preferred that surface 14 and surface 15 be selected in order to provide an efficacious and / or even distribution of a flowable solids material 19 upon an object passing under flowable solids dispensing apparatus 10 . flowable solids dispensing apparatus 10 can optionally comprise trough 12 having a longitudinal axis and a generally planar shape . trough 12 can be disposed above surface 14 or can be unibodily attached to surface 14 . in any regard , if trough 12 is utilized with flowable solids dispensing apparatus 10 , it is preferred that a flowable solids material 19 be capable of traversing trough 12 until contacting surface 14 . further , at least one optional oscillator or vibrator ( vibrator ) 13 can be attached to flowable solids dispensing apparatus 10 and / or trough 12 . if trough 12 and surface 14 are present in a unibody form , vibrator 13 can oscillate or vibrate both trough 12 and surface 14 . further , if trough 12 , surface 14 , and surface 15 are provided in a unibody form , vibrator 13 can oscillate or vibrate all surfaces thereto attached . it is also believed that vibrator 13 can oscillate or vibrate one or more selected surface of flowable solids dispensing apparatus 10 if so desired . however , as would be known to one of skill in the art , any conveying methodology can be utilized that channels a flowable solid through a finger applicator . exemplary , but non - limiting flowable solids 19 including spices , seasonings , confections , sprinkles , nuts , powdered coatings , other topical coatings and / or additives , and the like , can be introduced to first surface 14 and / or trough 12 via hopper 11 . however , it should be realized that it is possible to introduce any metered and / or unmetered flowable solids 19 by numerous methodologies to surface 14 and / or trough 12 that include , but are not limited to , conveyor belts , screw augers , blades , rotary valves , feeder rolls , chutes , vibratory trays , and combinations thereof . it is also preferred that flowable solids 19 be fed evenly across the dimension of first surface 14 and / or trough 12 . however , one of skill in the art could also provide flowable solids 19 directly to surface 14 and / or trough 12 without the use of hopper 11 . as a non - limiting example , vibrator 13 can be attached to flowable solids dispensing apparatus 10 and / or trough 12 through a mounting bracket . in a preferred embodiment , trough 12 extends approximately the length of flowable solids dispensing apparatus 10 and terminates at wall 17 . wall 17 can be a device such as a weir , however , wall 17 should preferably retain flowable solid 19 within the confines of trough 12 . preferably , trough 12 is generally substantially planar , however , other non - limiting geometries can be used , such as “ v ”- shaped , “ u ”- shaped , and / or a corrugated shape . however , it should be realized that the geometry chosen should permit flowable solids 19 , such as granules , to flow continuously and uniformly across the surface of trough 12 . when the vibrator 13 is activated , the attachment of the vibrator 13 to surface 14 and / or trough 12 causes surface 14 and / or trough 12 to vibrate . any vibrator 13 common in the industry can be used and the rate of vibration , and / or vibration amplitude can be varied by user controls on vibrator 13 or by any electronic controller directly on or remote to vibrator 13 . in the preferred embodiment of fig1 hopper 11 is positioned relative to trough 12 so the outlet of hopper 11 aligns with trough 12 . it is preferred that hopper 11 be isolated from the vibration of trough 12 so that hopper 11 and trough 12 do not directly contact each other . this can allow the flowable solids 19 contained within trough 12 to migrate toward wall 17 during vibration of trough 12 by vibrator 13 . additional flowable solids stored within or about hopper 11 can replenish flowable solids 19 used in processing . as fig2 shows , a flowable solid can be oscillated or vibrated in a direction generally parallel to the longitudinal axis of trough 12 toward break 20 in trough 12 . in a preferred embodiment surface 14 and trough 12 generally define break 20 . surface 14 preferably extends away from trough 12 in a direction generally normal to the surface ( the negative z - direction ) and elongate axis of trough 12 . it is preferred that trough 12 and surface 14 be generally substantially planar . to this end , it was surprisingly found that planar surfaces could promote an even flow of flowable solid 19 . one of skill in the art will also realize that break 20 can extend entirely or partially across the entirety of trough 12 . as is further shown in fig4 - 7 , slot 18 and break 20 generally define surface 14 . the relative area of surface 14 generally increases as flowable solids 19 move in the direction a of the longitudinal axis of trough 12 . it should be remembered that slot 18 should be at least slightly larger than the maximum diameter of flowable solid 19 in order to facilitate movement of flowable solid 19 through slot 18 to surface 15 . without desiring to be bound by theory , it is believed that dimensioning slot 18 to be smaller than the average diameter of flowable solid 19 could cause degradation of flow in flowable solid 19 . as flowable solids approach break 20 , the general direction of movement changes from direction a to direction b that can be generally parallel to surface 14 . while the flowable solids 19 traverse surface 14 , flowable solids 19 can still have movement in the direction of the elongate axis of trough 12 . however , it is believed that flowable solids 19 will move in a direction substantially perpendicular to the elongate axis of trough 12 due to the normal force of gravity and the angle selected for surface 14 . it should also be recognized that slot 18 can be completely or partially co - extensive along the length of surface 14 . it is also preferred that the angular displacement of surface 14 with respect to the horizon be uniformly maintained . it has been found that this angle should be maintained from about zero degrees from horizontal to about 90 degrees from horizontal . however , it has been preferably found that about a 40 - degree angle from the horizon provides the best flow characteristics for generally most flowable solids 19 . it is also possible that other multi - angular surfaces can be used to facilitate the movement of flowable solid 19 across surface 14 . as particularly shown in fig2 the terminus of break 20 is selected so that remaining flowable solids 19 that reach surface 14 at the terminus of break 20 and a sidewall of trough 12 will contact surface 14 . without wishing to be bound by theory , it is believed that the location of the terminus of break 20 is believed to be dependent upon the physical and flow characteristics of flowable solid 19 . it is also believed that the position of the terminus of break 20 is dependent on the amount of forward vibration needed to move flowable solid 19 . thus , the terminus of break 20 can be placed to facilitate movement of flowable solid 19 onto surface 14 properly . however , it is preferred that the placement of break 20 be related to both the angle of surface 14 and the type of flowable solid 19 to provide for flowable solid 19 to reach the end of slot 18 and not contact wall 17 . additionally , the distal end of surface 14 can be linear , curved , discontinuous , or have any shape or design . it was surprisingly found that forming the distal end of surface 14 in a triangular shape could provide increased flexibility when conveying or transporting materials having varying flowabilities . in any regard , it is preferred that the flowable solid 19 not contact wall 17 . referring to fig2 and 4 - 7 , after flowable solid 19 contacts and traverses surface 14 , flowable solid 19 flows through slot 18 toward surface 15 . surface 15 is generally angled away from the plane of surface 14 and / or trough 12 . surface 15 can have an angle with respect to the horizon from about zero degrees to about 90 degrees . further , surface 15 can form an angle with respect to surface 14 , this angle preferably being an acute included angle . however , it was found that an angle of about 30 degrees with respect to the horizon produced generally the best flow characteristics for a generally wide array of flowable solids 19 . surface 15 is preferably generally planar , however one having skill in the art would be able to provide surface 15 in any shape , including those of surface 14 , as described supra , including , but not limited to “ c ”- shaped , “ u ”- shaped , and / or triangular shaped . as shown in fig8 a portion of surface 15 has at least one opening 16 disposed thereon . the opening or openings 16 can have any dimension or shape . exemplary and non - limiting opening 16 shapes include round , curvilinear , triangular , convex curved , concave curved , mesh , screen , and combinations thereof . it should be realized that openings 16 should be dimensioned to provide the most efficacious dispersal of flowable solid 19 . as a non - limiting example , the use of a triangular , or serrated pattern , as shown in fig8 can produce the general flowable solid 19 dispersal pattern as is shown in fig9 . without wishing to be bound by theory , as is shown in fig8 it is believed that the dimension “ w ” should be determined by the average particle size of flowable solid 19 . this can reduce clogging and facilitates the flow of large particles from surface 15 . it is also believed that dimension “ l ” can determine the total width of dispersion achieved by flowable solid 19 . thus , it is believed that openings 16 should be dimensioned to have a ratio of “ l ” to “ w ” greater than one in order to provide for an efficacious deposition of a flowable solid onto an object positioned and / or passing thereunder . the materials used to construct the flowable solids dispensing apparatus 10 can range from a wide variety of materials . in a preferred embodiment , flowable solids dispensing apparatus 10 is constructed from stainless steel or food - grade plastic . however , one of skill in the relevant art would be able to select a material that would be suitable for construction of the flowable solids dispensing apparatus 10 . further , the flowable solids dispensing apparatus 10 can have a surface coating applied thereto or inherently reside therein or thereon to provide flowable solids dispensing apparatus 10 with non - stick surface characteristics . referring again to fig2 and 8 , while dimension “ l ” of opening 16 can provide flowable solid 19 distribution across the width of a product processing , or conveyance , line , the length of the slot 18 and surface 15 provide the length of distribution or the residence time for the flowable solids 19 in trough 12 . it was surprisingly found that dispersing flowable solids 19 over the proper width ( of the product ) could provide total coverage of the surface of the product . further , dispersing flowable solids 19 , such as a seasoning , over an extended length can provide a longer residence time for the surface of the product and the applied flowable solid 19 to meet . thus , it is believed that flowable solids 19 should completely impact a processing line passing proximate to surface 15 between the initiation and terminus of slot 18 . thus , the lengths of slot 18 and break 20 can be set by the required residence time needed for the application of the flowable solids 19 onto the product located proximate to surface 15 . without wishing to be bound by theory , it is believed that slot lengths from four to 12 inches , more preferably from about 8 inches to about 12 inches in length , provide the optimal residence time required for most flowable solids 19 for a typical snack food product . typical products , or snack foods , believed suitable include , but are not limited to : potato chips , nacho chips , tortilla chips , corn chips , breads , cookies , cakes , pies , doughnuts , other extruded snacks , other baked snacks , other fried snacks , candies , other food items , and combinations thereof . additionally , trough 12 can be disposed to allow flowable solid 19 to impinge on a product in a drum feeder . as product traverses the length of the drum feeder , the product passes under flowable solids dispensing apparatus 10 . flowable solid 19 is dispersed from flowable solids dispensing apparatus 10 , as discussed supra , and impinges the product as the product passes substantially parallel to trough 12 . in this manner , it is possible for flowable solids dispensing apparatus 10 to impinge flowable solid 19 onto any number of sides of product . additional exemplary flowable solids dispensing embodiments are shown in fig1 a , 1b , 1 c , and 1 d . in fig1 a , flowable solids dispensing apparatus 10 a is shown without a flowable solids storage hopper . this can facilitate the supply of flowable solids 19 by a conveyor belt , screw auger , blade , rotary valve , feeder roll , chute , vibratory tray , and combinations thereof , or other device to dispensing apparatus 10 a . [ 0045 ] fig1 b shows an alternative embodiment of flowable solids dispensing apparatus 10 b . trough 12 b can have at least a portion of the trough extend vertically to allow for a region of acceleration for flowable solids 19 prior to contact with the first surface 14 . [ 0046 ] fig1 c shows an alternative embodiment of flowable solids dispensing apparatus 10 c . as shown , divider 21 has been placed on trough 12 c to effectively divide trough 12 c into at least two discrete flowable solids dispensing lines . divider 21 can completely separate any number of troughs 12 d , 12 e , so that flowable solids 19 are confined to one trough . optionally , divider 21 can only partially separate the trough to provide a common trough area 12 c . while trough 12 c is vibrating , flowable solids 19 can be placed in trough 12 c and divided into two sub - troughs 12 d , 12 e through the vibratory process described supra . the divided flowable solids 19 are then dispensed onto a passing substrate in accordance with the disclosure supra . it is fully intended that flowable solids 19 can be divided into any number of lanes to suit the application . further , divider 21 can have virtually any design . this includes simple geometric splits at the same point in the trough 12 c , and staged splits where - a divider 21 splits flowable solids 19 flow into two lanes that can further subdivide downstream with additional dividers 21 . additionally , it is envisioned that dividers 21 can be adjustable to provide point - of - source flow to allow a specific flowable solid 19 to be concentrated in a particular trough , for example 12 d or 12 e . further the adjustable dividers can be adjusted in situ if such a need would arise . [ 0047 ] fig1 d discloses yet another embodiment in which surface 15 can be positioned so flowable solid 19 flows directly from surface 14 to surface 15 . as shown , the flow direction of flowable solid 19 on surface 15 remains substantially parallel to the direction of flow of flowable solid 19 on surface 14 . it is also believed that one of skill in the art would be able to fabricate either of surface 14 or surface 15 to encompass the benefits derived by combining both surface 14 and surface 15 into one surface without the need for an angular displacement between surface 14 and surface 15 . as shown in fig1 , an alternative flowable solids dispensing apparatus 10 f is provided with a first surface 14 f having an inverted substantially vortical shape and centered about an axis . in this regard , hopper 11 f can provide a flowable solids material ( not shown ) in direction a of first surface 14 f . as flowable solids material ( not shown ) traverses first surface 14 f , flowable solids material ( not shown ) progresses along first surface 14 f in direction b . when the flowable solid reaches the terminus of first surface 14 f , the flowable solid ( not shown ) progresses across break 18 f onto second surface 15 f . the flowable solid material ( not shown ) then progresses along second surface 15 f to opening 16 f wherein the flowable solids material ( not shown ) then impinges a product positioned and / or passing thereunder . the flowable solids material ( not shown ) can be released from surface 15 f through openings 16 f onto a substrate disposed and / or passing thereunder . while particular embodiments of the present invention have been illustrated and described , it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention . it is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention .

