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hind limb ischemia / reperfusion injury may occur clinically after a release of tourniquets during orthopedic surgery , or extrication of a trauma victim who is compressed with a heavy weight for a prolonged period ( crush syndrome ) . several reports have indicated that the pathophysiology of the injury varies according to the duration and grade of the ischemia ( 13 ) . it is well recognized that sustained ischemia can induce cell death and tissue necrosis , which are mainly caused by energy insufficiency . many studies have shown that tissue injury in many organs occurs not only during the ischemic period but also in the reperfusion period . skeletal muscle ischemia / reperfusion is associated with a systemic inflammatory response and determines the effect on remote organs ( liver , lung , kidney , myocardium and testis ) structure and function ( 49 ) . the development of remote organ dysfunction was observed only following reperfusion , which implies that humoral and/or cellular mediators produced locally in the limb were responsible for mediating remote organ injury ( 1012 ) . ptx through effects of increasing intracellular cyclic amp on red blood cells improve the oxygen delivery to ischemic tissues and also increases the cyclic amp on polymorph nuclear leukocytes and decreases oxygen free radical production ( 10 , 13 - 16 ) . in addition , ptx limit the inflammatory response with reduction in cellular activation , phagocytosis and endothelium adhesion . recent studies have indicated that ptx improves ischemia / reperfusion injury in many organs ( 1719 ) . however , the effects of ptx on remote testicular injury caused by skeletal muscle ischemia / reperfusion are not clear . the objective of the present study was to investigate the role of ptx on remote testicular injury caused by unilateral hind limb ischemia / reperfusion of rats . for this purpose , the biochemical and pathological effects of skeletal muscle ischemia / reperfusion and ptx in testicular tissues of rats have been investigated . the results of our investigation would help to clarify the potential importance of the use of ptx in situations of oxidative damage . these findings may encourage the use of antioxidants to reduce remote organ injury after skeletal muscle ischemia / reperfusion . the study was conducted on 20 healthy male wistar rats , 12 - 16 weeks old and weighing between 270 - 300 g . all rats of this study were kept according to the norms of the islamic azad university college of veterinary medicine tehran iran laboratory of animal experimentations ; this investigation was approved by the committee of ethics in research with animals of islamic azad university . the study was designed so as to minimize the number of animals required for the experiments . the rats were housed in individual cages under temperature controlled standard conditions , 12h/12h light / dark cycle with free access to standard rodent food and filtrated tap water . the animals were allocated randomly into two experimental groups of ten rats each as follows : ischemia / reperfusion ( ir group ) and ischemia / reperfusion + pentoxifylline ( ir+ptx group ) . anesthesia was induced with a mixture of ketamine and xylazine ( 50 mg / kg and 10 mg / kg , respectively ) via intramuscular injection . the level of anesthesia was continuously monitored by observing the respiratory patterns and toe pinch reflex . after the induction of anesthesia , fur was completely removed from left hind limbs with an electric shaver to facilitate the measurement of limb perfusion . unilateral hind limb ischemia was induced by placing an orthodontic rubber band at the hip joint . before using the tourniquet , the animals were kept anesthetized throughout the duration of ischemic period with additional anesthetic doses as needed . body temperature was maintained with a heating pad whilst the animals were under anesthesia . in ir+ptx group , pentoxifylline tablets were dissolved in normal saline as explained in previous studies ( 20 ) . the analgesic nalbuphine hydrochloride after 24h of reperfusion , all animals were anesthetized again with the same mixture and a longitudinal incision of approximately 2 cm was made to the scrotal raphe for bilateral orchiectomies ( a procedure involving cord clamping and hemostasis ) . right testes of seven rats were processed for histopathological examination and left testes were washed with normal saline and stored in a 80c refrigerator for the evaluation of biochemical parameters . then the rats were euthanized with an overdose of intraperitoneal pentobarbital by injection ( 300mg / kg ) . the left testicular tissues were washed three times in cold normal saline solution ( 0.9% ) . then , the tissues were homogenized in ice - cold tris - hcl buffer solution , within a homogenizer for 2min at 11200g . the levels of mpo were determined in the supernatant , and mda levels were studied in the homogenate . for a further extraction procedure , the supernatant was extracted in ethanol/ chloroform mixture ( 5/3 v / v ) . after a second centrifugation at 3500g for 20min , the clear upper layer was taken and used for sod activity determination ( 21 ) . the study was conducted on 20 healthy male wistar rats , 12 - 16 weeks old and weighing between 270 - 300 g . all rats of this study were kept according to the norms of the islamic azad university college of veterinary medicine tehran iran laboratory of animal experimentations ; this investigation was approved by the committee of ethics in research with animals of islamic azad university . the study was designed so as to minimize the number of animals required for the experiments . the rats were housed in individual cages under temperature controlled standard conditions , 12h/12h light / dark cycle with free access to standard rodent food and filtrated tap water . the animals were allocated randomly into two experimental groups of ten rats each as follows : ischemia / reperfusion ( ir group ) and ischemia / reperfusion + pentoxifylline ( ir+ptx group ) . anesthesia was induced with a mixture of ketamine and xylazine ( 50 mg / kg and 10 mg / kg , respectively ) via intramuscular injection . the level of anesthesia was continuously monitored by observing the respiratory patterns and toe pinch reflex . after the induction of anesthesia , fur was completely removed from left hind limbs with an electric shaver to facilitate the measurement of limb perfusion . unilateral hind limb ischemia was induced by placing an orthodontic rubber band at the hip joint . before using the tourniquet , the animals were kept anesthetized throughout the duration of ischemic period with additional anesthetic doses as needed . body temperature was maintained with a heating pad whilst the animals were under anesthesia . in ir+ptx group , pentoxifylline tablets were dissolved in normal saline as explained in previous studies ( 20 ) . the analgesic nalbuphine hydrochloride ( 2 mg / kg ) was used via subcutaneous during observation time . after 24h of reperfusion , all animals were anesthetized again with the same mixture and a longitudinal incision of approximately 2 cm was made to the scrotal raphe for bilateral orchiectomies ( a procedure involving cord clamping and hemostasis ) . right testes of seven rats were processed for histopathological examination and left testes were washed with normal saline and stored in a 80c refrigerator for the evaluation of biochemical parameters . then the rats were euthanized with an overdose of intraperitoneal pentobarbital by injection ( 300mg / kg ) . the left testicular tissues were washed three times in cold normal saline solution ( 0.9% ) . then , the tissues were homogenized in ice - cold tris - hcl buffer solution , within a homogenizer for 2min at 11200g . the levels of mpo were determined in the supernatant , and mda levels were studied in the homogenate . for a further extraction procedure , the supernatant was extracted in ethanol/ chloroform mixture ( 5/3 v / v ) . after a second centrifugation at 3500g for 20min , the clear upper layer was taken and used for sod activity determination ( 21 ) . the principle of the sod activity determination method was based on the inhibition of nitroblue tetrazolium reduction described by sun et al . one unit of sod was defined as the enzyme activity causing 50% inhibition in the nitroblue tetrazolium reduction rate . the mda levels in testicular tissues were analyzed by a method based on the reaction with thiobarbituric acid at 95c ( 24 ) . in the thiobarbituric acid test reaction , mda or mda - like substances and thiobarbituric acid react together to produce a pink pigment with an absorption maximum of 532 nm . the results were expressed as nanomol per gram wet tissue ( nmol / g tissue ) . the principle of the assay is based on determination of the rate constant k ( s ) of h2o2 decomposition at 240 nm . testicular injury was quantified by measuring testicular mpo activity , the activity of infiltrated polymorphonuclear leukocytes , using a protocol modified from a previous report ( 26 ) . the wet / dry weight ratio , the tissue edema index , was measured to evaluate testicular injury . briefly , freshly harvested testes were weighed , placed in an oven for 24h at 60c and weighed again when dry ( 26 ) . the principle of the sod activity determination method was based on the inhibition of nitroblue tetrazolium reduction described by sun et al . one unit of sod was defined as the enzyme activity causing 50% inhibition in the nitroblue tetrazolium reduction rate . the mda levels in testicular tissues were analyzed by a method based on the reaction with thiobarbituric acid at 95c ( 24 ) . in the thiobarbituric acid test reaction , mda or mda - like substances and thiobarbituric acid react together to produce a pink pigment with an absorption maximum of 532 nm . the results were expressed as nanomol per gram wet tissue ( nmol / g tissue ) . the principle of the assay is based on determination of the rate constant k ( s ) of h2o2 decomposition at 240 nm . testicular injury was quantified by measuring testicular mpo activity , the activity of infiltrated polymorphonuclear leukocytes , using a protocol modified from a previous report ( 26 ) . the wet / dry weight ratio , the tissue edema index , was measured to evaluate testicular injury . briefly , freshly harvested testes were weighed , placed in an oven for 24h at 60c and weighed again when dry ( 26 ) . the wet / dry weight ratio was then calculated . the tissue specimens were placed in paraffin blocks , sectioned at 5m , and stained with hematoxylin and eosin ( h&e ) for light microscopic analysis . an experienced pathologist , who was blinded to the experiment and data , examined the samples histopathologically . ( 27 ) classification as follows : grade - i : showed normal testicular architecture with an orderly , arrangement of germinal cells ; grade - ii : injury showed less orderly , non - cohesive germinal cells and closely packed seminiferous tubules ; grade - iii : injury exhibited disordered sloughed germinal cells with shrunken pyknotic nuclei and less distinct seminiferous tubule borders ; grade - iv : injury defined seminiferous tubules that were closely packed with coagulative necrosis of the germinal cells . kruskal - wallis test was used to compare the biochemical and histopathological parameters between groups . when kruskal - wallis test results were significant , bonferroni adjusted mann - whitney u test was used in the paired comparison . kruskal - wallis test was used to compare the biochemical and histopathological parameters between groups . when kruskal - wallis test results were significant , bonferroni adjusted mann - whitney u test was used in the paired comparison . one of the most interesting observations at the histopathological examination of the testicular tissues is the presence of sloughed germinal cells within the seminiferous tubules and disorganization in rat testes after the unilateral hind limb ischemia / reperfusion . the testicular injury score increased significantly in the ir group compared with the ir+ptx group ( p<0.05 ) ( table-1 ) . in the ir group , coagulative necrosis with loss of seminiferous tubule epithelium , edema and sloughed germinal cells were predominant features in sections ( figure-1 ) . however , the rats in the ir+ptx group had essentially normal seminiferous tubule morphology ( figure-2 ) . table 1the tissue cat and mpo activities and levels of sod and mda in testicular tissues and score of testicular histological changes and muscle wet / dried weight ( w / d ) ratio.ischemia/reperfusionischemia/reperfusion + pentoxifyllinesod ( u / mg protein)4.0160.288.120.13 * cat ( k / g protein)81.034.1798.102.73 * mpo ( u / g tissue)1.030.200.610.08 * mda ( nmol / g tissue)2.740.331.850.21 * histological grading2.300.671.400.51 * w / d ratio2.200.131.640.09 * * p < 0.05 compared with the ischemia - reperfusion group . p < 0.05 compared with the ischemia - reperfusion group . figure 1light microscopic view of testis tissues from ir group showing coagulative necrosis with loss of seminiferous tubule epithelium , edema and sloughed germinal cells . figure 2light microscopic view of testis tissues from ptx treated group showing normal seminiferous tubule morphology with orderly arrangement of germinal cells . . activities of sod and cat in testicular tissues were decreased by ischemia / reperfusion , but administration of ptx increased these levels ( p<0.05 ) ( table-1 ) . the tissue levels of mda increased in the ir group in comparison to the ir+ptx group ( table-1 ) . mpo activity in testicular tissues in the ir group was significantly higher than in the ir+ptx group ( p<0.05 ) ( table-1 ) . the wet / dry weight ratio of testicular tissues in the ir group was significantly higher than in the ir+ptx group ( p<0.05 ) ( table-1 ) . the systemic inflammatory response syndrome is a consequence of many conditions , such as surgery , trauma , burn , shock , or bacterial infection ( 28 ) , that results in the development of potentially fatal complication known as multiple organ dysfunction syndrome . hind limb ischemia / reperfusion has been extensively used in our laboratory as a model of systemic inflammatory response syndrome , which closely resembles the acute traumatic and ischemic insult seen in systemic inflammatory response syndrome patients ( 29 ) . it has been demonstrated that hind limb ischemia / reperfusion causes cellular injury in remote organs ( kidney , lung , and myocardium ) and contributes to the development of multiple organ dysfunction syndrome ( 5 , 29 ) . as far as we know , there are only a few reports demonstrating testicular remote injury following muscle ischemia / reperfusion injury ( 8) . the results of takhtfooladi et al . ( 8) indicated that skeletal muscle ischemia / reperfusion induces severe testicular damage and n - acetylcysteine has protective effects on testicular injury after hind limb ischemia / reperfusion . their data supported this view that temporary occlusion of the femoral artery induced testicular injury in rats ( 8) . previous studies indicate that inflammatory response and injury to remote organs can be caused by the systemic release of the pro - inflammatory mediators and free oxygen radicals upon reperfusion of ischemic limbs ( 5 , 30 ) . despite decades of research in this area , ischemia / ptx is one of the phosphodiesterase inhibitors that have been reported to increase intracellular cyclic amp and reduce superoxide anion production by both monocytes and polymorphonuclear cells dose dependently in vitro ( 31 ) . ( 32 ) indicated that ptx led to a marked increase in cyclic amp levels , whereas cyclic gmp levels were only marginally elevated in lipopolysaccharide stimulated human monocytes . ptx has received considerable attention with respect to its action on leukocytes in many organs ( 3335 ) . ( 19 ) reported that after reperfusion , myeloperoxidase activity and blood neutrophil count were lower with ptx than with saline , and changes in the filtration coefficient were correlated to the percent changes in blood neutrophils during reperfusion . they suggested that this effect may be mainly caused by a decrease in sequestration of neutrophils in the lung during reperfusion . their group also reported that ptx prevented endothelial injury during ischemia / reperfusion by decreasing neutrophil sequestration in isolated perfused rat and rabbit lungs and in pigs after left lung allotransplantation ( 33 ) . recently administered ptx was shown to protect against ischemia / reperfusion injuries in local and remote organs and it was suggested that this protective effect may be due to its ability to inhibit of free radical generation ( 12 , 20 ) . there is growing evidence regarding its beneficial effects in ameliorating testicular ischemia / reperfusion injury ( 39 ) . in an experimental study savas et al . ( 39 ) suggested that the administration of ptx at a dose of 50 mg / kg 15 min . before spermatic cord torsion their results suggest that pentoxifylline treatment attenuates reperfusion damage on both sides , possibly with its effects on blood flow and neutrophils ( 39 ) . ( 40 ) , who demonstrated that ptx may be a potential protective agent for preventing the negative changes related to oxidative stress in testicular injury caused by spermatic cord torsion in miniature horse stallions . however , the protective effect of ptx on testes from skeletal muscle ischemia / reperfusion injury has not been studied to date . in the current study , we tested the hypothesis that ptx could protect the testes from remote organ injury after skeletal muscle ischemia / reperfusion . oxidative stress is associated with an increased rate of cellular damage induced by oxygen and oxygen - derived oxidants , commonly known as reactive oxygen species ( 41 , 42 ) . the major targets of reactive oxygen species are membrane lipids , in a process known as lipid peroxidation . it is also acknowledged that testicular tissues and spermatozoa are very sensitive to reactive oxygen species attack and lipid peroxidation . the susceptibility of testicular tissues to oxidation is attributed to the high polyunsaturated fatty acid content of sperm membranes ( 42 , 43 ) . many tissues contain powerful endogenous scavengers that provide protection against free radical damage , including sod , cat , glutathione peroxidase , ascorbic acid and -tocopherol ( 44 ) . ( 45 ) have reported that adequate levels of antioxidants such as sod , cat and possibly glutathione peroxidase and reductase , maintain the scavenging potential in gonads and seminal fluids , which is referred to as oxidative stress status . tissue cat and mpo activities , and sod and mda levels are considered to indicate oxidative stress . in the present study , sod level and cat activity were decreased significantly in ir group compared with ir+ptx group . the tissue mda level and mpo activity in testes were increased significantly in ir group compared with ir+ptx group . according to the observations of this study , the histopathological injury score was significantly decreased in ir+ptx group compared with that of ir group . in the ptx treated group , histopathological features such as edema , congestion , hemorrhage , and necrosis of the germinal cells were markedly less than in ir group . the findings in this study indicate that reperfusion of the ischemic limb leads , within 24h of reperfusion , to a systemic response as demonstrated by the biochemical and histological impairment of the testis . also , data on cat and mpo activity , and sod and mda levels suggested a protective effect of ptx against testicular remote injuries after unilateral hind limb ischemia / reperfusion . these data together with previous findings ( 39 ) confirm the potent anti - oxidation capacity of ptx . these data also support the concept that ptx may be an effective therapeutic adjunct to reperfusion injury . the clinical relevance of this manuscript refers to the previous use of ptx in situations requiring procedures ischemia with reperfusion to reduce or prevent distant organs damage . the results of this study showed that unilateral hind limb ischemia / reperfusion induced testicular injury in rats . nevertheless , ptx administration significantly decreased testes injury induced by skeletal muscle ischemia / reperfusion according to our histological and biochemical findings . ptx is already in clinical use for the treatment of vascular diseases and these results suggest the possibility of clinical application of ptx in testicular remote organ injury following skeletal muscle ischemia / reperfusion .

abstractobjectivethe objective of the present study was to investigate the role of pentoxifylline ( ptx ) on remote testicular injury caused by unilateral hind limb ischemia / reperfusion of rats.materials and methodstwenty healthy male wistar rats were allocated randomly into two groups : ischemia / reperfusion ( ir group ) and ischemia / reperfusion + pentoxifylline ( ir+ptx group ) . ischemia was induced by placement of a rubber tourniquet at the greater trochanter for 2h . rats in ir+ptx group received ptx ( 40 mg / kg ip ) before the reperfusion period . at 24h after reperfusion , testes were removed and levels of superoxide dismutase ( sod ) , malondialdehyde ( mda ) , catalase ( cat ) and myeloperoxidase ( mpo ) activity were determined in testicular tissues . three rats of each group were used for wet/ dry weight ratio measurement . testicular tissues were also examined histopathologically under light microscopy.resultsactivities of sod and cat in testicular tissues were decreased by ischemia/ reperfusion ( p<0.05 ) . significantly increased mda levels in testicular tissues were decreased by ptx treatment ( p<0.05 ) . mpo activity in testicular tissues in the ir group was significantly higher than in the ir+ptx group ( p<0.05 ) . the wet / dry weight ratio of testicular tissues in the ir group was significantly higher than in the ir+ptx group ( p<0.05 ) . histopathologically , there was a statistically significant difference between two groups ( p<0.05).conclusionsaccording to histological and biochemical findings , we conclude that ptx has preventive effects in the testicular injury induced by hind limb ischemia / reperfusion .

SECTION 1. SHORT TITLE. This Act may be cited as the ``White Clay Creek Wild and Scenic Rivers System Act''. SEC. 2. FINDINGS. Congress finds that-- (1) Public Law 102-215 (105 Stat. 1664) directed the Secretary of the Interior, in cooperation and consultation with appropriate State and local governments and affected landowners, to conduct a study of the eligibility and suitability of White Clay Creek, Delaware and Pennsylvania, and the tributaries of the creek for inclusion in the National Wild and Scenic Rivers System; (2) as a part of the study described in paragraph (1), the White Clay Creek Wild and Scenic Study Task Force and the National Park Service prepared a watershed management plan for the study area entitled ``White Clay Creek and Its Tributaries Watershed Management Plan'', dated May 1998, that establishes goals and actions to ensure the long-term protection of the outstanding values of, and compatible management of land and water resources associated with, the watershed; and (3) after completion of the study described in paragraph (1), Chester County, Pennsylvania, New Castle County, Delaware, Newark, Delaware, and 12 Pennsylvania municipalities located within the watershed boundaries passed resolutions that-- (A) expressed support for the White Clay Creek Watershed Management Plan; (B) expressed agreement to take action to implement the goals of the Plan; and (C) endorsed the designation of the White Clay Creek and the tributaries of the creek for inclusion in the National Wild and Scenic Rivers System. SEC. 3. DESIGNATION OF WHITE CLAY CREEK. Section 3(a) of the Wild and Scenic Rivers Act (16 U.S.C. 1274(a)) is amended by adding at the end the following: ``(162) White Clay Creek, Delaware and Pennsylvania.--The 190 miles of river segments of White Clay Creek (including tributaries of White Clay Creek and all second order tributaries of the designated segments) in the States of Delaware and Pennsylvania, as depicted on the recommended designation and classification maps (dated June 2000), to be administered by the Secretary of the Interior, as follows: ``(A) 30.8 miles of the east branch, including Trout Run, beginning at the headwaters within West Marlborough township downstream to a point that is 500 feet north of the Borough of Avondale wastewater treatment facility, as a recreational river. ``(B) 15.0 miles of the east branch beginning at the southern boundary line of the Borough of Avondale to a point where the East Branch enters New Garden Township at the Franklin Township boundary line, including Walnut Run and Broad Run outside the boundaries of the White Clay Creek Preserve, as a recreational river. ``(C) 4.0 miles of the east branch that flow through the boundaries of the White Clay Creek Preserve, Pennsylvania, beginning at the northern boundary line of London Britain township and downstream to the confluence of the middle and east branches, as a scenic river. ``(D) 6.8 miles of the middle branch, beginning at the headwaters within Londonderry township downstream to a point that is 500 feet north of the Borough of West Grove wastewater treatment facility, as a recreational river. ``(E) 14 miles of the middle branch, beginning at a point that is 500 feet south of the Borough of West Grove wastewater treatment facility downstream to the boundary of the White Clay Creek Preserve in London Britain township, as a recreational river. ``(F) 2.1 miles of the middle branch that flow within the boundaries of the White Clay Creek Preserve in London Britain township, as a scenic river. ``(G) 17.2 miles of the west branch, beginning at the headwaters within Penn township downstream to the confluence with the middle branch, as a recreational river. ``(H) 12.7 miles of the main stem, excluding Lamborn Run, that flow through the boundaries of the White Clay Creek Preserve, Pennsylvania and Delaware, and White Clay Creek State Park, Delaware, beginning at the confluence of the east and middle branches in London Britain township, Pennsylvania, downstream to the northern boundary line of the city of Newark, Delaware, as a scenic river. ``(I) 5.4 miles of the main stem (including all second order tributaries outside the boundaries of the White Clay Creek Preserve and White Clay Creek State Park), beginning at the confluence of the east and middle branches in London Britain township, Pennsylvania, downstream to the northern boundary of the city of Newark, Delaware, as a recreational river. ``(J) 16.8 miles of the main stem beginning at Paper Mill Road downstream to the Old Route 4 bridge, as a recreational river. ``(K) 4.4 miles of the main stem beginning at the southern boundary of the property of the corporation known as United Water Delaware downstream to the confluence of White Clay Creek with the Christina River, as a recreational river. ``(L) 1.3 miles of Middle Run outside the boundaries of the Middle Run Natural Area, as a recreational river. ``(M) 5.2 miles of Middle Run that flow within the boundaries of the Middle Run Natural Area, as a scenic river. ``(N) 15.6 miles of Pike Creek, as a recreational river. ``(O) 38.7 miles of Mill Creek, as a recreational river.''. SEC. 4. BOUNDARIES. With respect to each of the segments of White Clay Creek and its tributaries designated by the amendment made by section 3, in lieu of the boundaries provided for in section 3(b) of the Wild and Scenic Rivers Act (16 U.S.C. 1274(b)), the boundaries of the segment shall be 250 feet as measured from the ordinary high water mark on both sides of the segment. SEC. 5. ADMINISTRATION. (a) By Secretary of the Interior.--The segments designated by the amendment made by section 3 shall be administered by the Secretary of the Interior (referred to in this Act as the ``Secretary''), in cooperation with the White Clay Creek Watershed Management Committee as provided for in the plan prepared by the White Clay Creek Wild and Scenic Study Task Force and the National Park Service, entitled ``White Clay Creek and Its Tributaries Watershed Management Plan'' and dated May 1998 (referred to in this Act as the ``Management Plan''). (b) Requirement for Comprehensive Management Plan.--The Management Plan shall be considered to satisfy the requirements for a comprehensive management plan under section 3(d) of the Wild and Scenic Rivers Act (16 U.S.C. 1274(d)). (c) Cooperative Agreements.--In order to provide for the long-term protection, preservation, and enhancement of the segments designated by the amendment made by section 3, the Secretary shall offer to enter into a cooperative agreement pursuant to sections 10(c) and 11(b)(1) of the Wild and Scenic Rivers Act (16 U.S.C. 1281(e), 1282(b)(1)) with the White Clay Creek Watershed Management Committee as provided for in the Management Plan. SEC. 6. FEDERAL ROLE IN MANAGEMENT. (a) In General.--The Director of the National Park Service (or a designee) shall represent the Secretary in the implementation of the Management Plan, this Act, and the Wild and Scenic Rivers Act with respect to each of the segments designated by the amendment made by section 3, including the review, required under section 7(a) of the Wild and Scenic Rivers Act (16 U.S.C. 1278(a)), of proposed federally- assisted water resources projects that could have a direct and adverse effect on the values for which the segment is designated. (b) Assistance.--To assist in the implementation of the Management Plan, this Act, and the Wild and Scenic Rivers Act with respect to each of the segments designated by the amendment made by section 3, the Secretary may provide technical assistance, staff support, and funding at a cost to the Federal Government in an amount, in the aggregate, of not to exceed $150,000 for each fiscal year. (c) Cooperative Agreements.--Any cooperative agreement entered into under section 10(e) of the Wild and Scenic Rivers Act (16 U.S.C. 1281(e)) relating to any of the segments designated by the amendment made by section 3-- (1) shall be consistent with the Management Plan; and (2) may include provisions for financial or other assistance from the United States to facilitate the long-term protection, conservation, and enhancement of the segments. (d) National Park System.--Notwithstanding section 10(c) of the Wild and Scenic Rivers Act (16 U.S.C. 1281(c)), any portion of a segment designated by the amendment made by section 3 that is not in the National Park System as of the date of the enactment of this Act shall not, under this Act-- (1) be considered a part of the National Park System; (2) be managed by the National Park Service; or (3) be subject to laws (including regulations) that govern the National Park System. SEC. 7. STATE REQUIREMENTS. State and local zoning laws and ordinances, as in effect on the date of the enactment of this Act, shall be considered to satisfy the standards and requirements under section 6(c) of the Wild and Scenic Rivers Act (16 U.S.C. 1277(c)) with respect to the segment designated by the amendment made by section 3. SEC. 8. NO LAND ACQUISITION. The Federal Government shall not acquire, by any means, any right or title in or to land, any easement, or any other interest along the segments designated by the amendment made by section 3 for the purpose of carrying out the amendment or this Act. Speaker of the House of Representatives. Vice President of the United States and President of the Senate.

Requires the segments to be administered by the Secretary of the Interior, in cooperation with the White Clay Creek Watershed Management Committee pursuant to the plan prepared by the White Clay Creek Wild and Scenic Study Task Force and the National Park Service. Deems the management plan to satisfy the Act's requirements for a comprehensive management plan. Prohibits any portion of a segment designated by this Act that is not in the National Park System (NPS) as of the enactment of this Act from being: (1) considered a part of the NPS; (2) managed by the National Park Service; or (3) subject to NPS laws or regulations. Bars the Federal Government from acquiring, by any means, any right or title in or to land, any easement, or any other interest for the purposes of carrying out this Act.