US-30580702-A

a spill - proof aerator is disclosed that is adapted to flamelessly diffuse a liquid solution into the atmosphere . the device comprises a liquid solution having less than 20 % volatile organic compounds housed in a vessel with at least one wall , wherein an opening is disposed in the wall . the device further includes a wick assembly including at least a wick of porous material capable of being disposed in the opening of the vessel for at least partial submergence in the liquid solution . the wick is further disposed for drawing up the liquid solution thorough capillary action . the wick assembly is reusable and adapted to removably seal the opening in the vessel .

referring now to the drawings , wherein the showings are for purposes of illustrating preferred embodiments of this invention only and not for purposes of limiting the same , fig2 illustrates one exemplary embodiment of the spill - proof aerator assembly 2 fully assembled , in accordance with the present invention . aerator assembly 2 includes a two - piece wick assembly comprising solid top 8 and wick 6 , inserted into the solid top 8 and partially submerged in vessel 4 . alternatively , the wick assembly could be one continuous piece . vessel 4 is filled with a liquid solution ( not shown ) preferably comprising a mixture of volatile / non - volatile liquids having a volatile organic compound ( voc ) level below 20 %. the liquid solution may include fragrances , deodorizers , insecticides , decongestants , and the like . the exact solution composition may be optimized according to a manufacturer &# 39 ; s specific products . however , mixing various liquids must be proportioned such that solvents with naturally higher vocs will require the addition of a lower voc liquid to ensure the emission is below the 20 % threshold . similarly , when the solvent has a low voc , a higher voc content may be implemented in the liquid . fig3 displays aerator assembly 2 from a side angle with solid top 8 resting snugly against vessel 4 . wick 6 , extends from the solid top 8 partially through vessel 4 . the aerator assembly is not limited to the particular shape or assembly displayed , and may take any form desired without affecting the function of the aerator . as illustrated in fig4 ( a )-( d ), the aerator assembly may have a cube shaped vessel 13 with a square top 11 ( a ), a cylinder shaped vessel 17 and top 15 ( b ), a pyramid shaped vessel 21 and top 19 ( c ), or a cylindrical vessel 17 with a dome top 23 ( d ). however , the aerator assembly is not limited to the exemplary shapes listed herein . it is to be appreciated that the aerator referred to herein takes on a generic shape unless otherwise specified . as seen in fig5 , solid top 8 includes at least a top surface 14 and bottom surface 16 . solid top 8 is generally shaped so as to provide multiple evaporation faces to facilitate the release of liquid into the atmosphere ; however a single face of the solid top can be used as the evaporative surface . the shape of solid top 8 is not critical , and may be , for example , a disk , square , rectangle , cone or sphere , with walls that are smooth , undulated , ribbed , grooved , flat , or formed in any other way , providing the solid top is able to evaporate the particular liquid used . solid top 8 may be formed of a fibrous material with absorptive qualities , such as wood and ceramics , or the like . as best displayed in fig6 , one exemplary embodiment of solid top 8 includes a first hole 10 and a second , larger hole 12 , each disposed in bottom surface 16 . neither first hole 10 nor second hole 12 fully traverse the solid top 8 . second hole 12 is larger in diameter , but shallower than first hole 10 . therefore , first hole 10 is concentrically disposed inside second hole and extends deeper into solid top 8 , toward top surface 14 . the solid top 8 may be formed to any thickness providing the thickness is sufficient to allow for a first hole 10 and a second hole 12 , if such holes are used in the top 8 . in another embodiment , solid top 2 may comprise only one hole , or no holes at all . fig7 illustrates an exemplary vessel 4 according to the present invention . vessel 4 is depicted as being substantially cube - shaped ; however , as stated previously , the particular shape and / or volume is not critical to the assembly and substantially depends on aesthetic requirements . generally , vessel 4 includes an upper wall 20 , a lower wall 22 , and at least one end wall 23 . vessel 4 is preferably formed of glass . however , the vessel 4 may alternatively comprise any suitable material such as metal , porcelain , plastic , etc . according to one exemplary embodiment of the present invention , vessel 4 includes a neck portion 24 , circumferentially surrounding an opening 32 . neck portion 24 is preferably more narrow than the rest of the vessel and raised above upper wall 20 to releasably engage second hole 12 of solid top 8 . in this exemplary embodiment , vessel 4 includes a crimp - top neck 24 that fits snuggly inside second hole 12 , creating a spill - proof seal between the solid top 8 and the vessel 4 . a screw top neck on the bottle can also be utilized to the same effectiveness . when solid top engages vessel 4 creating a seal , a second spill - proof seal is created by the insertion of wick 6 through opening 32 . therefore , this particular embodiment comprises a double spill - proof seal . fig8 displays two additional exemplary embodiments of the vessel opening 32 . the vessel in fig8 ( a ) contains the narrow neck portion 24 raised above the upper wall 20 . the neck portion 24 may be threaded or non - threaded for mating with the solid top 8 and wick 6 assembly . the vessel displayed in fig8 ( b ) does not include a neck portion and instead maintains a wide opening 32 . wick 6 comprises a porous or fibrous material , including but not limited to wood , ceramics , fibers , plastics , or any other materials providing significant absorption . as opposed to known diffusers , the wick 6 according to the present invention may be re - used multiple times , even if the particular type of liquid is changed . once the wick 6 completely dries and is rid of the previous liquid , it may be re - used regardless of the scent or composition of the previous liquid . due to the particular cut , moisture level and wood material , the wick will not experience the problem of clogging known diffusers face , wherein the wicks may only be used once and then must be changed . in one embodiment , wick 6 comprises wood cut longitudinally with the wood grain in a vertical fashion . this assists in liquid uptake . if the wood was cut horizontally , capillary action will be retarded and the device will not diffuse efficiently . moreover , it is preferable if the wood has a moisture content of less than 15 % to maximize absorption and further limit clogging . as shown in fig9 , wick 6 comprises a first end 28 extended opposite a second end 30 . first end 28 is formed such that it may be releasably received by first hole 10 , as best seen in fig1 and 11 . wick 6 is preferably inserted into first hole 10 by hand and the fit should be exact , thereby eliminating any need for extra tools . wick 6 may alternatively be mated with solid top 8 in any way known in the art , such as threading , use of adhesives and interlocking connectors , so long as the liquid solution is effectively communicated from the wick 6 to solid top 8 . in one embodiment , wick 6 is cylindrical in shape , with second end 30 being tapered such that first end 28 has a larger radius than second end 30 . although depicted in the figures as a cylinder , wick 6 may take on any shape appropriate for the particular aerator to be used . for example , if first hole 10 is shaped as a square , it may be necessary for first end 28 of wick 6 to be shaped as a complementary square . additionally , an aerator may employ multiple wicks , as seen in fig1 and 13 . fig1 and 13 illustrate the use of three separate wicks , each mated with first holes 10 of solid top 8 . however , any number of wicks may alternatively be used . the spill - proof aerator of the present invention according to one exemplary embodiment , is assembled by first filling vessel 4 with a desired volatile and , optionally , nonvolatile liquid ( maintaining total voc levels below 20 %). once the liquid is disposed in vessel 4 , first end 28 of wick 6 is inserted into first hole 10 of solid top 8 . second end 30 of wick 6 is then inserted through opening 32 and into vessel 4 . due to the tapered shape of wick 6 , as the wick 6 is lowered into vessel 4 , the width of the wick 6 increases until the wick 6 seals off the opening 32 of vessel 4 , as best seen in fig1 . as described above , the opening 32 may alternatively , or additionally , be sealed by the engagement of solid top 8 and opening 32 . second hole 12 may be secured to neck portion 24 using a snap arrangement , screw arrangement , or any other suitable method known in the art . solid top is preferably removable from the vessel by hand , without the use of external tools . therefore , once assembled , solid top 8 rests flush up against vessel 4 and opening 32 is sealed off creating a spill - proof effect that will endure even if it were knocked on its side or even turned over . fig1 illustrates another embodiment of the spill - proof seal of the present invention , using a gasket 38 to form a pressure seal . gasket 38 can be either attached to solid top 8 or to vessel opening 32 . gasket 38 may be made out of any flexible material known in the art that is resistant to liquid and does not corrode or wear easily . common gasket / seal materials that may be used include rubber , neoprene and various soft plastics . the pressure seal is created when the top / wick combo is inserted into the vessel 4 and pressed down gently . fig1 displays yet another embodiment of the spill - proof seal according to the present invention . vessel 4 includes a threaded neck 26 that is adapted to engage a threaded cap 40 that fits over first end 28 of wick 6 and creates a tight seal . fig1 shows how the threaded cap 40 / wick 6 arrangement is then securely mated with an opening 32 . in another embodiment of the present invention seen in fig1 , a stopper / gasket 48 is attached to wick 6 , close to first end 28 . wick 6 is then inserted into opening 32 of vessel 4 to create a spill - proof seal . the stoppered wick 6 can then be mated to solid top 8 through the various methods described above . similar to the gasket seal , the stopper 48 can be made of a number of flexible materials that are impervious to liquids including , but not limited to rubbers , plastics , neoprene , and similar materials . in yet another embodiment of the present invention , as seen in fig1 , a spill - proof seal is created by employing a tongue and groove mechanism between the solid top 8 , wick 6 and the vessel 4 . vessel 4 has a tongue 50 protruding inwards on opening 32 , similar to an inner tube . tongue 50 can be made from a number of flexible , liquid impervious material such as rubber or various plastics . solid top 8 has a separate grooved piece 52 , which is made to fit the tongue 50 and fits snuggly when the top / wick combo is pressed unto vessel 4 . additionally , fig1 displays another exemplary embodiment for creating a spill - proof seal between the vessel 4 and solid top 8 . an adhesive may be applied to hole 53 of solid top 8 , which is then mated on to vessel neck 24 . the adhesive may be a commercially available adhesive . this method of adhesion may also be used on no - neck vessels . the spill - proof aerator assembly may alternatively not include a solid top , and diffusion into the atmosphere occurs completely through the wick 6 , as displayed in fig2 . the wick 6 preferably expands as it extends out of the vessel opening 32 creating a larger surface area to optimize diffusion . the spill - proof aerator for low volatile organic compound liquids , once assembled and filled with the liquid solution , uses the natural properties of the solid top 8 and the wick 6 to diffuse the liquid into the air . the one or more wicks 6 act as a sponge and soak up the liquid contained in the vessel through capillary action . the liquid then travels through the wick 6 and into the solid top 8 , whereby through further capillary action , the solid top becomes soaked in the liquid . this wicking action through the wick and the top begins the diffusion process through the air as the liquid reaches the surface of the top . since solid top 8 is solid and the vessel 4 is sealed , through either a single or double seal , there is no need for maintenance of the spill - proof aerator . after initial assembly and insertion , no further user action is required . the solid top will continue to diffuse and the wick will continue to “ wick ” until all of the liquid solution in the vessel has been used . once all the liquid has been used , the solid top 8 / wick 6 assembly may be removed from engagement with vessel 4 and vessel 4 may be refilled with liquid to be diffused . the exemplary embodiment has been described with reference to the preferred embodiments . obviously , modifications and alterations will occur to others upon reading and understanding the preceding detailed description . it is intended that the exemplary embodiment be construed as including all such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof .

US-42666009-A

a device that is a shoe heel attachment is provided , the device functioning to increase the surface area of the distal end of the heel portion of a high - heeled shoe , the device including an anchor portion and a planar portion . the device protects the heel of a high value shoe from abrasion and moisture that results from walking on permeable ground surfaces such as grass , mud , and snow , and improves the safety of the wearer from falls that would otherwise result from insertion of the heel into catching spaces such as sidewalk cracks and subway grate coverings .

currently commonly worn high heeled shoes , such as stiletto heels , are often characterized by having very little surface area of the base of the heel that contacts the ground . the distal end of the heel of a high heeled shoe may be as small as 25 mm 2 ( 5 mm × 5 mm ) or even smaller , so that a woman having a weight of at least about 50 kg would exert more than about 200 kg / cm 2 of force on the heel during each step . thus , the large force on the small contact area causes instability , imbalance , fatigue , and / or risk of injury for the wearer . further , this force and the narrow tapered shape of the heel causes the heel to penetrate a soft or uneven walking surface , such as grass , cobblestone , gravel , or a metallic grid such as a subway vent , and even soft macadam , degrading the decorative surface of the heel by abrasion and / or adhesion of unwanted particles . these types of processes adversely affect the appearance , value , and integrity of the decorative surface of the heel . an embodiment of the device herein is an attachment that attaches to the distal or lower or inferior portion ( distal relative to a central location of the wearer ) of a heel to increase the surface area of the distal end of the heel portion of a high - heeled shoe . the device further increases the wearer &# 39 ; s stability , comfort , and / or balance while traversing surfaces , thereby reducing risk , fatigue , or discomfort and / or protecting the heel from adverse surfaces . the device herein includes a planar portion 101 shown in fig1 , and an anchor portion 201 fig2 . with respect to fig1 , alternative treads or mixtures of treads can be used on the bottom ( inferior ) surface of the planar portion such as scoring in a hatch pattern 102 ; ridges ; serrations ; protuberances ; or other patterns . the planar portion , for example , is a planar “ cell ”, which has a flat surface platform having a diameter much larger than that of the heel of the shoe , for example , a 10 - fold , 20 - fold , or 30 - fold or more increase in surface area contacting the walking surface . the planar surface of the device results in a functional increase to the area of contact surface of the heel . for example , a diameter of the device that is 3 -, 4 -, or 5 - fold greater than the diameter of the actual shoe heel , results in a larger area of surface contact by a factor that is 9 -, 16 -, or 25 - fold , respectively , thus protecting the tip ( distal end ) of the heel from penetrating a permeable walking surface , and stabilizing the heel of the benefit of the wearer . see fig4 - 6 for a view of enlarged surface area of the heel compared to the heel inserted into the device . in related embodiments the shape and texture of the planar portion is specifically designed to be selected in a customized manner for surfaces commonly encountered by the user , i . e ., lawns , city sidewalks , gardens as described herein . the anchor portion of the present invention is configurable to accept a plurality of different styles of the planar portion , providing the wearer with a choice of color and styles as well as textures of the inferior surface , each unit providing improved stability to the wearer , and protection for the high - heel . the superior surface of the planar base is contiguous with or attaches to the anchor portion , and also serves as a platform for additional components that serve to secure the device to the heel . an embodiment of the device provided herein is a heel attachment for a shoe , the device being compact and easily and quickly attached and detached via a receptacle suitable for a high - heeled shoe without irreversibly altering the appearance or integrity of the shoe . the device anchors to the distal end of the heel portion of a high - heeled shoe , and increases the surface area by having a receptacle with a contiguous planar surface that attaches to the distal end of the heel . the device is manufactured by any of standard conventional means , such as molding , injection molding and milling . the manufacture can be unitary molding , in which a mold for the entire device is filled with for example unpolymerized material which is then polymerized in the mold to obtain its final form , or can be molded in two parts which are later joined , a seam between the two halves is filled with epoxy , adhesive or fairing compound and the seam is optionally sanded to conform to the surrounding surface . the method of manufacture of the composite construction device further includes allowing the device to cure and once cured removing it from the mold . the device is manufactured to have one of a variety of diameters of the planar surface that is related to the height of the heel or the weight of the wearer . the device as manufactured is characterized as being small and light so that it is easily carried in a compact carrier or carrying compartment , such as a purse , a compartment of a purse , or a pocket of a dinner jacket or stole . a kit is provided having also a container and optionally a cleaning cloth , so that upon removal and prior to storage , the device is wiped clean to avoid soiling the wearer &# 39 ; s clothing . when a wearer finds it necessary to walk across an adsorptive , permeable or abrasive walking surface , the device is easily attachable . the device has a weight that is light enough to be transported easily , for example the device is less than 8 oz , 6 oz , or 4 oz , or even 2 oz . the device in various embodiments is manufactured from water resistant material to protect it from wear and tear from contacting moist or wet surfaces , and in related embodiments is entirely water resistant or water proof . the devise contains no or essentially no highly technological mechanical mechanisms or moving parts and is manufactured inexpensively . certain embodiments are intended to be disposable , and alternative embodiments are intended to be reused . further , the device in various embodiments is manufactured and used to add ornamental value , for example , designed to match particular colors or textures such as seasonal colors ( pastels ; bright primary colors ; earth tones ), or to add to the glamour of a dress shoe for example by addition of decorative elements such as stones , sequins , glass or crystal . each of the entire device or the planar portion is quickly and easily removable from the shoe , and can be alternated by the wearer with other variously shaped , colored and designed planar portions , to accommodate specific physical and / or design needs . for example , a planar portion having a larger surface area is more suitable than a planar portion with a smaller surface area for walking on a lawn , a mud , or a soft tuft . for protection from rain or flooding , however , the size and shape of the planar portion is of less consideration than a smaller planar portion that is manufactured of a water resistant material . thus , planar portions are designed in a plurality of shapes to increase stability in a variety of different terrains , or for the purposes of style . in related embodiments , the bottom of the planar base is manufactured of a material to be malleable to conform to an uneven surface . the malleable layer can further stabilize and protect the heel from a non - uniform surface . alternatively , the entire planar base is manufactured of a malleable material , having however sufficient support directly underneath the receptacle to withstand the force due to concentrated weight of the user during walking . additionally , for walking on a slippery surface such as ice , snow , or partially frozen mud the inferior surface of the planar portion is scored as shown in fig1 , 102 , and can also be serrated , or provided with additional combinations of textures or another feature , such as increased diameter for walking on snow or hard spikes for walking on ice , to increase traction and thereby enhance the safety of the user . the exemplary anchor portion shown in fig2 and 3 is centrally located on the superior surface of the planar portion 101 of the device , and has a receptacle 301 or hollow cavity , which receives the distal end of the heel of a high - heeled shoe as shown in fig4 - 6 . alternatively an asymmetrical location of the receptacle on the planar base is within the scope of the invention . the form of the receptacle is a closed structure such as a cylinder having a central axis perpendicular to the plane of the planar base , or the form can be an open or discontinuous structure such as a set of structures that are gripping members as described herein . the device is engaged by the user by aligning the distal end of a heel of a high - heeled shoe with the receptacle , such that the axis of the heel is perpendicular to or somewhat oblique to the plane of the planar portion , then sliding or impelling the heel into the receptacle 301 . the anchor portion 201 of the device contacts , receives , and anchors the distal end of the heel . in certain embodiments herein the planar - base of the device includes a material having the characteristics of substantial resistance and durability to withstand repeated physical wear , and possibly also to wear by electrical ( for example due to current leaking from metal plates on a sidewalk ) and / or thermal processes ( exposure to summer heat in a car interior ), as well as dimensional stability . the material is characterized by sufficient strength to support the pressure and weight exerted on a high heel by the ordinary force from walking by a wearer , as well as light enough to be easily transportable . the planar base includes in various embodiments a support layer inferior to ( under ) the anchor portion , for example the support layer is a malleable material , alternatively the support layer is adjacent to and superior to ( above ) a malleable material . alternatively , the support layer is coextensive with or even substantially comprises the planar base . in various embodiments the planar base and / or the support layer is manufactured from a plastic such as high - density polyethylene , polyaryletheretherketone , aromatic polyamide or polycarbonate , or from a lightweight metal such as aluminum . in certain embodiments , the device has a malleable material on the inferior surface of the planar base , and the support layer is coextensive or is substantially coextensive with the malleable material . multiple layers are manufactured by addition of unpolymerized subsequent layers during the molding process , or by addition of fully polymerized materials using epoxy or other glue . the receptacle in fig3 , 301 in certain embodiments forms a descending bore having a size gradient , i . e ., the bore of the receptacle is greater in diameter at the superior surface of the device above the planar base than at the inferior surface , the superior surface having the receptacle opening and the inferior surface being in contact with the planar base closer to the ground . thus with this design , as the distal end of the heel is inserted into the receptacle , composed of a deformable material , the heel is received and gripped . the heel fits increasingly more tightly as a function of the extent of the insertion of the heel into the receptacle , and the receptacle offers increasing resistance to the force impelling the heel and increases contact between the heel and the device . the inner surface of the receptacle in certain embodiments is lined with a layer of smooth , flexible material , for example polyurethane , polyurethane foam , polyethylene , polypropylene , polybutylene , polystyrene , and polymethylpentene . the smooth flexible material causes the distal end of the heel to be inserted and anchored within the anchor portion using a minimum of force , and the heel is similarly removed from the device when desired . the anchor portion is temporarily or permanently mounted within or affixed to the superior surface of the planar portion of the device . the receptacle of the anchor portion in various embodiments includes a set of radial cuts at the superior or proximal end of the receptacle , or the receptacle is lined with a plurality of adjacent beads , the beads being arranged tangent to each other circumferentially , and attached to the inner wall of the receptacle . the receptacle having the lining or ring of beads or the surface with cuts is further made compressible as a result of the beads or cuts , such that the distal end of the heel is held in place in the receptacle , without damage to the exterior of the heel . in alternative embodiments the distal end of the heel is secured within the receptacle with a clamp , clasp , ribbon , or strap that is additionally attached to the device , generally to the superior surface of the planar base , or to the anchor , or to the proximal ( top ) of the receptacle . for example , the strap or ribbon is decorative , and functions to affix the device to the ankle or upper surface of the instep of the foot . for example , the clamp or clasp is fixed to the superior surface of the planar portion of the device , and engages the portion of the heel to be secured within the cavity of the receptacle after insertion of the distal end of the shoe heel . clamps and clasps suitable for use in the device can be chosen from any among a selection of ornamental and decorative elements well known to one of ordinary skill in design or manufacture of shoes , sandals , or , textiles , or from the fabrics used in construction of a shoe for the upper end of the shoe market . examples of a device having a clamp are show in fig7 - 9 . the anchor portion of the device has three gripping members 701 contiguous with and extending upwards from the superior surface of the device platform . the gripping members are arranged to form a receptacle , and are molded to be contiguous to the superior surface of the planar base , as shown in fig8 . each gripping member extends upward and also inward , and the shape of the inner surface of each member bulges inward proximately , which adds to the gripping properties of the member . as a result of several factors , the deformability of the material of manufacture , an inward incline of each gripping member , and a bulge inward in the shape of the interior surface of the gripping member , the act of insertion of the heel causes an inward force to be applied upon the heel by each gripping member , so that the aggregate force by these characteristics of the plurality of the gripping members holds the device in place on the heel . an alternative embodiment is shown in fig1 in which two gripping members 701 extend upwards from the superior surface of the device platform and a third gripping member 701 is located , if the device is not engaged , on a tab 1001 for inserting into a slot or channel 1003 on the superior surface of the base platform , which interact to lock the gripping member on the tab into place around the bole or body of a high heel . serrations are shown in the embodiment in fig1 along lateral edges of the tab 1001 and corresponding serrations in edges of the channel 1003 on the device platform for receiving the tab for interlocking the tab and the platform . a bridge 1002 is located over the channel 1003 for receiving the tab 1001 at the posterior or dorsal end of the planar surface platform , the bridge acting to hold the end of the tab 1001 in the channel 1003 after insertion . the tab 1001 has an anterior end with optionally smooth lateral surface edges and a central section with serrated lateral surface edges . the posterior end of the channel 1003 is smooth with interior lateral dimensions that correspond to the external lateral dimensions of the smooth anterior section of the tab 1001 . use of the device is facilitated by contacting the heel of a shoe to the receptacle formed by the upright members circumferentially around the heel of the shoe and inserting the tab into the channel with sufficient force to lock the tab in place by matching the serrations of the tab with the corresponding serrations of the channel . to remove the device the user unlocks the tab from the serrations with an upward force , and pulls the deformable gripping members away from the shoe heel . an embodiment of the device anchor portion 1101 as shown in fig1 includes additional components , a plurality of alternative sizing inserts , of which two are shown . the outer dimensions of the sizing inserts are manufactured to be slightly smaller than internal dimensions of the receptacle of the anchor component 1101 , thereby providing that insertion of the inserts into the anchor receptacle causes a snug fit . the plurality of different sizes of the inserts provides for utility of the device with a variety of different shapes , sizes and heights of heels , that will fit into the same planar base platform . for example , fig1 shows a first insert 1102 which has three ribs extending into its interior aperture , and a second insert 1103 that has two ribs extending into its interior aperture . a strap is used to secure the device in an embodiment seen in fig1 . the planar portion or platform , 101 is connected to an embodiment of the receptacle 1202 for a shoe heel and a strap 1203 is further connected to the wall of the receptacle . the embodiment receptacle 1202 has an elongated dorsal or posterior surface ( back ) that extends proximally ( upward ) beyond the height of the ventral ( anterior or front ) portion of the receptacle , and the strap 1203 extends from the side sections of the receptacle 1202 wall . two conjoined rings 1204 that are manufactured in the shape of an “ 8 ” or “ eight ” extend from the strap 1203 at about a 90 degree angle from the direction of the strap 1203 . the ring proximate to the strap 1203 has a diameter that is smaller than , i . e ., is about 80 percent , of the diameter of the ring most distal to the strap 1203 . for use of this embodiment of the device , the heel of a shoe is inserted through both rings 1204 and into the receptacle 1202 on the superior surface of the planar base platform . for a snug fit , the wearer pulls the rings 1204 upwardly and onto the broader end of the heel . upon fitting both rings 1204 over the exterior of the heel , the rings 1204 that are manufactured of a deformable mater , flex and stretch and by such force , the rings 1204 grip the heel of the shoe to secure the device onto the heel . an embodiment of the device shown in fig1 has a receptacle that is a generally cylindrical tube 1302 of elastic material and that is contiguous with and extends proximally ( upward ) from the superior surface of the planar platform 101 . one or a set of tabs 1304 on the side or sides of the top of the tube 1302 provide a grip for a user to pull the tube 1302 over a shoe heel . in various embodiments , the length of the tube 1302 optionally has regularly arranged cut out portions , e . g ., staggered regularly spaced diamond - shaped voids 1303 giving the appearance of the tube 1302 a looks of a latticework . the distal end ( bottom ) of the tube 1302 includes at least one bracing struts 1301 in the shape of approximately equilateral triangles that also connects or is contiguous to the superior surface of the platform 101 . in various alternative embodiments , a wall 1401 of the receptacle seen in fig1 , 14 and 15 , extends proximally up from the superior surface of the planar base 101 and one side 1402 of the receptacle 1401 so that it is substantially higher than other portions of the wall , for example , approximately three times as high as the lowest edge of the top of the receptacle 1401 , although the height and ratio are selected by the manufacturer and user to be suitable to a particular height of a heel and are not to be considered as construed to be further limiting . as shown in fig1 , the exterior vertical surface of the device further has a “ t ” shaped tab 1403 on the uppermost portion of the surface . included with this embodiment of the device is a double ring 1404 in a “ c ” shape which is shown in the figure as positioned above the receptacle 1401 . the ring 1404 is stretched by the user around the heel that has been inserted into the receptacle , and the loops of the ring 1404 fit over the “ t ” shaped tab 1403 such that the ring 1404 grips the heel of the shoe and the device is secured on the heel . an alternative embodiment of the device includes a receptacle 1501 extending proximally ( upward ) up from the superior surface of the planar base 101 and , as shown in fig1 , an exterior vertical surface of the device further has a peg protrusion 1503 and further has a strap 1504 protruding from at least one lateral surface . the peg protrusion shown in fig1 is mushroom shaped , i . e ., the head of the peg is broader than the stem closer to the exterior vertical surface , however other shapes are suitable for the peg as is well known in the art . the strap 1504 has apertures 1505 or voids having a shape suitable so that a larger parameter of an aperture 1505 , here a keyhole shaped aperture , fits smoothly over the largest diameter of the mushroom shaped peg 1503 and the narrow section of the aperture 1505 fits the shaft of the peg 1503 . the strap 1504 is wrapped about the ankle of the user or around the heel of the shoe , and the user fastens the device in place by selecting and engaging one of the apertures 1505 at a location over the mushroom shaped peg 1503 , and pulling the strap tight with the appropriate aperture engaged on the peg . tension in the strap from the lock of the aperture in place over the peg secures the device on the heel . the device is manufactured of at least one material of the group of a metal , plastic , rubber , leather , wood , bone , paper , or other synthetic or natural materials , and in certain embodiments includes one or more high value materials such as metals , minerals or gem decorations , naturally occurring or synthetic , or any combination thereof . in certain embodiments the device is manufactured in a plurality of colors and designs . the colors and designs can be matched to a specific shoe design or generic colors . the device described herein is compact and therefore easier to transport and store than a second pair of shoes , or a bulky prior art device having a substantial mechanical attachment apparatus ( see robbins , u . s . patent application number 2006 / 0196082 , published on feb . 28 , 2006 ) as it will have less weight and / or smaller size . the device is in various embodiments , inexpensive and easy to store , disposable , and even is easy to replace , providing a less bulky and less costly alternative to a second pair of shoes . the invention having now been fully described , it is further exemplified by the following claims , which are exemplary only and are not to be construed as further limiting . the contents of all references cited are hereby incorporated herein by reference in their entireties .

US-31772408-A

a teat cup liner for use in a milking cup is disclosed . the teat cup liner has a head with an insertion opening for an animal &# 39 ; s teat . joined to the head is a shaft and a holding rim . the holding rim at least partially surrounds and is spaced apart from the shaft . the teat cup liner holding rim has an inner surface that defines a number of recesses to enhance the durability of the liner . the recesses can be disposed circumferentially around the inner surface of the holding rim , and they can be disposed so that they are in contact with or near an end of the teat cup sleeve .

in fig1 a teat cup liner 1 for use in a milking cup is shown schematically . the teat cup liner 1 has a head part 2 . the head part 2 has an insertion opening 3 for a teat of an animal . the representation of the head part 2 is schematic . the design and execution of the head part may be various . the head part 2 is attached to a shaft part 4 . a holding rim 5 is provided below the head part 2 . the holding rim 5 surrounds the shaft part 4 . a sleeve 6 is provided between the shaft part 4 and the holding rim 5 . the holding rim 5 lies on the outer lateral surface of the sleeve 6 and attaches the teat cup liner to the sleeve 6 at least partly . in the practical example shown , the teat cup liner has recesses 7 . the recesses 7 extend partly in the circumferential direction of the holding rim 5 . they are designed to lie opposite to the end face 8 of the sleeve 6 . the end face 8 of the sleeve 6 preferably lies against the region that is between the recesses 7 . fig2 shows schematically a development of the holding rim , specifically of the region in which the end face 8 of the sleeve 6 lies against the teat cup liner . recesses 7 are provided , which are distributed on an imaginary circumference . the recesses 7 are arranged in an equidistant manner to one another . they form a first set of recesses . the representation according to fig2 shows further recesses 9 . the recesses 9 are arranged in an equidistant manner to one another . they form a second set of recesses . the recesses of the first set and the recesses of the second set are displaced with respect to one another in the circumferential direction so that at least one recess 9 of the second set is provided between two neighboring recesses 7 of the first set . the recesses of the first set and the recesses of the second set can also be displaced in the axial direction . it is possible for the recesses 7 , 9 to overlap partially . such a design of the teat cup liner is shown in fig3 , whereby fig3 shows the contour of recesses 7 , 9 . the recesses 7 , 9 are designed alternately and they overlap partly . they have a cross - section that expands in the axial direction , in the direction of head part 2 . hereby a design is preferred in which the recesses transition into a rounded region 10 . the recesses may also have other forms or shapes . it is not absolutely necessary that all recesses have the same shape . it is possible for groups of recesses to be provided that are of different shape and form . moreover , it is also possible for the recesses to extend into the region of sleeve 6 adjacent to end face 8 . recesses may also be provided that are designed to lie opposite to an end region of the sleeve 6 . fig4 to 9 show further embodiments of the teat cup liner . in these embodiments of the teat cup liner , the representation of the recesses was omitted for the sake of clarity . however , it is also possible for the teat cup liners shown in fig4 to 9 to be manufactured without recesses . these embodiments of the teat cup liner without recesses may also , themselves , be considered essential for the invention . fig4 shows a teat cup liner 11 with a head part 12 and a shaft part 13 . the shaft part 13 is surrounded by a holding rim 14 which is designed below the head part 12 . it can be seen from the representation that an elastic layer 15 is provided on the outer lateral surface of the holding rim , especially in the shoulder region there , designed in such a way that it damps the effects of forces on the teat cup liner . alternatively or additionally , a layer 16 may be provided in the inner region of the holding rim 14 . the layer 15 or 16 may be manufactured with the teat cup liner using a two - component injection method . fig5 shows still another variation of a teat cup liner . the teat cup liner has a conventional structure with a head part 12 , a shaft part 13 and a holding rim 14 . it can be seen from the representation according to fig5 that especially in the shoulder region of the holding rim 14 another layer 17 is provided . the layer 17 can be designed , for example , in the form of a film , which is placed into the mold . it is also possible to create the layer 17 in the form of a ring . there is also the possibility that only layer 17 is provided . layer 17 can be manufactured with the teat cup liner using a two - component injection method . fig6 shows an even further embodiment of a teat cup liner with a head part 2 , a shaft part 13 and a holding rim 14 . the holding rim 14 has regions 17 , 18 , which are designed to dampen impact . these regions may consist of a material that is preferably softer than the material of the teat cup liner . especially , the regions should be designed in such a way that these will exhibit an improved puncture resistance in the sense that when the forces occur they will not cause damage to the teat cup liner in the region of the end face of the sleeve and of the teat cup liner . the regions or individual regions may be formed from a foam . fig7 and 8 show two additional practical examples of a teat cup liner . the teat cup liners have a head part 12 and a shaft part that is connected to the head part 12 . the shaft part 13 is surrounded by a holding rim 14 . a sleeve 19 is provided between the shaft part 13 and the holding rim 14 . the end face 8 of the sleeve 19 is covered at least partly by a profile , especially by a profiled cord 20 . thus , the profile that is especially made of rubber forms a damping element . the profile may be coated with polyurethane or another plastic . it is also possible for the profile to have hollow chambers that are filled with a medium , especially air . instead of using a profile 20 or in addition to using a profile 20 , there is also the possibility of designing the end face 8 with a border in such a way that high surface pressures between the teat cup liner and the sleeve are avoided . in the practical example shown in fig8 , an inner ring 21 is arranged between the teat cup liner and the end face 8 of the sleeve 19 . the end face 8 of the sleeve 19 is covered by the inner ring 21 . it also lies against the end face . the inner ring is designed so that it can expand both in the radial direction as well as in the axial direction of the teat cup liner when forces act from the outside , especially on the holding rim 14 . the inner ring can be placed as an insert part before the injection of the silicone into the tool . it can be designed as a two - component part . optionally , the inner ring can be a rubber - metal component with a vulcanized border . fig9 shows a teat cup liner 11 with a head part 12 . a shaft part 13 joins onto the head part 12 . the shaft part 13 is surrounded by a holding rim 14 . a recess 22 is provided in the region between the holding rim 14 and the shaft part 13 and this recess extends in the circumferential direction of the holding rim 14 . the recess 22 is partially delineated by a lip 23 . the lip 23 is designed so that it rests on the end region of a sleeve 19 when the teat cup liner is joined to the sleeve . the teat cup liner rests on the end face 8 of the sleeve . the recess 22 forms an air pillow through which impacts , for example , the unit falling on the floor , are damped . the recess 22 is designed so that essentially the surface pressure of the material of the rubber will not exceed a critical value . with the aid of the teat cup liner according to the invention and the milking cup according to the invention , damage to the teat cup liner by impact , stepping on it by a cow , falling of the milking machine or similar , is essentially avoided .

US-30923707-A

a device is provided for neatly organizing and storing containers and lids by combining a unique attachment mechanism and hanging system . the attachment mechanism and containers and lids are uniquely designed to provide stationary and compact storage . the attachment mechanism may include a lip to ensure the containers and lids remain in their desired location . the containers and lids are centered on the device and snap together for added security . the device can be attached to counter tops , drawers , and closet doors for easy access .