Days after giving birth to twins, a Greenville County mother has been hospitalized for what doctors say is a rare flesh-eating infection. The development follows the similar affliction of a Georgia graduate student, who lost her left leg and may lose her fingers. But experts say the South Carolina case, though serious, is less severe than the Georgia one and caused by a different bacterium. Lana Kuykendall, 36, gave birth to healthy twins at an Atlanta hospital last week. When the new family of four returned to their home in Piedmont, the mother — who is also a paramedic — noticed a pain and rash on her left leg. As the spot began to spread, Kuykendall went to a local hospital, where she has since undergone several surgeries but was improving Thursday. "She's stable," Darren Kuykendall, the woman's husband, told The Associated Press in a phone interview from Greenville Memorial Hospital. Friends and family are helping care for the couple's week-old twins, who are healthy. A fund has been set up to help with Kuykendall's care. The condition is called necrotizing fasciitis, the same disorder that has Georgia graduate student Aimee Copeland fighting for her life in a hospital several hundred miles away. Doctors say Copeland, 24, has lost a leg and could lose all her fingers from the infection that spread days after she suffered a deep cut while zip-lining. In that case, doctors have said Copeland has been infected by Aeromonas hydrophila, a flesh-eating bacterium that emits toxins that cut off blood flow to parts of the body, destroying muscle, fat and skin tissue. Flesh-eating Aeromonas cases are so rare that only a handful of infections have been reported in medical journals in recent decades. Dr. William Schaffner, an infectious disease expert at Vanderbilt University Medical Center, said the South Carolina woman's case has its root in Group A streptococcus. That's the same bacteria that can cause strep throat, of which millions of cases are reported annually in the U.S., according to the Centers for Disease Control and Prevention. But when it finds an area of the body that has recently undergone a trauma — like a cut or deep bruise, which Kuykendall may have experienced during the delivery of her twins — Group A strep can manifest itself into the flesh-eating disorder that has landed Kuykendall in the hospital, Schaffner said. "It causes a lot of pain," Schaffner said. "It can evade diagnosis for a period of time." According to the CDC, between 9,000 and 11,500 cases of invasive Group A strep happen each year in the United States, resulting in upward of 1,000 deaths. Not contagious, the bacterium is best treated by antibiotics and surgeries to remove dead tissue, which Schaffner said can spread so rapidly that doctors must go in multiple times to cut out more areas. Kuykendall, who has been keeping vigil at the hospital, said he knows his wife will improve but is sad she has missed time bonding with their babies. "The sad part about it is that she hasn't gotten to see the babies for the first week of their lives," Kuykendall told WYFF-TV (http://bit.ly/KBkzMd). "I talk to her every day. I tell her how good she's doing, and how strong she is, and that she's a fighter. She can make it." Fund for Kuykendall's care: GHS Federal Credit Union, 864-455-7112 Kinnard can be reached at http://twitter.com/MegKinnardAP ||||| (CNN) -- A South Carolina woman undergoing treatment for infection with a rare case of "flesh-eating" bacteria was in critical but stable condition Thursday at Greenville Memorial Hospital, a hospital spokeswoman said. Lana Kuykendall, 36, "underwent her fifth debridement surgery to remove necrotic, or dead, tissue from her lower leg," said Sandy Dees, senior media relations coordinator for Greenville Hospital System University Medical Center, in a news release. Kuykendall was admitted and diagnosed last Friday with necrotizing fasciitis, the release said. A team of surgeons, critical-care physicians and infection disease specialists was monitoring her condition, which is typically managed by surgery, antibiotics and aggressive supportive care, it said. "She remains very ill but stable," Dr. Bill Kelly, the hospital epidemiologist, said in the release. Kuykendall was healthy when she gave birth to twins on May 7 in Atlanta but went to the hospital near her home in South Carolina a few days later after noticing a rapidly expanding bruise on her leg, her husband, Darren, told CNN on Wednesday. Doctors there removed dead skin and tissue from her legs and she was put on a ventilator, he said. Kuykendall is a nurse and paramedic; her husband is a firefighter. The twins are healthy, he said. A two-hour drive south of Greenville, in Augusta, Georgia, 24-year-old Aimee Copeland was battling similarly aggressive bacteria on Thursday. Doctors have amputated one of her legs and surgically removed part of her abdomen. Her father, Andy Copeland, told CNN on Wednesday that her fingers, too, will have to be amputated. Still, "Aimee continues to be in good spirits," said a blog posted on the website of the Psychology Department at the University of West Georgia, where Aimee Copeland is a graduate student. "Two major medical developments today for Aimee," it said. "Those will be announced later today once Andy has the opportunity to type them out. Stay tuned." Copeland contracted the flesh-devouring bacteria Aeromonas hydrophila when she fell May 1 from a homemade zip line that broke and cut her leg. The gash required 22 staples. Days later, still in pain, she went to the Augusta hospital, where doctors diagnosed her with necrotizing fasciitis. The psychology student is on a ventilator and has undergone a tracheotomy. Flesh-eating bacteria explained A number of bacteria can cause the condition, which attacks and destroys healthy tissue and is fatal about 20% of the time, according to the Centers for Disease Control and Prevention. The bacteria are common in the environment but rarely cause an infection; when they do, the body's immune system is almost always able to fight them off, according to experts. Occasionally, however, the bacteria find their way into the bloodstream -- either through a cut or an abrasion. In such cases, doctors move aggressively, excising even healthy tissue near the infection site to ensure none of the dangerous bacteria remain. Necrotizing fasciitis is rare. Dr. William Schaffner, chairman of the Department of Preventive Medicine at the Vanderbilt University Medical Center, estimated in a telephone interview on Wednesday that fewer than 250 cases occur each year in the United States, though such estimates are imprecise since doctors do not have to report the cases to health authorities. CNN's Melissa Gray contributed to this report

– As Aimee Copeland continues to fight necrotizing fasciitis, another woman in the Southeast is battling the flesh-eating bacteria, too. Just days after giving birth to twins, Lana Kuykendall had severe pain in her leg—and then husband Darren noticed a spot that looked like a bruise or a blood clot that was spreading quickly. “Literally, you could almost watch it grow as you're standing there,” he says. By the time he got her to the hospital, where she is currently in critical condition, the affected tissue “had almost encircled her leg,” he says. No word on where the South Carolina woman picked up the infection, which is typically spread through an open wound or cut but can also enter the bloodstream through internal bleeding such as a black-and-blue mark, CNN reports. An epidemiologist tells WLTX that people shouldn’t panic even though both cases are in the Southeast (Copeland is in Georgia). "It's just chance, it doesn't mean we're going to see another one any sooner,” he says. “It's very uncommon here." Kuykendall, 36, has had skin and tissue removed from her legs and is using a ventilator, but her husband is optimistic for her recovery and says she is stable.

stigler @xcite developed an asymptotic result for the trimmed mean without requiring continuity of the underlying distribution function associated with the observations . this result was extended to non - degenerate @xmath0-statistics based on trimmed samples in borovskikh and weber @xcite . an alternative method for developing robust versions of @xmath0-statistics is to consider the statistic formed by trimming the kernel values , rather than the observations upon which the statistic is based . this idea is discussed in , for example , serfling @xcite , choudhury and serfling @xcite and gijbels , janssen and veraverbeke @xcite . in this paper , we use the generalized @xmath2-statistic representation developed in serfling @xcite to obtain an asymptotic result for trimmed @xmath0-statistics under quite general conditions . we will not require continuity of the relevant , associated distribution at the truncation points . let @xmath3 be independent identically distributed random variables , taking values in a measurable space @xmath4 and having common distribution @xmath5 let @xmath6 be a symmetric function from @xmath7 to @xmath8 and denote by @xmath9 the right - continuous distribution function of the random variable @xmath10 . set @xmath11 and let @xmath12 be an enumeration of the values of @xmath13 taken over the @xmath14 @xmath15-tuples in @xmath16 note that these random variables @xmath17 are , in general , dependent . let @xmath18 denote the ordered values of @xmath19 . the original @xmath0-statistic is defined as an average taken over the @xmath20 possible outcomes @xmath21 , that is , @xmath22 where the empirical distribution function @xmath23 of @xmath0-statistical structure is defined by @xmath24 and @xmath25 denotes the indicator of the set @xmath26 . for any @xmath27 , let @xmath28 $ ] , where @xmath29 $ ] denotes the largest integer less than or equal to @xmath30 if @xmath31 , then put @xmath32 the trimmed versions of @xmath0 are based on trimming the second sum in ( 1 ) , @xmath33 or on trimming of the range of integration in ( [ for1 ] ) , @xmath34 with @xmath35 and @xmath36 where @xmath37 , \gamma= \alpha,\beta.$ ] for the results that follow , it is important to note that the lower bound for the integral in ( [ for4 ] ) is included and the upper bound excluded . this is critical since @xmath38 is a step function . with this constraint , we are able to obtain the asymptotic distribution of @xmath39 without imposing any conditions on the nature of @xmath40 in lemma [ lem2.3 ] , we show that @xmath41 thus , @xmath42 and @xmath43 differ in terms of their divisors , and there are possible subtle differences in the number of summands . a class of generalized @xmath2-statistics , which includes ( [ for3 ] ) and ( [ for4 ] ) , was introduced by serfling @xcite . the trimmed @xmath0-statistics ( [ for3 ] ) and ( [ for4 ] ) are directly connected with generalized lorenz curves , which are important in financial mathematics ( see , for example , goldie @xcite , helmers and zitikis @xcite ) . clearly , @xmath44 is an unbiased estimator of @xmath45 in the case @xmath46 and @xmath47 @xmath38 reduces to the usual empirical distribution function . define the left - continuous quantile function @xmath48 for any distribution function @xmath40 the empirical quantile function @xmath49 has the form @xmath50 a large number of authors have studied the weak convergence of such @xmath2-statistics in the case @xmath51 a partial list consists of chernoff _ et al . _ @xcite , bickel @xcite , shorack @xcite , stigler @xcite , csrgo _ et al . _ @xcite , griffin and pruitt @xcite , cheng @xcite , mason and shorack @xcite . for @xmath52 , under various sets of regularity conditions , asymptotic normality of various types of generalized @xmath2-statistics has been investigated by silverman @xcite , serfling @xcite , akritas @xcite , janssen _ et al . _ @xcite , helmers and ruymgaart @xcite , gijbels _ et al . _ @xcite and hssjer @xcite . in the aforementioned papers , for @xmath53 , the results always assumed that @xmath54 is continuous or smooth . however , in modern statistical robust procedures and for bootstrap procedures , results allowing for the discontinuity of the underlying distribution function @xmath54 are needed . we study the asymptotic behavior of @xmath55 and @xmath56 for any @xmath57 without imposing the requirement of continuity . the conditions of our theorem and the limit random variable are defined via the values of quantile function @xmath58 at the points @xmath59 and @xmath60 existing results handle the cases where @xmath61 our main result is derived without this assumption of continuity . we represent the trimmed @xmath0-statistic as a sum of classical @xmath0-statistics with bounded , non - degenerate kernels plus some smaller terms and then we apply standard results to such statistics . for convenience , in what follows , for the distribution function @xmath62 we denote the smallest quantile @xmath63 and the largest quantile @xmath64 as , respectively , @xmath65 and @xmath66 with @xmath67 . let @xmath68 note that @xmath69 and @xmath70 are valid for all @xmath71 and the following events coincide : @xmath72 introduce the functional @xmath73 , where @xmath74\,\mathrm{d}h_f(x)\ ] ] and the following functions with @xmath75 : @xmath76 \nonumber\\ & & { } - \bigl [ ei\ { h(x , x_2,\ldots , x_m ) < \xi^+_\alpha\}\bigl(h(x , x_2,\ldots , x_m ) - \xi^+_\alpha\bigr)+\alpha\xi^+_\alpha\bigr ] -\theta,\nonumber\\ g_\alpha(x ) & = & ei\{h(x , x_2,\ldots , x_m ) < \xi^+_\alpha\}-\theta _ \alpha , \qquad \theta_\alpha = h_f(\xi^+_\alpha-),\\ g_\beta(x ) & = & ei\{h(x , x_2,\ldots , x_m ) \leq\xi^-_\beta\}-\theta _ \beta \nonumber\\ & = & 1-\theta_\beta- ei\{h(x , x_2,\ldots , x_m ) > \xi^-_\beta\},\qquad \theta_\beta = h_f(\xi^-_\beta).\nonumber\end{aligned}\ ] ] note that for all @xmath77 and @xmath75 , we have @xmath78 let @xmath79 and @xmath80 [ teo1.1 ] if @xmath81 then for any underlying distribution function @xmath82 , we have @xmath83 where @xmath84 is a trivariate gaussian random vector with mean vector zero and covariance matrix @xmath85 [ cor1.2 ] for any underlying distribution function @xmath54 , we have , when @xmath86 , @xmath87 where @xmath84 is a trivariate gaussian random vector defined as in theorem [ teo1.1 ] . [ cor1.3 ] suppose that the quantile function @xmath88 is continuous at the points @xmath59 and @xmath60 if @xmath89 then @xmath90 for the simple case @xmath91 , the functions in ( [ for7 ] ) reduce to @xmath92 a useful application of the theorem for the @xmath93 case is for the kernel @xmath94 @xmath95 this provides the asymptotic behavior of a natural , alternative robust version of the sample variance . we will now develop explicit expressions for the terms in a more interesting example . let @xmath96 with @xmath52 . let @xmath97 be the distribution function of @xmath98 and let @xmath99 then @xmath100 and @xmath101}y\,\mathrm{d}h_f(y ) \nonumber\\ & = & i\{\xi^+_\alpha\leq x \leq\xi^-_\beta\ } x ( f(x))^{m-1 } - \int_{[\xi^+_\alpha,\xi^-_\beta ] } y ( f(y))^{m-1 } \,\mathrm{d } f(y ) \nonumber \\ & & { } + \int_{[\xi^+_\alpha,\xi^-_\beta ] } \bigl(i\{x < y\ } - f(y-)\bigr)y \,\mathrm{d}(f(y))^{m-1 } , \nonumber\\ g_\alpha(x ) & = & i\{x < \xi^+_\alpha\}(f(\xi^+_\alpha-))^{m-1 } - ( f(\xi^+_\alpha-))^{m } , \nonumber\\ g_\beta(x ) & = & i\{x \leq \xi^-_\beta\}(f(\xi^-_\beta))^{m-1}-(f(\xi^-_\beta))^{m}.\end{aligned}\ ] ] in addition , @xmath102 ^ 2\\ & & { } + 2eg_{\alpha\beta}(x ) [ \xi^+_\alpha g_\alpha(x ) - \xi^-_\beta g_\beta(x)],\\ \sigma_{g_\alpha}^2 & = & ( f(\xi^+_\alpha-))^{2m-1}\bigl(1 - f(\xi^+_\alpha-)\bigr),\qquad \sigma_{g_\beta}^2 = ( f(\xi^-_\beta))^{2m-1}\bigl(1 - f(\xi ^-_\beta)\bigr ) , \\ eg_{\alpha}(x)g_{\beta}(x ) & = & ( f(\xi^+_\alpha-)f(\xi^-_\beta ) ) ^{m-1 } f(\xi^+_\alpha- ) \bigl(1 - f(\xi^-_\beta)\bigr ) , \\ eg_{\alpha\beta}(x)g_{\alpha}(x ) & = & ( f(\xi^+_\alpha-))^{m } \int _ { [ \xi^+_\alpha,\xi^-_\beta ] } \bigl(1 - f(y-)\bigr)y\ , \mathrm{d}(f(y))^{m-1 } \nonumber \\ & & { } - ( f(\xi^+_\alpha-))^{m } \int_{[\xi^+_\alpha,\xi^-_\beta ] } y ( f(y))^{m-1}\ , \mathrm{d } f(y),\\ eg_{\alpha\beta}(x)g_{\beta}(x ) & = & ( f(\xi^-_\beta ) ) ^{m-1}\bigl(1-f(\xi^-_\beta)\bigr ) \int_{[\xi^+_\alpha,\xi^-_\beta ] } y ( f(y))^{m-1}\ , \mathrm{d } f(y ) \nonumber \\ & & { } + ( f(\xi^-_\beta))^{m-1}\bigl(1-f(\xi^-_\beta)\bigr ) \int_{[\xi^+_\alpha,\xi^-_\beta ] } f(y- ) y\ , \mathrm{d}(f(y))^{m-1}.\end{aligned}\ ] ] consider the distribution function @xmath103 then @xmath104 , \qquad \sigma^2_g > 0\end{aligned}\ ] ] and the limiting behavior is given by @xmath105 however , for the simpler distribution function @xmath106 we have @xmath107 , \qquad \sigma^2_g > 0\end{aligned}\ ] ] and we get the asymptotic behavior covered by janssen _ et al . _ @xcite , @xmath108 the following two lemmas are key results for the proof . for @xmath114 , write @xmath115 since @xmath116 , @xmath117 = @xmath118 and , by ( [ for6 ] ) , @xmath119 we can write @xmath120\\[-8pt ] & & { } - \delta\xi_\beta i\{n^-_\beta < n_\beta\}(n^-_\beta - n_\beta ) .\end{aligned}\ ] ] note that @xmath121 and @xmath122 from ( [ for6 ] ) , we have @xmath123 @xmath124 hence , in ( [ for9 ] ) , @xmath125 equation ( [ for8 ] ) follows from ( [ for9 ] ) and ( [ for10 ] ) . this proves lemma [ lem2.1 ] . we shall estimate @xmath129 and @xmath130 taking into account the values of the distribution function @xmath131 at @xmath132 with @xmath133 figures [ fig1 ] and [ fig2 ] illustrate the different situations that need to be considered . * estimating @xmath142*. noting that @xmath143 , we write @xmath144 it is clear that if @xmath145 , then @xmath146 a.s . let @xmath147 , as is the case in fig . [ fig2 ] . in this case , @xmath148 and we can write @xmath149 since @xmath150 hence , we always have the relation a.s . to estimate @xmath151 , we note first that if @xmath152 , then the indicator @xmath153 for all @xmath154 therefore , we have the inequalities @xmath155\\[-8pt ] & \leq & i\{n_\alpha < n^-_\alpha\}(n^-_\alpha - n_\alpha ) ( \xi^-_\alpha- h_{nn_\alpha})i\{\xi^-_\alpha\geq h_{nn_\alpha } \}.%\nonumber\end{aligned}\ ] ] further , we shall apply the technique used in smirnov @xcite with a probability inequality from hoeffding @xcite ( or see , for example , serfling @xcite , pages 75 and 201 ) . thus , @xmath156 with some positive constants @xmath157 and @xmath158 depending only on @xmath159 and @xmath160 further , @xmath161 @xmath162 for any small values of @xmath163 , by the definition of the smallest @xmath164-quantile @xmath165 under the conditions of the lemma , @xmath166 as @xmath167 hence , @xmath168 in probability as @xmath169 next , we consider @xmath170 by definition , @xmath171 and since @xmath172 and @xmath173 , it follows that the indicator @xmath174 for @xmath175 and we can write @xmath176 in ( [ for13 ] ) , we need to consider two cases : @xmath177 and @xmath178 in the first case , @xmath179 and we have the weak convergence @xmath180 as @xmath181 and the following estimates which are similar to ( [ for12 ] ) : @xmath182 where @xmath183 in addition , @xmath184 for any small values of @xmath163 because of the definition of the largest @xmath59-quantile @xmath185 hence , in the case @xmath179 , we have @xmath186 in probability as @xmath169 in the second case in ( [ for13 ] ) , @xmath187 and we have the representation @xmath188 where @xmath189 and @xmath190 ) = \mathrm{o}(n^{-1/2 } ) $ ] as , but the positive term @xmath191 is unbounded . therefore , in this case , we shall apply the estimate ( [ for14 ] ) with @xmath192 instead of @xmath193 that is , @xmath194 @xmath195 @xmath196 since the distribution function @xmath54 is continuous from the right at the point @xmath197 it follows that @xmath198 for any small @xmath199 and sufficiently large @xmath200 hence , in the second case , @xmath201 and ( [ for14 ] ) is replaced by the inequality @xmath202 which provides the desired convergence @xmath203 in probability as @xmath167 thus , we have proven that @xmath204 in probability as @xmath167 * estimating @xmath205*. noting that @xmath206 , we write @xmath207 here , by analogy with ( [ for12 ] ) , we have @xmath208\\[-8pt ] & & \quad = p\ { h_n(\xi^-_\beta-\varepsilon ) - h(\xi^-_\beta-\varepsilon ) \geq n^{-1}n_\beta- h(\xi^-_\beta-\varepsilon)\ } \nonumber\\ & & \quad \leq c_1 \exp\ { -c_2 n \theta^2_\beta(\xi^-_\beta,\varepsilon ) \}%\nonumber\end{aligned}\ ] ] with @xmath209 and by analogy with ( [ for15 ] ) , @xmath210 here , we need to consider two cases : @xmath211 and @xmath212 in the first case , we apply the inequality ( [ for17 ] ) with sufficiently small @xmath213 in the second case , we use ( [ for17 ] ) again , but with parameter @xmath214 , as in ( [ for16 ] ) , to get @xmath215 since the distribution function @xmath54 has a limit from the left at the point @xmath216 and @xmath217 . in this result , we have @xmath218 in probability as @xmath167 finally , we consider @xmath219 since @xmath220 , we write @xmath221 & = & - i\{n^-_\beta < n_\beta\}\sum_{i = n^-_\beta+1}^{n_\beta } ( \xi^+_\beta- h_{ni})i\{\xi^-_\beta < h_{ni } < \xi^+_\beta\ } i\ { n^-_\beta < i \leq\dot n^+_\beta\}\nonumber\\[-1pt ] & & { } + i\{n^-_\beta < n_\beta\}\sum_{i = n^+_\beta+1}^{n_\beta}(h_{ni } - \xi^+_\beta)i\{h_{ni } > \xi^+_\beta\ } i\ { i > \dot n^+_\beta\ } \nonumber\\[-1pt ] & = & -\bar j^-_\beta+ \bar j^+_\beta.\end{aligned}\ ] ] if @xmath222 , then @xmath223 a.s . now , assume that @xmath224 in this case , @xmath225 and we have @xmath226 since @xmath227 hence , we always have @xmath223 a.s . to estimate @xmath228 , we write @xmath229 and apply the estimates ( [ for13])([for16 ] ) with @xmath230 instead of @xmath231 we have @xmath232 in probability as @xmath233 and hence @xmath234 in probability as @xmath167 proof of theorem [ teo1.1 ] let @xmath235 be a @xmath236-statistic of the form ( [ for1 ] ) with the kernel @xmath237 \nonumber\\ & & { } - \bigl [ i\ { h(x_1,\ldots , x_m ) < \xi^+_\alpha\}\bigl(h(x_1,\ldots , x_m ) - \xi^+_\alpha\bigr)+\alpha\xi^+_\alpha\bigr ] . \nonumber\end{aligned}\ ] ] we see that @xmath238 it is not difficult to verify for this function that @xmath239 and @xmath240 ; in addition , @xmath241 , by the condition of the theorem . hence , the kernel @xmath242 is non - degenerate and , by the central limit theorem for @xmath236-statistics with such bounded kernels , we have the weak convergence @xmath243 as @xmath181 ( see , for example , borovskikh @xcite ) . by the same central limit theorem , we have @xmath244 and @xmath245 as @xmath167 under the conditions of the theorem , we have @xmath246 if @xmath247 ( in this case , @xmath248 ) and @xmath249 if @xmath250 ( in this case , @xmath251 ) . further , it is easy to prove that the covariances @xmath252 as @xmath181 , where @xmath253 now , apply lemma [ lem2.2 ] to complete the proof of theorem [ teo1.1 ] . choudhury , j. and serfling , r.j . generalized order statistics , bahadur representations and sequential nonparametric fixed - width confidence intervals . _ j. statist . plann . inference _ * 19 * 269282 .

we adapt the techniques in stigler [ _ ann . statist . _ * 1 * ( 1973 ) 472477 ] to obtain a new , general asymptotic result for trimmed @xmath0-statistics via the generalized @xmath1-statistic representation introduced by serfling [ _ ann . statist . _ * 12 * ( 1984 ) 7686 ] . unlike existing results , we do not require continuity of an associated distribution at the truncation points . our results are quite general and are expressed in terms of the quantile function associated with the distribution of the @xmath0-statistic summands . this approach leads to improved conditions for the asymptotic normality of these trimmed @xmath0-statistics .