illustrative embodiments of the invention are described below . the following explanation provides specific details for a thorough understanding of and enabling description for these embodiments . one skilled in the art will understand that the invention may be practiced without such details . in other instances , well - known structures and functions have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments . unless the context clearly requires otherwise , throughout the description and the claims , the words “ comprise ,” “ comprising ,” and the like are to be construed in an inclusive sense as opposed to an exclusive or exhaustive sense ; that is to say , in the sense of “ including , but not limited to .” words using the singular or plural number also include the plural or singular number respectively . additionally , the words “ herein ,” “ above ,” “ below ” and words of similar import , when used in this application , shall refer to this application as a whole and not to any particular portions of this application . when the claims use the word “ or ” in reference to a list of two or more items , that word covers all of the following interpretations of the word : any of the items in the list , all of the items in the list and any combination of the items in the list fig1 illustrates a container system 10 comprising an l - shaped first rack 20 and a plurality of containers 60 . the l - shaped first rack 20 comprises a bottom side 30 substantially orthogonally fixed with a rear side 40 and an elongated first slidable attachment means 50 . the elongated first slidable attachment means 50 is further fixed to the rear side 40 with a front surface 48 of the rear side 40 . in an alternative embodiment , the first slidable attachment means 50 of the first rack 20 is integrally formed with the rear side 40 and the bottom side 30 thereof . the first rack 20 is preferably made from a rigid , easily washed material such as plastic , wood , metal , or the like . each of the plurality of containers 60 has a rim 70 defining an opening 80 ( fig3 ) thereof . a first hanger 90 projects away from the rim 70 and is adapted to slidably engage the first slidable attachment means 50 of the first rack 20 . the plurality of containers 60 are mutually nestable . the first hanger 90 of each container 60 may be successively introduced to the first slidable attachment means 50 and slid towards the bottom side 38 of the first rack 20 . each successive container 60 is nested with the next adjacent container 60 , the first slidable attachment means 50 cooperating with each first hanger 90 of each container 60 to retain each container 60 onto the first rack 20 . the first rack 20 is mounted either horizontally with the rear side 40 up or vertically with the bottom side 30 down . although not shown in any of the figures , each container 60 may include more than just one of the first hangers 90 projecting away therefrom . in fig1 , the first slidable attachment means 50 of the first rack 20 may include a lip 100 proximate to a top end 58 thereof . when the first hanger 90 of one of the containers 60 is placed onto the first slidable attachment means 50 , the lip 100 contacts the top end 58 , requiring increased force to allow passage of the first hanger 90 thereby . once it has passed the top end 58 , the first hanger 90 will need increased force for it to be removed from the first slidable attachment means 50 , to prevent inadvertent detachment . alternately , in fig2 , the first attachment means 50 includes a jog 101 proximate the top end 58 thereof for retaining the first hanger 90 of each container 60 thereon , but maintaining a consistent thickness of the first attachment means 50 . other suitable means ( not shown ) for retaining the containers 60 on the first slidable attachment means 50 , such as magnets , may alternately be used , provided that such means are able to be overcome by applying additional force to any container 60 that is to be removed from the first rack 20 . the top surface 38 of the bottom side 30 may include a projecting form 110 that snuggly fits inside the opening of the container 60 . the projecting form 110 operates to properly position the container 60 on the bottom side 30 . each successively nested container 60 is also properly positioned with respect to the bottom side 30 of the first rack 20 due to the projecting form 110 . the first rack 20 may be set on a countertop , for example ( as illustrated in fig2 ), or fixed to a vertical or horizontal surface ( fig4 ) with a mounting means 160 , such as a two - sided foam adhesive tape ( fig4 ), a hook - and - loop type fastener ( not shown ), mechanical screws ( not shown ) fixed through apertures ( not shown ) of the bottom side 30 or rear side 40 , or other suitable mechanical fasteners . as such the first rack 20 may be set on a countertop , fixed with a countertop , wall , fixed with a lower surface of a cupboard or countertop , fixed within a drawer , or mounted to other locations as deemed suitable by the user . fig3 and 4 illustrate a container system 10 wherein the first slidable attachment means 50 is an elongated solid 120 having at least one shoulder 125 . the elongated solid 120 is fixed with the front surface 48 of the rear side 40 with an elongated shank 130 . the first hanger 90 includes a c - shaped portion 140 adapted for slidable engagement with the elongated solid 120 . an open portion 150 of the first hanger 90 allows passage of the elongated shank 130 such that the c - shaped portion 140 is supported against the pull of gravity by the at least one shoulder 125 of the elongated solid 120 . in an alternative embodiment , the top end 58 of the elongated solid 120 is tapered to facilitate initial engagement of the first hanger 90 therewith . the elongated solid 120 is preferably substantially cylindrical , but may take any suitable cross - sectional shape . fig5 illustrates a container system 10 that further including an l - shaped second rack 220 and a plurality of lids 260 . the l - shaped second rack 220 comprises a bottom side 230 substantially orthogonally fixed with a rear side 240 and an elongated second slidable attachment means 250 . the elongated second slidable attachment means 250 is further fixed with the rear side 240 at a front surface 248 of the rear side 240 . in an alternative embodiment , the second slidable attachment means 250 of the second rack 220 is integrally formed with the rear side 240 and the bottom side 230 thereof . the second rack 220 is preferably made from a rigid , easily washed material such as plastic , wood , metal , or the like . each of a plurality of lids 260 has a rim seal 270 interlockably engageable with the rim 70 of one of the containers 60 to seal the container 60 . a second hanger 290 projects away from the rim seal 270 and is adapted to slidably engage the second slidable attachment means 250 of the second rack 220 . the plurality of lids 260 are mutually nestable . the second hanger 290 of each lid 260 may be successively introduced to the second slidable attachment means 250 and slid towards the bottom side 238 of the second rack 220 . each successive lid 260 is nested with the next adjacent lid 260 , the second slidable attachment means 250 cooperating with each second hanger 290 of each lid 260 to retain each lid 260 onto the second rack 220 . the second rack 220 is mounted either horizontally with the rear side 240 facing upwardly or vertically with the bottom side 230 facing downwardly . as with the first rack 20 , the second rack 220 may be set on a countertop , for example , or fixed to a vertical or horizontal surface with the mounting means 160 , such as a two - sided foam adhesive tape ( fig7 ), a hook - and - loop type fastener ( not shown ), mechanical screws ( not shown ) fixed through apertures ( not shown ) of the bottom side 230 or rear side 240 , or other suitable mechanical fasteners . as such the second rack 220 may be set on a countertop , fixed with a countertop , wall , fixed with a lower surface of a cupboard or countertop , fixed within a drawer , or mounted to other locations as deemed suitable by the user . fig6 illustrates a container system 11 comprising the second slidable attachment means 250 of the second rack 220 including a lip 300 proximate a top end 258 ( fig5 ) thereof . when the second hanger 290 of one of the lids 260 is placed onto the second slidable attachment means 250 , the lip 300 contacts the top end 258 , requiring increased force to allow passage of the second hanger 290 thereby . once it has passed top end 258 , the second hanger 290 will need increased force for it to be removed from the second slidable attachment means 250 . the top surface 238 of the bottom side 230 of the second rack 220 includes a projecting form 310 that snuggly fits inside the opening of the lid 260 . the projecting form 310 operates to properly position the lid 260 on the bottom side 230 . each successively nested lid 260 is also properly centered with respect to the bottom side 230 of the second rack 220 due to the projecting form 310 . fig7 , 8 and 8 a illustrate the container system 10 wherein the second slidable attachment means 250 is an elongated c - shaped channel 320 . the elongated c - shaped channel 320 is fixed with the front surface 248 of the rear side 240 of the second rack 220 . the second hanger 290 includes at least a shank 292 and at least one shoulder 295 adapted for slidable engagement within the elongated c - shaped channel 320 . an open side 325 of the c - shaped channel 320 allows passage of the shank 292 of each lid 260 such that the at least one shoulder 295 is supported against the pull of gravity by the c - shaped channel 320 . the top end 258 of the c - shaped channel 320 is open to allow introduction of the second hanger 290 of each lid 260 therein . in one embodiment , the first hanger 90 of each container 60 and the second hanger 290 of each lid 260 are mutually engageable ( fig9 ) to properly position and retain each lid 260 on one container 60 and to further aid in the sealing of the lid 260 to the container 60 . the first hanger 90 and second hanger 290 are each shown with a mutually - cooperative shape , but such shapes may vary as desired provided that they each are engageable with their associated attachment means 50 , 250 and , optionally , with each other . the first and second attachment means 50 , 250 may be interchanged such that the second attachment means 250 is included with the first rack 20 and the first attachment means 50 is included with the second rack 220 . likewise , the corresponding hangers 90 , 290 of the containers 60 and lids 260 , in such an embodiment , are also be mutually interchanged . further , while a certain form for the first and second attachment means 50 , 250 has been illustrated , other slidable attachment means ( not shown ) that incorporate magnets or other mechanical attachment means such as rails , tabs and slots , tongue - in - groove arrangements , or the like may be utilized , provided that such attachment means allow for the slidable engagement of the container 60 or lid 260 with the rack 20 , 220 , and the subsequent nesting of the containers 60 or lids 260 . the present invention may be used for foods and other edible items . as such , the materials used are suitable for food use and are further microwave safe . it is anticipated that hot items , liquids , and other degradable items will be placed in the containers . as such , the present invention is constructed with a rigid , preferably transparent or translucent material , but also possibly opaque material , that is not damaged at temperatures associated with food preparation or storage , and that can create a tight hermetic seal . plastic polymers , ceramics , glass , rubber , metal , paper or other materials can be used so long as they meet the above qualifications . moreover , herein a container 60 may take a variety of shapes different than those illustrated in the drawings . for example , the container 60 may have a square or rectangular shape when viewed from above . further , the container 60 may also include tableware , such as a dinner plate , bowl , beverage cup or mug , or the like , and may not be associated with any particular lid 260 in such an embodiment . further , such containers 60 are not necessarily for use only with food items , but may be used for household organization of items like office supplies , hardware such as nails and screws , arts and crafts supplies , or the like . particular terminology used when describing certain features or aspects of the invention should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics , features , or aspects of the invention with which that terminology is associated . in general , the terms used in the following claims should not be construed to limit the invention to the specific embodiments disclosed in the specification , unless the above detailed description section explicitly defines such terms . accordingly , the actual scope of the invention encompasses not only the disclosed embodiments , but also all equivalent ways of practicing or implementing the invention . the above detailed description of the embodiments of the invention is not intended to be exhaustive or to limit the invention to the precise form disclosed above or to the particular field of usage mentioned in this disclosure . while specific embodiments of , and examples for , the invention are described above for illustrative purposes , various equivalent modifications are possible within the scope of the invention , as those skilled in the relevant art will recognize . also , the teachings of the invention provided herein can be applied to other systems , not necessarily the system described above . the elements and acts of the various embodiments described above can be combined to provide further embodiments . all of the above patents and applications and other references , including any that may be listed in accompanying filing papers , are incorporated herein by reference . aspects of the invention can be modified , if necessary , to employ the systems , functions , and concepts of the various references described above to provide yet further embodiments of the invention . changes can be made to the invention in light of the above “ detailed description .” while the above description details certain embodiments of the invention and describes the best mode contemplated , no matter how detailed the above appears in text , the invention can be practiced in many ways . therefore , implementation details may vary considerably while still being encompassed by the invention disclosed herein . as noted above , particular terminology used when describing certain features or aspects of the invention should not be taken to imply that the terminology is being redefined herein to be restricted to any specific characteristics , features , or aspects of the invention with which that terminology is associated . while certain aspects of the invention are presented below in certain claim forms , the inventor contemplates the various aspects of the invention in any number of claim forms . accordingly , the inventor reserves the right to add additional claims after filing the application to pursue such additional claim forms for other aspects of the invention .

US-201113118112-A

a new partnering game and method of playing same for enabling male and female players to anonymously select a player of their liking and determining whether or not the selected player likes them in such manner that only a mutually self - selected male - female couple knows of the selection . a method for revealing admirers of the players is also provided .

with reference now to the drawings , and in particular to fig1 through 17 thereof , a new partnering game and method of playing same embodying the principles and concepts of the present invention will be described . with reference to fig1 - 3 , a preferred embodiment of the partnering game is shown including a representative card 12 of a first set of cards , hereinafter referred to as male private cards , a representative card 20 of a second set of cards , hereinafter referred to as female private cards , and a representative card 30 of a third set of cards , hereinafter referred to as bluff cards . the male private card 12 includes a front side 13 upon which are shown disposed an indicia 14 from a first set of indicia , which in the preferred embodiment include the names of males , and a selection portion 15 including a dot matrix consisting of ten adjoining 3 × 3 dot matrices . the indicia 14 is shown disposed upon the front side 13 in a male private card top portion 16 and the selection portion 15 is shown disposed upon the front side 13 in a male private card bottom portion 17 . the cards of a fourth set of cards are identical to the male private cards in every respect . the female private card 20 is shown including a front side 21 upon which is disposed an indicia 22 from a second set of indicia , which in the preferred embodiment include the names of the female counterparts of the male indicia such as juliet / romeo and eve / adam . a selection portion 23 includes a dot matrix consisting of ten adjoining 3 × 3 dot matrices . the indicia 22 is disposed upon the front side 23 in a female private card bottom portion 25 and the selection portion 23 is disposed upon the front side 23 in a female private card top portion 24 . the cards of a fifth set of cards are identical to the female private cards of in every respect . a back side of the male private card 12 , a back side of the female private card 20 , and a back side of the bluff card 30 are identical one to the other and include a decorative design ( not shown ). the male private card 12 , the female private card 20 , and the bluff card 30 are dimensionally identical and made from a material having a smooth and firm surface . the bluff card 30 is shown having a blank first face 31 . to play the partnering game with the five sets of cards , a play area is selected , such as a table top and the players position themselves around the play area . a host for the game , who may also be a player , is selected . the game is preferably played by an equal number of male and female players , there being preferably at least three male players and three female players to ensure anonymity . the host of the game forms three decks of cards from the five sets of cards by shuffling the male private cards and inserting behind each male private card the identical card from the fourth set of cards thereby forming a first deck of cards . a second deck of cards is formed by shuffling the female private cards and inserting behind each female private card the identical card from the fifth set of cards . a third deck of cards includes the bluff cards . each player is given two identical cards from the first deck if the player is male and two identical cards from the second deck if the player is female . additionally , each player is given a plurality of cards from the third deck , the number being determined by dividing the number of players by two , squaring the result , and subtracting one from the squared result . thus , by way of example , if five male players and five female players are playing the partnering game , each player is given twenty four cards from the third deck . all of the cards are given to the players such that the back sides of the cards having the decorative design are showing . each player then holds in their hand , in such manner that the other players cannot see the front sides of the cards , a plurality of cards equal to the number of players of the opposite sex playing the game . the cards held by each player include the card from the male private cards if the player is male , or the card from the female private cards if the player is female , complemented by a plurality of cards from the set of bluff cards . each male player memorizes the indicia appearing on his male private card . in like manner , each female player memorizes the indicia appearing on her female private card . each male player then selects a female player of his liking and positions his male private card in such manner that when the cards held in his hand are dealt to the female players , the male private card is dealt to the selected female player . in similar fashion , each female player selects a male player of her liking and positions her female private card in such manner that when the cards held in her hand are dealt to the male players , the female private card is dealt to the selected male player . each male player deals out the cards held in his hand to the female players as described above and in similar fashion , each female deals out the cards held in her hand to the male players . each player then has a new set of cards . the male players then give the host of the game their card from the fourth set of cards and the female players give the host their card from the fifth set of cards in such manner that the players do not see the front side of the cards . the host shuffles and arranges the cards from the fourth set of cards into a matrix column heading row and the cards from the fifth set of cards into the matrix row heading column . each male players arranges his new set of cards with his remaining bluff cards in such manner that upon placing one card in each matrix cell front side down any female private cards received from a female player are positionable in the matrix in the column corresponding to his card from the fourth set of cards and the row corresponding to the indicia of the female private card . in similar fashion , each female player arranges her new set of cards with her remaining bluff cards in such manner that upon placing one card in each matrix cell front side down any male private cards received from a male player are positionable in the matrix in the row corresponding to her card from the fifth set of cards and the column corresponding to the indicia of the male private card . the host of the game then shuffles the cards front side down in each matrix cell , sorts the cards front side up to reveal any male or female private cards , and places any such cards back in the matrix cell . any matrix cell having a pair of cards reveals a mutual attraction and any matrix cell having only one card reveals an admirer of the player in whose row or column the card appears . in another preferred embodiment of the partnering game , the male players arrange themselves about the play area in a line so that each male player represents a matrix column heading . in similar fashion , the female players arrange themselves about the play area in a line so that each female player represents a matrix row heading . the host of the game forms three decks of cards from the five sets of cards by shuffling the male private cards and inserting behind each male private card the identical card from the fourth set of cards thereby forming a first deck of cards . a second deck of cards is formed by shuffling the female private cards and inserting behind each female private card the identical card from the fifth set of cards . a third deck of cards includes the bluff cards . each player is given two identical cards from the first deck if the player is male and two identical cards from the second deck if the player is female . additionally , each player is given a plurality of cards from the third deck , each male player receiving from the third deck one card less than the number of male players playing the game and each female player receiving from the third deck one card less than the number of female players playing the game . thus , by way of example , if five male players and four female players are playing the partnering game , each male player is given four cards from the third deck and each female player is given three cards from the third deck . all of the cards are given to the players such that the back sides of the cards having the decorative design are showing . each player then hides his or her card from the fourth or fifth set of cards for subsequent use in the game . each male player memorizes the indicia appearing on his male private card . in like manner , each female player memorizes the indicia appearing on her female private card . each male player then selects a female player of his liking and positions his male private card in such manner that when the cards held in his hand are positioned in the matrix cells corresponding to his column , the male private card is positioned in the row corresponding to the female player of his liking . in similar fashion , each female player selects a male player of her liking and positions her female private card in such manner that when the cards held in her hand are positioned in the matrix cells corresponding to her row , the female private card is positioned in the column corresponding to the male player of her liking . in a first mode of play designed to reveal only mutual attractions , each male and female player then positions , back side up , his or her cards in the matrix cells , each matrix cells containing two cards . the host of the game then randomly picks up each two card stack , back side up , to form a deck in his hand . the host then randomly places , back side up , each two card stack back in the matrix cells . with the removal by the host of all of the bluff cards from each two card stack , any stack containing two cards reveals or confirms a mutual attraction between the male and female players whose indicia appear on the cards . alternatively , in a second mode of play designed to reveal both mutual attractions and admirers , each male player picks up all of the cards in the matrix cells corresponding to his column back side up in such manner that the order of two card stacks is not destroyed , as by first picking up the two card stack closest to himself and progressing in a direction away from himself . to the top of each resulting deck , each male player adds his card from the fourth set of cards back side up and binds the stack as with a rubber band . the host collects the stacks from the male players , shuffles the stacks and returns a stack to each male player . each male player removes the top card from his deck and places it front side up in front of him and then places each two card stack front side down in the matrix cells corresponding to each female player in his column . in similar fashion , each female player picks up all of the cards in the matrix cells corresponding to her row back side up in such manner that the order of two card stacks is not destroyed , as by first picking up the two card stack closest to herself and progressing in a direction away from herself . to the top of each resulting deck , each female player adds her card from the fifth set of cards back side up and binds the stack as with a rubber band . the host collects the stacks from the female players , shuffles the stacks and returns a stack to each female player . each female player removes the top card from her deck and places it front side up in front of her and then places each two card stack front side down in the matrix cells corresponding to each male player in her row . the host of the game then removes from each two card stack all of the cards from the third set of cards . any two card stack confirms or reveals a mutual attraction and any matrix cell having one card reveals an admirer to the person designated by the indicia of the column or row the card appears in . in another preferred embodiment of the partnering game , the host of the game forms three decks of cards from the five sets of cards by shuffling the male private cards thereby forming a first deck of cards . a second deck of cards is formed by shuffling the female private cards . a third deck of cards includes the bluff cards . each male player is given a male private card from the first deck of cards and each female player is given a female private card from the second deck of cards . each male player memorizes the indicia appearing on his male private card . in like manner , each female player memorizes the indicia appearing on her female private card . additionally , each player is given a plurality of cards from the third deck of cards , each male player receiving from the third deck one card less than the number of male players playing the game and each female player receiving from the third deck one card less than the number of female players playing the game . each player holds his or her cards in such manner that the other players cannot see the front sides of the cards . each male player then selects a female player of his liking and positions his male private card in such manner that when the cards held in his hand are dealt to the female players , the male private card is dealt to the selected female player . in similar fashion , each female player selects a male player of her liking and positions her female private card in such manner that when the cards held in her hand are dealt to the male players , the female private card is dealt to the selected male player . after the cards are dealt by the male and female players , each player has a new hand consisting of five cards which may or may not include a male or female private card . each player then sorts through their hand and retrieves all female private cards if the player is male , and all male private cards , if the player is female . each player then writes their memorized indicia upon the selection portion of each retrieved card with an erasable marker in such manner that the other players cannot see the marked indicia . if a player does not retrieve a male or female private card from his or her hand , he or she must bluff that he or she is writing their indicia upon a card . each player then places their hand front side down in the center of the play area . the host of the game then shuffles the stack front side down and then with the front sides showing , removes all the cards from the third set of cards . the host further sorts out any two cards sharing identical indicia thereon . two such coupled cards confirm or reveal a mutual attraction between the male and female player corresponding to the indicia . any non - coupled male or female private cards reveal admirers of the player whose indicia appears in the selection portion of the card . for each of the above variations of the partnering game , the occurrence of a pairing of indicia corresponding to a famous couple , such as romeo and juliet , reveals a “ magical ” match . this type of match is “ magical ” because it is a rare occurrence . with reference to fig4 - 13 , another preferred embodiment of the partnering game includes a hand held device 40 including a housing 41 having a front portion 42 , a left side portion 43 , a right side portion 44 , a back portion 45 , and a top portion 46 shown including a slot 78 for accessing a bar code reader . the front portion further includes a keypad 47 having ten keys 48 , a speaker and speaker grill 49 , and a display means 50 . the left side portion 43 is shown including an on / off switch and volume control means 51 . the right side portion 44 includes a phono jack 52 . a battery compartment 53 is shown disposed in the back portion 45 for receiving a plurality of batteries to power the circuitry ( not shown ) disposed within the housing 41 . the circuitry includes a microprocessor operably coupled to a read only memory device ( rom ) for storing a computer program , the function of which will be described below . a random access memory device ( ram ) is also operably coupled to the microprocessor and functions to store program variables . a non volatile random access memory device ( nv ram ) is operably coupled to the microprocessor for storing values generated by the program which are permanently saved in case of device turn - off or battery failure until reset to new values as hereinafter described . a data input means and a data output means are operably coupled to the microprocessor for performing standard data input and output functions . the data input means include a first data input means including the numeric key pad 47 having ten keys 48 . the keys 48 are used to enter selections and control codes as described below . a second data input means includes a conventional led / photodiode bar code reader for reading an eight bit