ultraluminous infrared galaxies ( ulirgs ) are known to emit the bulk of their energy in the infrared and their infrared luminosities ( @xmath2 ) are equivalent to the bolometric luminosities of optically selected quasars . for the past decade , there have been extensive studies of the nature of these ulirgs ( sanders & mirabel 1996 ) . imaging studies at optical and near - infrared wavelengths show that most of these galaxies are either interacting or merging ( sanders et al . 1988 , zou et al . 1991 , leech et al . 1994 , murphy et al . 1996 , borne et al . 2000 , kim et al . 2001 ) . the fraction of ulirgs in interacting or merging ranges from at least 61% ( 25 objects out of 41 , zou et al . 1991 ) to possibly as high as 100% for all 10 nearby ulirgs ( sanders et al . 1988 ) . the rather small fraction of interacting systems derived by zou et al . ( 1991 ) resulted from the use of poss images in which faint tidal tails are almost impossible to detect . recent imaging data by kim et al . ( 2001 ) showed that close to 100% of ulirgs in the complete 1 jy sample have faint tidal tails , a signature of recent interaction and merger . one of the most basic issues of ulirgs is the energy source powering the enormous amount of their infrared radiation . spectroscopic studies in the optical , near - infrared , and mid - infrared suggest that about 70% and 30% of these galaxies are powered by starburst activities and active galactic nuclei ( agns ) respectively ( veilleux et al . 1999a , veilleux et al . 1999b , genzel et al . the huge infrared luminosity of the ulirgs suggests that they contain a large reservoir of molecular gas to provide fuel for the star formation activity and/or a central agn . extensive searches for co emission have indeed shown that all ulirgs possess a huge amount of molecular gas ( @xmath3 10@xmath0 m@xmath1 ) and that there is a trend of increasing molecular gas content with the far - infrared emission ( downes et al . 1993 , solomon et al . recent interferometric observations of nearby ulirgs ( downes & solomon 1998 ) and luminous infrared galaxies ( bryant & scoville 1999 ) have determined that the molecular gas is concentrated in a circumnuclear disk of typically 1 kpc in size . from the interferometric observations of double - nucleus ulirgs with projected nuclear separations of 3 - 5 kpc , evans et al . ( 1999 , 2000 ) find that one of the interacting pair contains the majority of molecular gas in warm ulirgs whereas both components contain molecular gas in cool ulirgs . based on observational evidence , sanders et al . ( 1988 ) proposed that ulirgs originate from the merger of two gas - rich spiral galaxies . the large amount of molecular gas accumulated in the center of the galaxies due to the gravitational interaction can sustain strong star formation activities as well as provide fuel to the central agn . as the merger proceeds , the molecular gas reservoir is eventually depleted by the star formation ( gao & solomon 1999 ) and dispersed by the agn activities and supernovae . finally the agn reveals itself as an optical quasar . the estimated lifetime of the ulirg phase is about 10@xmath4 to 10@xmath5 yr . genzel et al . ( 1998b ) reviewed most recent observational evidence in favor of this scenario . numerical simulations of interacting galaxies have shown that violent star formation activity can be triggered in the merger of two massive disk galaxies ( barnes & hernquist 1996 , mihos & hernquist 1996 , springel 2000 ) . furthermore , star formation activities are found to be dependent mainly on the galaxy structure and the orbital geometry plays only a modest role ( mihos & hernquist 1994 , 1996 ) . they suggest that galaxies with dense central bulges show strong star formation activities at the final stages of merging , while bulgeless galaxies show weaker star formation activity at the early stage of interacting and do not show any subsequent strong star formation activities . thus , according to the numerical simulations , the majority of ulirgs would be in the final stages of merger . recently , kim et al . ( 2001 ) have completed an optical and near - infrared imaging survey of the iras 1 jy sample of ulirgs ( kim & sanders 1998 ) and find that all of the ulirgs show signs of tidal interaction and therefore are in a merging or interacting process ( kim et al . 2001 ) . more interestingly , we also find that 6 out of 118 ulirgs have projected nuclear separation larger than 20 kpc . the large nuclear separation observed in these ulirgs seems to contradict the conventional view of the origin of ulirgs and the numerical simulation results outlined above . to become an ulirg in the early phase of interaction , the galaxies must have accumulated a large amount of molecular gas and it is still unclear how the star formation activities are triggered in these cases . + the position uncertainty associated with the poor resolution of iras in the far - infrared did not allow us to determine the distribution of far - infrared emission as well as the molecular gas in these galaxies . without that information , it is difficult to clarify the nature of these unusual ulirgs . in this paper we present high angular resolution co(j=1 - 0 ) observations and new k-band imaging to study the widely separated ulirgs . co emission and the molecular gas are known to be associated with the source of far - infrared emission . thus observations of co emission will allow us to determine the location and the distribution of far - infrared luminosity of these ulirgs , in addition to the distribution of molecular gas . also making use of the optical imaging data ( kim et al . 2001 ) and our new k-band images , we discuss the nature of these widely separated ulirgs . we will use @xmath6 and @xmath7 km s@xmath8 mpc@xmath8 throughout this paper . we used the bima ( berkeley - illinois - maryland association ) array ( welch et al . 1996 ) to search for the co(j=1 - 0 ) emission line from the selected ulirgs . each galaxy in our sample was observed in various runs during 1998 and 1999 ( table . 1 ) in the b - configuration with baselines ranging from 5 k@xmath9 to 80 k@xmath9 , and the c - configuration with baselines ranging from 3 k@xmath9 to 30 k@xmath9 . the digital correlator was configured to cover a velocity range of 1600 km s@xmath8 centered at the velocity of the ulirgs calculated from their redshift . phase calibration was achieved by observing nearby quasars every 20 to 30 minutes . we also observed planets to determine the absolute flux scale . we used the miriad data reduction package ( sault et al . 1994 ) to calibrate and process our data . after phase calibration and flux calibration the visibilities were fourier - transformed to make the images . these images were then cleaned using the standard task clean of the miriad package . the final maps have angular resolutions of about 4 arcsec for b - configuration and 8 arcsec for c - configuration , respectively . the k-band ( 2.1 @xmath10 ) images of 4 galaxies iras f11180 + 1623 , iras f14394 + 5332 , iras f17028 + 5817 , iras f23327 + 2913 were obtained with the quirc 1024 x 1024 near - infrared camera on july 15 , 2000 , at the uh 88 `` telescope on mauna kea . the plate scale of the quirc is 0.1886@xmath11/pixel with f/10 and the seeing is estimated about 0.5@xmath11 to 0.7@xmath11 . the sky frames were constructed by median filtering of 9 dithered ( 20@xmath11 rectilinear motion ) object frames . dome flats were obtained by turning a lamp in the dome on and off at the beginning and end of each night . the dark subtracted and normalized flats were used for flat - fielding the sky - subtracted images . flat - fielded images were then coadded after shifting in fractional pixel units with respect to the object center . the final coadded images were calibrated from observations of infrared standard stars ( elias et . k-band images of two other galaxies ( iras f10485 - 1447 , iras f12359 - 0725 ) together with r - band images of all the galaxies in our sample were taken from the work of kim et al . the optical spectra of the nothern object of iras f23327@xmath122913 were taken in october 1995 at the uh 88 '' telescope with spectral resolution of 8 @xmath13 in the spectral range of @xmath14 4500 - 8500@xmath13 . the spectra were processed with the standard data reduction procedures . we detected co(j=1 - 0 ) emission from 4 galaxies iras f11180@xmath121623 , iras f14394@xmath125332 , iras f17028@xmath125817 , iras f23327@xmath122913 at @xmath15 3@xmath16 in the channel maps . in iras f12359 - 0725 we found possible co(j=1 - 0 ) emission of 3@xmath16 with channel width of 200 km s@xmath8 which is coincident within the synthesized beam with one of the galaxy in the system . fig 1 . shows the integrated intensity maps for the galaxies observed in our program together with their r - band and k-band images . the co emission line profiles of the detected nuclei are shown in fig . 2 . some of the properties of these ulirgs are provided in table . the co emitting regions are not resolved by our synthesized beams . in the case of iras f14394@xmath125332 , which is the only ulirg mapped in b - array , we can infer an upper limit to the size of the co emitting region to be @xmath3 1 " or @xmath3 2 kpc in linear scale . to estimate the molecular gas content from the total flux of co(j=1 - 0 ) line we adopt the same conversion factor as for the milky way galaxy ( bryant & scoville 1999 ) : @xmath17 where m@xmath18 is the molecular gas mass in m@xmath1 , f@xmath19 is the integrated flux in jy km s@xmath8 , d@xmath20 is the luminosity distance in mpc , and @xmath21 is the redshift . the molecular gas mass derived for the galaxies in our sample is similar to that found in other ultraluminous galaxies ( solomon et al . 1997 ) and in some high redshift galaxies ( combes et al . 1999 ) using the same galactic conversion factor as ours . the 1@xmath16 upper limit of the co flux is rms*@xmath22/@xmath23 where rms is the noise level in the channel maps , @xmath22 is the linewidth determined from the gaussian fitting to the line profiles and @xmath24 is the channel width . the 1@xmath16 upper limit to the molecular gas mass of the companion is then derived following the above equation . for the ulirgs with detected co emission , the companion may possess a molecular gas content of up to 10% to 20% the molecular gas content of the main component ( table . the upper limit is in the range of several 10@xmath25 m@xmath1 which implies the companions are not as gas rich as the main component but may possess a molecular gas content comparable to that of normal spiral galaxies . gaussian fitting to the line profiles gives the fwhm of 200 to 400 km s@xmath8 except for the case of iras f11180@xmath121623 . the weak co(j=1 - 0 ) emission from iras f11180@xmath121623 did not allow us to determine accurately its linewidth . thus , the value of 600 km s@xmath8 should be regarded as upper limit to the true linewidth of iras f11180@xmath121623 . although we did not succeed to detect co(j=1 - 0 ) emission from iras f10485@xmath261447 , the 1@xmath16 upper limit to the molecular gas mass of @xmath3 4@xmath2710@xmath25 m@xmath1 is still quite high . in addition , this galaxy has been observed only with the b - array which provides long baselines data with high phase scattering due to the atmospheric fluctuation . it would be very useful to search again for co emission with improved sensitivity . + using optical spectra , veilleux et al . ( 1999a ) determined the spectral type of all ulirgs in the 1 jy sample . in all cases , the galaxy detected in co(j=1 - 0 ) line has liner or seyfert ii spectral type while the companion has no emission line except for iras f17028@xmath125817e galaxy , which has spectral type hii , typical of starburst galaxies ( table 3 . ) . + the magnitudes of each component of the ulirgs are derived from our k-band images and presented in table . 3 . in most cases the galaxies have compact light distribution in k-band ( fig . 1 ) . however , k-band image of iras f14394@xmath125332 shows the extended emission with distortion in the e component , suggestive of a recent merger . * iras f10485@xmath261447 * - this system is close to two bright foreground stars which are visible on the upper left of both r - band and k-band images ( fig . 1 ) . on the r - band image , the e component shows short tidal tails in two opposite directions and the w component has a long curved tidal tail of about 10 kpc . the w component also has a distortion toward sw direction . the r - band luminosity of the w component is only slightly brighter than that of the e component , whereas in the k-band the w component is more than one magnitude brighter than the e component . the optical emission lines were detected from the w component with liner spectral type ( veilleux et al . the presence of absorption lines in the spectrum of the e galaxy ( s. veilleux , private communication ) indicates that both galaxies are at the same redshift and are interacting . though we did not detect any co emission in this system , the general trend of finding molecular gas in the active component of the widely separated ulirgs suggests that most of the gas could reside in the w component . + * iras f11180@xmath121623 * - the optical morphology of the e component ( fig . 1 ) shows two tidal tails in two opposite directions whereas the w component does not show any strong disturbances . the spectral type of the e component is liner ( veilleux et al . 1999a ) and no detectable optical emission lines were observed in the w component . the co emission was detected only on the e component . the e component may itself be a merger because it has two opposite tidal tails . one of the tidal tails on the e component tends to be curved and directed to the w component . there is also a small distortion on the east side of the w component , suggesting that the two galaxies are interacting . the lack of co emission as well as the non - detection of optical emission lines in the w component imply that this galaxy contains only a small amount of gas and is in the early stage of tidal interaction with the e component . because there is no measured redshift for the w component , we classify this pair as a tentative merger system . there are 3 additional galaxies around the system , and if they are at the same redshift as the two galaxies considered , then this whole system is likely an example of the hickson compact groups ( hickson 1982 ) . + * iras f12359@xmath260725 * - on the r - band image ( fig . 1 ) , the s component shows a curved tidal tail whereas the n component has no visible tail except a small depression on the western part of the galaxy . the two galaxies are found to be at the same redshift and are likely in the early phase of interaction . a foreground star is present to the west of the system on both r - band and k-band images . the r - band magnitudes of both components are similar , whereas k-band magnitude of the n component is 1.1 magnitude brighter than that of the s component . the n galaxy with liner spectral type is more active than the s component which has hii spectral type . we found possible co(j=1 - 0 ) emission coincident with the n component within the synthesized beam of 10``@xmath276 '' . as the n component is the most active in the system , the detection follows the same trend for other widely separated ulirgs in our sample . + * iras f14394@xmath125332 * - this system has large nuclear separation and shows long tidal tail ( @xmath3 35 kpc , fig . the r - band luminosity of the e component is slightly higher than that of the w component . on k-band , the e component is about 1.1 magnitudes brighter than the w component . furthermore , the e component shows strong optical emission lines and has a seyfert ii spectral type . in contrast , the w component shows no detectable emission lines . we detected co(j=1 - 0 ) emission from the e component only . the e component has seyfert ii spectra and bright near - infrared nucleus . radio continuum observations at 20 cm with the vla - b array ( 4 arcsec resolution ) detected a fairly strong continuum source of 38 mjy ( crawford et al . 1996 ) at the same position of this galaxy . this result is expected as seyfert galaxies are known to be strong continuum sources . an obscured agn at the center of the e component is likely the source of most of the continuum emission . our new k-band image of iras f14394@xmath125332 ( fig . 1 ) under good seeing condition ( 0.5@xmath11 ) reveals that the e component has two nuclei in the center with nuclear separation of 1.29@xmath11 . thus , k-band morphology suggests that this galaxy is already a merging system . + * iras f17028@xmath125817 * - on the r - band image ( fig . 1 ) , the w component is larger than the e component , but it has a more diffuse light distribution . faint emission resembling tidal tails can be seen in the w component , in the r - band images of kim et al . ( 2001 ) and murphy et al . on k-band image , the w component is much brighter than the e component and shows a compact light distribution . the co emission was detected in this w component . the w component also has a very red nuclear color as observed in the typical merger ulirgs ( kim et al . strong optical emission lines detected from both components indicate that they are at the same redshift . the spectral types of the w & e components are liner and hii region , respectively . + * iras f23327@xmath122913 * - on the r - band image ( fig . 1 ) , the s component resembles a normal spiral with very thick bar structure , whereas the n component looks much more disturbed with a big plume on the northern direction and has small protrusion on the eastern direction . both components have comparable r - band magnitudes . in k-band the s component shows a compact distribution and is brighter than the n component . interestingly , the optical emission lines were detected only from the s component and not from the much disturbed n component , except for the strong stellar absorption line of mg ib @xmath95175 ( ew ( mg ib ) = 5.5 , fig . the spectral type of the s component is liner and the co emission line was detected only from this component . radio continuum emission at 20 cm and 6 cm has been detected in this component ( crawford et al . the continuum emission at 6 cm was resolved by the 4 arcsec beam of the vla . + the large equivalent width of the mg ib absorption line which originates from the intermediate stellar population ( @xmath28 yr , bica , alloin , & schmidt 1990 ) , and the lack of balmer absorption lines ( originating from stellar population of age @xmath29 yr ) both suggests that star formation activity in this galaxy has already ceased some time ago . it is unclear whether the big northern plume on the n component is a remnant of past tidal interaction or caused by recent tidal interaction with the s component . the latter is more likely , since if the plume was caused by the past tidal interaction more than 10@xmath25 years ago then , it should already have been relaxed at this time and not be observable . + the most interesting result of our observations is the detection of co emission from only one component in the pair of the selected ulirgs . the molecular gas content in this component is quite high ( several times 10@xmath0 m@xmath1 ) if we adopt the milky way conversion factor . however , the value of the conversion factor has been suggested to be lower for ulirgs ( solomon et al . 1997 ) . by modelling the high resolution observations of co lines from nearby ulirgs , downes & solomon ( 1998 ) derived molecular gas masses which are a factor of 5 lower . from the iras fluxes at 60 @xmath10 and 100 @xmath10 we have estimated the dust temperatures in the ulirgs detected with co emission . the dust temperatures are roughly the same in these galaxies , @xmath3 40 k ( table . 4 ) . if we assume that the gas is in thermal equilibrium with the dust , namely t@xmath30 = t@xmath31 , we can estimate the radius of the co emitting region from the observed co flux f@xmath19 ( solomon et al . 1997 ) : @xmath32 where f@xmath33 is the velocity filling factor , @xmath34v@xmath35 is the linewidth and @xmath36 is the observed frequency in ghz , d@xmath37 is the luminosity distance in mpc . for simplicity , we assume that the velocity filling factor f@xmath33 is equal to unity . we also assume the thermalization and optical thickness of co(j=1 - 0 ) line , with the co(j=1 - 0 ) brightness temperature equal to the gas temperature . the dynamical ( virial ) mass ( table . 4 ) contained inside the co emitting region is r@xmath38/g , where g is the gravitational constant . we find that the dynamical masses are a factor of 3 to 4 lower than the molecular gas masses . as a result , the h@xmath39-to - co luminosity conversion factor for ulirgs must be lower than the galactic value . it was suggested by downes et al . ( 1993 ) and solomon et al . ( 1997 ) that in ulirgs the dynamical mass is dominated by the molecular gas mass . in this case , the dynamical masses estimated above are the upper limit to the actual molecular gas mass . + the component containing most of the molecular gas is also the most active galaxy in the pair , having either seyfert ii or liner - like spectral type . the other component is less active having either a hii spectral type typical of starburst galaxies or no detectable emission lines . since there is a correlation between co emission and the 100 @xmath10 flux from luminous and ultraluminous galaxies ( solomon et al . 1997 ) , the galaxy detected in co is likely to be the source of most of the far - infrared luminosity coming from the system and presumably the site of vigorous star formation activity . our result is consistent with the evans et al . ( 1999 , 2000 ) who found most of the molecular gas in several warm double - nucleus ulirgs to be associated with only the seyfert nuclei . all ulirgs in our sample are also found to be associated with 20 cm continuum sources ( becker et al . 1994 , condon et al . the continuum sources have flux densities ranging from a few mjy to @xmath3 40 mjy . for two galaxies iras f14394@xmath125332 and iras f23327@xmath122913 , high angular continuum observations have been reported ( becker et al . 1994 , crawford et al . 1996 ) . the continuum sources in these two galaxies coincide with the position of co(j=1 - 0 ) emission . in particular , the spectral index of radio continuum emission derived from 20 cm and 6 cm observations of iras f23327@xmath122913 is -0.52 ( crawford et al . 1996 ) , suggesting a non - thermal nature of the emission . for other ulirgs in our sample , due to the lack of observations at other frequencies , we could not determine the nature of the continuum emission . however , iras f14394@xmath125332e , a seyfert ii galaxy , appears to have stronger radio continuum flux relative to co luminosity , compared to other ulirgs in this sample . significant fraction of the radio continuum could arise from an agn in this galaxy . from the optical and k-band images we found evidence that the active component of iras f14394@xmath125332 possesses two nuclei . iras f14394@xmath125332 and 3 other systems identified by kim et al . ( 2001 ) in the 1 jy sample of ulirgs by imaging and spectroscopic data can be classified as multipled mergers . recent survey with the hst images of 113 ulirgs by borne et al . ( 2000 ) found that the fraction of multiple merger among ulirgs might be as high as 20% . however , this percentage could be overestimated since borne et al . ( 2000 ) did not identify real interacting members with spectroscopic observations . studies of the ulirgs and luminous infrared galaxies ( lig ) , which are less luminous in the infrared than ulirgs , by gao ( 1996 , 1997 ) also found that ulirgs and ligs have strong clustering . they suggested that some ligs and ulirgs were formed by the merger of groups of gas - rich galaxies . other systems studied in our paper appear to be in the early stage of interaction . thus , these systems do not fit into the standard interpretation of the ulirgs because the star - formation activity is expected to happen at the late stage of interaction . murphy et al . ( 1996 ) also found 7 ulirgs in their sample with separation greater than 10 kpc . they suggest several possible scenarios to explain these particular systems such as the presence of a third nucleus from previous encounter or the ulirg phenomenon can occur early in the interaction . if the second scenario applies to the ulirgs considered here , our detection of molecular gas in only one component of the system indicates that the ulirg phenomenon might be triggered during the early phase of interaction in a system comprised of a gas - rich galaxy and a much less gas - rich galaxy . the iras f23327@xmath122913 system is unique in the whole 1 jy sample of the ulirgs compiled by kim & sanders ( 1998 ) . the presence of absorption features in the optical spectrum of the northern component suggests that the n component did not experience star formation episode for the last @xmath40 yrs at least . the molecular gas is detected in the southern component which has a liner spectrum . thus , spectroscopic evidence suggests that the s component is more active than the n companion . more surprisingly , in the r - band image the s component appears as a spiral galaxy with a large bar - like structure at the center . therefore , the morphology of the s component is very different from other ulirgs which have either elliptical appearance or strongly disturbed morphology ( sanders et al . 1988 , borne et al . 2000 , kim et al . numerical simulations of the merger involving two massive disk galaxies ( mihos & hernquist 1996 , springel 2000 ) showed that the two galaxies are strongly disturbed during the interacting phase and the final product of the merger resembles an elliptical galaxy . therefore , iras f23327@xmath122913 does not fit into the commonly accepted scenario of merger between two disk galaxies for ulirgs . other mechanisms should be considered to explain the presence of the large reservoir of molecular gas as well as the huge far - infrared luminosity of the s component . the extended 6 cm radio continuum emission reported by crawford et al . ( 1996 ) indicates that the star formation activity is not concentrated in the nuclear region as in other ulirgs ( downes & solomon 1998 , bryant & scoville 1999 ) but spread over the galaxy . the existence of the thick bar in a system of two merging disk galaxies can be observed in the early stage of the tidal interaction in the numerical simulations ( eg . noguchi 1988 , barnes 1992 , barnes & hernquist 1996 ) . if this is the case , then we are witnessing the earliest stage of interaction in ulirgs . in order to become an ulirg at this early phase of the interaction , the s component should have a large amount of gas initially or the timescale to collect gas into the nuclear region is very short . in addition , the presence of a bar - like structure suggests that the molecular gas might be driven to the center of the galaxy under the influence of a non - axisymmetric gravitational potential . however , ho et al . ( 1997 ) and mulchaey & regan ( 1997 ) found that seyfert and liner galaxies do not show any significant preference for bars . as a result , it s still unclear whether a bar is effective enough to drive the large amount of molecular gas currently found in the s component . higher resolution observations of co emission lines and radio continuum are needed to better understand the origin of this galaxy . we have detected co(j=1 - 0 ) emission line in 5 out of 6 widely separated ulirgs selected from the complete 1 jy sample . the molecular gas mass present in these ulirgs indicates that they are gas - rich . our high angular resolution observations also reveal the concentration of the molecular gas in only one galaxy of the pair . optical spectra suggest that galaxy is also the most active in the pair , having either liner or seyfert ii spectral type . using optical and k-band images of the ulirgs , we found evidence in support of the multiple merger scenario for iras f14394 + 5332 . other systems are likely in the early phase of interaction . in particular , optical image of iras f23327@xmath122913 reveals that a large amount of molecular gas is concentrated in a spiral - like galaxy with no evidence for strong tidal interaction . our observation results suggest that the conventional view of ulirg phenomenon as the final phase of the merger of two massive disk galaxies probably does not apply to the widely separated ulirgs . other mechanisms are needed to explain their origin . future sensitive and high resolution observations will help to clarify the nature of these unusual ulirgs . we would like to express our thanks to an anonymous referee for critical comments which are very helpful in improving our paper . we also thank dr . s. veilleux for providing us the data prior to publication . barnes , j.e . , & hernquist , l.e . , 1991 , apjl , 370 , l65 barnes , j.e . , 1992 , apj , 393 , 484 barnes , j.e . , & hernquist , l.e . , 1996 , apj , 471 , 115 becker , r. h. , white , r. l. , & helfand , d. j. 1994 , asp conference series , v. 61 , eds . d. r. crabtree , r. j. hanisch , j. barnes , p. 165 bica , e. , alloin , d. , & schmitt , h.r . , 1994 , a&a 285 , 868 borne , k.d . , bushouse , h. , colina , l. , & lucas , r.a . , 2000 , apjl , 529 , l77 bryant , p.m. , & scoville , n.z . , 1999 , aj , 117 , 2632 combes , f. , maoli , r. , & omont , a. , 1999 , a&a 345 , 369 condon , j.j . et al . , 1998 , aj , 115 , 1693 . crawford , t. , marr , j. , partridge , b. , & strauss , m. , 1996 , apj 460 , 225 downes , d. , solomon , p.m. , & radford , s.j.e . , 1993 , apjl , 414 , l13 downes , d. , & solomon , p.m. , 1998 , apj 507 , 615 elias , j.h . , frogel , j.a . , matthews , k. , & neugebauer , g. , 1982 , aj 87 , 1029 evans , a.s . , kim , d.c . , mazzarella , j.m . , scoville , n.z . , & sanders , d.b . , 1999 , apjl , 521 , l107 evans , a.s . , surace , j.a . , mazzarella , j.m . , & sanders , d.b . , 2000 , in science with the atacama large millimeter array , ed . a. wootten , in press . gao , y. , 1996 , ph.d thesis , univ . of new york at stony brook gao , y. , 1997 , pasp , 109 , 1189 gao , y. , & solomon , p.m. , 1999 , apjl , 512 , l99 genzel , r. , lutz , d. , sturm , e. , egami , e. , kunze , d. , moorwood , a.f.m . , rigopoulou , d. , spoon , h.w.w . , sternberg , a. , tacconi - garman , l.e . , tacconi , l. , & thatte , n. , 1998a , apj 498 , 579 genzel , r. , lutz , d. , & tacconi , l. , 1998b , nature 395 , 859 hickson , p. , 1982 , apj , 255 , 382 ho , l.c . , filippenko , a.v . , & sargent , w.l.w , 1997 , apj , 487 , 591 kim , d - c . , 1995 , ph.d . thesis , univ . of hawaii kim , d - c . , & sanders , d.b . 1998 , apjs , 119 , 41 kim , d - c . et al . , 2001 , in preparation leech , k.j . , rowan - robinson , m. , lawrence , a. , & hughes , j.d . , 1994 , mnras 267 , 253 lutz , d. , veilleux , s. , & genzel , r. , 1999 , apjl , 517 , l13 mihos , j.c . , & hernquist , l. 1994 , apjl , 431 , l9 mihos , j.c . , & hernquist , l. 1996 , apj , 464 , 641 mulchaey , j.s . , & regan , m.w . , 1997 , apjl , 482 , l135 murphy , t.w . , armus , j.l , soifer , b.t . , mazzarella , j.m . , shupe , d.l . , strauss , m.a . , & neugebauer , g. , 1996 , aj , 111 , 1025 noguchi , m. , 1988 , a&a 203 , 259 sanders , d.b . , soifer , b.t . , elias , j.h . , neugebauer , g. , & matthews , k. , 1988 , apjl , 328 , l35 sanders , d.b . , & mirabel i.f . , 1996 , araa , 34 , 749 sault , r.j . , teuben , p.j . , & wright , m.c.h . , 1995 , in asp conf . 77 , astronomical data analysis software and systems iv , ed . shaw , h.e . payne , j.j.e . hayes ( san francisco : asp ) , 443 solomon , p.m. , downes , d. , radford , s.j.e . , & barret , j.w . , 1997 , apj , 478 , 144 springel , v. , 2000 , mnras 312 , 859 taniguchi , y. , & shioya , y. , 1998 , apjl , 501 , l167 veilleux , s. , kim , d - c . , & sanders , d.b . , 1999a , apj , 522 , 113 veilleux , s. , sanders , d.b . , & kim , d .- , 1999b , apj , 522 , 139 welch , w.j . , et al . 1996 , pasp , 108 , 93 zou , z. , xia , x. , deng , z. , & su , h. , 1991 , mnras , 252 , 593 lcccl name & redshift & obs . freq & num . of tracks & remarks + & & ( ghz ) & & + iras f10485@xmath261447 & 0.133 & 101.739 & 4 b - array tracks & no detection + & & & & + iras f11180 + 1623 & 0.166 & 98.860 & 4 b - array tracks & no detection + & & & 2 c - array tracks & co(j=1 - 0 ) detection + iras f12359@xmath260725 & 0.138 & 101.291 & 3 b - array tracks & no detection + & & & 1 c - array tracks & possible detection of co(j=1 - 0 ) + iras f14394 + 5332 & 0.105 & 104.317 & 4 b - array tracks & co(j=1 - 0 ) detection + & & & 3 c - array tracks & co(j=1 - 0 ) detection + iras f17028 + 5817 & 0.106 & 104.222 & 4 b - array tracks & no detection + & & & 2 c - array tracks & co(j=1 - 0 ) detection + iras f23327 + 2913 & 0.106 & 104.160 & 1 b - array track & no detection + & & & 3 c - array tracks & co(j=1 - 0 ) detection + cccccccc name & coordinates ( j2000.0)@xmath41 & d@xmath37 & beam & total co flux & m@xmath42 & @xmath34m@xmath42@xmath43 + & r. a. & dec . & ( mpc ) & ( @xmath44 ) & ( jy km s@xmath8 ) & ( 10@xmath0 m@xmath1 ) & ( 10@xmath0 m@xmath1 ) + iras f10485@xmath261447 & 10@xmath4551@[email protected] & -15@xmath480319``.8 & 548.6 & [email protected] & @xmath49 1 & @xmath49 0.4 & 0.4 + iras f11180 + 1623 & 11@xmath4520@[email protected] & 16@xmath480656''.6 & 689.5 & [email protected] & 11 & 5.4 & 0.8 + iras f12359@xmath260725 & 12@xmath4538@[email protected] & -07@xmath484232``.1 & 569.8 & [email protected] & 6@xmath50 & 2 & 0.4 + iras f14394 + 5332 & 14@xmath4541@[email protected] & 53@xmath482007''.9 & 430.5 & [email protected] & 21 & 4.2 & 0.4 + iras f17028 + 5817 & 17@xmath4503@[email protected] & 58@xmath481344``.5 & 433.7 & [email protected] & 14 & 2.8 & 0.3 + iras f23327 + 2913 & 23@xmath4535@[email protected] & 29@xmath483005''.8 & 438.9 & [email protected] & 8 & 1.7 & 0.2 + llccccccc name & spectral type@xmath41 & z & proj . separation & f@xmath51 & f@xmath52 & total magnitude + & & & ( kpc ) & ( 10@xmath53 l@xmath1 ) & ( mjy ) & r - band & k-band + iras f10485 - 1447e & absorption lines & 0.134@xmath43 & & & & 18.1 & 15.9 + iras f10485 - 1447w & liner & 0.133 & [ 0cm]20.0 & [ 0cm]1.48 & [ 0cm]4.4 & 17.7 & 14.7 + iras f11180 + 1623e & liner & 0.166 & & & & 17.9 & 14.7 + iras f11180 + 1623w & no emission lines & - & [ 0cm]21.8 & [ 0cm]1.74 & [ 0cm]4.7 & 19.4 & 16.1 + iras f12359 - 0725n & liner & 0.138 & & & & 18.2 & 14.8 + iras f12359 - 0725s & hii & 0.138 & [ 0cm]22.9 & [ 0cm]1.29 & [ 0cm]4.5 & 18.2 & 15.9 + iras f14394 + 5332e & seyfert ii & 0.105 & & & 38.0 & 16.3 & 13.1 + iras f14394 + 5332w & no emission lines & - & [ 0cm]50.5 & [ 0cm]1.10 & - & 16.9 & 14.2 + iras f17028 + 5817e & hii & 0.106 & & & & 17.4 & 14.8 + iras f17028 + 5817w & liner & 0.106 & [ 0cm]23.3 & [ 0cm]1.26 & [ 0cm]16.7 & 17.1 & 13.5 + iras f23327 + 2913n & absorption lines & 0.106 & & & - & 16.5 & 14.1 + iras f23327 + 2913s & liner & 0.107 & [ 0cm]22.7 & [ 0cm]1.15 & 8.4 & 16.8 & 13.6 + ccccccccc name & @xmath54 & t@xmath31 & l@xmath55 & @xmath34v@xmath56 & radius & dynamical mass + & 60 @xmath10 & 100 @xmath10 & ( k ) & ( 10@xmath25k km s@xmath8pc@xmath57 ) & ( km s@xmath8 ) & ( kpc ) & ( 10@xmath25 m@xmath1 ) + iras f11180 + 1623 & 1.19 & 1.60 & 41.5 & 11.0 & 600 & 0.38 & 31.0 + iras f14394 + 5332 & 1.95 & 2.39 & 43.3 & 8.6 & 380 & 0.40 & 13.3 + iras f17028 + 5817 & 2.43 & 3.91 & 36.9 & 5.8 & 330 & 0.40 & 10.0 + iras f23327 + 2913 & 2.1 & 2.81 & 37.9 & 3.4 & 200 & 0.38 & 3.5 +

in the complete sample of ultraluminous infrared galaxies ( ulirgs ) compiled by kim ( 1995 ) about 5% consists of widely separated galaxies which are presumably in the early phase of interaction . this fact is contrary to the conventional view that ulirgs are in the final stages of the merger of two gas - rich disk galaxies . we have undertaken high resolution co(j=1 - 0 ) observations for the ultraluminous infrared galaxies that have nuclear separations larger than 20 kpc . we have detected the co emission in 5 out of 6 systems , but only in one component of the ulirg pairs . 4 of them have liner spectral type and 1 galaxy has seyfert ii spectral type . in k-band images these components are also brighter than the other components which have either hii - region spectra or no detectable emission lines . using the standard conversion factor , the molecular gas content is estimated to be a few times 10 @xmath0 m@xmath1 , similar to that of the other ultraluminous galaxies . the result indicates that the galaxy containing the molecular gas is also the source of most , if not all , of the huge far - infrared luminosity of the system . the optical and k-band imaging observations and optical spectra suggest multiple merger scenario for 1 system . if the remaining systems are in an early stage of a binary tidal interaction , the commonly accepted interpretation of the ulirg phenomenon as the final merger stage of two disk galaxies may need to be re - examined .

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Park Bonds and Capital Improvements Act of 1997''. SEC. 2. DEFINITIONS. For purposes of this Act: (1) The term ``National Park Capital Improvement Fund'' means the fund established under this Act containing the revenues collected by the National Park Service from all park units in the National Park System and held in trust by the Department of the Treasury for the purpose of paying the debt service on the National Park Capital Improvement bonds. (2) The term ``National Park Capital Improvement bonds'' means bonds sold by the Department of the Treasury under this Act to generate capital to make appropriate capital improvements of National Park units as specified in this Act. (3) The term ``capital improvements'' means more than physical construction projects such as roads, visitor centers, and other infrastructure projects. The term includes one-time and periodic projects such as resource inventories, monitoring activities, and educational and interpretive programs, as well as transportation systems. The term also includes data gathering and planning needed to design projects aimed at protecting park resources. (4) The term ``National Park System'' has the meaning provided in section 2(a) of the Act of August 8, 1953 (16 U.S.C. 1c(a)). SEC. 3. FINDINGS. Congress finds the following: (1) Our Nation's parks are among our Nation's greatest treasure and an integral part of our national heritage. We have an obligation to protect them for future generations to enjoy, learn from, and experience. (2) Unfortunately, in recent years we have failed to take proper care of our parks. In particular, more and more people are visiting our parks and fewer and fewer real dollars are being spent to protect the resources for which they were set aside--their spectacular vistas, clean and clear water, significant wildlife habitats, historic buildings, etc. (3) While it is incumbent upon Congress to appropriate adequate funds for the operation of our national parks, the backlog of natural and cultural resource protection needs together with other needs for transportation improvements, building repairs, etc., is now so great that a new source of funding to meet these needs must be found. (4) All park needs, however, are not equal. Of utmost importance and urgency is the need to protect the cultural, historic, and natural resources for which our parks were set aside to protect. These resources are our parks' capital. Unless we preserve them, there will be little reason for Americans and visitors from other countries to visit our parks. Projects that are needed to prevent ongoing or threatened harm to the resources of our parks must be given the highest priority when funding priorities are set. Similarly, projects designed to rehabilitate damage done in the past to park resources should be given the next highest priority. (5) In considering the needs of our parks, care must be taken to avoid exacerbating problems, particularly those involving visitors. Emphasis must be placed now, and into the future, on designing and implementing transportation systems which will minimize use of private cars and resultant traffic problems within the parks, while providing safe, reliable, and flexible alternatives. (6) In considering the needs of our parks, activities which do not require on the ground construction must not be slighted. In particular, educational and interpretive programs are central to the mission of our parks. Similarly, reliable and sound information is central to the solution of the problems facing them. Accordingly, these kinds of projects should be recognized as essential investments in our parks. SEC. 4. NATIONAL CAPITAL IMPROVEMENT FUND AND BONDS ISSUED BY SECRETARY OF TREASURY. (a) Fund.--There is hereby established in the Treasury a National Park Capital Improvement Fund. The Secretary of the Treasury shall deposit all the revenues collected by the National Park Service from all park units in the National Park System in such Fund. Such Fund shall be held in trust by the Secretary of the Treasury for the purpose of paying the debt service on the National Park Capital Improvement bonds. (B) Bonds.--The Secretary of the Treasury shall issue taxable bonds, the interest on which shall be paid from the National Park Capital Improvement Fund. SEC. 5. MEMORANDUM OF AGREEMENT. The Secretary of the Interior shall enter into a memorandum of agreement with the Secretary of the Treasury for the purpose of managing the National Park Capital Improvement Fund and issuing National Park Capital Improvement bonds. The memorandum shall specify each of the following: (1) The aggregate face amount of the bonds issued. Such amount may not exceed $1,500,000,000. (2) The maturity of the bonds, not to exceed 20 years. (3) The per capita amount required to amortize the bond issue, pay the interest on the bonds, and maintain a sufficient reserve consistent with Department of the Treasury standards. (4) The kinds of projects that will be funded with the bond proceeds. SEC. 6. NATIONAL PARK CAPITAL IMPROVEMENT FUND. (a) In General.--Notwithstanding any other provision of law, the Secretary of the Interior is authorized and directed to credit all funds collected from the following to the National Park Capital Improvement Fund: (1) Funds collected pursuant to section 4 of the Land and Water Conservation Fund Act of 1965 (16 U.S.C. 4601-6a). (2) Funds collected from the operation of concessions within the entire National Park System under the National Park Concessions Act of 1965 (16 U.S.C. 20 and following). (3) Funds collected as special use fees pursuant to the National Park Organic Act of 1916 (39 Stat. 535; 16 U.S.C. 1,2,3, and 4) and the National Park Administration Act (16 U.S.C. 1b, 1c, and 1d. (b) Use.--The National Park Capital Improvement Fund or a set-aside portion thereof shall be used by the Secretary of the Treasury to amortize the bond issue, pay the interest on the bonds, and maintain a sufficient reserve consistent with industry standards. (c) Excess Funds.--Any funds collected in excess of the amount necessary to amortize the bond issue and maintain a sufficient reserve, as determined by the Secretary of the Treasury, shall be held for use in amortizing and paying the interest on future National Park Capital Improvement bonds for the benefit of all units of the National Park System. SEC. 7. USE OF BOND PROCEEDS. (a) Eligible Projects.-- (1) In general.--Subject to such allocation of funding as may be provided in annual appropriations legislation, and subject to paragraph (2), bond proceeds under this Act may be used for projects that will-- (A) protect the natural, historic, cultural, scenic, and other resources of a park including activities which do not require on the ground construction such as obtaining reliable and sound information; (B) provide educational and interpretative programs to enrich the park resource based experience of visitors; and (C) rehabilitate, replace, or repair existing facilities or design and construct new facilities in a park unit provided that it does not create or exacerbate damage to park resources nor degrade the experience of visitors. (2) Limitation.--A project referred to in paragraph (1) shall be consistent with-- (A) the laws governing the national Park System; (B) any law governing the park unit; (C) the general management plan for the park; and (D) the current list of priority projects necessary to meet park needs. In developing the list referred to in subparagraph (D) and in carrying out projects, the resources to be protected by each project shall always be specifically identified and the highest priority shall be given, first, to projects designed to prevent ongoing resource harm and second, to rehabilitate past damage. The next highest priority shall be given to projects that protect resources and enhance the experience of visitors. In considering the needs of our parks, care must be taken to avoid exacerbating problems particularly those involving visitors. Emphasis must be placed on designing and implementing transportation systems which will minimize use of private cars and resultant traffic. No project shall be approved for funding or funded pursuant to this Act if harm to any park resources will result therefrom. (b) Interest on Bond Proceeds.--Any interest earned on bond proceeds shall be transferred into the National Park Capital Improvement Fund. SEC. 8. ADMINISTRATION. (a) Joint Regulations.--The Secretary of the Interior and the Secretary of the Treasury shall jointly issue regulations to carry out this Act. (b) Priorities.--The Secretary of the Interior shall issue regulations for the identification and prioritization of projects to be funded pursuant to this Act.

National Park Bonds and Capital Improvements Act of 1997 - Establishes in the Treasury a National Park Capital Improvement Fund. Directs the Secretary of the Treasury (the Secretary) to: (1) deposit all revenues collected by the National Park Service from all park units in the National Park System into such Fund (and requires that the Fund be held in trust by the Secretary for the purpose of paying the debt service on the National Park Capital Improvement bonds); and (2) issue taxable bonds, with the interest paid from the Fund. Requires the Secretary of the Interior to enter into a memorandum of agreement with the Secretary for the purpose of managing the Fund and issuing bonds. Directs the Secretary of the Interior to credit to the Fund specified funds collected pursuant to the Land and Water Conservation Fund Act of 1965 from the operation of concessions within the National Park System under the National Park Concessions Act of 1965 and as special use fees pursuant to the National Park Organic Act of 1916 and the National Park Administration Act. Authorizes the use of bond proceeds, subject to specified restrictions, for projects that will: (1) protect the natural, historic, cultural, scenic, and other resources of a park; (2) provide educational and interpretative programs to enrich the park resource based experience of visitors; and (3) rehabilitate, replace, or repair existing facilities or design and construct new facilities in a park unit. Sets forth provisions regarding limits on such projects, interest on bond proceeds, and regulations for the identification and prioritization of projects to be funded pursuant to this Act.

steroids are frequently used drugs for the treatments of sudden hearing loss and facial palsy , known to have effectiveness of anti - inflammation and immunosuppression , when used at high - doses.1 ) the mechanism for steroid in sudden hearing loss to express the effectiveness in its treatment has still been unknown accurately , but assumed to reduce the inflammation of cochlea and acoustic nerve.2 ) also , steroid has been known as preventing autonomic disturbance incurring due to denervation of facial nerve in patients with facial palsy , and also preventing the progression of incomplete paralysis to complete paralysis.2 ) in spite of its positive effectiveness , long term use of steroid can cause adverse effects , including osteoporosis , renal impairment , infection , gastrointestinal disorder , depression , hypertension and diabetes.3 ) aforementioned adverse effects incur when using steroid over a long time in general . but ear nose throat ( ent ) practice uses high - dose steroid over a short time more frequently than a long time . meaning , the adverse effects of steroid that ent doctors may experience during actual medical care is possibly different from the description contained in the drug information . there are not so many cases identified in terms of potential adverse effects , and their prevalence from the use of a short term high - dose steroid even in the literatures . according to a report , the use of a short - term steroid therapy in children with sudden hearing loss , it reported on the incidences of nasal bleeding , hepatic impairment , acne , gastroenteritis and rump abscess after using steroid.4 ) however , these reports had focused on nothing but listing the phenomena , while treating children rather than focusing on the adverse effects of steroid . there are little reports on the types of adverse effects and the prevalence of each adverse effect likely to appear when prescribed high - dose steroid for 1 to 2 weeks in patients with sudden hearing loss or facial palsy who were usually healthy . to this end , this study aimed to investigate the types , prevalence and occurrence time of adverse effects when used a short - term high - dose steroid therapy and to identify whether there were any difference in the prevalence of adverse effects between those who received in - patient treatment opposed to those who received out - patient treatment . the study was conducted according to the principles of the declaration of helsinki and to good clinical practice guidelines . medical records of 500 patients were retrospectively analyzed , who had received high - dose steroid therapy , either as in - patient or from out - patient prescription , from january 2008 to december 2011 . the underlying reasons for using steroid had included sudden sensorineural hearing loss , bell 's palsy , ramsay - hunt syndrome and herpes zoster oticus . herpes zoster oticus , described in this study , denotes herpes zoster incurred in the ear without accompanying facial palsy . in this study , the schedule of steroid use was to administer methyl prednisolone for 1 week at dose of 48 mg / day , followed by reducing 10 mg daily ( intakes of 12 days in total ) . in order to control the errors that adversely effects patients but they failed to accurately inform the applicable details to medical staff , all involved patients were fully informed of the adverse effects that were likely to appear prior to the use of the drug , and received a list of adverse effects ( fig . 1 ) . in addition , at every visit for an out - patient medical care , from 0.5 to 2 times weekly , the onset of adverse effects had been confirmed in patients ; thus , this study was conducted as having those patients with accurate description contained in the records for the presence / absence of adverse effects as the study subjects . although the study was designed as a retrospective structure , it was ensured not to be confused between " adverse effects not checked " and " no adverse effects " by taking aforementioned measures . the abdominal discomforts included all disturbances in the gastrointestinal system , such as abdominal distention and dyspepsia . 2 ) , but without including small number of rashes like 1 - 2 spots or pimples . other adverse effects , except skin rash were defined based on the subjective feelings of patient rather than any objective signs . meaning , some patients complained of discomfort subjectively , but there were cases without a clear abnormality when medical staff evaluated such discomfort . out of the 500 patients in total , 424 patients ( 84.8% ) were with sudden sensorineural hearing loss , followed by 49 patients ( 9.8% ) with bell 's palsy , 13 patients ( 2.6% ) with ramsy - hunt syndorme and 14 patients ( 2.8% ) with herpes zoster oticus . the mean age of patients was 45.717.0 years old and the gender ratio was 278 : 222 . the numbers of those treated as in - patient and those treated as out - patient were 250 and 250 patients , respectively . the out - patient group and the in - patient group were constituted with each 250 patients intentionally , taking age and gender into account . the mean age of patients was 46.517.2 years old in the in - patient group and 45.016.8 years old in the out - patient group , and each applicable gender ratio was 137 : 113 in the in - patient group ; whereas , it was 141 : 109 in the out - patient group . there was no significant difference in the mean age , as well as the gender ratio between the two groups . hospital admission was determined by personal choice of patients , as well as depending on the overall health conditions , and the in - patient duration was 7 days . there was no difference in steroid prescription method and dosage between the in - patient group and the out - patient group . however , there were differences in the administration of digestives , blood circulation promoter and anti - viral agent other than digestives . more treatments with aforementioned drugs were implemented in the in - patient group additionally , and as the route of administration , injection was used more than the oral form . first of all , this study had investigated the types , prevalence and onset timing of adverse effects after the intake of steroid in the entire patient group . the onset timing of adverse effects was calculated based on the time point that the applicable symptoms were found for the first time . thereafter , the study had performed a comparative analysis to identify whether there was any difference in the prevalence of adverse effects between the in - patient group and the out - patient group . computer software ( spss v12.0 , ibm , armonk , ny , usa ) was used for statistical analysis with student 's t - test and chi - square test . the incurrences of adverse effects were confirmed in 165 patients ( 33.0% ) out of 500 patients in total , who had received steroid therapy . among those adverse effects , 62 patients ( 26.8% ) had shown abdominal discomfort as the most , followed by 34 patients ( 14.7% ) with skin rash , 31 patients ( 13.4% ) with edema , and 16 patients ( 6.9% ) with hot flushes in order ( fig . abdominal discomfort and hot flushes had the highest prevalence in the first week , but were reduced in the prevalence at week 2 to 4 ; whereas , edema presented the highest prevalence at week 2 , and skin rash at week 3 ( fig . , there were patients to whom serious adverse effects had incurred , such as avascular necrosis of hip bone ( n= 1 ) and toxic hepatitis ( n=4 ) . there were significant difference in diagnosis of the in - patient group and the out - patient group ( p=0.011 ) . sudden hearing loss was diagnosed in 200 in - patients ( 80% ) and in 224 out - patients ( 89% ) , showing it was more in the out - patient group . whereas , bell 's palsy were found in 30 in - patients ( 12% ) and 19 out - patients ( 8% ) , 11 in - patients ( 4% ) and 2 out - patients ( 1% ) as ramsay - hunt syndrome , and 9 in - patients ( 4% ) and 5 out - patients ( 2% ) as herpes zoster oticus , presenting there were more numbers of in - patients in each diagnosis . incidences of adverse effects had been identified in 62 patients ( 25% ) out of 250 in - patients and in 103 patients ( 41% ) out of 250 out - patients . the prevalence of adverse effects was significantly lower in the in - patients compared to the out - patients ( p<0.001 ) . also , there were significant differences in the types of adverse effects between the in - patient group and the out - patient group ( p=0.022)(fig . the adverse effects in - curred from the in - patients were abdominal discomfort from 23 patients , skin rash from 20 patients , edema from 8 patients and constipation from 6 patients , in order ; whereas , the adverse effects incurred from the out - patients were abdominal discomfort from 39 patients , edema from 23 patients , skin rash from 14 patients and hot flush from 14 patients , in order . the incurrences of adverse effects were confirmed in 165 patients ( 33.0% ) out of 500 patients in total , who had received steroid therapy . among those adverse effects , 62 patients ( 26.8% ) had shown abdominal discomfort as the most , followed by 34 patients ( 14.7% ) with skin rash , 31 patients ( 13.4% ) with edema , and 16 patients ( 6.9% ) with hot flushes in order ( fig . abdominal discomfort and hot flushes had the highest prevalence in the first week , but were reduced in the prevalence at week 2 to 4 ; whereas , edema presented the highest prevalence at week 2 , and skin rash at week 3 ( fig . , there were patients to whom serious adverse effects had incurred , such as avascular necrosis of hip bone ( n= 1 ) and toxic hepatitis ( n=4 ) . there were significant difference in diagnosis of the in - patient group and the out - patient group ( p=0.011 ) . sudden hearing loss was diagnosed in 200 in - patients ( 80% ) and in 224 out - patients ( 89% ) , showing it was more in the out - patient group . whereas , bell 's palsy were found in 30 in - patients ( 12% ) and 19 out - patients ( 8% ) , 11 in - patients ( 4% ) and 2 out - patients ( 1% ) as ramsay - hunt syndrome , and 9 in - patients ( 4% ) and 5 out - patients ( 2% ) as herpes zoster oticus , presenting there were more numbers of in - patients in each diagnosis . incidences of adverse effects had been identified in 62 patients ( 25% ) out of 250 in - patients and in 103 patients ( 41% ) out of 250 out - patients . the prevalence of adverse effects was significantly lower in the in - patients compared to the out - patients ( p<0.001 ) . also , there were significant differences in the types of adverse effects between the in - patient group and the out - patient group ( p=0.022)(fig . the adverse effects in - curred from the in - patients were abdominal discomfort from 23 patients , skin rash from 20 patients , edema from 8 patients and constipation from 6 patients , in order ; whereas , the adverse effects incurred from the out - patients were abdominal discomfort from 39 patients , edema from 23 patients , skin rash from 14 patients and hot flush from 14 patients , in order . from the study results , it was identifiable that the percentage of patients who had experienced adverse effects , among the total population of patients who has been treated by a short - term high - dose steroid , was 33.0% , indicating a quite high rate . therefore , the information on adverse effects should be explained to patients before making the steroid prescription . this would reduce the anxiety of patients , prevent the distrust on the medical staff and increase the compliance to the treatment , even if any adverse effects incur . however , such values included non - specific and minor subjective symptoms complained by the patient in all , and the prevalence of clinically significant adverse effects was likely lower . another fortunate fact was that the most adverse effects were not serious and recoverable after discontinuity of drug administration . the interesting matter at the incidence of each adverse effect is that some adverse effects begin to appear concurrently with the drug intake , whereas some adverse effects incur belated after completion of the drug intake . for example , abdominal discomfort had begun within 1 week immediately after taking the drug in many cases , while there was no case of having abdominal discomfort newly at week 3 when the drug administration was ended . meanwhile , the most cases of skin rash had begun at week 3 , when the drug administration was complete . this was assumed because it took about 1 to 2 weeks until the skin reaction appeared , as the immune mechanism acted . given the fact that the drug administration period was 12 days , it indicated these adverse effects could incur even 1 to 2 weeks after the completion of drug intake . meaning , because there is a possibility to have belated onset of aforementioned adverse effects even after the completion of drug taking , it would be better to continue the observation of patients up to 3 to 4 weeks . according to an existing report , adverse effects had been found in patients who took steroid after kidney transplant , such as hypertension ( 15% ) , diabetes ( 10% ) , fracture ( 2% ) , avascular necrosis of hip bone ( 8% ) and cataract ( 22%).5 ) however , this study had inconsistency in the doses of steroid administration and the follow - up observation time for patients . it had limitations in making comparison of a certain dose - induced adverse effects , since some patient had used the short - term therapy , while some other patients had used the long - term therapy . a study pointed out that steroid can cause adrenal suppression in patients with severe chronic obstructive pulmonary disease.6 ) another study had reported that when performed the steroid therapy in 75 patients with polymyalgia rheumatica or giant cell arteritis , adverse effects had incurred , such as fracture ( 10 patients ) , dyspepsia ( 5 patients ) , gastric ulcer ( 4 patients ) , diabetes ( 4 patients ) and cataract ( 2 patients).7 ) this study was performed in patients who had been treated with prednisolone at the dose of 10 - 40 mg / day for over 18 months , and the doses were properly increased or decreased , depending on the systemic conditions of patients . the time that had confirmed the onset of adverse effects was 1 time in 2 weeks for the first 2 months , and thereafter 1 time in 2 - 3 months . as aforementioned , the existing reports had focused on the adverse effects caused by the long - term steroid therapy , so it had difficulties in comparing with the results of this study . nevertheless , the important difference , identified from the existing reports , and this study focused on the adverse effects predicted for a short - term prescription , which were mostly minor and recoverable , but the adverse effects predicted for a long - term prescription were more severe and harmful to the health . when a simple comparison was performed between the in - patient group and the out - patient group , this may imply that the in - patient treatment was helpful for decreasing the adverse effects . however , several different explanations can be made for this result and it seems difficult to derive a solid conclusion on which the treatment measure is better . when reasons for the lower incidence of adverse effects in the in - patient group is speculated , first , the in - patient group took sufficient rest , escaping from the daily life , whereas , the out - patient group had to take steroid as performing various routine job - related duties . due to such difference , the drug metabolism of the patients may have been different between the two groups , and consequently , the prevalence of adverse effects may differ . secondly , the in - patient group took healthy meal regularly in optimized quantity , as provided by the hospital , whereas , it was impossible for medical staff to control the eating hours , meal quantity and its content in the out - patients group . thereby , some significant differences are likely to incur in abdominal discomfort felt by patients . as shown in fig . 5 , several differences exist between the 2 groups , but also it was identified that the difference in abdominal discomfort would be the largest . thirdly , the in - patient group may have had immediate resolution of discomfort before medical record on the adverse effect was made . this is because the patients can meet the medical staff , including doctors and nurses , for 7 days at any time on a daily basis and the medical staff will manage the discomfort more readily than the out - patient group . when immediate symptomatic therapy has been done , patients may not consider the discomfort as a problem anymore and no record may be left . for example , more antacid may have been prescribed in the in - patients group , and this may have reduced the incidence of abdominal discomfort in this group . lastly , since these two groups were not assigned randomly , it is likely that there is a selection bias . the in - patients were those who had selected to get more active treatment , regardless what the reasons were . for example , they had selected to be admitted to the hospital because either the disease for which steroid had been used , got more aggravated , or due to other past medical history . accordingly aforementioned matters are important weaknesses of this study , and because of such , it is difficult to prove whe - ther there is any difference in the actual prevalence of the adverse effects between the in - patient group and the out - patient group . however , given the fact that most adverse effects appear within the first week , the in - patient treatment during the first 1 week may be clinically relevant . in addition , acute management is available when any important adverse effects do occur and this may be an advantage of hospitalized treatment . toxic hepatitis and avascular necrosis of hip bone were considered as serious adverse effects . and however , it is unclear whether a short - term steroid prescription has a direct causal relationship with these diseases , or coincidently accompanied otherwise . in particular , 1 patient with toxic hepatitis had died of the disease , but this case also could not be identified whether the cause of death was steroid or not . it was impossible to analyze the risk factors of serious adverse effects because there were not many incidences . but in case of toxic hepatitis , the liver - related baseline disease is considered as an important factor from the fact that the patient was already a carrier of hepatitis virus even before the drug administration or that the hepatitis had incurred from the patient whose serum aspartate transaminase ( ast ) level or alanine transaminase ( alt ) level were already high from the beginning . therefore , it is considered that we can be prepared against the onset of such serious adverse effects by checking whether the patient is a carrier of hepatitis virus , and by checking the liver function test results in terms of serum ast and alt levels in advance , before administering the high - dose steroid . although the results are interesting , there are several shortcomings that may need careful interpretation to this study . first , due to the retrospective design , we may have neglected some important adverse effects , which can not be detected by the patient , such as hyperglysemia . second , in all the patients , antacids were prescribe together with the steroid and in about half of the patients antiviral agents and ginkgo leaf extraction agents were prescribed together with the steroid . accordingly , some adverse effects may have been due to these adjunctive medications other than steroid . but since adjunctive medications were prescribed in low does and it has been already known that these medications are not related with such adverse effects , we believe that most of the adverse effect is due to steroid . monitoring should be performed until 3 - 4 week , since some adverse effects may not be detected until this time point .

background and objectivesalthough the adverse effect of long term steroid usage is well known , the adverse effect of short term high dose steroid usage has not been studied thoroughly . the purpose of this study was to identify the characteristics of the adverse effects when using a high dose steroid for a short term . we also compared the adverse effect of steroid between in- and out-patients.subjects and methodsthe medical record of 500 patients , who were treated with methylprednisolone 48 mg / day for 1 - 2 weeks , was retrospectively reviewed . steroid was prescribed due to ssnhl , bell 's palsy , ramsay - hunt syndrome and herpes zoster oticus . the incidence of each adverse effect was analyzed , and also the time point of detection was analyzed . the 500 patients were composed of 250 in - patients and 250 out - patients . the adverse effect was compared between these two groups , as well.resultsadverse effect of steroid was found in 33.0% of the patients . among these adverse effects , abdominal discomfort ( 26.8% ) was most common , followed by skin rash ( 14.7% ) , swelling ( 13.4% ) , and hot flush ( 6.9% ) . abdominal discomfort and hot flush was mostly detected on the first week . meanwhile , the skin rash was usually detected on the third week . the incidence of adverse effect was significantly higher in the out - patient group.conclusionsthe incidence of high dose short term steroid treatment may be very high . the patients should be warned about these adverse effects . monitoring should be performed until 3 - 4 week , since some adverse effects may not be detected until this time point .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Get America Moving Again Act of 2009''. SEC. 2. TEMPORARY CREDIT FOR PURCHASE OF PASSENGER VEHICLES. (a) In General.--Subpart B of part IV of subchapter A of chapter 1 of the Internal Revenue Code of 1986 is amended by inserting after section 30D the following new section: ``SEC. 30E. TEMPORARY CREDIT FOR PURCHASE OF PASSENGER VEHICLES. ``(a) Allowance of Credit.--There shall be allowed as a credit against the tax imposed by this chapter for the taxable year an amount equal to the purchase price of any qualified passenger vehicle placed in service by the taxpayer during the taxable year. ``(b) Maximum Credit.-- ``(1) New vehicles.--In the case of each qualified passenger vehicle the original use of which begins with the taxpayer, the credit allowed by subsection (a) shall not exceed-- ``(A) $5,000 in the case of a vehicle placed in service before January 1, 2010, and ``(B) $2,500 in the case of a vehicle placed in service during 2010. ``(2) Used vehicles.--In the case of each qualified passenger vehicle the original use of which does not begin with the taxpayer, the credit allowed by subsection (a) shall not exceed-- ``(A) $2,000 in the case of a vehicle placed in service before January 1, 2010, and ``(B) $1,000 in the case of a vehicle placed in service during 2010. ``(c) Limitation Based on Adjusted Gross Income.-- ``(1) In general.--In the case of a natural person, the amount allowable as credit under this section (without regard to this subsection) for any taxable year shall be reduced (but not below zero) by the amount which bears the same ratio to the amount so allowable as-- ``(A) the excess (if any) of-- ``(i) the taxpayer's modified adjusted gross income for such taxable year, over ``(ii) $125,000 ($250,000 in the case of a joint return), bears to ``(B) $10,000. ``(2) Modified adjusted gross income.--For purposes of paragraph (1), the term `modified adjusted gross income' means the adjusted gross income of the taxpayer for the taxable year increased by any amount excluded from gross income under section 911, 931, or 933. ``(d) Qualified Passenger Vehicle.--For purposes of this section-- ``(1) In general.--The term `qualified passenger vehicle' means any motor vehicle (as defined by section 30(c)(2)) if-- ``(A) the model year of such vehicle is (at the time such vehicle is placed in service by the taxpayer) not more than 3 years earlier than the most recent model year of such vehicle which is available for purchase, ``(B) such vehicle is acquired for use by the taxpayer and not for resale, ``(C) the amount paid by the taxpayer for such vehicle does not exceed $50,000, and ``(D) such vehicle has a gross vehicle weight rating of not more than 8,500 pounds. ``(2) Determination of price.--Rules similar to the rules of sections 4002(d) and 4003(c) shall apply. ``(e) Application With Other Credits.-- ``(1) Business credit treated as part of general business credit.--So much of the credit which would be allowed under subsection (a) for any taxable year (determined without regard to this subsection) that is attributable to property of a character subject to an allowance for depreciation shall be treated as a credit listed in section 38(b) for such taxable year (and not allowed under subsection (a)). ``(2) Personal credit.-- ``(A) In general.--For purposes of this title, the credit allowed under subsection (a) for any taxable year (determined after application of paragraph (1)) shall be treated as a credit allowable under subpart A for such taxable year. ``(B) Limitation based on amount of tax .--In the case of a taxable year to which section 26(a)(2) does not apply, the credit allowed under subsection (a) for any taxable year (determined after application of paragraph (1)) shall not exceed the excess of-- ``(i) the sum of the regular tax liability (as defined in section 26(b)) plus the tax imposed by section 55, over ``(ii) the sum of the credits allowable under subpart A (other than this section and sections 23, 25D, and 30D) and section 27 for the taxable year. ``(f) Special Rules.--For purposes of this section-- ``(1) Basis reduction.--The basis of any property for which is credit is allowed under this section shall be reduced by the amount of such credit. ``(2) Property used outside united states, etc., not qualified.--No credit shall be allowed under subsection (a) with respect to any property referred to in section 50(b) or with respect to the portion of the cost of any property taken into account under section 179. ``(g) Application of Section.--This section shall apply to vehicles placed in service after the date of the enactment of this section and before January 1, 2011.''. (b) Conforming Amendments.-- (1) Paragraph (1) of section 26(a) of such Code is amended by striking ``and 30D'' and inserting ``30D, and 30E''. (2) Subsection (a) of section 1016 of such Code is amended by striking ``and'' at the end of paragraph (36), by striking the period at the end of paragraph (37) and inserting ``, and'', and by adding at the end the following new paragraph: ``(38) to the extent provided by section 30E(f)(1).''. (3) The table of sections for subpart B of part IV of subchapter A of chapter 1 of such Code is amended by inserting after the item relating to section 30D the following new item: ``Sec. 30E. Temporary credit for purchase of passenger vehicles.''. (c) Effective Date.--The amendments made by this section shall apply to taxable years ending after the date of the enactment of this Act.

Get America Moving Again Act of 2009 - Amends the Internal Revenue Code to allow a tax credit for the purchase of a new or used passenger vehicle before or during 2010. Requires that such vehicle have a purchase price not exceeding $50,000 and have a gross vehicle weight rating of not more than 8,500 pounds.

UPDATED: The inspiration for the book and upcoming Angelina Jolie film "Unbroken" and a former Olympian died following a case of pneumonia, according to a spokesperson for Universal Pictures. World War II hero and Unbroken inspiration Louis Zamperini has died at age 97, according to a spokesperson for Universal Pictures. A statement released by the studio on Thursday morning included a message from his family, which read: "Having overcome insurmountable odds at every turn in his life, Olympic runner and World War II hero Louis Zamperini has never broken down from a challenge." PHOTOS Hollywood's Notable Deaths of 2014 The staement continued: "He recently faced the greatest challenge of his life with a life-threatening case of pneumonia. After a 40-day-long battle for his life, he peacefully passed away in the presence of his entire family, leaving behind a legacy that has touched so many lives. His indomitable courage and fighting spirit were never more apparent than in these last days." Angelina Jolie, who directed the upcoming film about his life based on the best-selling book Unbroken by Laura Hillenbrand, immediately expressed her condolences. "It is a loss impossible to describe. We are all so grateful for how enriched our lives are for having known him. We will miss him terribly," she said in a statement. Universal, which will release the film adaptation of Zamperini's incredible story on Dec. 25, 2014, went on to say in a statement: "We are so profoundly sad at this moment and all of our thoughts and prayers are with the Zamperini family. Louis was truly one of a kind. He lived the most remarkable life, not because of the many unbelievable incidents that marked his near century's worth of years, but because of the spirit with which he faced every one of them. PHOTOS Hollywood's 100 Favorite Films "Confronting challenges that would cause most of us to surrender, Louie always persevered and always prevailed, and he spent the better part of his lifetime sharing the message that you could do the same. His example of grace, dignity and resilience inspired all of us lucky enough to know him and the millions who got to know him from the pages of Laura's book. We move forward to the release of Unbroken with a renewed sense of responsibility in bringing Louie's abundant life and indomitable spirit to the screen. Now more than ever, we join Angelina in honoring the lessons and legacy of this extraordinary man who has meant so much to so many." Born in Olean, N.Y., on Jan. 26, 1917, to Italian immigrant parents, Zamperini and his family moved to Torrance, Calif., when he was a child. He was a member of the 1936 U.S. Olympic track team in Berlin running the 5,000 meters, and at 19, was the youngest American qualifier ever in that event. In 1941, he enlisted in the U.S. Army Air Force and was deployed to the Pacific as a bombardier on a B-24 Liberator bomber. The story of Unbroken, originally a best-selling book by Hillenbrand set in 1943, follows Zamperini as his Air Force plane crashes in the Pacific. He and two others survived without food and water for 47 days before washing ashore on a Japanese island behind enemy lines, where he was held as a prisoner of war for two years. PHOTOS Going for Gold: 10 Medal-Worthy Olympics Movies Zamperini was first declared missing at sea and then killed in action, but after the war he returned to his family in America with a hero's welcome and married Cynthia Applewhite in 1946. He remained with her until her death in 2001. On his 81st birthday in 1988, the former athlete returned to Japan and ran a leg in the Olympic Torch relay for the Winter Olympics in Nagano. Torrance Airport was renamed Zamperini Field in the 1960s, his former high school named its stadium after him and the entrance plaza at USC's track and field stadium was named Louis Zamperini Plaza in 2004. The football fan continued to attend USC games well into his 90s and became friends with then-quarterback Matt Barkley in 2009. In May, Zamperini was named grand marshal of the 2015 Rose Parade in Pasadena, which on New Year's Day will feature the theme "Inspiring Stories." In accepting the honor, Zamperini, wearing a USC cap, recalled that Hillenbrand, in researching the book, asked to interview his friends from college and the Army. "And now after the book was finished all of my college buddies are dead, all of my war buddies are dead. It's sad to realize that you've lost all your friends," he said. "But I think I made up for it. I made a new friend — Angelina Jolie. And the gal really loves me, she hugs me and kisses me, so I can't complain." LIST The Hollywood Reporter Reveals Hollywood's Favorite Films After meeting Zamperini last year, Jolie, who lived near his Hollywood Hills home, revealed that they had "become close friends." "It will be hard to make a film worthy of this great man," she said in October while filming the biopic in Australia. "I am deeply honored to have the chance and will do all I can to bring Louie’s inspiring story to life." Jolie produced Unbroken with Matthew Baer and Erwin Stoff. Jack O’Connell stars as Zamperini, and Garrett Hedlund and Domhnall Gleeson also appear in the film. In February, Jolie and Zamperini sat down with NBC News' Tom Brokaw for an interview at Zamperini's home. The film previously received the below Brokaw-narrated preview during the Winter Olympics. During the interview, Zamperini told Brokaw what Adolf Hitler had said to him after the American ran a fast final lap to finish a strong eighth in the 5,000 meters at the Olympics. "All that he said was 'the boy with the fast finish,' and I couldn't really shake hands — he was up pretty high — so I just reached up and touched his hand," he said. Jolie said in her February interview that she felt an incredible commitment to telling Zamperini's story. "[I have] such a huge responsibility to get it right because I love him so much and because he's helped me so much in my life," Jolie said. Hilary Lewis and The Associated Press contributed to this report. ||||| Former Olympian, World War II hero and Grand Marshall of the 2015 Rose Parade Louis Zamperini has died at the age of 97. Louis Zamperini, an American prisoner of war in World War Two and Olympic runner whose life inspired the book and upcoming feature film "Unbroken," has died at age 97.Zamperini died after a 40-day bout with pneumonia, his family said on Thursday in a statement released by Universal Pictures, the studio behind the film."It is a loss impossible to describe," said Angelina Jolie, who is directing the film. "We are all so grateful for how enriched our lives are for having known him. We will miss him terribly."The film, which is to open Dec. 25, is based on the best-selling 2010 book "Unbroken" by author Laura Hillenbrand on the life of Zamperini, particularly the harrowing time he spent as a prisoner of war under the Japanese.An American-born son of Italian immigrants, the Southern California athlete surpassed more experienced runners to qualify for the U.S. team for the 1936 Olympics in Berlin. He ran the 5,000-meter race, finishing eighth, but with a fast final lap that drew a personal compliment from German leader Adolf Hitler."His fighting spirit was a true representation of Team USA and our country, both in Berlin and throughout his life," the U.S. Olympic Committee said.After the 1940 Olympics were canceled due to war, Zamperini enlisted as a U.S. Army airman and began flying missions as an officer and bombardier over the Pacific in late 1942.In 1943, his plane crashed into the ocean and he spent 47 days in a life raft battling sharks, with only a scarce supply of water and food, with a fellow survivor before they were picked up by a Japanese boat.For two years, until the war ended, Zamperini was held by the Japanese at camps where beatings, starvation and hard labor were common."Louis was truly one of a kind," Universal Pictures said. "He lived the most remarkable life, not because of the many unbelievable incidents that marked his near century's worth of years, but because of the spirit with which he faced every one of them."Zamperini had been active up to this year, doing television appearances early in the year with Jolie for the movie.In May, Zamperini was named grand marshal of the 2015 Rose Parade, in Pasadena, California.Parade organizers Tournament of Roses indicated that Zamperini will be honored as the marshal despite his death."We will remember and honor the courage and grace that made Louis who he was, and hope that by sharing his life's story, we can uphold the values which built his strength, perseverance and his ability to forgive others," the organization said in a statement.

– Louis Zamperini had a resume that truly impressed: Olympian, World War II POW/hero, and the subject of best-selling book Unbroken and the upcoming Angelina Jolie film based on it. Zamperini has died at 97 following a bout of pneumonia, "having overcome insurmountable odds at every turn in his life," reads a statement released by his family today, per the Hollywood Reporter. Born in New York in 1917, Zamperini made the US Olympic track team in 1936, placing 8th in the 5,000 meters in Berlin. His 56-second final lap, however, was so impressive it earned him a one-on-one meeting with Adolf Hitler, the Chicago Tribune reports. In 1941, he'd fight Hitler's ideals as a B-24 Liberator bomber with the US Army Air Forces. When his plane crashed into the Pacific in 1943, he and two others survived on a raft in shark-infested waters for 47 days without food or water before being captured by the Japanese and held as prisoners of war for two years—a story told in Laura Hillenbrand's bestseller Unbroken: A World War II Story of Survival, Resilience and Redemption. Jolie—who directed the film based on the book, which opens Christmas Day—says the death of her "close friend" is "a loss impossible to describe."