binary bar code . four input cards 60 , 62 , 70 , and 76 are shown in fig1 - 13 and are receivable in the bar code reader through a slot 78 formed in the bottom portion of the housing 41 . the data output means include a first data output means including a display screen 50 such a liquid crystal display ( lcd ). the display screen 50 is capable of displaying four distinct alphanumeric characters under four headings 79 as shown in fig4 . a second data output means includes an audio speaker operably coupled to a sound synthesis device which is in turn operably coupled to the microprocessor . the phono jack 52 is operably coupled to the sound synthesis device for outputting an audio signal to an external speaker . a stand 80 of conventional design is shown in fig5 and 6 for propping the housing 41 at an inclined angle upon a flat surface . with reference to fig1 , a representative male input card 60 is shown including an indicia 64 from a first set of indicia upon a front side of the card for identifying a male player of the game . the male input card 60 further includes a number 65 upon the front side of the card and a pair of corresponding bar codes 61 having the eighth bit set to one . the male input card 60 further includes the indicia “ private card ” 81 upon the front side of the card to indicate it &# 39 ; s function as will be further described hereinafter . the game includes a plurality of male input cards 60 having different indicia 64 . with reference to fig1 a female input card 62 is shown including an indicia 66 from a second set of indicia upon a front side of the female input card for identifying a female player of the game . the female input card 62 further includes a number 67 upon the front side of the card and a pair of corresponding bar codes 63 having the eighth bit set to one . the female input card 62 further includes the indicia “ private card ” 82 upon the first face of the card to indicate it &# 39 ; s function as will be further described hereinafter . the game includes a plurality of female input cards 60 having different indicia 66 . the first set of indicia include the male names from a set of famous couples and the second set of indicia include the female names corresponding to the male names . with reference to fig1 , a means for giving the game players a public identity is shown including a card 70 having the indicia “ public card ” 83 upon a first face thereof . the card 70 further includes a number 72 for publicly identifying the player and an eight bit bar code 71 corresponding thereto , the eighth bit being set to zero . the card 70 is further shown including a pair of apertures 84 formed at opposite corners for receiving a string . in use the player puts the string around his or her neck to display the card 70 . the game includes a plurality of cards 70 totaling the sum of the plurality of male and female cards 60 and 62 . with reference to fig1 , there is shown a card 76 including an indicia “ host control card ” 86 upon a front side thereof . the card 76 also includes a set of instructions 85 for it &# 39 ; s use . the card 76 further includes an eight bit bar code 77 set to the numeral 254 . the microprocessor firmware includes a means for decoding this numeral and entering into a control mode . in this mode the host of the game can reset the microprocessor by entering a first unique code upon the key pad , process male and female input cards entered during the course of a game by entering a second unique code upon the key pad , or enter other control commands as further described hereinafter . as in the previously described embodiments of the partnering game , the hand held device provides a means by which players that may have a mutual attraction to each other can confirm this attraction with total anonymity . to play the partnering game , the hand held device is placed in a location where all the players can see it . in the preferred embodiment , an equal number of male and female players play the game and at least three players of each sex play . a host of the game is selected who may also be a player . the host of the game shuffles all of the male private cards 60 to form a first deck of cards and all of the female private cards 62 to form a second deck of cards . the host additionally shuffles all of the public cards 70 to form a third deck of cards . each male player is dealt one male private card 60 and one public card 70 which he hangs around his neck . each female player is dealt one female private card 62 and one public card 70 which she hangs around her neck . each player then selects a player of the opposite sex of their liking . a first player inserts their private card 60 , 62 into the bar code reader through slot 78 and removes it when the number appearing on the card appears on the display screen 50 . the player then inserts his or her public card 70 into the bar code reader and when the number appearing on the public card 70 appears on the display screen 50 , the player enters a selection number corresponding to the number appearing on the public card 70 of the player he or she has selected . the microprocessor includes firmware for processing and forming a triplet of numbers including a private number corresponding to the number appearing on the private card 60 , 62 , a public number corresponding to the number appearing on the public card 70 and the selection number . each player in turn performs the steps of inserting and removing their private card 60 , 62 , inserting their public card 70 and entering the number appearing on the public card 70 of the player selected . the microprocessor firmware matches the triplets of each player in such manner that a first triplet corresponding to a first player is compared to all other triplets , a second triplet is compared to all other triplets excluding the first triplet , a third triplet is compared to all other triplets excluding the first and second triplets , this comparison being repeated until all triplets are compared to each other . the firmware compares the selection number of a first triplet to the public number of a second triplet and then compares the selection number of the second triplet to the public number of the first triplet . if both comparisons match , the two triplets indicate a reciprocal selection and the triplets are stored by the microprocessor . the firmware performs the comparisons for each pair of triplets and stores all reciprocal selections . the firmware of the game is such that the names of famous couples are encoded into sequential private numbers and a “ magical couple ” can be determined by subtracting the private numbers of all reciprocal selections and flagging a “ magical couple ” when the difference between the private numbers is one or minus one . the matches found are outputted to the speaker 49 by announcing the private names of the matched players . additionally , any “ magical couple ” is indicated in the announcement . the firmware further includes a means for determining the number of admirers of each player . the firmware performs a tally / sort comparison by comparing the selection number of each triplet to the selection number of all the other triplets . when a match is found , a unilateral attraction is established and the microprocessor increments an admirer count for the triplet being compared . the firmware then sorts the triplets in such manner that the triplet with the highest admirer count is placed first in an admirer list . the private names and corresponding admirer counts of all players having admirers are then outputted to the speaker 49 and announced . if the partnering game is played by the same players a plurality of times , new admirers may be revealed in successive rounds . the host of the game then may cause the device to repeat the matched selections and admirer counts by means of the host control card . the matches found and the admirer counts are stored in memory until the device is reset by means of the host control card . in another preferred embodiment , the private cards are not utilized . in this embodiment , each player inserts a public card 70 into the bar code reader and the microprocessor program includes a means for randomly generating a private name for each player . the private name and the public number are outputted to the display 50 together with a prompt for the player to enter his or her selection . each player memorizes his or her private name and enters the selection using the key pad . by removing the public card 70 the selection is stored in memory . these steps are repeated by each player and the microprocessor runs the same programs described hereinabove . in another preferred embodiment , the slot 78 ( fig9 ), and the cards 60 , 62 , and 76 are not included . in this embodiment , a control key 88 is provided ( fig1 ). pressing the control key 88 once places the device in a selection / entry mode . in this mode , each player enters his or her public number and his or her selection . the microprocessor program includes a means for generating a random and exclusive private number and private name for each public number entered by each player . after entering his or her public number and his or her selection and memorizing his or her generated private name , each player again presses the control key 88 to enable the next player to enter his or her public number and selection . pressing the control key 88 twice places the device in an action mode . in this mode , pressing the “ 1 ” key three times , the host of the game enables the microprocessor program to announce the reciprocal matches and admirer counts . in another preferred embodiment , a thermal printer is operably coupled to the microprocessor . the thermal printer is operable to print a receipt of the private name / private number . in still another preferred embodiment , video output circuitry is operably coupled to the microprocessor for displaying matches and admirer tallies as graphics on video screens . in another preferred embodiment , additional microprocessor functions to include time and date functions , dictionary functions , and calculator functions are included in the firmware . in another preferred embodiment , a device 90 having the shape of a watch includes housing 91 having a liquid crystal display screen 92 disposed adjacent headings 99 , an infrared light emitting diode 94 , an infrared sensor 93 in a directional sensor hole , and three control buttons 95 - 97 . the device is operational in a first mode wherein it operates as a conventional watch and in a second mode wherein it operates as the partnering game . in the second mode the infrared light emitting diode 94 broadcasts an infrared signal which contains the private number of the device and a selection number , if a selection has been made . the transmission range of the light emitting diode is fifteen feet or greater . when the device is initially powered up , a microprocessor program generates a random private number within the range of 1 to 999 . this code is saved permanently until the watch is powered off , as in the case where the batteries are replaced . if the device encounters another device having the same private number , the microprocessor program generates another private number unique within the range of the device . as shown in fig1 , a zone within which the device is able to transmit to other similar devices is maximized by providing that the transmission span the plane of the watch face and span from 67 . 5 to 90 degrees from the normal to the watch face . the infrared sensor 93 is shown disposed at the end of a hole formed in a side portion of the watch . the front of the hole is covered by a conventional infrared filter which absorbs visible light but is transparent to infrared light . upon the receipt of an infrared signal from a similar device , the microprocessor of the device runs the programs of the partnering game as previously described . in the second mode of operation the liquid crystal display screen 92 under the three headings 99 is capable of displaying a participant count by means of the hours numeral in the first mode , a numeral representing the number of participants that have selected another player by means of the minutes numeral in the first mode , a numeral representing the number of admirers of the watch wearer by means of the second numeral in the first mode , and a graphic of a heart 98 to indicate that selection of a participant is permissible in which case the graphic is lit or verification of a match in which case the graphic blinks . three control buttons 95 - 97 are shown in fig1 and 16 and include a mode button 95 , an adjust button 96 , and a selection / settings button 97 . the adjust button 96 is used by in the first mode to adjust the time setting . the selection / settings button 97 in the first mode is used to select which time setting to adjust . in the second mode , the selection / settings button 97 enables a player to select a player of the opposite sex . in the second mode of operation , the liquid crystal display 92 clears and the infrared light emitting diode 94 is operative and continuously transmits an infrared pulse . when three or more females and three or more males having the device set to the second mode of operation enter the range of the devices , each device will vibrate or beep once and display the number of participants within it &# 39 ; s range . if a player directs his or her watch at another player of the opposite sex , the graphic 98 will appear on the display 92 . if the player presses the selection button 97 while the graphic 98 is displayed , the player in whose direction the watch is directed is selected . the position of the player selected acts as the public number of the previously described embodiments . the selection of the player selected will appear on the display 92 of the person selected under an admirer heading . if other players select the same player the total number of admirers is displayed . the selection will also appear on all devices under a selectors heading . in the event of a mutual selection , the graphic 98 will blink indicating the mutual selection . to play the partnering game , each player scans the other players of the opposite sex by moving their devices in a continuous horizontal arc . each player presses their selection button when the graphic indicator appears on the screen of their device in response to the device being directed at a player being selected . each player must perform bluff scans to insure that no one can detect their selection . as the players make their selections , all the devices simultaneously display the updated admirer count and selector count . if there are any reciprocal matches , blinking graphics 98 are displayed on the watches of the matched participants only . when the selector count equals the participant count , the game is over . the devices will then reset the selector count and admirer count to zero to await the start of another game or round . in another preferred embodiment of the invention , a radio - frequency transmitter / receiver means transmits and receives the signal that contains the private number . selection of another player is accomplished through infrared signaling as previously described . for each of the above preferred embodiments of the partnering game , a male or female player can determine his or her overall attractiveness by tracking the overall number of admirers and matches obtained over the course of playing the game successive times . as to a further discussion of the manner of usage and operation of the present invention , the same should be apparent from the above description . accordingly , no further discussion relating to the manner of usage and operation will be provided . with respect to the above description then , it is to be realized that the optimum dimensional relationships for the parts of the invention , to include variations in size , materials , shape , form , function and manner of operation , assembly and use , are deemed readily apparent and obvious to one skilled in the art , and all equivalent relationships to those illustrated in the drawings and described in the specification are intended to be encompassed by the present invention . therefore , the foregoing is considered as illustrative only of the principles of the invention . further , since numerous modifications and changes will readily occur to those skilled in the art , it is not desired to limit the invention to the exact construction and operation shown and described , and accordingly , all suitable modifications and equivalents may be resorted to , falling within the scope of the invention .