SECTION 1. SHORT TITLE. This Act may be cited as the ``Individual Investment Account Act of 2005''. SEC. 2. ESTABLISHMENT OF INDIVIDUAL INVESTMENT ACCOUNTS. (a) In General.--Part VII of subchapter B of chapter 1 of the Internal Revenue Code of 1986 (relating to additional itemized deductions for individuals) is amended by redesignating section 224 as section 225 and by inserting after section 223 the following new section: ``SEC. 224. INDIVIDUAL INVESTMENT ACCOUNTS. ``(a) Deduction Allowed.--In the case of an individual, there shall be allowed as a deduction an amount equal to the aggregate amount paid in cash for the taxable year by such individual to an individual investment account established for the benefit of such individual. ``(b) Definitions and Special Rules.--For purposes of this section-- ``(1) Individual investment account.--The term `individual investment account' means a trust created or organized in the United States for the exclusive benefit of an individual, but only if the written governing instrument creating the trust meets the following requirements: ``(A) No contribution will be accepted unless it is in cash. ``(B) The trustee is a bank (as defined in section 408(n)) or another person who demonstrates to the satisfaction of the Secretary that the manner in which that person will administer the trust will be consistent with the requirements of this section. ``(C) No part of the trust assets will be invested in any collectible (as defined in section 408(m)). ``(D) The assets of the trust will not be commingled with other property except in a common trust fund or common investment fund. ``(2) Time when contributions deemed made.--A taxpayer shall be deemed to have made a contribution on the last day of a taxable year if the contribution is made on account of such taxable year and is made not later than the time prescribed by law for filing the return for such taxable year (not including extensions thereof). ``(c) Tax Treatment of Distributions.-- ``(1) In general.--Except as otherwise provided in this subsection, any amount distributed out of an individual investment account shall be included in gross income by the distributee unless such amount is part of a qualified first- time homebuyer distribution. ``(2) Qualified first-time homebuyer distribution.--For purposes of this subsection-- ``(A) In general.--The term `qualified first-time homebuyer distribution' has the meaning given to such term by section 72(t)(8). ``(B) Dollar limitation.--The aggregate amount which may be treated as qualified first-time homebuyer distributions for all taxable years shall not exceed $15,000. ``(C) Basis reduction.--The basis of any principal residence described in subparagraph (A) shall be reduced by the amount of any qualified first-time homebuyer distribution. ``(3) Transfer of account incident to divorce.--The transfer of an individual's interest in an individual investment account to his former spouse under a divorce decree or under a written instrument incident to a divorce shall not be considered a taxable transfer made by such individual notwithstanding any other provision of this subtitle, and such interest at the time of the transfer shall be treated as an individual investment account of such spouse and not of such individual. Thereafter such account shall be treated, for purposes of this subtitle, as maintained for the benefit of such spouse. ``(d) Tax Treatment of Accounts.-- ``(1) Exemption from tax.--An individual investment account shall be exempt from taxation under this subtitle unless such account has ceased to be such an account by reason of paragraph (2). Notwithstanding the preceding sentence, any such account shall be subject to the taxes imposed by section 511 (relating to imposition of tax on unrelated business income of charitable, etc. organizations). ``(2) Loss of exemption of account where individual engages in prohibited transaction.-- ``(A) In general.--If, during any taxable year of the individual for whose benefit the individual investment account is established, that individual engages in any transaction prohibited by section 4975 with respect to the account, the account shall cease to be an individual investment account as of the first day of that taxable year. ``(B) Account treated as distributing all its assets.--In any case in which any account ceases to be an individual investment account by reason of subparagraph (A) on the first day of any taxable year, paragraph (1) of subsection (c) shall be applied as if there were a distribution on such first day in an amount equal to the fair market value (on such first day) of all assets in the account (on such first day). ``(3) Effect of pledging account as security.--If, during any taxable year, an individual for whose benefit an individual investment account is established uses the account or any portion thereof as security for a loan, the portion so used shall be treated as distributed to that individual. ``(4) Rollover contributions.--Subsection (c)(1) shall not apply to any amount paid or distributed out of an individual investment account to the individual for whose benefit the account is maintained if such amount is paid into another individual investment account for the benefit of such individual not later than the 60th day after the day on which he receives the payment or distribution. ``(e) Cost-of-Living Adjustment.-- ``(1) In general.--In the case of any taxable year beginning in a calendar year after 2005, the $15,000 amount contained in subsection (c)(2)(B) shall be increased by an amount equal to-- ``(A) such dollar amount, multiplied by ``(B) the cost-of-living adjustment determined under section 1(f)(3) for the calendar year in which the taxable year begins by substituting `calendar year 2004' for `calendar year 1992' in subparagraph (B) thereof. ``(2) Rounding.--If any dollar amount (as increased under paragraph (1)) is not a multiple of $10, such dollar amount shall be increased to nearest multiple of $10. ``(f) Custodial Accounts.--For purposes of this section, a custodial account shall be treated as a trust if the assets of such account are held by a bank (as defined in section 408(n)) or another person who demonstrates, to the satisfaction of the Secretary, that the manner in which he will administer the account will be consistent with the requirements of this section, and if the custodial account would, except for the fact that it is not a trust, constitute an individual investment account described in subsection (b). For purposes of this title, in the case of a custodial account treated as a trust by reason of the preceding sentence, the custodian of such account shall be treated as the trustee thereof. ``(g) Reports.--The trustee of an individual investment account shall make such reports regarding such account to the Secretary and to the individual for whose benefit the account is maintained with respect to contributions, distributions, and such other matters as the Secretary may require under regulations. The reports required by this subsection shall be filed at such time and in such manner and furnished to such individuals at such time and in such manner as may be required by those regulations.''. (b) Deduction Allowed in Arriving at Adjusted Gross Income.-- Subsection (a) of section 62 of such Code (defining adjusted gross income) is amended by inserting before the last sentence the following new paragraph: ``(21) Individual investment account contributions.--The deduction allowed by section 224 (relating to individual investment accounts).''. (c) Individual Investment Accounts Exempt From Estate Tax.--Part III of subchapter A of chapter 11 of such Code is amended by redesignating section 2046 as section 2047 and by inserting after section 2045 the following new section: ``SEC. 2046. INDIVIDUAL INVESTMENT ACCOUNTS. ``Notwithstanding any other provision of law, there shall be excluded from the value of the gross estate the value of any individual investment account (as defined in section 224(b)). Section 1014 shall not apply to such accounts.''. (d) Nonrecognition of Gain on Sale of Principal Residence Where Amount Equal to Otherwise Taxable Gain Deposited Into Individual Investment Account.--Part III of subchapter B of chapter 1 of such Code is amended by inserting after section 121 the following new section: ``SEC. 121A. EXCLUSION OF GAIN FROM SALE OF PRINCIPAL RESIDENCE IF REINVESTMENT IN INDIVIDUAL INVESTMENT ACCOUNT. ``(a) General Rule.--Gross income does not include gain from the sale or exchange of property if, during the 5-year period ending on the date of the sale or exchange, such property has been owned and used by the taxpayer as his principal residence for periods aggregating 2 years or more. ``(b) Limitation.--The amount of gain excluded from gross income under subsection (a) shall not exceed the amount paid in cash (during the 1-year period beginning on the date of the sale or exchange) to an individual investment account (as defined in section 224(b)) established for the benefit of the taxpayer or his spouse. ``(c) Certain Rules on Ownership and Use to Apply.--Rules similar to the rules of section 121(d) shall apply for purposes of determining ownership and use under this section.''. (e) Tax on Prohibited Transactions.-- (1) Paragraph (1) of section 4975(e) of such Code (relating to prohibited transactions) is amended by redesignating subparagraphs (F) and (G) as subparagraphs (G) and (H), respectively, and by inserting the following new subparagraph after subparagraph (E): ``(F) an individual investment account described in section 224(b), ''. (2) Subsection (c) of section 4975 of such Code is amended by adding at the end the following new paragraph: ``(7) Special rule for individual investment accounts.--An individual for whose benefit an individual investment account is established shall be exempt from the tax imposed by this section with respect to any transaction concerning such account (which would otherwise be taxable under this section) if, with respect to such transaction, the account ceases to be an individual investment account by reason of the application of section 224(d)(2)(A) to such account.''. (f) Failure to Provide Reports on Individual Investment Accounts.-- Paragraph (2) of section 6693(a) of such Code is amended by redesignating subparagraphs (D) and (E) as subparagraphs (E) and (F), respectively, and by inserting after subparagraph (C) the following new subparagraph: ``(D) section 224(g) (relating to individual investment accounts),''. (g) Adjustment of Basis of Residence Acquired Through Use of Account.--Subsection (a) of section 1016 of such Code is amended by striking ``and'' at the end of paragraph (30), by striking the period at the end of paragraph (31) and inserting ``, and'', and by adding at the end thereof the following new paragraph: ``(32) to the extent provided in section 224(c)(2)(C), in the case of a residence the acquisition of which was made in whole or in part with funds from an individual investment account.''. (h) Clerical Amendments.-- (1) The table of sections for part III of subchapter B of chapter 1 of such Code is amended by inserting after the item relating to section 121 the following new item: ``Sec. 121A. Exclusion of gain from sale of principal residence if reinvestment in individual investment account.''. (2) The table of sections for part VII of subchapter B of chapter 1 of such Code is amended by striking the item relating to section 224 and inserting the following: ``Sec. 224. Individual investment accounts. ``Sec. 225. Cross reference.''. (3) The table of sections for part III of subchapter A of chapter 11 of such Code is amended by striking the item relating to section 2046 and inserting the following new items: ``Sec. 2046. Individual investment accounts. ``Sec. 2047. Disclaimers.''. (i) Effective Date.--The amendments made by this section shall apply to taxable years beginning after December 31, 2004.

Individual Investment Account Act of 2005 - Amends the Internal Revenue Code to allow an individual taxpayer a tax deduction from gross income (whether or not the taxpayer itemizes deductions) for cash contributions to an individual investment account. Permits tax free distributions up to $15,000 from such accounts for the purchase of a principal residence by a first-time homebuyer. Allows an annual inflation adjustment to the $15,000 limit beginning in 2006. Excludes individual investment accounts from the calculation of the gross estate for estate tax purposes. Excludes from gross income gain from the sale of a principal residence if such gain is reinvested in an individual investment account.

we recently obtained a new hamiltonian for a lattice which includes interactions with internal nuclear degrees of freedom @xcite . we started with a dirac model for electrons and for nucleons on equal footing , then allowed the nuclei to be described by a finite basis expansion , and finally developed an approximation appropriate for low nuclear velocity . our original motivation for this was to obtain a model capable of describing the mass shift associated with excited nuclear states in a configuration interaction calculation . however , the new model unexpectedly contains a new coupling term which provides for a direct interaction between lattice vibrations and nuclear transitions . on the face of it , this new interaction term looks like it should allow for the strongly - coupled transitions that we have sought @xcite in connection with the generalized lossy spin - boson models @xcite that we proposed to account for some of the anomalies ( such as excess heat @xcite and collimated x - ray emission @xcite ) that have been reported in experiments in recent years . what is needed at this point is an explicit calculation for some nuclear system to see how it works , what states are coupled to , and how big the interaction is . in general nuclear structure models are much more complicated than atomic structure models due to the more complicated strong force interaction . we would like to work with empirical strong force models derived from scattering experiments and few - body bound state binding energies . in recent years these models have achieved impressive results @xcite ; however , some of these strong force models involve a fair amount of work to implement . if we go back a few decades we can find simpler versions of strong force models that are easier to work with , and are sufficiently accurate to clarify the issues of interest here . in the computations that follow we will focus on the old hamada - johnston potential model @xcite . without question the simplest compound nucleus which should show the effects of interest is the deuteron , and so we will focus on this system in what follows . in this formulation we have modeled the nucleons as elementary dirac particles . as nucleons are made up of strongly interacting quarks , we know that they are not elementary dirac particles . to do better in the case of coupling with the deuteron , we would require a description in terms of the six constituent quarks . we would expect from such a model a coupling matrix element likely somewhat different from what we calculated in this work . even so , it makes sense here to pursue this simpler deuteron model based on simple dirac nucleons as a step forward in the modeling process . in a recent paper we discussed the derivation of a finite basis approximation for a moving nucleus in the many - particle dirac model which leads to the new coupling that we are interested in . we begin with the ( relativistic ) finite basis model that we obtained . in @xcite we developed finite basis eigenvalue relations in the form @xmath2 where the off - diagonal matrix elements were written as @xmath3 here @xmath4 is the relative coupling matrix element @xmath5 we defined @xmath6 as @xmath7 the notation for the two - body version of the problem is a bit different than what we used for the many - particle problem . it is useful to recast the relative matrix element as @xmath8 the relative part of the off - diagonal matrix element corresponds to the rest frame interaction terms , which might come about from strong force interactions as in the development above for the nonrelativistic deuteron problem . what is new is the coupling with the center of mass momentum @xmath9 that appears in @xmath10 . we are interested in these new matrix elements . in @xcite we discussed the reduction of the new interaction matrix element to the nonrelativistic case . the results can be expressed as @xmath11 @xmath12 ( { \mbox{\boldmath$\sigma$}}_j \cdot c \hat{{\mbox{\boldmath$\pi$}}}_j ) \bigg | \phi_i \bigg \rangle\ ] ] @xmath13 ( { \mbox{\boldmath$\sigma$}}_j \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle \bigg ] \ ] ] as above , this is written for the many - particle problem , and we wish to recast it in terms of the two - body problem ; we may write @xmath14 @xmath15 ( { \mbox{\boldmath$\sigma$}}_1 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle\ ] ] @xmath16 ( { \mbox{\boldmath$\sigma$}}_1 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle \bigg ] \ ] ] @xmath17 ( { \mbox{\boldmath$\sigma$}}_2 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle\ ] ] @xmath18 ( { \mbox{\boldmath$\sigma$}}_2 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle \bigg ] \ ] ] it is possible to split up this new interaction term into a contribution that takes the nucleon masses to be equal , and a small correction term that depends on the difference between the nucleon masses . in what follows our focus will be on the larger equal mass terms , which is equivalent to making an equal mass approximation . in this case we may write @xmath19 ( { \mbox{\boldmath$\sigma$}}_1 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ ] ] @xmath20 ( { \mbox{\boldmath$\sigma$}}_1 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle \bigg ] \ ] ] @xmath21 ( { \mbox{\boldmath$\sigma$}}_2 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle\ ] ] @xmath22 ( { \mbox{\boldmath$\sigma$}}_2 \cdot c \hat{\bf p } ) \bigg | \phi_i \bigg \rangle \bigg ] \ ] ] where we have assumed that @xmath23 in this approximation there is no longer an explicit dependence on the state energy @xmath24 . it is possible to develop a nonrelativistic approximation using @xmath25 in this case , a finite basis model that includes center of mass dynamics to lowest order could be developed starting from a nonrelativistic hamiltonian of the form @xmath26 where @xmath27 is an operator that returns the rest mass energy of the nuclear state , and where @xmath28 in the equal mass approximation is @xmath29 @xmath30\ ] ] we know from the literature that the deuteron at rest can be modeled using a triplet s and triplet d state , since the tensor interaction mixes the two . since the kinetic energy and potential terms preserve @xmath31 and @xmath32 , each of the triplet s states mixes with a triplet d state that has the same @xmath31 and @xmath32 . the new interaction term causes these states to mix with singlet p states . in general , the new term does not preserve @xmath32 , so that we would require a finite basis approximation that distinguishes the different sublevels . however , it is possible to focus on a special case of the new interaction which does preserve @xmath32 . this occurs if we restrict our attention to @xmath34 we find in this case that mixing occurs for @xmath35 , but not for @xmath36 . in response , we might write @xmath37 with the understanding that @xmath38 nuclear state construction is usually carried out in the isospin scheme , with antisymmetry enforced through the application of the generalized pauli principle . the two - body problem is particularly simple in this regard , with spin , isospin and spatial components restricted to being either symmetric @xmath39 or antisymmetric @xmath40 ; we may write for the three states @xmath41 @xmath42 @xmath43 the antisymmetric spin and isospin terms @xmath44 and @xmath45 are singlets , and the symmetric spin and isospin terms @xmath46 and @xmath47 are triplets . the s state is a triplet spin state , so we may write it as @xmath48 @xmath49 the @xmath50 are spherical harmonics ; we choose @xmath51 and @xmath52 since we are working with an s state . the @xmath53 are spin functions for the neutron and proton spins ; the @xmath54 are isospin functions , and we have used an isospin singlet function here . we can develop a d state by applying the tensor @xmath55 operator on an s state . this approach was used early on as a convenient way of generating few - body wavefunctions for variational calculations in nuclear physics . we may write @xmath56\ ] ] this construction is convenient since @xmath57 - 2 \psi_{^3d}\ ] ] the singlet p state for a particular calculation can be specified using @xmath58 @xmath59 including an @xmath60 here leads to real coupling coefficients in what follows . we can evaluate the normalization integral for these states simply ; we write @xmath61 @xmath62 we are interested in developing coupled channel equations that include the new interaction . for the problem in the rest frame , this is most easily accomplished by developing an expression for the total energy and then using the variational principle . we can use the same basic approach here for the moving frame version of the problem . we begin with @xmath63 @xmath64 @xmath65 @xmath66 we can evaluate the diagonal matrix elements directly using mathematica to obtain @xmath67 u(r ) dr\ ] ] @xmath68 v(r)dr\ ] ] @xmath69 w(r ) dr\ ] ] in the case of the hamada - johnston potential , there occur off - diagonal matrix elements between the triplet s and singlet d states , which are given by @xmath70 the superscript @xmath71 in the associated potentials here is connected with the even triplet channel , since the hamada - johnston potentials are fit for the different channels separately . for the off - diagonal matrix elements of the new interaction , we have used mathematica to compute @xmath72 @xmath73 u(r ) dr\ ] ] @xmath74 dr\ ] ] @xmath75 u(r ) dr\ ] ] @xmath76 dr\ ] ] @xmath77 dr \bigg \rbrace\ ] ] @xmath78 @xmath79 v(r ) dr\ ] ] @xmath80 dr\ ] ] @xmath81 v(r ) dr\ ] ] @xmath82 dr\ ] ] @xmath83 v(r ) dr\ ] ] @xmath84 dr\ ] ] @xmath85 v(r ) dr \bigg \rbrace\ ] ] @xmath86 @xmath87 w(r ) dr\ ] ] @xmath88 dr\ ] ] @xmath89 w(r ) dr\ ] ] @xmath90 dr\ ] ] @xmath91 w(r ) dr\ ] ] @xmath92 dr\ ] ] @xmath93 w(r ) dr \bigg \rbrace\ ] ] @xmath94 @xmath95 2(r ) dr\ ] ] @xmath96 dr\ ] ] @xmath97 w(r ) dr\ ] ] @xmath98 dr\ ] ] @xmath99 v(r ) dr\ ] ] @xmath100 dr\ ] ] @xmath101 v(r ) dr \bigg \rbrace\ ] ] we have specified a finite basis problem with three channels , which would produce three complicated coupled - channeled equations if we decided to treat the different basis states on equal footing . however , since the momentum @xmath9 that we are interested in for applications of this model is small , the triplet s and d channels are then best considered to constitute the unperturbed deuteron problem , and the singlet p channel will contain the weak response of the deuteron to the @xmath102 perturbation . in this case , it seems appropriate to develop the coupled triplet s and d channels consistent with the rest frame deuteron problem . once the associated wavefunctions are known , then we can use them to approximate the occupation of the singlet p channel . given the approach outlined above , we can optimize the channel wavefunctions @xmath103 and @xmath104 by minimizing the rest frame energy @xmath105 @xmath106 u(r ) dr\ ] ] @xmath107 v(r)dr\ ] ] @xmath108 the minimization of this rest frame energy leads to the constraints @xmath109 u(r ) + \bigg [ - 3\sqrt{8 } v_{t}^{et}(r ) \bigg ] v(r)\ ] ] @xmath110 v(r)\ ] ] @xmath111 u(r)\ ] ] where @xmath112 is the relative energy . we recognize these as the rarita - schwinger equations based on the hamada - johnston potential model . we have solved the rarita - schwinger equations to obtain the channel wavefunctions plotted in figure [ deuteron1 ] . the triplet s channel wavefunction @xmath103 is larger and extends out to a relatively large radial separation , and the triplet d channel wavefunction @xmath104 is smaller and localized to much smaller radial separation . we can see the effect of the hard core potential in the zero boundary condition at the cut off radius . = 4.00 in = 3.200 in [ t ] in the perturbation theory approach outlined above , we can approximate the occupation of the singlet p channel in terms of known triple s and d channel wavefunctions . the associated constraint on the channel wavefunction can be written as @xmath113 w(r ) ~=~ m_j \left ( { 1 \over 2 mc^2 } \right ) \left ( { 1 \over 2 m_{av } c^2 } \right ) ( \hbar c ) ( c \hat{p}_z ) \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ \ ] ] @xmath114 u(r ) + 12 \sqrt{3 } v_t^{et}(r ) \left [ { d \over dr } u(r ) + { u(r ) \over r } \right ] + 8 \sqrt{3 } \left [ { d \over dr } v_t^{et}(r ) \right ] u(r)\ ] ] @xmath115 - 2 \sqrt{3 } v_{ll}^{et}(r ) \left [ { d \over dr } u(r ) - { u(r ) \over r } \right ] \bigg \rbrace\ ] ] @xmath116 v(r)\ ] ] @xmath117 + 4 \sqrt{6 } \left [ { d \over dr } v_t^{et}(r ) \right ] v(r ) - \sqrt{8 \over 3 } v_{ls}^{et}(r ) \left [ { d \over dr } v(r ) + 2{v(r ) \over r } \right ] \ ] ] @xmath118 v(r ) - 2 \sqrt{6 } v_{ll}^{et}(r ) \left [ { d \over dr } v(r ) + 2{v(r ) \over r } \right ] - \sqrt{6 } \left [ { d \over dr } v_{ll}^{et}(r ) \right ] v(r ) \bigg \rbrace\ ] ] we have solved this equation numerically assuming that @xmath103 and @xmath104 are fixed solutions of the rarita - schwinger equations , and the resulting normalized solution for @xmath119 is shown in figure [ singletp ] . = 4.00 in = 3.200 in [ t ] from the computation outlined above we can derive an equivalent two - level system model in the form @xmath120 we compute @xmath121 @xmath122 @xmath123 the off - diagonal coupling matrix elements are somewhat smaller than we were hoping for , and future work will be needed to understand if this coupling is sufficiently large to account for experimental results . in addition , we have found that these off - diagonal matrix element depend on the nuclear spin , which suggests that the system may respond to net spin alignment . we recently proposed a new fundamental hamiltonian for condensed matter lattice problems that includes coupling to nuclear internal degrees of freedom . from our perspective this new coupling seems to be what is needed to account for the excess heat effect in the fleischmann - pons experiment . what has been needed in order to evaluate the models that result is an estimate for the coupling matrix element . the development of an estimate for this matrix element is challenging for a variety of reasons . we have presumed in the derivation of the fundamental hamiltonian that it is sufficient to model the nucleons as elementary dirac particles . however , we know that nucleons are composite particles made up of quarks and gluons , and that it is unlikely that using a dirac model as we have done is going to give accurate results . to do better we probably need to go back and develop a better fundamental hamiltonian based on quarks and electrons . if it is possible to obtain reasonable nucleon models from empirical potentials , then we may be able to develop a better estimate for the deuteron coupling matrix element . working directly with bound state qcd at this stage does not seem to be an attractive option . once we have decided on the simpler model that adopts an elementary dirac particle model for nucleons , then it is an issue of whether to use a relativistic or nonrelativistic model , and further it is an issue of what potential to use . since these computations involve a fair amount of work , it seemed sensible to adopt a nonrelativistic model since it is simpler , and to work with an older relatively simple nuclear model . the hamada - johnston potential fits the bill in this regard , as it is sufficiently simple that we are able to complete a calculation in relatively short order . perhaps the most work in this computation was the evaluation of the spin , isospin , and angular momentum algebra ; for this we relied on brute force mathematica calculations . in the end , we have developed a model for the coupling between the different nuclear spin states of the ground state deuteron and lattice - induced coupling to a highly - excited singlet p virtual state . the energy of this virtual state is about 125 mev in this model , which is consistent with our expectations . the coupling matrix element fell short of what we had hoped for by about an order of magnitude . we will need to clarify in future calculations if this is sufficiently large to be relevant to experimental results . the coupling matrix element in this model is proportional to @xmath32 , which is interesting in connection with the reported dependence of excess heat on the strength of an applied magnetic field . since the matrix element is proportional to @xmath32 , there is the potential for a larger coupling if the deuteron spins can be aligned . we are interested in pursuing this possibility in future work . 0 a. b. karabut and s. a. kolomeychenko , `` experiments characterizing the x - ray emission from a solid - state cathode using a high - current glow discharge , '' _ condensed matter nuclear science , proc . iccf10 _ , edited by p. l. hagelstein and s. r. chubb , p. 585 ( 2003 ) . a. b. karabut , `` research into characteristics of x - ray emission laser beams from solid state cathode medium of high - current glow discharge , '' _ condensed matter nuclear science , proc . iccf11 _ , edited by j. p. biberian , p. 253 ( 2004 ) . a. b. karabut , `` study of energetic and temporal characteristics of x - ray emission from solid state cathode medium of high - current glow discharge , '' _ condensed matter nuclear science , proc . iccf12 _ , edited by a. takahashi , k .- ota , and y. iwamura , p. 344 ( 2005 ) . a. b. karabut , e. a. karabut , p. l. hagelstein , `` spectral and temporal characteristics of x - ray emission from metal electrodes in a high - current glow discharge , '' _ j. cond . mat . ( in press ) . h. kamada , a. nogga , w. glckle , e. hiyama , m. kamimura , k. varga , y. suzuki , m. viviani , a. kievsky , and s. rosati , `` benchmark test calculation of a four - nucleon bound state , '' _ phys . c _ * 64 * ( 2001 ) 044001 .

we recently put forth a new fundamental lattice hamiltonian based on an underlying picture of electrons and deuterons as elementary dirac particles . within this model there appears a term in which lattice vibrations are coupled to internal nuclear transitions . this is interesting as it has the potential to provide a connection between experiment and models that describe coherent energy transfer between two - level systems and an oscillator . in this work we describe a calculation of the coupling matrix element in the case of the deuteron based on the old empirical hamada - johnston model for the nucleon - nucleon interaction . the triplet s and d states of the the deuteron in the rest frame couples to a singlet p state through this new interaction . the singlet p state in this calculation is a virtual state with an energy of 125 mev , and a coupling matrix element for @xmath0-directed motion given by @xmath1 .

black hole demographics has become a common and important ingredient of cosmological studies in recent years . one reason is the indication that black holes and their activity play a crucial role in the formation and evolution of galaxies ( granato 2004 ; springel , di matteo , & hernquist 2005 ; somerville 2008 ) and galaxy clusters ( mcnamara & nulsen 2007 ) . to fully understand the impact of black holes on mass structures and their evolution we need to understand much better how they form , grow , and interact with their surroundings . a first step toward this goal is to take inventory of the population of supermassive black holes across the history of the universe . unfortunately , it is not possible to study supermassive black holes in all types of galaxies with the same ( mass estimation ) method ( cf . magorrian 1998 ; vestergaard 2004b , 2009 ; peterson 2004 ) , due to the varying physical conditions of their host galaxies , the varying activity level of the black holes themselves , and the large range of physical distances to the black hole host galaxies . due to their faintness and the small angular extent of the central region that needs to be studied , quiescent or weakly active black holes can typically not be well studied beyond the local neighborhood of a few hundred mpc ( ferrarese 2003 ) . since actively accreting black holes power the luminous quasars that are observable across the universe ( fan 2006 ) , quasars offers a convenient way to trace the black hole population in the distant universe . the goal is that the combination of studies of active black holes with empirical and theoretical insight on the relationship between active and quiescent black holes and between obscured and unobscured black holes will eventually lead to realistic representations of the true and complete black hole population . we can study the population of actively accreting supermassive black holes by studying the large catalogs of quasars and active galaxies obtained through the numerous large , extensive quasar and agn uv and optical surveys that have been made since the discovery of quasars [ the multi - color survey of stellar objects by koo & kron ( 1982 ) , palomar - green survey ( schmidt & green 1983 ) , uk - schmidt telescope survey ( kibblewhite 1984 ; hewett 2001 ) , canada - france - hawaii telescope survey ( crampton , cowley , & hartwick 1987 ) , cfa redshift survey ( huchra & burg 1992 ) , palomar transit grism survey ( schmidt , schneider , & gunn 1995 ) , 2-degree - field survey ( 2df ; smith 2005 ) , and sloan digital sky survey ( sdss ; york 2000 ) ] . notably , any survey with its own set of selection criteria will tend to preferentially select either for or against objects with particular spectral or broad band properties . therefore , by studying only quasars studied by a single selection method there is a risk that we may limit ourselves to only part of the actual underlying black hole population . we aim to minimize this potential issue by including in our ongoing study of the black hole population and the black hole mass functions several quasar samples . the current work focuses on the mass functions based on the following samples : the bright quasar survey ( bqs ; schmidt & green 1983 ) , the large bright quasar survey ( lbqs ; hewett , foltz , & chaffee 1995 ) , and the color - selected sample from the fall equatorial stripe ( fan 2001a ) of the sdss . the bqs , lbqs , and the sdss color - selected samples are each based on different selection criteria , namely uv excess , spectral shape on objective prism plates , and broad - band colors , respectively . especially , the bqs and the lbqs are each complementary to the sdss dr3 quasar selection ( richards 2002 ) . for example , the sdss selection probability decreases significantly for quasars at redshifts of about 2.8 to 3.2 because the colors of quasars at these redshifts coincide with the stellar locus in the selected color spaces ( richards 2006 ) . this limits the usefulness of the dr3 quasar black hole mass function ( vestergaard 2008 ) at and near this redshift range which is particularly important since this is the epoch at which the quasar space density peaks ( osmer 1982 ; warren , hewett , & osmer 1994 ; schmidt 1995 ; fan 2001a , 2001b ) . the different selection criterion of the lbqs can instead help shed light on the mass distribution at the affected redshift range , especially given the large size of this quasar sample ( 1067 quasars ) and its wide redshift range . the favorable properties of the somewhat smaller bqs sample are that it is selected over a very large sky area ( 10700 square degrees ) and includes the brightest quasars in the nearby universe . therefore , the bqs is suitable for anchoring the bright end of the luminosity function and the high mass end of the black hole mass function in the nearby universe . also , the colors of the bqs quasars are not typical of sdss quasars ( jester 2005 ) and the bqs thus makes a different contribution to our insight on black hole mass distribution than the sdss alone can provide . the value of the sdss color - selected sample studied here is that it is a well - defined , complete ( to within the color - selection criteria , the survey area , and the flux density limits ) and homogeneous quasar sample at redshift [email protected] that is highly suitable for statistical studies . this redshift range is beyond that of the lbqs ( @xmath103.0 for the mass functions ) and is where the number statistics of the sdss dr3 mass function quasar sample is lower . the availability of a well - defined selection function for this color - selected sample ( fan 2001a ) therefore gives us an excellent opportunity to determine the black hole mass function for a homogeneous and well - defined sample at high redshift which thus renders an additional opportunity for constraining the black hole mass distribution at earlier epochs . the added values of the samples studied here are that luminosity functions have been determined for both the lbqs ( boyle 2000 ) and the sdss color - selected samples ( fan 2001a ) . potentially , by combining the luminosity and black hole mass functions for the same quasar samples we can break the degeneracies ( related in part to the unknown mass dependency of the radiative efficiency and mass accretion rate ) that limit the use of the luminosity functions alone ( wyithe & radmanabhan 2006 ) . by combining the three quasar samples studied here with the sdss dr3 quasar sample for which the luminosity and mass functions have already been determined ( richards 2006 ; vestergaard 2008 ) we anticipate to gain a better understanding of the true underlying black hole mass distribution than is possible by studying either of these samples alone . in this work we present the black hole mass functions of the bqs , lbqs , and the sdss color - selected quasar samples which collectively cover the entire redshift range up to @xmath11 and contain nearly 1200 sources . we adopt the most recently calibrated mass scaling relations utilizing broad line widths and continuum luminosities ( vestergaard & peterson 2006 ; vestergaard 2008 and references therein ) in cases where the more robust reverberation mapping mass determinations ( peterson 2004 ) are not available . although the mass estimates based on scaling relations are less robust than the reverberation mapping masses and are potentially prone to systematic uncertainties ( krolik 2001 ; richards 2002 ; vestergaard 2004a , 2004b , 2009 ) they perform surprisingly well considering the circumstances ( vestergaard 2004b , 2009 ; vestergaard & peterson 2006 ; marconi 2008 ) . in fact , there is suggestive evidence based on h@xmath8 data that scaling relations can be improved to yield mass estimates that are within a factor 1.6 ( or 0.2dex ) of the reverberation masses when radiation pressure on the broad line gas is taken into account ( marconi 2008 ) . this uncertainty rivals the scatter of the quiescent black holes in the m_bh @xmath1@xmath12 relationship ( @xmath13dex ; tremaine 2002 ) . source inclination is known to affect the velocity dispersion of the broad line region as measured using the widths of broad optical and uv emission lines ( wills & browne 1986 ; vestergaard , wilkes , & barthel 2000 ) . in fact , source inclination is expected to be one of the factors that account for at least part of the scatter in the m_bh @xmath1 values around the m_bh @xmath1@xmath12 relationship ( although the inclination is not trivially connected to object location relative to the m_bh @xmath1@xmath12 relationship ; collin 2006 ) and which at present limits the accuracy of mass determinations of active black holes to some degree . considerations have also been made on the relative usefulness of the various line widths ( the line dispersion versus the fwhm width ) ( peterson 2004 ; denney 2008 ) and a correction scheme was suggested ( collin 2006 ) to correct mass estimates based on fwhm measurements of h@xmath8 to mass estimates based on the line dispersion values which are preferred for the high - quality reverberation mapping database ( peterson 2004 ) . unfortunately , for neither of these effects ( radiation pressure , inclination , and the potential inadequacies of the fwhm parameter ) are the influences on our determination of black hole masses understood or parametrized well enough that corrections can be applied to our mass estimates for all three emission lines , h@xmath8 , mgii , and civ , used here . also , for this study we need our entire data base to be coherent and homogeneously analyzed and all mass estimates to be based on similar assumptions . for these reasons , we make no attempt to correct the mass estimates at this time . the mass functions presented here will be analyzed further in relation to the black hole mass functions of the sdss dr3 quasar sample ( vestergaard 2008 ) for the purpose of extracting the true underlying mass distribution using the statistical methods introduced and discussed for the luminosity function by kelly , fan , & vestergaard ( 2008a ) and for the mass function by kelly , vestergaard & fan ( 2009 ) . if , at that time , we are capable of making corrections for any of the effects outlined earlier such that the mass estimates or the associated error distribution change significantly , the mass functions will be updated accordingly . a cosmology of h@xmath14 = 70 @xmath15 , @xmath16 = 0.7 , and @xmath17 = 0.3 is used throughout . the three quasar samples for which we determine the black hole mass functions are summarized in the following sections , in order of their redshift coverage . as outlined in section 3 , the black hole mass estimates are based on measurements of the widths of the h@xmath8 , mgii , and civ profiles and nuclear continuum luminosities . these spectral measurements are therefore also summarized in the following . the bright quasar survey ( bqs ; schmidt & green 1983 ) is a subset of the quasars discovered in the palomar - green survey of uv excess sources ( @xmath18 ; green , schmidt , & liebert 1986 ) undertaken in 1973 @xmath19 1974 using the 18 inch palomar schmidt telescope with classification spectroscopy obtained with the hale 5 m telescope . this survey was done using photographic @xmath20 plates that were later digitized . it has an impressive area coverage of 10714 deg@xmath21 and a flux limit of about @xmath22 mag . here , we include the 87 objects at @xmath10 0.5 for which boroson & green ( 1992 ) present spectroscopic data . we use the spectral measurements ( line widths and continuum luminosities ) adopted by vestergaard & peterson ( 2006 ) where the details of the data are also described . the mass distribution of the bqs sample was previously studied by vestergaard ( 2004a ) . since that work , the mass scaling relationships have been updated owing to improvements made to the reverberation mapping database ( peterson 2004 ) . therefore , for the few bqs quasars for which robust black hole mass measurements have been obtained using reverberation mapping ( peterson 2004 ) , we adopt these mass determinations in our analysis with exception of pg2130@xmath23099 for which the mass has recently been further improved ( grier 2008 ) . for the remaining sources we adopt the mass estimates based on the most recently updated mass scaling relationships . these mass values are listed in table 7 of vestergaard & peterson ( 2006 ) . the large bright quasar survey ( lbqs ; foltz 1987 ; hewett 2001 ) is the largest published spectroscopic survey of optically selected quasars at bright ( @xmath24 mag ) apparent magnitudes as of 1995 . it consists of 1067 quasars located at redshifts between 0.2 and 3.4 and it covers an effective area of 453.8 deg@xmath21 on the sky . the quasar candidates were selected from the automated plate measuring machine scans of the united kingdom schmidt telescope direct and objective - prism plates based on their spectral energy distribution shapes on these plates . the details of the survey are published in a series of papers and most recently summarized by hewett ( 2001 ) who also present an updated account of the survey completeness as a function of redshift . spectroscopic observations were obtained in the late 1980 s at a resolution of 6 @xmath19 10 using the 4.5 m multi mirror telescope ( mmt ) with a wavelength range of @xmath25@xmath253300 @xmath19 7500 or with the las campanas 2.5 m du pont telescope with a wavelength range of @xmath25@xmath253400 @xmath19 7000 ( morris 1991 ) . in these configurations the h@xmath8 , mgii , and civ emission lines are observed in the spectra of quasars at redshifts between 0.2 to about 0.4 @xmath19 0.5 , between 0.2 to 1.5 @xmath19 1.65 , and between 1.2 @xmath19 1.26 to a redshift of about 3.4 , respectively . the presence of two different spectral wavelength ranges should not affect our results since each spectrum will contain at least one of the h@xmath8 , mgii , and civ emission lines for the redshift range from 0.2 to 3.0 . forster ( 2001 ) performed automated spectral modeling of the lbqs spectra and , in particular , present line width measurements for 993 of the 1067 quasars of the full lbqs sample . the remaining quasars were not modeled because of strong broad and narrow absorption in the ly @xmath26 and civ emission lines . the spectra were modeled with a powerlaw continuum component , uv and optical feii emission templates ( vestergaard & wilkes 2001 ; boroson & green 1992 ) , and gaussian emission and absorption line functions . most of the broad emission lines were modeled with a single gaussian profile from which the fwhm was obtained . a small fraction of the spectra are of high enough quality to allow two gaussian functions to be fitted to the lines . for the single gaussian models we adopted the measurements of the fwhm and uncertainties tabulated by forster ( their table 5 ) . to determine the fwhm of the emission lines modeled with multiple gaussian components we first regenerated the modeled line profile from the tabulated model parameters of all the components . then we measured the fwhm of the regenerated profile ( i.e. , as the full width at the half maximum peak value ) . the measurement uncertainties of the fwhm in this case were obtained by a suitable weighting of the uncertainties in the tabulated measurements of the individual gaussian components . these weights were estimated as the weights to be applied to the fwhm measurements of the individual gaussian components so to obtain the fwhm of the sum of the components ( determined from the regenerated line profile , described above ) . for each of the broad emission lines ( h@xmath8 , mgii , civ ) a separate weight was determined . we note that only a few quasars had emission lines modeled with multiple gaussian components : 7 h@xmath8 , 118 mgii , and 79 civ lines , respectively ( out of a total of 148 h@xmath8 , 677 mgii , and 488 civ profiles , respectively ) . for profiles for which forster fixed the line width ( no uncertainties were estimated ) we adopt a typical measurement error of 10% ( brotherton 1996 ) . because the lbqs spectra are not flux calibrated , we determined the nuclear monochromatic continuum luminosities not from the spectra but from the survey @xmath20 magnitudes . given the modest quality of the spectra we visually inspected the spectra of quasars with fwhm measurements listed by forster to be either below 2000 ^-1 kms@xmath27 or above 12,000 ^-1 kms@xmath27 . the reason is that very small and very large line widths measurements are more prone to be spurious in spectra of modest quality and they can significantly affect the mass functions owing to the relatively smaller number of such extreme objects . the fact that the forster profile measurements above 12,000 ^-1 kms@xmath27 tend to have large uncertainties confirm our general suspicion . most of the very broad line profile fits of forster are typically listed for profiles of quite poor quality ( with a few having strong absorption in addition ) ; in a couple of cases , the fitting must have gone bad . we found all civ profiles with fwhm @xmath28 17,000 ^ -1 kms@xmath27 had to be discarded for these reasons and a few profiles of about 12,500 @xmath19 14,000 ^ -1 kms@xmath27 have too noisy profiles to be useful . in addition , most of the mgii fwhm measurements listed to be above 12,000 ^ -1 kms@xmath27 are based on very noisy , unreliable data ; these measurements were discarded from further analysis . for the profiles listed to have fwhm @xmath29 2000 ^ -1 kms@xmath27 , we find that for some of the h@xmath8 and mgii profiles the single ( or the second ) gaussian component was fitted to noise spikes or what appears to be a strong contribution from the narrow line region ( judging from the strength of the [ oiii ] @xmath255007 line , when available ) which gives the appearance of intrinsically very narrow broad - line profiles . for these profiles , the narrow component was discarded and the broad component alone , if available , was used to characterize the profile . for profiles fitted with only a single gaussian component , the emission line was discarded from further analysis . a total of 6 h@xmath8 and 7 mgii narrow profiles were discarded . after this filtering of the data with the most uncertain measurements , we are left with measurements of a total of 139 h@xmath8 , 654 mgii , and 480 civ profiles ; a total of 134 quasars have measurements of both h@xmath8 and mgii , while 161 quasars have both mgii and civ measurements . of the original 993 quasars analyzed by forster we were able to estimate the black hole masses for 978 quasars . the adopted fwhm values and the continuum luminosities used for the mass estimates are listed in table [ lbqs_fwl.tab ] . the black hole masses , bolometric luminosities , and eddington luminosity ratios for the lbqs are listed in table [ lbqs_ml.tab ] . table [ lbqs_lz_missingq.tab ] lists the basic properties ( name , redshift , @xmath20 magnitudes , and luminosity ) of the lbqs quasars without mass estimates . the determination of the m_bh @xmath1 values are described in section 3 . fan ( 2001a ) present a well - defined color - selected sample of 38 quasars at 3.6 @xmath30 5.0 from a 182 deg@xmath21 field in the sdss fall equatorial stripe for which they determine the quasar luminosity function . the quasars were selected based on @xmath31 and @xmath32 colors to be complete in the survey area down to @xmath33 = 20 mag . the continuum luminosities measured from the spectra were recalibrated to the dereddened ab(1450 ) magnitudes ( see vestergaard 2004a ; see fan 2001a for details on these data ) . for four of the 38 quasars we are unable to obtain black hole mass estimates , because the ( discovery ) spectrum did not include the civ emission line ( [email protected] , [email protected] , [email protected] ) or the quality of the spectrum was too poor to measure fwhm(civ ) reasonably reliably ( [email protected] ) . for quasar [email protected] another spectrum is available in the sdss archive , but we were unable to reliably measure spectral parameters for the mass estimate from that spectrum . fan originally presented 39 quasars in this sample , but one source ( [email protected] ) has since been reclassified as a star ; the spectrum is also missing from the discovery papers ( fan 2001a ; schneider 2001 ) and the sdss data release 6 archives . this quasar sample was also included in the study by vestergaard ( 2004a ) on the distributions of black hole mass and eddington luminosity ratios for distant quasars . since improved mass estimation relations have been published more recently ( vestergaard & peterson 2006 ) , we redetermine the black hole masses for this sample . we adopt the measurements of fwhm(civ ) and 1350 continuum luminosities obtained and analyzed by vestergaard ( 2004a ) . the fwhm and continuum luminosity measurements used for the mass estimates of the sdss color - selected sample are listed in table [ sdss_fwl.tab ] . the black hole masses , bolometric luminosities , and eddington luminosity ratios for these quasars are listed in table [ sdss_ml.tab ] . the computations are described in the next section . we determine black hole mass estimates using the socalled mass scaling relationships which utilize the widths of the broad emission lines and the nuclear continuum luminosities ( wandel , peterson , & malkan 1999 ; vestergaard 2002 , 2004b , 2009 ; mclure & jarvis 2002 ; warner 2003 ; see also dietrich & hamann 2004 ) . this method is preferred for several reasons ( see also vestergaard 2009 ) . only a couple of methods are applicable both to active galaxies in the nearby universe as well as the most distant quasars . of these , mass scaling relationships have some of the lowest associated uncertainties ( vestergaard 2004b ) which can be further improved upon in the future ( marconi 2008 ) . and quite importantly , these relationships are anchored in robust black hole mass determinations of low redshift active nuclei based on the reverberation mapping method ( blandford & mckee 1982 ; peterson 1993 ) which have recently been updated following a homogeneous reanalysis of the available reverberation database ( peterson 2004 ; onken 2004 ) . moreover , the evidence in favor of our application of this method to more distant sources is quite strong ( see vestergaard 2004b , 2009 , and references therein ) . black hole mass estimates can be obtained using one or more of the h@xmath8 , mgii , or civ emission lines . for mass estimates based on h@xmath8 and civ we use equations ( 5 ) and ( 7 ) , respectively , presented by vestergaard & peterson ( 2006 ) ; these relationships are calibrated to the most recently updated robust reverberation mapping mass determinations ( peterson 2004 ; onken 2004 ) . at present , there is no published relationship for the mgii emission line which is ( re)calibrated to the improved reverberation masses and also intercalibrated to the mass estimates based on the civ emission line0.36 and do not include a relation for civ . we remind the reader that our ultimate intent is to compare and combine the mass functions presented here with those published by vestergaard ( 2008 ) on the sdss dr3 quasar survey . for this particular purpose we need to use the _ exact same _ mass estimation relationships for all the individual mass functions . ] . we therefore obtained a new relationship for mgii using several thousand high - quality spectra from the sdss dr3 quasar sample ( schneider 2005 ) . this relationship has been applied to the subset of the dr3 quasar sample used to establish the luminosity ( richards 2006 ) and black hole mass ( vestergaard 2008 ) functions . for completeness , we here present the relationships used . we obtained a relation for each of four monochromatic continuum luminosities because the 3000 luminosity may not always be accurately determined , sitting below the strong feii line emission at those wavelengths . we use the relation pertaining to the nuclear monochromatic continuum luminosity that can be best and most accurately measured in the observed spectrum . we refrain from extrapolating or adopting an assumed continuum slope in any of our work . for a given wavelength , @xmath25 , the black hole mass based on mgii was obtained according to : @xmath34 ^ 2 \left[\frac{\lambda l_{\lambda}}{10^{44 } \,erg / s}\right]^{0.5}\ ] ] where @xmath35 is 6.72 , 6.79 , 6.86 , and 6.96 for @xmath251350 , @xmath252100 , @xmath253000 , and @xmath255100 , respectively . the 1@xmath36 scatter in the absolute zero - points , @xmath37 , is 0.55dex which includes the factor @xmath42.9 uncertainties of the reverberation mapping masses to which these mass estimation relations are anchored [ see e.g. , vestergaard & peterson ( 2006 ) and onken ( 2004 ) for details ] . on average , these relations are consistent to within about 0.1dex of the h@xmath8 and civ mass estimates . the relationships will be discussed further in a forthcoming paper ( m. vestergaard et al . , in preparation ) . a few of the bqs sources have been targeted by reverberation mapping . for those sources , we adopt the reverberation mass listed by peterson ( 2004 ) . since the objects in the bqs are all located at @xmath38 we use the h@xmath8 relationship to estimate the black hole mass for the remaining sources in this sample . those mass estimates are listed in table 7 of vestergaard & peterson ( 2006 ) and by grier ( 2008 ) for pg2130@xmath23099 . the quasars in the lbqs span a large range of redshifts and therefore we applied all three emission line relations as follows . for any given source for which the fwhm of any of the three emission lines ( h@xmath8 , mgii , civ ) could be reliably measured we determined an estimate of the mass based on each of these emission lines . if more than one emission line estimate is available for a given quasar , the final mass estimate of that source was determined as the weighted average of the available individual mass estimates . the adopted weights are the inverse variance determined from the propagated measurement errors . therefore , for redshifts between 0.2 and 0.66 the mass estimate for each object is based on both the h@xmath8 and mgii emission lines while for redshifts between 1.04 and 1.71 the mass is based on both the mgii and civ lines . the black hole mass estimates for the lbqs are listed in table [ lbqs_ml.tab ] . the quasars in the sdss color - selected sample all reside at redshifts for which only the civ emission line can be observed using optical spectroscopy . we therefore use equation ( 7 ) of vestergaard & peterson ( 2006 ) to estimate the black hole masses for this sample . the mass values are tabulated in table [ sdss_ml.tab ] . the distribution of ( bolometric ) luminosities and black hole masses with redshift is shown for all three samples in figures [ lzfig ] and [ mlolzfig ] , respectively . the bolometric luminosities , @xmath39 , are obtained for the lbqs quasars by scaling monochromatic continuum luminosities at 1350 , 2100 , 3000 , and 5100 with a constant ( average ) bolometric correction factor values in addition to those stemming from assuming a constant bolometric correction given that a range of spectral energy distributions exist of quasars ( elvis 1994 ; kuhn 2001 ; richards 2006 ) . given that a robust adjustment scheme for the bolometric corrections has not been isolated and that the eddington luminosity ratios are not analyzed further here , adopting a more complex correction factor is unnecessary at this time . ] ( of [email protected] , [email protected] , [email protected] , and [email protected] , respectively ) extracted from richards ( 2006 ) . for each quasar the @xmath39 value is determined from the monochromatic luminosity that is as closely centered in its optical observing window . for the sdss color - selected sample , the 1350 continuum luminosity were similarly corrected for an estimate of the @xmath39 values . the bqs bolometric luminosities are adopted from sanders ( 1989 ) with appropriate cosmological corrections applied to conform to the cosmological model used in this work . figures [ lzfig ] and [ mlolzfig ] clearly demonstrate that since we can probe to lower luminosity limits in the nearby universe , we can also probe less massive black holes than at high redshift . while the bqs spans a large range in masses , it does not go very deep ; recall , the limiting magnitude is @xmath41 16.2 mag . the lbqs is also a ` bright ' survey but has a lower flux limit ( fig . [ lzfig ] ) . this is also clear from the relative distributions of black hole masses at low redshifts for which there is some redshift overlap between the lbqs and the bqs ( fig . [ mlolzfig ] ) . the masses of the high-@xmath0 color - selected sample and of the lbqs sources above a redshift of 1 are all of order a billion solar masses . for completeness , we display the redshift distributions of the eddington luminosity ratios , @xmath42 , in figure [ mlolzfig ] . the quasars beyond @xmath43 1 typically have @xmath42 values between @xmath40.1 and @xmath41.0 , while in the nearby universe the surveys can probe sources that accrete at rates down to about 1/100th of the eddington limit . this distribution is consistent with earlier studies ( warner 2003 ; shemmer 2004 ; mclure & dunlop 2004 ; vestergaard 2004 ; kollmeier 2006 ; shen 2008 ; netzer & traktenbrot 2007 ) and results showing that distant quasars are more actively accreting than local quasars and active nuclei ( peterson 2004 ) . it is important to keep in mind , here , that distant quasars also tend to be more luminous ( figure [ lzfig ] ) . also , we show the distribution of fwhm of the emission lines with redshift in figure [ fwzfig ] . there is no significant change in fwhm with redshift with the exception that the sdss quasars do not have the extreme wide lines that some lbqs quasars do . the quasar black hole mass function , @xmath44(m_bh @xmath1,@xmath0 ) , is defined as the comoving space density of black holes per unit black hole mass as a function of black hole mass and redshift . to determine the space density ( the number of black holes per unit comoving volume ) in a given mass and redshift bin , we use the 1/@xmath45 method presented by warren , hewett , & osmer ( 1994 ) , where @xmath45 is the accessible volume , defined by avni & bahcall ( 1980 ) . the mass function and its statistical uncertainty is described as @xmath46^{1/2 } , \label{mf.eq}\end{aligned}\ ] ] respectively . the sum is performed over the objects ( denoted by @xmath47 ) with redshift in the range @xmath48 and @xmath49 and with masses in the range @xmath50 and @xmath51 . we follow the method of fan ( 2001a ) and vestergaard ( 2008 ) of including the selection function of the quasar survey in the computation of the accessible volume : @xmath52 the `` accessible redshift '' , @xmath53 , is the minimum of @xmath54 , the maximum redshift that object @xmath47 can have and still be detected by the survey , and the upper redshift limit in the survey or in the adopted redshift bin , @xmath55 $ ] . the volume element , @xmath56 , is defined by hogg ( 1999 ) for a @xmath57cdm cosmology . for the bqs a constant survey completeness of @xmath58 = 0.88 , determined by schmidt & green ( 1983 ) , was adopted . for the lbqs we adopt the survey completeness as a function of redshift presented by hewett ( 2001 ; their table 7 ) . the selection function for the sdss color - selected sample was presented by fan ( 2001a ) and is a function of both luminosity , redshift , and spectral energy distribution , @xmath59 . we show the black hole mass functions of the three samples as a function of black hole mass in figure [ mfallfig ] . we limit the lbqs mass functions to redshifts below 3 since there are only nine quasars between redshifts 3 and 3.4 ; the lbqs mass functions are thus based on 969 quasars at @xmath60 . the lbqs sample is large enough to allow the mass functions to be determined for a range of redshift bins ; they are shown in whole or in part in the various panels of figure [ mfallfig ] . this also allows us to display the mass functions as a function of redshift for a given black hole mass ( figure [ mfzfig ] ) . the mass functions for the three quasar samples are tabulated in tables [ bqs_mf.tab ] , [ lbqs_mf.tab ] , and [ sdss_mf.tab ] . table [ lbqs_mf_zdep.tab ] tabulates the redshift dependent mass function of the lbqs . for 89 quasars ( or about 8% ) of the complete lbqs sample there is no spectral modeling available and therefore no black hole mass estimates exist for these sources . we refer henceforth to this subset as the ` missing subset ' ( figure [ lmissqfig ] ) . this affects the mass functions to some degree as we will underestimate the space density of certain black hole masses . in an attempt to estimate the most likely mass function for the entire lbqs sample we have used the observed distribution of black hole masses ( for those quasars with reliable spectral modeling ) to determine for each quasar in the missing subset the most likely black hole mass and the reasonably expected mass range around this value . from the observed distribution of lbqs black hole masses we determined the median mass and the standard deviation @xmath36 around this mass value in bins of @xmath0 and @xmath20 of widths @xmath61 = 0.1 and @xmath62 = 0.5 ; each bin has typically between 10 and 45 objects . for each of the 89 sources in the missing subset we used the observed redshift and @xmath20 magnitude ( see fig . [ lmissqfig ] ) to identify three mass values : the most likely mass ( the median mass value of the observed distribution in the appropriate @xmath0 and @xmath20 bin ) and the @xmath401@xmath36 mass values relative thereto , respectively . we then generated three catalogs of 1058 black hole mass estimates at @xmath60 , each consisting of the original 969 black hole mass estimates based on spectral measurements plus for the missing subset either the most likely mass value , the most likely mass @xmath63(m_bh @xmath1 ) , or the most likely mass @xmath64(m_bh @xmath1 ) , respectively . for each of these three mass catalogs we redetermined the mass functions for lbqs . by adopting the same type of mass estimate for each quasar in the missing subset we get a handle on the most likely mass functions and the @xmath65 extremes . notably , this is in practice different from running monto carlo simulations but gives us similar insight on the possible distributions of the mass functions . we show these adjusted mass functions as a function of mass in figure [ lbqs_mf_missq.fig ] . for comparison the mass functions based on only the 969 quasars ( at @xmath60 ) with spectral measurements ( shown in figure [ mfallfig ] ) are also shown . the adjusted mass functions are shown as a function of redshift in figure [ mfzfig ] . our omission ( or inclusion ) of the missing subset clearly has no significant effect on the lbqs mass function . figure [ lbqs_mf_missq.fig ] shows that inclusion of the sources without mass estimates does not change the lbqs mass function ( to within the statistical uncertainties ) for redshifts below 2 . at higher redshifts the missing sources will at one extreme ( m_bh @xmath1(median ) @xmath12 ) tend to increase the peak amplitude of the mass function slightly , and at the other extreme ( m_bh @xmath1(median ) @xmath66 ) the mass function will broaden slightly toward higher masses . the latter has the stronger effect due to the lower number of sources with mass estimates above @xmath67 m _ @xmath3 . however , these variations are all within the statistical uncertainties with exception of the ( m_bh @xmath1 @xmath66 ) mass function which is marginally more deviant . notably , in reality the mass function of the full lbqs sample , that we could obtain if higher quality data were available of the missing subset , is more likely to be between the two extreme cases ; as expected , assigning the median mass of the relevant @xmath0 and @xmath20 bin does not change the mass function . we therefore conclude that we are not making a significant error at this point in excluding the sources with low quality spectra ( the missing subset ) in determining the lbqs black hole mass function . we repeated this exercise for the sdss color - selected sample since for four of the 38 quasars the black hole mass could not be estimated . the effects of assigning m_bh @xmath1(median ) @xmath12(m_bh @xmath1 ) or m_bh @xmath1(median ) @xmath66(m_bh @xmath1 ) to these few sources are shown in figure [ sdss_mf_missq.fig ] . the differences in the mass functions are most noticeable when the extreme mass values of m_bh @xmath1(median ) @xmath66 are adopted : the mass function flattens slightly toward higher mass values . nonetheless , this extreme case mass function is still consistent to within the statistical uncertainties with the `` original '' mass function based on the 34 quasars with spectral measurements ( figure [ mfallfig ] ) . therefore , exclusion of the four sources without mass estimates does not significantly affect the mass function of the sdss color - selected sample . we will reassess this issue of missing black hole masses in future work when analyzing the mass functions from this work with respect to the sdss dr3 mass functions of vestergaard ( 2008 ) . the black hole mass functions for the lbqs and the sdss color - selected samples with these adjustments applied are listed in tables [ lbqs_mfcor.tab ] and [ sdss_mf.tab ] , respectively . the integrated mass density above a certain mass value in each sample is computed by summing the contribution of each individual object with central mass above a progressively increasing mass limit , @xmath68 : @xmath69 figure [ cummdens.fig ] shows the cumulative mass densities for each of the sdss , bqs , and lbqs samples . the mass densities are tabulated in table [ bqs_sdss_cummdens.tab ] for the sdss and bqs samples and in tables [ lbqs_mf.tab ] and [ lbqs_mfcor.tab ] for the lbqs . in figure [ mfall2fig ] we show the distributions of @xmath70 for comparison . this representation is closer to the comoving volume ( number ) density of active black holes as a function of mass and makes the space density differences more apparent . the mass functions for the three quasar samples are shown as a function of black hole mass for different redshift bins in figure [ mfallfig ] . three features are apparent : ( 1 ) the mass functions of the lbqs tend to turn over at the low mass end , ( 2 ) there is a general consistency of the slope of the high mass end between the mass functions in most of the redshift bins , and ( 3 ) the amplitude of the high mass end increases rapidly between mean redshifts of 4 to 2.5 and then decrease again below a redshift of 1 . this is particularly significant for the cumulative mass density ( fig . [ cummdens.fig ] ) . we briefly comment on each feature in the following . the turnover at the low mass end tends to occur when the low mass bins are incompletely populated [ cf . with fig . [ mlolzfig ] ; see also the discussion of the sdss dr3 mass functions by vestergaard ( 2008 ) and the statistical analysis of kelly , vestergaard , & fan ( 2009 ) ] . however , the analysis of the bqs mass function by kelly indicates that part of such turnovers ( at least at low redshift ) are real , suggesting that the number of low mass active black holes does not necessarily stay constant or increase with decreasing mass . we determine the high mass end slopes , @xmath8 , of each mass function in fig . [ mfallfig ] ( _ top panel _ ) following the method of vestergaard ( 2008 ) where @xmath71 . we first discuss the mass functions located at redshifts below 3.5 and thereafter discuss the case at @xmath723.5 . for the lbqs mass functions a typical high end slope were obtained for the redshift bins [ 0.2:0.5 ] , [ 0.5:1.0 ] , [ 1.0:1.5 ] , [ 1.5:2.0 ] , and [ 2.0:3.0 ] , respectively , for mass bins at or above 8.8dex , 9.2dex , 9.6dex , 9.6dex , and 10.0dex , respectively . the limits on the mass bins were adopted to ensure the mass bins are complete or nearly complete . note that given the uncertainties of between 0.4 to 1.4 there are no reasons to believe the apparent flattening of the mass functions toward higher redshifts is real . ] @xmath8 between about @xmath73 to @xmath74 was obtained with uncertainties ranging between 0.4 to 1.4 . for the bqs we find a slope of @xmath75 for mass bins at 8.6dex and above . these slopes are all consistent to within the uncertainties . also , they agree with the slope of @xmath7 observed for the sdss dr3 mass function below redshifts of about 3.8 ( vestergaard 2008 ) . it is interesting to note that the high - end slopes of the sdss dr3 luminosity functions also have values of @xmath7 ( richards 2006 ) . however , for the mass function above redshift 3.5 , i.e. , of the sdss color - selected sample , we see a somewhat flatter slope of @xmath76 , determined for mass bins at 8.6dex and above . the reality of this flatter slope is also evident from figure [ mfallfig ] . vestergaard also reported an apparent flattening of the dr3 mass function slopes at @xmath77 but attributed this to the large errors and small number statistics in those redshift bins . since the color - selected sample is a well - defined and complete sample within the survey area and flux limits , the result for this sample should be robust , suggesting that there is indeed a real trend toward the high - mass black hole distribution to flatten at the highest redshifts . the constancy of the high mass end slope and of the amplitude of the mass function with redshift ( at @xmath78 ) may appear surprising , especially considering the large changes occurring for the evolution of the luminosity function ( boyle 2000 ; richards 2006 ) . for example , the amplitude of the sdss dr3 luminosity function drops more than two orders of magnitude at an absolute magnitude of @xmath1927 between redshifts two and 0.5 . in comparison , the dr3 black hole mass function normalization changes only by a factor of a few and displays a similar constancy of the high mass end slope and amplitude at a wide range of redshifts . while this slope constancy may be real , we note the possibility that the statistical uncertainties in the black hole mass estimates of a factor of a few prohibits us from detecting subtle differences or any cosmic evolution of the high mass end slope . one issue to keep in mind is that contrary to the quasar luminosity , the mass of black holes does not decrease with time . the only way for the black holes to change the shape of the mass functions with cosmic time is by growing in mass or by their activity to decrease sufficiently to drop out of the quasar survey owing to its lower flux limits . the mass function and the cumulative mass density distribution both display a rapid increase in amplitude at the highest masses by a factor of @xmath45 and @xmath410 , respectively , over a period of a giga - year from redshifts 4 ( sdss ) to 2.5 ( lbqs , 2@xmath93 ) . this is an interesting feature , especially considering the slower amplitude decrease below @xmath43 1 ; it is even more evident in the particular representation of the mass function shown in figure [ mfall2fig ] . we are evidently directly seeing the population of massive black holes build up at these epochs as the density of actively accreting ( massive ) black holes rises rapidly toward lower redshift . this is also consistent with the observed rise in the quasar space density at these redshifts ( osmer 1982 ; schmidt 1995 ; warren 1994 ; fan 2001b ) and the relatively high eddington luminosity ratios observed for the sdss color - selected sample ( fig . [ mlolzfig ] ) . we note that the space density information revealed by the luminosity functions does not make the mass functions obsolete . the luminosity functions tell us the space density of active black holes radiating at a given luminosity and redshift . the luminosity itself tells us how fast the black hole is accreting matter given the efficiency by which it converts matter to radiation but does not reveal whether we are observing a highly accreting , low mass black hole or a massive black hole accreting at moderate or low rates . the mass estimates confirm the latter scenario . the dashed line in fig . [ mlolzfig ] ( top panel ) shows the sdss flux limits folded with the cut - off in line widths of 1000 ^ -1 kms@xmath27 adopted for the sdss quasars ( schneider 2003 ) . if the former scenario was reality we would see the data points accumulate on and just above this dashed line . instead , we see a much wider distribution well above this limit . this is an important fact to keep in mind . the mass estimates and the mass functions also serve to break the degeneracy of the luminosity functions due to the loosely constrained radiative efficiency ( wyithe & radmanabhan 2006 ) , as noted in the introduction . the distinctly lower amplitudes of the mass function and the cumulative mass density distribution for the sdss sample at redshift four ( fig . [ mfallfig ] ) show that there are somewhat fewer active black holes at a given mass and/or less massive active black holes at that epoch than at later cosmic times . in particular , high-@xmath0 quasars contribute very little to the mass density of active black holes . to examine this a little further and to test if this is merely a consequence of our inability to detect very low mass black holes at @xmath43 4 , we extrapolated the sdss mass function to very low masses based on the observed slope at the lower mass end ( @xmath79 m _ @xmath3 ) . this extrapolation is shown in the top panel of figure [ extrapolfig ] ( dashed line ) , allowing a comparison with the mass functions of the bqs and lbqs samples . we also show with a dotted line the general slope along which the lbqs mass functions at redshifts lower than two move with cosmic time . it is quite conceivable that , in the case of no survey flux limits , the lbqs mass functions would extend approximately along this line , since the sdss dr3 mass functions ( vestergaard 2008 ) exhibit a similar behavior . the dotted line is hence a guideline to the maximum growth that can occur from the earliest epochs according to observations . the extrapolated mass function at @xmath434 is clearly parallel to the dotted line , offset by about [email protected] in mass and about 1.25dex in space density . this parallel offset suggests that the sdss quasars are either rarer than at lower epochs by a factor of @xmath417 or they need to grow in mass by an average factor of 4 to 4.5 by redshift 2.5 ( ignoring black hole mergers ) . given the time passed between redshifts of four and 2.5 ( of order 1 gyr ) and quasar life times of much less than a giga year ( martini 2004 ; hopkins & hernquist 2008 ) , the massive black holes that are contributing to the mass function at @xmath434 are not the same most massive black holes observed at @xmath432.5 . the most massive black holes at @xmath434 would have ceased their activity and dropped out of our surveys by @xmath432.5 . hence , the shift in the mass functions at the highest masses is not due to simple mass growth and a space density increase must dominate . since galaxy mergers ( and hence black hole mergers ) are expected to occur more frequently in the earlier universe than at present , we expect that the less massive black holes ( than typically observed at redshift four ) undergo a combination of both minor and major mergers as well as growth by mass accretion between the epochs at redshifts four and two . this will cause these black holes to shift to higher masses and the mass function amplitude at the high mass end to shift upwards . in the lower panel of figure [ extrapolfig ] we show the cumulative mass density for the sdss extrapolated mass function . unless the distribution of low - mass black holes is significantly steeper than the extrapolated power - law discussed here then it is clear that the lack of detectable low - mass black holes at @xmath434 is not the reason for the large amplitude discrepancies ( both panels ) between the quasar populations observed at very early ( @xmath43 4 ) and at later ( @xmath802 ) epochs . a significant build - up of existing and future supermassive black holes is required to explain the quasar populations at later times . we therefore conclude that the active black hole population at high redshift must be different since significantly fewer active black holes exist and with lower mass density at @xmath43 4 than at @xmath43 2.5 and @xmath43 0.5 , respectively . an interesting theoretical exercise would be to place lower limits on the distribution of seed ( low mass ) black holes at redshifts of four required to explain the local distribution of ( lower mass ) black holes ( m_bh @xmath1@xmath81 m _ @xmath3 ) for later observational tests of this prediction , for example , similar to the work by volonteri ( 2008 ) . when comparing all the samples at redshifts below three the high - mass end of the mass functions show little mass growth in these black holes . in fact , the density of the highest mass black holes decreases with cosmic time at epochs later than @xmath431 , consistent with a general decrease in activity of the most massive black holes . this is also and more clearly seen in the representation of the mass function shown for different mass bins as a function of redshift , as we discuss next . although the lbqs only has about 1000 quasars distributed over a range of redshifts , it is still large enough to allow a determination of how the mass function depends on redshift for a given mass bin ( fig . [ mfzfig ] ) . ( the value of the lbqs in this regard will become particularly apparent when discussed in relation to the mass function of the sdss dr3 quasar sample which is statistically limited near a redshift of 3 . ) this representation of the mass function directly shows at which epochs active black holes at a given mass are the most abundant . for example , the black holes of lower masses of 7.8 @xmath19 8.6 dex peak in their comoving space density in the local universe , while the more massive black hole of 10@xmath82 m _ @xmath3 are the most active at redshifts of 2 @xmath19 3 . figure [ mfzfig]f shows that the expected density of such black holes is more than two orders of magnitude lower in the local universe . by comparing the mass functions for individual mass bins the cosmic downsizing ( ueda 2003 ) of active black holes is clearly evident : the most massive black holes are the most active at high redshifts while the lowest mass black holes are the most active at low redshift . we present the mass functions of actively accreting black holes for the bright quasar survey , the large bright quasar survey , and the sdss color - selected sample in the fall equatorial stripe and the database from which these mass functions are derived . we find similar amplitudes and slopes ( of about @xmath7 with uncertainties between 0.4 and 1.4 ) of the high mass end of the mass functions for different redshift bins and across quasar samples for redshifts below @xmath43.5 . this is similar to what was seen for the dr3 mass functions at a similar redshift range ( vestergaard 2008 ) . however , for the well - defined and complete sdss color - selected sample of quasars at redshifts between 3.6 and 5 we find a somewhat flatter slope of @xmath83 . comparison of the mass functions and the cumulative mass density distributions for the different samples shows that the active black hole population at redshifts of about 4 must be different than the black hole populations below a redshift of about 2.5 . in fact , we may be witnessing a fast build - up of the black hole population between redshifts of 4 and redshifts of @xmath42 . the mass functions presented here will be discussed in further detail in relation to other existing black hole mass functions and , in particular , the sdss dr3 mass functions ( vestergaard 2008 ) in a future paper ( m. vestergaard 2009 , in preparation ) . at that time we will also apply sophisticated statistical analysis ( kelly 2008a , 2009 ) to investigate the nature of the actual underlying mass distribution free of measurement uncertainties and , to a certain extent , of survey flux limits . we thank dave sanders for providing his tabulation of observed bolometric luminosities of the bqs sample , xiaohui fan for comments on the manuscript , and brandon kelly for discussions . mv thanks for their hospitality the astronomy departments at the ohio state university and the university of arizona where most of this work was performed . we 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41.12@xmath100 + lccccc q0000@xmath230159 & 1.073 & 18.43 & 8.92@xmath101 & 46.57@xmath102 & @xmath190.441@xmath103 + q0001@xmath190050 & 1.459 & 18.74 & 9.13@xmath104 & 46.74@xmath105 & @xmath190.483@xmath106 + q0002@xmath190243 & 0.432 & 18.27 & 8.32@xmath107 & 45.71@xmath108 & @xmath190.713@xmath109 lccc q0004@xmath230147 & 1.710 & 18.13 & 47.14 + q0010@xmath190012 & 2.154 & 18.46 & 47.22 + q0013@xmath190029 & 2.083 & 18.18 & 47.30 + q0018@xmath230047 & 1.835 & 17.82 & 47.32 + q0018@xmath190220 & 2.596 & 17.44 & 47.79 + lcccr [email protected] & 4.32 & 0.90 & 4706@xmath110 & 43.436@xmath111 + [email protected] & 4.75 & 0.99 & 2150@xmath112 & 43.366@xmath113 + [email protected] & 4.16 & 0.78 & 3325@xmath114 & 43.536@xmath115 + lcccr [email protected] & 4.32 & 9.345@xmath116 & 47.230@xmath117 & @xmath190.2146@xmath118 + [email protected] & 4.75 & 8.627@xmath119 & 47.160@xmath120 & 0.4330@xmath121 + [email protected] & 4.16 & 9.096@xmath122 & 47.330@xmath123 & 0.1342@xmath124 + cccccr 0.25 & 0.25 & 6.6 & 3.448e-05 & 3.448e-05 & 1 + & & 7.0 & 4.112e-05 & 2.108e-05 & 6 + & & 7.4 & 9.114e-06 & 6.162e-06 & 7 + & & 7.8 & 5.419e-06 & 3.634e-06 & 11 + & & 8.2 & 2.165e-06 & 1.529e-06 & 17 + & & 8.6 & 1.107e-06 & 4.501e-07 & 22 + & & 9.0 & 2.619e-08 & 1.297e-08 & 13 + & & 9.4 & 1.506e-09 & 5.765e-10 & 9 + & & 9.8 & 4.235e-11 & 4.235e-11 & 1 + cccccrc 0.35 & 0.15 & 6.8 & & & 0 & 461.03 + 0.35 & 0.15 & 7.2 & 2.4518e-06 & 2.4518e-06 & 1 & 460.50 + 0.35 & 0.15 & 7.6 & 1.8975e-06 & 1.1120e-06 & 5 & 459.29 + 0.35 & 0.15 & 8.0 & 5.7041e-06 & 2.2265e-06 & 26 & 423.53 + 0.35 & 0.15 & 8.4 & 2.4266e-06 & 3.5559e-07 & 75 & 335.24 + 0.35 & 0.15 & 8.8 & 3.7082e-07 & 6.5793e-08 & 39 & 196.06 + 0.35 & 0.15 & 9.2 & 6.5978e-08 & 2.3601e-08 & 15 & 37.805 + 0.35 & 0.15 & 9.6 & 1.5007e-09 & 1.5007e-09 & 1 & + + 0.75 & 0.25 & 7.6 & & & 0 & 322.67 + 0.75 & 0.25 & 8.0 & 1.9470e-07 & 7.6028e-08 & 9 & 322.07 + 0.75 & 0.25 & 8.4 & 4.0175e-07 & 7.4011e-08 & 54 & 315.12 + 0.75 & 0.25 & 8.8 & 2.0598e-07 & 2.7534e-08 & 90 & 268.67 + 0.75 & 0.25 & 9.2 & 6.0881e-08 & 8.4790e-09 & 77 & 145.79 + 0.75 & 0.25 & 9.6 & 3.1654e-09 & 8.8983e-10 & 13 & 51.704 + 0.75 & 0.25 & 10.0 & 3.6235e-10 & 1.8121e-10 & 4 & 8.9008 + + 1.25 & 0.25 & 7.6 & & & 0 & 394.74 + 1.25 & 0.25 & 8.0 & 5.3376e-09 & 5.3376e-09 & 1 & 394.70 + 1.25 & 0.25 & 8.4 & 2.5527e-08 & 1.0412e-08 & 7 & 394.38 + 1.25 & 0.25 & 8.8 & 3.0814e-08 & 6.2483e-09 & 27 & 391.50 + 1.25 & 0.25 & 9.2 & 4.5757e-08 & 5.0341e-09 & 105 & 338.64 + 1.25 & 0.25 & 9.6 & 1.0996e-08 & 1.3039e-09 & 76 & 182.61 + 1.25 & 0.25 & 10.0 & 1.2521e-09 & 3.0845e-10 & 20 & 63.610 + 1.25 & 0.25 & 10.4 & 2.1249e-11 & 2.1249e-11 & 1 & + + 1.75 & 0.25 & 8.4 & & & 0 & 374.11 + 1.75 & 0.25 & 8.8 & 4.7534e-09 & 1.9897e-09 & 6 & 373.94 + 1.75 & 0.25 & 9.2 & 1.3410e-08 & 2.3147e-09 & 38 & 367.59 + 1.75 & 0.25 & 9.6 & 9.5608e-09 & 1.1030e-09 & 79 & 282.15 + 1.75 & 0.25 & 10.0 & 1.9367e-09 & 3.0588e-10 & 41 & 98.379 + 1.75 & 0.25 & 10.4 & 5.3655e-11 & 3.0978e-11 & 3 & + + 2.50 & 0.50 & 8.0 & & & 0 & 291.62 + 2.50 & 0.50 & 8.4 & 9.9367e-10 & 9.9367e-10 & 1 & 291.62 + 2.50 & 0.50 & 8.8 & 2.1144e-09 & 1.1199e-09 & 4 & 291.21 + 2.50 & 0.50 & 9.2 & 4.5198e-09 & 1.0667e-09 & 24 & 289.26 + 2.50 & 0.50 & 9.6 & 4.1379e-09 & 6.0390e-10 & 55 & 259.84 + 2.50 & 0.50 & 10.0 & 1.4573e-09 & 2.1311e-10 & 52 & 150.49 + 2.50 & 0.50 & 10.4 & 1.3643e-10 & 3.5502e-11 & 15 & 24.924 cccccr 8.00 & 0.35 & 0.15 & 5.7292e-06 & 2.2287e-06 & 25 + 8.00 & 0.75 & 0.25 & 1.9470e-07 & 7.6028e-08 & 9 + 8.00 & 1.25 & 0.25 & & & 0 + 8.00 & 1.75 & 0.25 & & & 0 + 8.00 & 2.50 & 0.50 & & & 0 + + 8.40 & 0.35 & 0.15 & 2.4872e-06 & 3.5733e-07 & 78 + 8.40 & 0.75 & 0.25 & 4.0640e-07 & 7.4157e-08 & 55 + 8.40 & 1.25 & 0.25 & 2.5527e-08 & 1.0412e-08 & 7 + 8.40 & 1.75 & 0.25 & & & 0 + 8.40 & 2.50 & 0.50 & 9.9367e-10 & 9.9367e-10 & 1 + + 8.80 & 0.35 & 0.15 & 3.7392e-07 & 6.6183e-08 & 40 + 8.80 & 0.75 & 0.25 & 2.0598e-07 & 2.7534e-08 & 90 + 8.80 & 1.25 & 0.25 & 3.2505e-08 & 6.3618e-09 & 29 + 8.80 & 1.75 & 0.25 & 4.7534e-09 & 1.9897e-09 & 6 + 8.80 & 2.50 & 0.50 & 2.1144e-09 & 1.1199e-09 & 4 + + 9.20 & 0.35 & 0.15 & 6.4744e-08 & 2.3427e-08 & 15 + 9.20 & 0.75 & 0.25 & 6.2003e-08 & 8.5161e-09 & 79 + 9.20 & 1.25 & 0.25 & 4.6456e-08 & 5.0355e-09 & 108 + 9.20 & 1.75 & 0.25 & 1.3817e-08 & 2.3514e-09 & 39 + 9.20 & 2.50 & 0.50 & 4.6557e-09 & 1.0753e-09 & 25 + + 9.60 & 0.35 & 0.15 & 1.5007e-09 & 1.5007e-09 & 1 + 9.60 & 0.75 & 0.25 & 3.1654e-09 & 8.8983e-10 & 13 + 9.60 & 1.25 & 0.25 & 1.1309e-08 & 1.3366e-09 & 77 + 9.60 & 1.75 & 0.25 & 9.8252e-09 & 1.1188e-09 & 81 + 9.60 & 2.50 & 0.50 & 4.1379e-09 & 6.0390e-10 & 55 + + 10.00 & 0.35 & 0.15 & & & 0 + 10.00 & 0.75 & 0.25 & 9.3214e-11 & 9.3214e-11 & 1 + 10.00 & 1.25 & 0.25 & 9.2919e-10 & 2.7036e-10 & 15 + 10.00 & 1.75 & 0.25 & 1.8614e-09 & 2.9647e-10 & 40 + 10.00 & 2.50 & 0.50 & 1.4888e-09 & 2.1542e-10 & 53 + + 10.40 & 0.35 & 0.15 & & & 0 + 10.40 & 0.75 & 0.25 & & & 0 + 10.40 & 1.25 & 0.25 & & & 0 + 10.40 & 1.75 & 0.25 & 5.3655e-11 & 3.0978e-11 & 3 + 10.40 & 2.50 & 0.50 & 1.2549e-10 & 3.3775e-11 & 14 cccccr 4.3 & 0.7 & 8.7 & 4.690e-08 & 3.162e-08 & 6 + 4.3 & 0.7 & 9.1 & 8.607e-09 & 2.800e-09 & 13 + 4.3 & 0.7 & 9.5 & 1.325e-09 & 4.462e-10 & 9 + 4.3 & 0.7 & 9.9 & 3.798e-10 & 1.569e-10 & 6 + 4.3 & 0.7 & 8.7 & 4.690e-08 & 3.162e-08 & 6 + 4.3 & 0.7 & 9.1 & 1.072e-08 & 3.073e-09 & 17 + 4.3 & 0.7 & 9.5 & 1.325e-09 & 4.462e-10 & 9 + 4.3 & 0.7 & 9.9 & 3.798e-10 & 1.569e-10 & 6 + 4.3 & 0.7 & 8.7 & 4.690e-08 & 3.162e-08 & 6 + 4.3 & 0.7 & 9.1 & 8.607e-09 & 2.800e-09 & 13 + 4.3 & 0.7 & 9.5 & 1.715e-09 & 4.997e-10 & 12 + 4.3 & 0.7 & 9.9 & 5.597e-10 & 2.386e-10 & 7 + 4.3 & 0.7 & 8.7 & 4.975e-08 & 3.175e-08 & 7 + 4.3 & 0.7 & 9.1 & 9.585e-09 & 2.856e-09 & 16 + 4.3 & 0.7 & 9.5 & 1.325e-09 & 4.462e-10 & 9 + 4.3 & 0.7 & 9.9 & 3.798e-10 & 1.569e-10 & 6 + cccccrc 0.35 & 0.15 & 6.8 & & & 0 & 475.05 + 0.35 & 0.15 & 7.2 & 2.4518e-06 & 2.4518e-06 & 1 & 474.52 + 0.35 & 0.15 & 7.6 & 1.8975e-06 & 1.1120e-06 & 5 & 473.31 + 0.35 & 0.15 & 8.0 & 5.7292e-06 & 2.2287e-06 & 25 & 437.86 + 0.35 & 0.15 & 8.4 & 2.7017e-06 & 3.7761e-07 & 82 & 345.18 + 0.35 & 0.15 & 8.8 & 3.8550e-07 & 6.7189e-08 & 41 & 190.48 + 0.35 & 0.15 & 9.2 & 6.4744e-08 & 2.3427e-08 & 15 & 23.53 + 0.35 & 0.15 & 9.6 & 1.5007e-09 & 1.5007e-09 & 1 & + 0.75 & 0.25 & 7.6 & & & 0 & 318.57 + 0.75 & 0.25 & 8.0 & 1.9470e-07 & 7.6028e-08 & 9 & 317.97 + 0.75 & 0.25 & 8.4 & 4.3218e-07 & 7.8509e-08 & 56 & 311.02 + 0.75 & 0.25 & 8.8 & 2.2154e-07 & 2.8136e-08 & 98 & 259.42 + 0.75 & 0.25 & 9.2 & 6.5052e-08 & 8.6269e-09 & 84 & 130.77 + 0.75 & 0.25 & 9.6 & 3.1654e-09 & 8.8983e-10 & 13 & 29.34 + 0.75 & 0.25 & 10.0 & 9.3214e-11 & 9.3214e-11 & 1 & + 1.25 & 0.25 & 8.000 & & & 0 & 389.25 + 1.25 & 0.25 & 8.400 & 2.5527e-08 & 1.0412e-08 & 7 & 388.93 + 1.25 & 0.25 & 8.800 & 3.2505e-08 & 6.3618e-09 & 29 & 385.78 + 1.25 & 0.25 & 9.200 & 5.0448e-08 & 5.2050e-09 & 118 & 332.50 + 1.25 & 0.25 & 9.600 & 1.2247e-08 & 1.3828e-09 & 84 & 157.13 + 1.25 & 0.25 & 10.000 & 9.2919e-10 & 2.7036e-10 & 15 & 35.06 + 1.75 & 0.25 & 8.400 & & & 0 & 420.21 + 1.75 & 0.25 & 8.800 & 4.7534e-09 & 1.9897e-09 & 6 & 420.04 + 1.75 & 0.25 & 9.200 & 1.5414e-08 & 2.4894e-09 & 43 & 412.79 + 1.75 & 0.25 & 9.600 & 1.1405e-08 & 1.1958e-09 & 95 & 313.36 + 1.75 & 0.25 & 10.000 & 2.1402e-09 & 3.1767e-10 & 46 & 90.84 + 1.75 & 0.25 & 10.400 & 5.3655e-11 & 3.0978e-11 & 3 & + 2.50 & 0.50 & 8.000 & & & 0 & 338.39 + 2.50 & 0.50 & 8.400 & 9.9367e-10 & 9.9367e-10 & 1 & 338.39 + 2.50 & 0.50 & 8.800 & 2.1144e-09 & 1.1199e-09 & 4 & 337.98 + 2.50 & 0.50 & 9.200 & 4.6557e-09 & 1.0753e-09 & 25 & 336.03 + 2.50 & 0.50 & 9.600 & 5.2545e-09 & 6.7097e-10 & 71 & 306.28 + 2.50 & 0.50 & 10.000 & 1.8430e-09 & 2.3892e-10 & 66 & 147.96 + 2.50 & 0.50 & 10.400 & 1.2549e-10 & 3.3775e-11 & 14 & 24.92 + 0.35 & 0.15 & 6.8 & & & 0 & 502.79 + 0.35 & 0.15 & 7.2 & 2.4518e-06 & 2.4518e-06 & 1 & 502.25 + 0.35 & 0.15 & 7.6 & 1.8975e-06 & 1.1120e-06 & 5 & 501.05 + 0.35 & 0.15 & 8.0 & 5.7292e-06 & 2.2287e-06 & 25 & 465.59 + 0.35 & 0.15 & 8.4 & 2.4872e-06 & 3.5733e-07 & 78 & 377.61 + 0.35 & 0.15 & 8.8 & 4.5933e-07 & 8.2115e-08 & 44 & 224.05 + 0.35 & 0.15 & 9.2 & 6.9354e-08 & 2.3876e-08 & 16 & 35.714 + 0.35 & 0.15 & 9.6 & 1.5007e-09 & 1.5007e-09 & 1 & + 0.75 & 0.25 & 7.6 & & & 0 & 335.75 + 0.75 & 0.25 & 8.0 & 1.9470e-07 & 7.6028e-08 & 9 & 335.15 + 0.75 & 0.25 & 8.4 & 4.0640e-07 & 7.4157e-08 & 55 & 328.20 + 0.75 & 0.25 & 8.8 & 2.1765e-07 & 2.9418e-08 & 92 & 281.43 + 0.75 & 0.25 & 9.2 & 6.7637e-08 & 8.8044e-09 & 86 & 146.66 + 0.75 & 0.25 & 9.6 & 4.3793e-09 & 1.0455e-09 & 18 & 32.929 + 0.75 & 0.25 & 10.0 & 9.3214e-11 & 9.3214e-11 & 1 & + 1.25 & 0.25 & 8.0 & & & 0 & 409.27 + 1.25 & 0.25 & 8.4 & 2.5527e-08 & 1.0412e-08 & 7 & 408.95 + 1.25 & 0.25 & 8.8 & 3.2505e-08 & 6.3618e-09 & 29 & 405.79 + 1.25 & 0.25 & 9.2 & 4.6456e-08 & 5.0355e-09 & 108 & 353.76 + 1.25 & 0.25 & 9.6 & 1.3702e-08 & 1.4729e-09 & 93 & 176.43 + 1.25 & 0.25 & 10.0 & 9.8256e-10 & 2.7558e-10 & 16 & 35.057 + 1.75 & 0.25 & 8.4 & & & 0 & 473.23 + 1.75 & 0.25 & 8.8 & 4.7534e-09 & 1.9897e-09 & 6 & 473.06 + 1.75 & 0.25 & 9.2 & 1.3817e-08 & 2.3514e-09 & 39 & 465.81 + 1.75 & 0.25 & 9.6 & 1.0912e-08 & 1.1868e-09 & 89 & 376.75 + 1.75 & 0.25 & 10.0 & 2.5353e-09 & 3.4376e-10 & 55 & 162.89 + 1.75 & 0.25 & 10.4 & 7.5198e-11 & 3.7732e-11 & 4 & 14.133 + 2.50 & 0.50 & 8.0 & & & 0 & 402.11 + 2.50 & 0.50 & 8.4 & 9.9367e-10 & 9.9367e-10 & 1 & 402.11 + 2.50 & 0.50 & 8.8 & 2.1144e-09 & 1.1199e-09 & 4 & 401.69 + 2.50 & 0.50 & 9.2 & 4.6557e-09 & 1.0753e-09 & 25 & 399.74 + 2.50 & 0.50 & 9.6 & 4.1379e-09 & 6.0390e-10 & 55 & 369.99 + 2.50 & 0.50 & 10.0 & 1.9763e-09 & 2.4675e-10 & 71 & 255.72 + 2.50 & 0.50 & 10.4 & 2.4082e-10 & 5.1114e-11 & 24 & 34.871 + 2.50 & 0.50 & 10.8 & 3.4121e-12 & 3.4121e-12 & 1 & + 0.35 & 0.15 & 6.8 & & & 0 & 464.72 + 0.35 & 0.15 & 7.2 & 2.4518e-06 & 2.4518e-06 & 1 & 464.19 + 0.35 & 0.15 & 7.6 & 1.8975e-06 & 1.1120e-06 & 5 & 462.98 + 0.35 & 0.15 & 8.0 & 6.2681e-06 & 2.2497e-06 & 29 & 427.52 + 0.35 & 0.15 & 8.4 & 2.5162e-06 & 3.5851e-07 & 79 & 333.11 + 0.35 & 0.15 & 8.8 & 3.7392e-07 & 6.6183e-08 & 40 & 190.48 + 0.35 & 0.15 & 9.2 & 6.4744e-08 & 2.3427e-08 & 15 & 23.53 + 0.35 & 0.15 & 9.6 & 1.5007e-09 & 1.5007e-09 & 1 & + 0.75 & 0.25 & 7.6 & & & 0 & 310.60 + 0.75 & 0.25 & 8.0 & 1.9470e-07 & 7.6028e-08 & 9 & 310.00 + 0.75 & 0.25 & 8.4 & 4.7127e-07 & 7.9844e-08 & 64 & 301.02 + 0.75 & 0.25 & 8.8 & 2.1364e-07 & 2.7751e-08 & 95 & 252.17 + 0.75 & 0.25 & 9.2 & 6.2003e-08 & 8.5161e-09 & 79 & 126.47 + 0.75 & 0.25 & 9.6 & 3.1654e-09 & 8.8983e-10 & 13 & 29.34 + 0.75 & 0.25 & 10.0 & 9.3214e-11 & 9.3214e-11 & 1 & + 1.25 & 0.25 & 8.0 & & & 0 & 378.83 + 1.25 & 0.25 & 8.4 & 2.5527e-08 & 1.0412e-08 & 7 & 378.52 + 1.25 & 0.25 & 8.8 & 3.5906e-08 & 6.6951e-09 & 32 & 374.77 + 1.25 & 0.25 & 9.2 & 5.0778e-08 & 5.1932e-09 & 120 & 315.32 + 1.25 & 0.25 & 9.6 & 1.1577e-08 & 1.3500e-09 & 79 & 153.21 + 1.25 & 0.25 & 10.0 & 9.2919e-10 & 2.7036e-10 & 15 & 35.06 + 1.75 & 0.25 & 8.4 & & & 0 & 395.31 + 1.75 & 0.25 & 8.8 & 4.7534e-09 & 1.9897e-09 & 6 & 395.14 + 1.75 & 0.25 & 9.2 & 1.7965e-08 & 2.6306e-09 & 52 & 385.18 + 1.75 & 0.25 & 9.6 & 1.1090e-08 & 1.1821e-09 & 92 & 274.61 + 1.75 & 0.25 & 10.0 & 1.8614e-09 & 2.9647e-10 & 40 & 90.84 + 1.75 & 0.25 & 10.4 & 5.3655e-11 & 3.0978e-11 & 3 & + 2.50 & 0.50 & 8.0 & & & 0 & 310.87 + 2.50 & 0.50 & 8.4 & 9.9367e-10 & 9.9367e-10 & 1 & 310.87 + 2.50 & 0.50 & 8.8 & 2.1144e-09 & 1.1199e-09 & 4 & 310.45 + 2.50 & 0.50 & 9.2 & 5.7111e-09 & 1.1510e-09 & 32 & 308.50 + 2.50 & 0.50 & 9.6 & 5.7243e-09 & 7.0062e-10 & 77 & 257.20 + 2.50 & 0.50 & 10.0 & 1.4888e-09 & 2.1542e-10 & 53 & 144.92 + 2.50 & 0.50 & 10.4 & 1.2549e-10 & 3.3775e-11 & 14 & 24.92 + cccccc 6.4 & 278.2 & & & & + 6.6 & 277.8 & & & & + 6.8 & 277.8 & & & & + 7.0 & 277.5 & & & & + 7.2 & 272.9 & & & & + 7.4 & 272.3 & & & & + 7.6 & 267.4 & & & & + 7.8 & 265.8 & & & & + 8.0 & 243.3 & & & & + 8.2 & 238.9 & & & & + 8.4 & 190.8 & 56.56 & 61.07 & 67.89 & 58.41 + 8.6 & 64.72 & 49.96 & 54.46 & 61.29 & 51.80 + 8.8 & 31.52 & 48.25 & 52.76 & 59.58 & 50.09 + 9.0 & 22.43 & 46.69 & 51.20 & 58.02 & 46.69 + 9.2 & 8.656 & 41.33 & 45.84 & 52.67 & 41.33 + 9.4 & 2.168 & 31.99 & 31.99 & 43.32 & 31.99 + 9.6 & 1.334 & 25.95 & 25.95 & 33.10 & 25.95 + 9.8 & & 17.73 & 17.73 & 17.73 & 17.73 + 10.0 & & 10.69 & 10.69 & 10.69 & 10.69 +