US-88165301-A

a system for controlling blood flow through a zone of a patient limb , the zone being bounded by a proximal end and a distal end , comprises : a cuff configured for securing to the limb and for covering the zone , the cuff providing pressure to the zone for occluding the flow of blood flowing through the zone in the direction from the proximal to distal ends of the zone ; an array of sensors fitting between the cuff and the limb and arranged for sensing and signaling the amount of penetration of blood flow into the zone ; and a control instrument connected to the array and to the cuff for regulating the pressure in the cuff to occlude the blood flow in the zone depending upon the amount of blood flow penetration signaled by the array .

the embodiment illustrated is not intended to be exhaustive or limit the invention to the precise form disclosed . it is chosen and described in order to explain the principles of the invention and its application and practical use , and thereby enable others skilled in the art to utilize the invention . fig1 depicts the preferred embodiment in use applied to limb 2 of a patient . stretchable sleeve 4 is shown applied along a portion of the length of limb 2 . gel pad 6 forms part of sleeve 4 and provides a means for the efficient coupling of high - frequency acoustic energy between ultrasonic transducer array 8 and the tissues of limb 2 . ultrasonic transducer array 8 is connected to instrument 10 via cable 12 . contour tourniquet cuff 14 is applied over sleeve 4 and transducer array 8 to encircle limb 2 at a location desired by a user . this configuration permits ultrasonic transducer array 8 to insonify a volume of tissue within a zone 16 of limb 2 bounded by a proximal end 18 and a distal end 20 , as shown in fig1 and 2 , thereby permitting instrument 10 to measure the flow of blood in arteries within zone 16 via the doppler effect and to detect changes in blood flow that may occur in response to the pressurization of contour cuff 14 . as described further below instrument 10 may be configured to control the pressures applied by contour cuff 14 to limb 2 to maintain the blood flow in the insonified arteries at predetermined levels or at levels set by a user of instrument 10 . ultrasonic transducer array 8 comprises one or more arrays of piezoelectric crystal elements or capacitance micromachined ultrasonic transducer cells or other materials and technologies known in the art to be suitable for transmitting and receiving high frequency acoustic energy . by adjusting the relative phases of electronic signals applied to the crystal elements that comprise an array the ultrasound waves produced by the array may be steered and focused to insonify a selected region within zone 16 . instrument 10 operates ultrasonic transducer array 8 to scan volumes of tissue to detect arterial blood flow . ultrasonic waves are emitted by transducer 8 at scanning angles relative to the surface of transducer 8 and traverse the tissue underlying transducer 8 . the waves emitted by transducer 8 reflect off various tissue structures within the limb , doppler frequency shifts in the reflections indicate moving structures , such as flowing blood . regions where blood flow is detected may be localized in terms and scan angle and tissue depth and quantified by analyzing the magnitude of the doppler frequency shifts of the returned echoes . fig2 depicts stretchable sleeve 4 of the preferred embodiment applied to limb 2 . sleeve 4 has a tubular and elastically stretchable shape and is designed for use with tourniquet contour cuff 14 and to conform to limbs of varying tapers . gel pad 6 forms part of sleeve 4 and is comprised of ultrasound coupling gel contained within a thin polyurethane membrane or other material transparent to ultrasound . gel pad 6 may also be comprised of other conformable materials or substances suitable for coupling ultrasonic transducer 8 to limb 2 . in the preferred embodiment , ultrasonic transducer array 8 forms part of gel pad 6 ; however , it will be apparent however that ultrasonic transducer array 8 could be independent of gel pad 6 and interposed between contour cuff 14 and gel pad 6 of sleeve 4 . for clarity only a single gel pad 6 and transducer array 8 have been shown and described ; however , it will be apparent that sleeve 4 may contain multiple gel pads with transducer arrays spaced circumferentially around the sleeve and that sleeve 4 could be formed entirely of a stretchable ultrasound conducting substance or materials . sleeve 4 may include one or more gel pads suitable for the coupling of high - frequency acoustic energy between the tissues of limb 2 and ultrasonic transducer array 8 . sleeve 4 has a tubular and elastically stretchable shape , with an un - stretched circumference of less than the minimum limb circumference recommended for contour cuff 14 so that it may be elastically stretched when applied to a limb having the minimum recommended circumference . sleeve 4 may be elastically stretched in a radial direction to a circumference at least equal to the maximum limb circumference recommended for contour cuff 14 . when elastically stretched and applied to a limb having the maximum recommended circumference , the maximum pressure applied to the underlying limb by sleeve 4 may be less than the pressure required to occlude venous blood flow in the limb . when applied to a limb having the maximum recommended circumference , the length of the gel pad within sleeve 4 is not less than width of contour cuff 14 . when elastically stretched and applied to a limb having the minimum recommended circumference , the pressure applied to the underlying limb by sleeve 4 is sufficient to maintain sleeve 4 and gel pad 6 in full contact with the limb throughout the length of sleeve 4 and gel pad 6 . contour cuff 14 is similar in design and construction to the cuff described by mcewen et al . in u . s . patent application ser . no . 11 / 384695 . as shown in fig3 contour cuff 14 has a substantially arcuate shape with the width of the cuff reduced near the end edges . the arcuate shape of cuff 14 and the degree to which the width near the end edges is reduced are predetermined to allow cuff 14 to be applied to limbs with a predetermined range of tapers such that contour cuff 14 remains substantially in contact with the limb along its width around the circumference of the limb . when contour cuff 14 is correctly applied to a patient limb as shown in fig1 the side edge of contour cuff 14 with the greater radius is proximal and the side edge with the lesser radius is distal on the limb . contour cuff 14 is secured around the limb by securing straps 22 and 24 . securing straps 22 and 24 are non - releasably attached to a non - inflating region of contour cuff 14 near an end edge . securing straps 22 and 24 have fastening portions which releasably engage with the outer surface of cuff 14 and bending portions which permit the fastening portions to be positioned such that they can completely engage the outer surface within the side edges of contour cuff 14 . in the preferred embodiment the outer surface of contour cuff 14 and the fastening portions of securing straps 22 and 24 are formed from velcro - type materials . the outer surface of cuff 14 is a loop type material and the fastening portions of securing straps 16 and 18 are formed from hook type material . tie strap 26 shown in fig3 , provides a means for the user to align and pull cuff 14 snug around limb 2 . when contour cuff 14 has been secured around limb 2 the ends of tie strap 26 may be tied together to help maintain the overlapping portion of the cuff in alignment around limb 2 by preventing the cuff from twisting , telescoping and rolling on the limb when pressurized . for clarity , tie strap 26 is not shown in fig1 . contour cuff 14 has two independent cuff bladders , proximal cuff bladder 28 and distal cuff bladder 30 ; the perimeter 32 of the bladders is depicted in the top view of contour cuff 14 shown in fig3 . the proximal and distal cuff bladders are pressurized with fluid from instrument 10 to apply pressure to proximal and distal portions of limb 2 underlying cuff 14 . in the preferred embodiment the fluid used to pressurize ( inflate ) the cuff bladders of contour cuff 14 is air , it will be apparent that other fluids could be used , for example the fluid could be another gas such as nitrogen or the fluid could a liquid such as water . air from instrument 10 is supplied to proximal bladder 28 via tubing 34 and bladder port 36 , fluid is supplied to distal bladder 30 via tubing 38 and bladder port 40 . contour cuff 14 is known in the art as single port cuff , it will be apparent that cuff 14 could be configured as a dual port and instrument 10 adapted with separate connections to each bladder for the supply of fluid to the bladder and the measurement of pressure within the bladder . as can be seen in fig1 , instrument 10 has a user interface consisting of graphic display panel 42 and keypad 44 . display panel 42 is employed for the selective display of information in alphanumeric and graphical formats that may include : measured pressure levels in proximal bladder 28 and distal bladder 30 , reference or desired pressure levels in proximal bladder 28 and distal bladder 30 , blood flow measurements from transducer 8 , and other information required for the operation of instrument 10 . keypad 44 provides a means for a user of instrument 10 to control the operation of instrument 10 . referring to the block diagram of instrument 10 shown in fig4 , controller 46 comprises a microcomputer , associated memory and control software , analog and digital peripheral interface circuitry , and other necessary support components for the operation of instrument 10 . as shown in fig4 , pneumatic pump 48 is pneumatically connected to reservoir 50 . in response to control signals from controller 46 , pump 48 operates to pressurize reservoir 50 . reservoir pressure transducer 52 is pneumatically connected to reservoir 50 and generates a reservoir pressure signal . the reservoir pressure signal is communicated to controller 46 . controller 46 acts to maintain the pressure in reservoir 50 near a predetermined or calculated reservoir pressure level . instrument 10 is shown configured with two pressure regulators , first pressure regulator 54 and second pressure regulator 56 . first pressure regulator 56 maintains the pressure in proximal cuff bladder 28 near the level of the first cuff pressure reference level communicated from controller 46 . second pressure regulator 56 maintains the pressure in distal cuff bladder 30 near the level of the second cuff pressure reference level communicated from controller 46 . although instrument 10 has been described with two pressure regulators it will be apparent that additional pressure regulators could be included within instrument 10 to independently control the pressure in multiple cuff bladders to apply differing selected pressures to various selected portions of a limb . ultrasonic transducer interface 58 is the ultrasound engine of instrument 10 and includes transceivers for driving and receiving signals from the elements of transducer array 8 and electronics for beam forming , steering , focusing , signal amplification , filtering , and signal processing functions . interface 58 , under the direction of control of signals from controller 46 , acts to scan volumes of tissue within zone 16 to produce signals indicative of blood flow for communication to blood flow detection module 60 . blood flow detection module 60 receives signals from ultrasonic transducer interface 58 indicative of scan position and doppler blood flow magnitudes . the module uses this information to detect the volumes of tissue within the scanning area of transducer 8 where blood flow is present and to quantify and localize the blood flow information for communication to controller 46 and display to a user . signals from blood flow detection module 60 may be used by controller 46 to perform automatic measurements of limb occlusion pressure ( lop ). lop is the minimum pressure required , at a specific time in a specific tourniquet cuff applied to a specific patient &# 39 ; s limb at a specific location , to stop the flow of arterial blood into the limb distal to the cuff controller 46 of instrument 10 , in response to user input via keypad 44 , may measure lop by : first automatically scanning for arterial blood flow in the tissue of limb 2 immediately distal to contour cuff 14 , then after localizing and quantifying the blood flow automatically increasing the second cuff reference pressure level to increase the pressure applied by distal cuff bladder 30 to the tissues of limb 2 until the blood flow detected distal to contour cuff 14 falls below a predetermined minimum flow threshold , or until the pressure in distal cuff bladder exceeds a predetermined maximum bladder pressure . the pressure level within bladder 30 at which the detected blood flow distal to the contour cuff 14 first falls below the predetermined minimum flow threshold is the measured lop for distal bladder 30 . controller 46 can act similarly to determine the minimum pressure required in proximal cuff bladder 28 to prevent blood flow past bladder 28 . a measurement of lop as described above is valid only at the time the measurement is made , and physiological parameters that change over time such as blood pressure may cause changes in lop over time . to automatically maintain the minimum pressures required in proximal bladder 28 and distal bladder 30 to prevent blood flow past cuff 14 over a period of time when physiologic parameters may vary , such as during a time period suitably long for surgery , instrument 10 operates as follows : a ) first the lop for proximal bladder 28 and distal bladder 30 is automatically determined , as described above , and the bladders are pressurized by setting the first and second reference pressure levels to the respective lop values measured for each cuff bladder ; b ) the limb tissues insonified by ultrasonic transducer 8 are continuously scanned to localize and quantify blood flow within zone 16 which includes tissue volumes proximal and distal and beneath contour cuff 14 ; c ) controller 46 continuously measures the lop of proximal bladder 28 by first decreasing the first reference pressure level until the detected blood flow past proximal bladder 28 is above a predetermined flow threshold and then increasing the first reference pressure level until detected blood past proximal bladder 28 is below a predetermined flow threshold ; d ) the second reference pressure level , and thereby the pressure applied to limb 2 by distal cuff bladder 30 , is automatically adjusted to reflect any change in the value of lop measured for proximal bladder 28 ( for example , if the minimum pressure required to occlude blood flow past proximal bladder 28 decreases by 15 mmhg then the pressure applied by distal bladder 30 is reduced by 15 mmhg , and conversely if the pressure required to occlude blood flow past proximal bladder 28 increases by 15 mmhg then the pressure applied by distal bladder 30 is increased by 15 mmhg ); and e ) if at any time blood flow is detected distal to cuff 14 then controller 46 may incrementally increase the pressure level in distal bladder 30 by predetermined amounts until the detected flow stops . in another mode of operation , instrument 10 may operate to continuously maintain the minimum pressures necessary to occlude blood flow distally past contour cuff 14 . this is accomplished by first automatically increasing the pressure applied by distal bladder 30 and proximal bladder 28 until blood flow sensed beneath the cuff is less than a predetermined minimum . then , pressure is continuously varied by incrementally increasing and decreasing the pressure applied by proximal bladder 28 to maintain the rate of blood flow sensed beneath contour cuff 14 below and near the predetermined minimum threshold . in this mode of operation , the pressure in distal bladder 30 is automatically adjusted to reflect any change in the pressure required in the proximal bladder 28 to occlude blood flow beneath contour cuff 14 . fig5 , 6 , 7 , 8 a and 8 b depict an alternate embodiment of the invention . in fig5 emergency and military tourniquet ( emt ) cuff 62 is shown applied to patient limb 64 . emt cuff 62 is similar in design and construction to the cuff described in u . s . pat . no . 6 , 746 , 470 and is adapted for rapid application to a limb in an emergency or life threatening situation such as military combat . bladder 66 is fixed at one end to emt cuff clamp 68 . to apply cuff 56 to a limb bladder 66 encircles the limb and the free end of bladder 66 passes through the sealing surfaces of emt cuff clamp 68 . emt cuff clamp 68 retains cuff bladder 66 around limb 64 and seals the encircling bladder 66 across its width . the width of the sealing surfaces of clamp 68 are selected to be greater than the width of bladder 66 thereby allowing bladder 66 to be sealed across its width at angles other than 90 degrees relative to the bladder edge , such as is the case when bladder 66 assumes a conical shape when wrapped around a conical limb ( such as a typical thigh ). this is important in achieving a snug fit around limbs of various degrees of conical shape . the limb facing surface of emt cuff clamp 68 includes ultrasonic transducer array 70 which communicates with instrument 10 via cable 72 . ultrasonic transducer array 70 is similar to transducer array 8 described above and is shown in fig6 and 7 . ultrasound coupling gel or a gel pad may be placed between the face of ultrasonic transducer array 70 and limb 64 . emt cuff 62 is preferably applied to a limb such that clamp 68 with transducer array 70 is positioned over the major artery in the limb , for example when applied to the upper arm the camp is placed over the brachial artery or when applied to the upper thigh the clamp is placed over femoral artery . as shown in fig7 ultrasonic transducer array 70 insonifies a volume of tissue within zone 74 of limb 64 . zone 74 is bounded by a proximal end 76 and a distal end 78 . ultrasound transducer array 70 is used to measure blood flow in the portion of major artery 80 that lies within zone 74 . changes in blood flow in major artery 80 in response to pressures applied to the limb by emt cuff 62 can be detected by ultrasound transducer array 70 . in fig7 the direction of blood flow 82 in the major artery 80 is shown and the shaded area of major artery 80 represents penetration of blood flow beneath emt cuff 62 . encircling cuff bladder 66 is pressurized by first pressure regulator 54 of instrument 10 via tubing 84 and bladder port 86 . as shown in fig5 , 6 , 8 a and 8 b emt cuff 62 includes an auxiliary bladder 88 which is located on the limb facing surface of encircling bladder 66 . auxiliary bladder 88 is pressurized by second pressure regulator 56 of instrument 2 via tubing 90 and bladder port 92 . in the preferred embodiment the width of auxiliary bladder 88 is no greater than the width of encircling bladder 66 and the length of auxiliary bladder is less than the inflating portion of encircling bladder 66 when secured around a limb by clamp 68 . auxiliary bladder 88 is pressurized by instrument 10 to extend the reach of encircling bladder 66 in a predetermined location to occlude blood flow , as detected by ultrasonic transducer array 70 , in arteries lying deep within the tissues of limb 64 ( within a portion of zone 74 ) underlying auxiliary bladder 88 . this configuration of overlapping cuff bladders allows for the selective application of pressure to occlude deep arteries without increasing the overall pressure applied to the limb . it will be appreciated that to apply additional or supplemental pressure to other portions of limb 64 encircled by emt cuff 62 additional auxiliary bladders of varying shape and size may be selected to form part of emt cuff 62 , and that these bladders may not necessarily overlap with encircling bladder 66 . the invention may automatically maintain the pressures applied to a limb by emt cuff 62 at the minimum level required to prevent blood flow distal to the location of the cuff on the limb . typically , a user first applies ultrasound coupling gel or a gel pad to the transducer surfaces of emt clamp 68 . next , emt cuff 62 is applied to a limb 64 at a desired location by wrapping encircling bladder 66 around the limb at the location ; the end of bladder 66 is pulled through clamp 68 ; clamp 68 is approximately aligned above the major limb artery 80 ; and clamp 68 is secured to maintain bladder 66 snugly around the limb and clamp 68 in contact with the tissues of limb . instrument 10 is then directed via keypad 44 to automatically scan for arterial blood flow in the limb tissues underlying clamp 68 and to increase the pressure in encircling bladder 66 until a predetermined pressure threshold is reached or until the rate of blood flow distal to the midline 94 of emt cuff 56 is equal to or less than a predetermined minimum flow threshold . if the predetermined pressure threshold is reached in encircling bladder 66 and blood flow distal to the midline of emt cuff 62 remains above the predetermined minimum flow threshold , instrument 10 may act to pressurize auxiliary bladder 88 to occlude arteries lying deeper beneath emt cuff 62 . to maintain the pressure in encircling bladder 66 and auxiliary bladder 88 at the minimum necessary to prevent blood flow distal to emt cuff 62 , instrument 10 continues to monitor blood flow in limb tissues proximal to the midline 94 of emt cuff . instrument 10 continues to scan for arterial blood flow in tissues underlying clamp 68 and monitors the distance that blood flow penetrates beneath the cuff from the proximal edge towards the midline . instrument 10 automatically adjusts the pressure within bladders 66 and 88 within predetermined limits to prevent blood flow from penetrating beyond the midline 94 of emt cuff 62 , thereby maintaining the pressures in emt cuff 62 at the lowest level necessary to occlude blood flow past emt cuff 62 . it will be apparent that instrument 10 may be used to monitor blood flow beneath a cuff , and generate alarms perceivable by a user if the blood flow sensed beneath the cuff exceeds a predetermined penetration threshold . for example , an alarm may be generated if the sensed blood flow past the midline of the cuff exceeds a predetermined threshold , or an alarm may be generated to indicate that sensed blood flow beneath the cuff is nearing the midline of the cuff and thus alert the user to the possibility that blood flow past the cuff may be imminent , these alarms may be operable regardless of whether the cuff pressure level was established automatically as described above , or was established by user input to instrument 10 , or was established manually by application of the cuff in an emergency or military setting . auxiliary bladder 88 of emt cuff 62 may be adapted as described above to provide emt cuff 62 with additional reach in a selected area or may be adapted as described below and shown in fig8 a and 8 b to extend the volume of tissue that may be scanned by transducer array 70 . the maximum volume of tissue that can be insonified by transducer array 70 to detect blood flow is determined by the geometry and other physical and electrical characteristics of transducer array 70 . the face of clamp 68 containing transducer array 70 is normally tangent to the surface of limb 64 . by varying the angle of the face of transducer array 70 with respect to the surface of the limb additional tissue volumes may be scanned for blood flow . this would be much like a user varying the angle a hand held ultrasound probe held parallel to the limb to search for arterial blood flow . auxiliary bladder 88 may be positioned close to clamp 68 and act as a “ transducer scanning ” bladder so that when it is pressurized to a pressure above that of encircling bladder 66 it will inflate against the limb and cause clamp 68 to tilt relative to the limb surface as shown in fig8 b . instrument 10 , by varying the pressure within auxiliary bladder 88 , can mechanically scan ultrasonic transducer array 70 to extend the volume of tissue in which blood can be detected . this simple low - cost mechanical scanning of ultrasonic transducer array 70 may permit greater tolerance in the application of clamp 68 to the limb with respect to the position of the clamp relative to the major arteries of the limb . it will be apparent that additional auxiliary transducer scanning bladders ( as shown , for example , in dashed lines at 89 , fig6 ) may form part of cuff 62 to provide mechanical scanning in more than one direction and that scanning bladders may form part of contour cuff 14 described above , and be configured to control the angle of the face of ultrasonic transducer 8 with respect to limb 2 .

US-201313758094-A