we present mass functions of distant actively accreting supermassive black holes residing in luminous quasars discovered in the large bright quasar survey ( lbqs ) , the bright quasar survey ( bqs ) , and the fall equatorial stripe of the sloan digital sky survey ( sdss ) . the quasars cover a wide range of redshifts from the local universe to @xmath0 = 5 and were subject to different selection criteria and flux density limits . this makes these samples complementary and can help us gain additional insight on the true underlying black hole mass distribution free from selection effects and mass estimation errors through future studies . by comparing these quasar samples , we see evidence that the active black hole population at redshift four is somewhat different than that at lower redshifts , including that in the nearby universe . in particular , there is a sharp increase in the space density of the detected active black holes ( m_bh @xmath1@xmath2 m _ @xmath3 ) between redshifts @xmath44 and @xmath42.5 . also , the mass function of the sdss quasars at @xmath5 has a somewhat flatter high mass - end slope of @xmath6 , compared to the mass functions based on quasars below @xmath0 of 3 ( bqs and lbqs quasars ) , which display typical slopes of @xmath7 ; the latter are consistent with the mass functions at similar redshifts based on the sdss data release 3 quasar catalog presented by vestergaard et al . we see clear evidence of cosmic downsizing in the comoving space density distribution of active black holes in the lbqs sample alone . in forthcoming papers , further analysis , comparison , and discussion of these mass functions will be made with other existing black hole mass functions , notably that based on the sdss dr3 quasar catalog . we present the relationships used to estimate the black hole mass based on the mgii emission line ; the relations are calibrated to the h@xmath8 and civ relations by means of several thousand high quality sdss spectra . mass estimates of the individual black holes of these samples are also presented .

on the largest scales we can observe , our universe has a remarkably simple structure . it is homogeneous , isotropic , and spatially flat to very high accuracy . furthermore , the primordial curvature fluctuations which seeded the formation of structure apparently took an extremely minimal form : a statistically homogeneous , gaussian - distributed pattern of very small - amplitude curvature perturbations , with an almost perfectly scale - invariant power spectrum . while inflationary models are capable of fitting the data , it is nonetheless tempting to look for a simpler and more fundamental explanation . the early universe was dominated by radiation , a form of matter without an intrinsic scale . in fact , it is believed that any well - defined quantum field theory must possess a uv fixed point , signifying conformal invariance at high energies . these lines of argument encourage us to investigate a minimal early universe cosmology , namely a quantum universe filled with conformally invariant matter @xcite . we start by studying the quantum propagation of homogeneous background universes , uncovering a number of surprising features . then , we include inhomogeneous perturbations , treated semiclassically and perturbatively at both linear and nonlinear order . we shall not , in this paper , propose a realistic scenario . nor shall we proceed far enough to study the effects of renormalization and the running of couplings , although these are no doubt important . our focus will be on the technical calculation of the causal ( feynman ) propagator in some specific ( and quasi - realistic ) cosmologies . we shall also postpone a discussion of the important question of the _ interpretation _ of the propagator and its use to compute probabilities to future work . nevertheless , we believe our findings are instructive and form a useful starting point for such investigations . the simplest example of conformal matter is a perfect fluid of radiation . in the context of cosmology , this is extremely well - motivated since the early universe was , we believe , radiation - dominated . furthermore , if we add a single scalar field then at least at a classical level , minimal coupling is equivalent to conformal coupling under field redefinitions . so this case too may be considered as an example of conformal matter . it is then instructive to extend the discussion to include an arbitrary number of conformally and minimally coupled free scalar fields . since the matter lagrangian of interest is , by assumption , conformally ( weyl ) invariant at a classical level , it makes sense to lift " general relativity ( gr ) to a larger theory possessing the same symmetry . this is done by introducing an extra scalar field which is locally a pure gauge degree of freedom . the full theory is now classically weyl invariant and it may be viewed with advantage in various weyl gauges . its solutions contain all solutions of gr but the theory allows for extended and more general solutions that do not possess a global gauge - fixing to gr . in particular , it turns out that while classical cosmological ( homogeneous and isotropic ) background solutions are typically singular and geodesically incomplete in einstein gauge ( the weyl gauge in which the gravitational action takes einstein - hilbert form , with a fixed newton s gravitational constant @xmath0 ) , they are regular and geodesically complete in a more general class of weyl gauges , where @xmath0 is no longer constant and can even change sign . in these gauges , generic cosmological background solutions pass smoothly through the big bang singularity " and into new regions of field space , including antigravity " regions where @xmath0 is negative @xcite . strictly speaking , the lifted " classical theory is still incomplete because these highly symmetrical backgrounds are unstable to perturbations in the collapsing phase , leading to diverging anisotropies which can not be removed via a weyl gauge choice . it was argued nevertheless that the classical theory possesses a natural continuation across singularities of this kind @xcite . in this paper , following @xcite , we take a different tack . we ask whether _ quantum _ effects might rescue the theory from its breakdown at big bang "- type singularities . first , we show that for the simplest types of conformal matter , the feynman propagator for cosmological backgrounds may be computed exactly , allowing us to explore many issues with precision in this symmetry - reduced ( minisuperspace ) context . second , we extend the discussion to include anisotropies , resolving the ordering problems in the quantum ( wheeler - dewitt ) hamiltonian by imposing covariance under field redefinitions . we go further than the treatment of @xcite by defining the quantum theory along the real axis in superspace , and discovering some remarkable features . for a flat , isotropic universe , quantum effects indeed become large near the singularity . therefore , strictly speaking , one should not attempt to employ the real classical theory there . instead , one can solve the quantum wheeler - dewitt - type equation for the propagator in complexified superspace , along a contour which avoids the singularity in taking one from the incoming collapsing universe to the outgoing expanding one . provided the contour stays sufficiently far from the singularity , the semiclassical approximation remains valid all along it , so one can employ _ complex _ solutions of the classical theory to follow the quantum evolution across ( or more accurately , around ) the singularity . in doing so , we find that while quantum effects are large near the singularity , they take a very special form such that they are invisible " in the evolution between incoming and outgoing states . in the final section of this paper , we treat inhomogeneous perturbations , at linear and nonlinear order , showing how they may be followed smoothly and unambiguously across ( or , more accurately , around ) the big bang singularity , in a similar manner . the theory we consider consists of einstein gravity plus radiation and a number of free scalar fields . all of these forms of matter satisfy the strong energy condition , and any cosmological solution necessarily possesses a big bang singularity . however , there is no singularity in the feynman propagator for closed , open and flat friedmann - robertson - walker ( frw ) and for flat , anisotropic bianchi i cosmologies ; the propagator is well - behaved across a bounce " representing a transition from a large , collapsing classical universe to a large , expanding one . we also study inhomogeneous perturbations of the isotropic , radiation - dominated universe , studying the propagation of scalar and tensor perturbations across the bounce , at linear and nonlinear order . we find that , in the semiclassical approximation at least and with strictly conformal matter , the incoming vacuum state evolves into the outgoing vacuum state , with no particle production . the bounce may be viewed as an example of quantum - mechanical tunneling , and we use complex classical solutions as saddle points to the path integral , in a manner which generalizes the use of instanton solutions to describe tunneling in more familiar contexts . some of these results were anticipated in ref . @xcite ; here we present more details on their derivation , extend them to further cases not discussed in ref . @xcite , and provide more mathematical and conceptual background . an alternate interpretation of the antigravity " regions , not employing complex solutions , has been presented in ref . @xcite . the simplest example of a `` perfect bounce '' is provided by a spatially flat , homogeneous and isotropic frw universe , filled with a perfect radiation fluid . adopting conformal time ( denoted by @xmath1 ) , _ i.e. _ , choosing the line element to be ds^2=a^2()(-d^2+d^2 ) , [ frw ] one finds the scale factor @xmath2 . one way to see this is from the trace of the einstein equations . for the line element ( [ frw ] ) , @xmath3 and for conformal matter , the stress tensor is traceless . so the einstein equations imply @xmath2 . if spatial curvature is included , it is subdominant at small @xmath4 so that @xmath4 still vanishes linearly with @xmath1 . hence @xmath2 is a direct consequence of conformal invariance and cosmological symmetry . while the line element ( [ frw ] ) clearly contains a big bang / big crunch singularity at @xmath5 , it is regular everywhere else , not only along the real @xmath1-axis but also in the entire complex @xmath1-plane . any complex @xmath1 trajectory that connects large negative and large positive @xmath4 while avoiding @xmath6 gives a regular , complexified metric that asymptotes to a large , lorentzian universe in the past and the future , while circumventing the big bang singularity . such complex solutions have been discussed in quantum cosmology for a long time as saddle points of the path integral , for instance in the no - boundary proposal of hartle and hawking @xcite . the crucial difference in our proposal is that the complex solutions connect two large , lorentzian regions , identified with a collapsing incoming universe and an expanding outgoing one . the weyl - invariant lift of gr provides a convenient simplification of the geometry on superspace , cleanly exhibiting its lorentzian nature and the role of the scale factor @xmath4 as a single timelike coordinate for both gravity " regions . this leads us to a novel formalism for quantum cosmology in which , rather than restricting to positive @xmath4 and imposing boundary conditions at @xmath6 , @xmath4 is extended to the entire real line . the feynman propagator turns out to have simple behavior at large negative and positive @xmath4 , describing a contracting and re - expanding universe , respectively , and connecting them through a quantum bounce . the purpose of this paper is to flesh out the details of this formalism , and show how it leads to a novel form of singularity avoidance in the context of an extremely simple ( but not altogether unrealistic ) cosmology . some of the features of our discussion are not new . the possibility of solving minisuperspace quantum cosmology models exactly by recasting their dynamics as those of a relativistic free particle or harmonic oscillator was pointed out before ( see , _ e.g. _ , refs . @xcite ) . however , the crucial new feature in our work is the existence of regular solutions ( especially complex ones ) that connect two large lorentzian universes through a quantum bounce . this feature relies on having a positive energy density in radiation , a possibility which , as far as we know , was overlooked in previous work . in fact , our results suggest that the fact that the early universe was dominated by radiation may be sufficient in itself for a semiclassical quantum resolution of the big bang / big crunch singularity , without the need for less well - motivated ingredients such as exotic forms of matter @xcite , modified theories of gravity @xcite , or a proposed theory of quantum gravity @xcite . to avoid any potential confusion , let us re - emphasize that the theories we consider consist of general relativity with a radiation fluid and a number of free scalars , and nothing more : our use of the weyl lift of gr does not introduce any additional degrees of freedom . the plan of our paper is as follows . in sec . [ theorysec ] , we introduce the weyl lift of gr plus radiation and scalars , and show how the degree of freedom corresponding to the metric determinant can be isolated straightforwardly , leading us to a weyl - invariant notion of @xmath4 , the `` scale factor '' . we then study homogeneous , isotropic frw universes in sec . [ friedbounce ] , showing that in these cases , the einstein - matter action corresponds to that of a massive relativistic particle moving in minkowski spacetime , either freely or subject to a quadratic , lorentz - invariant potential . we discuss the classical and quantum dynamics of frw universes , using the classical hamiltonian analysis to define the wheeler - dewitt quantum hamiltonian . we discuss the klein - gordon - type inner product proposed by dewitt @xcite , but take the point of view that the fundamental quantity of interest is really the causal ( feynman ) propagator , which is naturally defined as a path integral over four - geometries @xcite . accordingly , in sec . [ feynman ] we calculate the propagator for various cases of interest . while the feynman propagator for frw universes is actually regular at the singularity @xmath6 , its asymptotic behavior for large arguments displays interesting pathologies both for closed and , in particular , open universes , so that only flat frw universes seem to consistently admit a quantum bounce . in sec . [ anisosec ] , we extend the treatment to anisotropic universes of bianchi i type , including for generality a number of free minimally - coupled scalar fields . we resolve the ordering problem in the quantum hamiltonian , and we are again able to explicitly derive the feynman propagator . a very special , singular potential arises centered on @xmath6 which , in the minisuperspace context , is harmless and actually invisible in the scattering amplitude between incoming and outgoing states . the coefficient of this singular potential turns out to take a special value for the isotropic universe with zero or one conformally coupled scalars , placing it on the edge of a potential quantum instability , as we shall discuss . the addition of further conformally coupled scalars moves the theory away from this edge , however . this is an intriguing result that deserves further attention , as it could be used to select between isotropic and strongly anisotropic universes . in sec . [ pertsec ] , we add inhomogeneities , treated linearly and nonlinearly in the semiclassical approximation where one employs complex classical solutions to the classical einstein equations . we show how this is sufficient to determine mixing between positive- and negative - frequency modes , and hence to compute the particle production across the `` quantum bounce '' . we find no particle production , but instead verify that the perturbation expansion breaks down at late times due to the formation of shocks in the fluid , a phenomenon which is now physically well understood @xcite . [ conclsec ] concludes . we start by studying the cosmology of a universe filled with perfectly conformal radiation and a number @xmath7 of conformally coupled scalar fields , with gravitational dynamics governed by a `` lift '' of gr to a classically weyl - invariant theory that contains an additional dilaton field @xmath8 . we stress again that the field @xmath8 is locally pure gauge , and possesses no non - trivial dynamics of its own . this formalism for gr was developed in ref . @xcite and works in any number of dimensions @xmath9 ( we will set @xmath10 shortly ) . the total action we consider is s&=&d^d x \{-j^(_+_a_^a)}.the independent dynamical variables are the spacetime metric @xmath11 ( assumed to be lorentzian throughout ) , the `` dilaton '' @xmath8 , @xmath7 physical scalar fields @xmath12 , and a densitized particle number flux @xmath13 characterizing the radiation fluid . the latter can be identified by @xmath14 , where @xmath15 is the particle number density and @xmath16 is the four - velocity vector field satisfying @xmath17 ; the energy density @xmath18 is only a function of @xmath15 , concretely @xmath19 for radiation which is the case we are interested in . there is a lagrange multiplier @xmath20 which enforces particle number conservation @xmath21 , and @xmath22 further lagrange multipliers @xmath23 , with @xmath24 , enforcing constraints @xmath25 that restrict the fluid flow to be directed along flow lines labeled by the fields @xmath26 which play the role of lagrangian coordinates for the fluid . in general , the fluid energy density @xmath18 would also depend on the entropy per particle . for simplicity , we henceforth assume an isentropic fluid for which this entropy per particle is a constant . the fluid part of our action is then the one given for isentropic fluids in eq . ( 6.10 ) of ref . @xcite , where further details on the construction of actions of relativistic fluids and their corresponding hamiltonian dynamics can be found . the action ( [ eq1 ] ) is invariant under a weyl transformation that takes g_^2 g _ , ( , ) ^(2-d)/2 ( , ) , [ weyl ] where @xmath27 is an arbitrary function on spacetime . such a transformation also takes @xmath28 . because of this local conformal symmetry , the field @xmath8 does not correspond to a physical degree of freedom ; indeed , if @xmath29 everywhere , one can gauge - fix the conformal symmetry to recover the usual einstein - hilbert formulation of gr . it is then clear that there is no physical ghost in the theory even though @xmath8 appears in eq . ( [ eq1 ] ) with the wrong - sign kinetic term . let us make this explicit . for @xmath29 , one can go to `` einstein gauge '' by performing a conformal transformation ( [ weyl ] ) that takes ^2 -^2 = : [ transf ] where @xmath0 is newton s constant . note that eq . ( [ transf ] ) does not entirely fix the gauge freedom as one can still perform a global rescaling that takes the constant to a different one ; the exact value of newton s constant is arbitrary and corresponds to a choice of units . einstein gauge corresponds to constraining the @xmath30-vector formed by @xmath31 to a hyperboloid @xmath32 in @xmath30-dimensional field space at each point in spacetime . one can introduce an explicit parametrization of this hyperboloid by @xmath7 coordinates @xmath33 , = ( ^1, ,^m),^i=^i(^1, ,^m ) , so that in this gauge the action ( [ eq1 ] ) reads s&=&d^d x \{-j^(_+_a_^a)},[newaction ] where @xmath34 is a positive definite metric of constant negative curvature on the gauge - fixed field space parametrized by the @xmath33 . again , eq . ( [ newaction ] ) shows that there are no physical ghosts in the theory , at least as long as @xmath35 . there are two different sectors in the space of field configurations where einstein gauge is available , corresponding to `` future - directed '' and `` past - directed '' ( in field space ) configurations , _ i.e. _ , to @xmath36 or @xmath37 . there are also regions where @xmath38 becomes negative , identified with `` antigravity '' in ref . @xcite as they would appear to correspond to a negative @xmath0 . we shall identify such regions with imaginary values of the `` scale factor '' and show how the passage of the universe through `` antigravity '' regions is a semiclassical representation of what is really a quantum bounce , similar to how quantum tunneling can be described by complex classical trajectories . the `` antigravity '' regions do contain a ghost , as now @xmath31 would be constrained to de sitter space @xmath39 which has a timelike direction . these regions and their ghost excitations do not appear in the physical in " and out " states of the theory , which are defined in asymptotic timelike regions where @xmath40 ; nevertheless , the existence of these regions can cause pathologies in the quantum theory if initial `` gravity '' states can propagate into the `` antigravity '' regions , as we will see in sec . [ feynfrw ] . setting @xmath10 , to make this more precise it is now useful to define a `` scale factor '' , or rather its square @xmath41 , with the following properties : it should be weyl invariant , so that it takes the same value in any conformal gauge . it should respect the @xmath42 isometry of the metric on the space of scalar fields ( defined by the kinetic terms ) and so depend only on the combination @xmath43 , the radiation density @xmath18 and the metric determinant @xmath44 . it should have physical dimensions of an area ( in the usual conventions @xmath45 ) , and scale like the square of the scale factor for an frw universe in einstein gauge in conformal time . these properties fix the `` squared scale factor , '' up to an overall constant , to be a^2(-g)^-(^2-^2 ) . [ scalefactor ] we shall use eq . ( [ scalefactor ] ) as a natural definition in general gauges ( the motivation for the factor @xmath46 will become clear shortly ) . note that @xmath41 will in general not be positive ; if we assume positive @xmath18 and a lorentzian metric , as we always will in the following , then in the `` antigravity '' regions @xmath47 and so @xmath4 is imaginary . this definition of @xmath4 differs from the one in ref . @xcite as it depends on the energy density of the radiation . in ref . @xcite , there was no such dependence . instead , factors of newton s constant were used to ensure the correct physical dimensions . for @xmath48 , we fix the sign of @xmath4 by choosing a time orientation in field space : @xmath4 is defined to have the same sign as @xmath8 . the minkowskian field space parametrized by @xmath49 is then partitioned into two regions with real @xmath4 and one region with imaginary @xmath4 , see fig . [ scalefactorim ] . note that the entire light cone corresponds to @xmath6 . this picture , as we have anticipated , gives physical meaning to positive , negative and imaginary @xmath4 , generalizing the case of pure radiation , @xmath50 , where there are no spacelike directions and @xmath4 takes values along the real axis , as in the example discussed in the introduction . ( 120,160 ) ( 10,25)(1,1)100(110,25)(-1,1)100 ( 10,25)(15,35)(60,38)(110,25)(105,35)(60,38 ) ( 10,25)(15,15)(60,12)(110,25)(105,15)(60,12 ) ( 10,125)(15,135)(60,138)(110,125)(105,135)(60,138 ) ( 10,125)(15,115)(60,112)(110,125)(105,115)(60,112 ) ( 55,100)@xmath51(55,45)@xmath52(85,70)``antigravity''(95,60)@xmath53 ( 0,70)(1,0)40(0,70)(0,1)40(35,75)@xmath54(2,105)@xmath8 ( 91,100)@xmath55(102,93)@xmath6 ( 45,23)``gravity''(45,123)``gravity '' apart from einstein gauge , another gauge that we will often employ , again following the framework introduced in ref . @xcite , is `` weyl gauge '' where the metric determinant @xmath44 is fixed to a constant ( typically @xmath56 ) . this gauge is available whenever the metric is non - singular ; in particular , it covers the entire field space pictured in fig . [ scalefactorim ] , encompassing both `` gravity '' and `` antigravity '' regions . it will often be a convenient gauge to work in . in weyl gauge , the expression for the scale factor reduces to @xmath57 , where for homogeneous models by energy - momentum conservation @xmath18 is constant . @xmath4 is then proportional to the ( signed ) timelike @xmath42-invariant distance from the origin in field space , making it a natural choice of time coordinate on superspace . for highly symmetric solutions such as frw universes , conformal symmetry can be used to eliminate curvature singularities in the metric by moving them into zeros of the quantity @xmath58 . since this quantity has no geometric interpretation , it is _ a priori _ reasonable for it to vanish or change sign . however , following the dynamical evolution through such points is in general problematic because the effective newton constant diverges so gravity becomes strongly coupled . this is reflected , for example , in the behavior of tensor ( gravitational wave ) perturbations , which diverge as the effective newton constant does . this leads to a diverging weyl curvature which can not be removed because it is conformally invariant . nevertheless , in the presence of scalar fields ( such as the electroweak higgs ) there is generically no mixmaster chaos and one expects the classical evolution to become ultralocal and kasner - like . there are a number of asymptotically conserved classical quantities , including the kasner exponents , suggesting a natural matching rule across the singularity @xcite but the issue has not been conclusively settled @xcite . in this paper , we take a different approach . we show that by extending the classical discussion to a quantum picture one can avoid the critical surface @xmath6 where the theory becomes problematic , independently of any weyl gauge choice . we will give a description of non - singular quantum bounces in terms of analytic continuation in @xmath4 , where the universe evolves from large negative @xmath4 to large positive @xmath4 along a contour in the complex @xmath4-plane which avoids @xmath6 . we shall argue that as long as the quantum mechanics of the @xmath4 degree of freedom make sense , the classical singularity at @xmath6 can be avoided without obstruction . as a first step , we perform the familiar symmetry reduction of our theory to homogeneous and isotropic frw universes , with metric assumed to be of the form ds^2=a^2(t)(-n^2(t)dt^2+h_ijdx^idx^j ) where @xmath59 is a fixed metric on hypersurfaces of constant @xmath60 , which has constant three - curvature @xmath61 . note our use of a conformal lapse function @xmath62 ; the usual definition of the lapse would be @xmath63 . we can now set the function @xmath64 to one by a conformal transformation , so that the metric becomes non - dynamical and all dynamics are in the scalar fields @xmath8 and @xmath54 . also , with frw symmetry @xmath65 , and the action ( [ eq1 ] ) reduces to s = v_0dt , [ eq2 ] where @xmath66 denotes derivative with respect to @xmath60 and @xmath67 is the comoving spatial volume ( which , as usual for minisuperspace models , must be assumed to be finite ) . we have simplified the last term including the lagrange multipliers which would be @xmath68 since the equations of motion involving @xmath23 and @xmath26 are clearly redundant in frw symmetry . as before , @xmath69 , and we can replace @xmath15 by @xmath18 as the independent variable . it is evident that eq . ( [ eq2 ] ) is the action for a relativistic massive free particle ( for @xmath70 ) or a relativistic massive particle in a harmonic potential or a harmonic `` upside - down '' potential ( for @xmath71 ) moving in @xmath30-dimensional minkowski spacetime . to make this more explicit , we can introduce new variables x^:=(,),=0, ,m , m:=2v_0 , [ newvariables ] so that eq . ( [ eq2 ] ) now takes the form s= dt [ eq3 ] where we have redefined the lagrange multiplier for simplicity , @xmath72 , and the minkowski metric on the space of scalar fields @xmath73 is used to raise and lower indices . a crucial role is played by the mass @xmath74 which corresponds to ( twice ) the total energy in the radiation ; the limit @xmath75 would correspond to a massless relativistic particle moving in a potential , which is the case well known in minisuperspace quantum cosmology with scalar fields @xcite . having a positive mass , and hence timelike trajectories as classical solutions , is one of the essential features of our model that leads to a bounce . with the definition ( [ newvariables ] ) , the weyl - invariant scale factor is simply @xmath76 , which explains the factor @xmath46 in eq . ( [ scalefactor ] ) . the variable @xmath4 is simply a time coordinate on superspace . one can introduce it explicitly by setting x^=av^,v^2=-1 [ vparam ] so that @xmath77 is restricted to a hyperboloid @xmath32 ( see fig . [ hyperbfig ] ) . ( 220,160 ) ( 110,10)(1,1)100(110,10)(-1,1)100 ( 10,110)(20,130)(110,135)(110,135)(200,130)(210,110 ) ( 10,110)(20,90)(110,85)(110,85)(200,90)(210,110 ) ( 20,110)(57,73)(110,68)(200,110)(163,73)(110,68 ) ( 20,110)(30,125)(110,130)(110,130)(190,125)(200,110 ) ( 20,110)(30,95)(110,90)(110,90)(190,95)(200,110 ) ( 110,10)(-1,4)15 ( 90,75)@xmath78(100,50)@xmath79 this parametrization , which isolates the physical scalar fields as the variables @xmath77 , will be useful below . starting from eq . ( [ eq3 ] ) , the classical equations of motion are & & ( ) + mx^=0 , [ eom1 ] + & & ^_+x^x_=-1 , + & & m = 0,= -^_+(x^x_+1)[lasteom ] . the general solution to these equations is @xmath80 , x^(t)&= & ( _ 0^t dtn(t ) ) + & & + ( -_0^t dtn(t ) ) [ classsol ] with @xmath81 , the lapse function @xmath82 is arbitrary and @xmath83 is determined from integrating eq . ( [ lasteom ] ) . for @xmath70 , the general solution is simply a general timelike straight line in minkowski spacetime , x^(t)=x_1^_0^t dtn(t ) + x_2^with @xmath84 . for @xmath70 , all solutions describe a bounce , similar to the example in the introduction : the universe comes in from negative real infinite @xmath4 , goes through @xmath6 followed in general by an `` excursion '' into imaginary @xmath4 , crosses @xmath6 again before going off to real positive infinity . when we go quantum , since the action is quadratic , the saddle point approximation is exact and the quantum dynamics is given purely in terms of these classical solutions . when viewed as saddle points , these trajectories can be deformed in the complex @xmath4-plane so that the singularity @xmath6 is avoided . the situation is more subtle for @xmath85 , where there are spacelike as well as timelike solutions , and for @xmath86 where there is a turnaround in the classical solutions and the universe must recollapse due to the spatial curvature . in sec . [ feynman ] , we will see how the more complicated structure of solutions for @xmath71 is reflected in a pathological behavior of the feynman propagator for large arguments . in order to pass to the hamiltonian formalism , following dirac s algorithm @xcite , one computes the canonical momenta for the action ( [ eq3 ] ) and finds p_==_,p_m- , p_n0 , p_0 . while the first equation can be inverted to express the velocities @xmath87 in terms of the momenta @xmath88 , the last three equations are _ primary constraints _ we use dirac s notion of `` weak equality '' @xmath89 for equations that hold on the constraint surface . the second and fourth constraint would be second class , meaning one has to introduce a dirac bracket and `` solve '' them . however , in this case , one can use the short cut of simply identifying @xmath90 with the momentum conjugate to @xmath74 and removing the separate variable @xmath91 . this is equivalent to saying that the term @xmath92 in eq . ( [ eq3 ] ) is part of the symplectic form @xmath93 so that one can read off @xmath94 . + the hamiltonian is then = n(+(x^2 + 1))+ p_n . [ frwhamilt ] preservation of @xmath95 under time evolution gives the secondary , hamiltonian constraint , c:=+(x^2 + 1)0 . @xmath62 can then be treated as a lagrange multiplier ; it only enters linearly in the hamiltonian , and its time evolution under @xmath96 is @xmath97 where @xmath98 is undetermined . removing @xmath99 from the phase space ( and setting @xmath100 in the hamiltonian ) , we are left with the canonical pairs @xmath101 and @xmath102 , subject to the constraint @xmath103 , which trivially satisfies @xmath104 . @xmath103 generates time reparametrizations , & & _ n x^=\{x^,nc}= , + & & _ n p_=-nmx _ , + & & _ n p_m =- n(-+(x^2 + 1 ) ) , which correspond to the lagrangian notion of time reparametrization , by the equations of motion ( [ eom1])-([lasteom ] ) . having set up the canonical formalism , we can proceed with quantization in the standard way . the hamiltonian constraint is imposed as an operator equation restricting the set of physical states . in the @xmath105 representation for the wavefunction , this is the wheeler - dewitt equation ( -_x+m^2(x^2 + 1))(x , m)=0 . [ wdw1 ] different @xmath74 sectors simply decouple , as a consequence of conservation of the total energy in the radiation , with no transitions between different @xmath74 values allowed . an alternative representation of wave functions is obtained by separating the scale factor from the physical scalar field degrees of freedom , as in eq . ( [ vparam ] ) , and introducing a set of coordinates @xmath33 , @xmath106 , on the hyperboloid @xmath32 . the wheeler - dewitt equation then becomes ( + -_h^m+m^2(1-a^2))(a,^i , m)=0 [ wdw2 ] where @xmath107 is the laplace - beltrami operator on @xmath7-dimensional hyperbolic space , _ i.e. _ , on the space parametrized by the coordinates @xmath33 . for example , using beltrami coordinates @xmath108 one would have _ h^m=(1-^2 ) . this coordinate choice on superspace makes the role of the timelike coordinate @xmath4 explicit . the wheeler - dewitt equation can then be simplified by fourier transforming from the @xmath33 coordinates to their conserved momenta @xmath109 , ( + -+m^2(1-a^2))(a,^i , m)=0 [ wdwfrw ] with c-(m-1)^2-^2 [ cpminimal ] corresponding to the eigenvalues of the laplacian on @xmath32 ( for @xmath110 ) . as we will see in sec . [ anisosec ] below , the same form of the wheeler - dewitt equation applies when including anisotropies in a bianchi i model or additional minimally coupled scalar fields , with the only change that the constant @xmath111 receives additional contributions from conserved anisotropy and scalar field momenta as well as from fixing ordering ambiguities . a natural inner product on solutions of a second order equation like eq . ( [ wdw2 ] ) is the klein - gordon - like norm & & -.^*(a,^i , m)(a,^i , m ) ) , [ norm ] with @xmath112 a constant negative curvature metric on @xmath32 , which is conserved under `` time evolution '' , _ i.e. _ independent of @xmath4 , for solutions of eq . ( [ wdw2 ] ) . this inner product was introduced by dewitt @xcite and has the well - known problem ( if it is used to define probabilities ) that it is only positive on positive - frequency solutions to eq . ( [ wdw2 ] ) , when they exist . for some simple cosmological models , this subspace is well - defined , and may be interpreted as the space of expanding quantum universes : if @xmath4 is taken to be positive , a wavefunction describing an expanding universe must be an eigenstate of @xmath113 with negative eigenvalue ( note that @xmath114 and so @xmath115 means @xmath116 ) , _ i.e. _ , a positive - frequency solution . this notion of positive frequency breaks down for cosmological models with recollapsing solutions , such as the frw universe with @xmath86 , where it is only well - defined until one reaches the turning point , and it is known that a decomposition into positive and negative frequencies of the type we are using here is not available in general @xcite . the question of how to define meaningful probabilities in quantum cosmology has , of course , been a matter of long debate ( see , _ e.g. _ , refs . @xcite ) . we shall not aim to resolve this debate here . the only use we shall make of the dewitt norm ( [ norm ] ) is to help us construct the feynman propagator from mode function solutions of the wheeler - dewitt equation . the expansion rate @xmath117 does play the role of an energy , which leads us to adopt feynman s picture for quantum field theory in which positive - energy ( _ i.e. _ , expanding ) states are propagated forward in proper time . the natural two - point function we consider below in sec . [ feynman ] is hence the feynman propagator . in what follows we shall alternate between the path integral and the feynman propagator as basic formulations of quantum cosmology , explicitly showing their equivalence in simple cases . so far , this is a completely standard definition of a minisuperspace model in wheeler - dewitt quantum cosmology . however , there is one crucial difference between our approach and previous treatments , in that we do not restrict the wave function to positive @xmath4 , nor do we impose any boundary condition at @xmath6 ( such as the popular choice @xmath118 ) . at fixed @xmath74 , the domain of the wavefunction is simply @xmath119 . any boundary condition at @xmath6 would seem artificial from the viewpoint of classical solutions such as classical frw bounces " which connect negative and positive @xmath4 , as we have described , and is also generally inconsistent with the wavefunction describing an expanding universe , _ i.e. _ a positive - frequency solution . in our proposal , the natural choice of wave functions corresponds to positive - frequency solutions that asymptote to plane waves at large @xmath120 , where the universe becomes semiclassical , while we allow for irregular behavior in the wavefunction at @xmath6 . the examples we consider all admit a semiclassical wentzel - kramers - brillouin ( wkb ) expansion in which one can deform the contour from the real @xmath4-axis into complex @xmath4 , avoiding @xmath6 entirely . the feynman propagator is one of the most basic ingredients in relativistic quantum theory . in quantum gravity , it plays the role of a causal green s function for the wheeler - dewitt equation , arising from a path integral in which one integrates only over positive values of the lapse function @xcite . if one considers amplitudes in which @xmath4 changes sign , as we shall , then the feynman propagator takes one from a contracting universe in the initial state to an expanding one in the final state , via a singularity of the big bang " type . such an amplitude provides a natural way to describe the emergence " of spacetime from quantum mechanical first principles @xcite . in this section , we show how to calculate the feynman propagator for frw universes directly from the path integral ; in particular , the path integral may be used to define the propagator without the need for an additional @xmath121 " prescription and , furthermore , the propagator directly defines the positive- and negative - frequency vacuum modes . as we have stressed , with frw symmetry the action is quadratic and the saddle - point approximation is therefore exact for the path integration over the phase space variables . however , we also have a constraint ( the friedmann equation ) which must be imposed via an additional integration over the lapse function or lagrange multiplier @xmath62 @xcite . this integral is no longer gaussian and will have to be considered with more care . things are considerably simpler for the flat frw case @xmath70 , where we have seen that the dynamics are just those of a massive relativistic free particle in minkowski spacetime . we shall therefore begin by reviewing how the feynman propagator for a relativistic particle is calculated both from a path integral and as a green s function for the differential equation satisfied by physical wavefunctions . we then extend these methods to treat general frw universes for the types of matter we consider . consider the action for a relativistic massive particle in @xmath30-dimensional minkowski spacetime , = dt ( -n ) , [ e1 ] where @xmath122 , @xmath123 is the parameterized particle world line and @xmath82 is the `` einbein . '' classically , @xmath62 may be eliminated using its equation of motion , obtaining the manifestly reparametrization - invariant action @xmath124 . quantum mechanically , it is more convenient to fix the reparametrization invariance ( see also the discussion of gauge fixing below eq . ( [ phsppathint ] ) ) : one can work in a gauge in which @xmath60 varies over a fixed range , conveniently taken to be @xmath125 , and @xmath62 is a @xmath60-independent constant , equal to the total , reparametrization - invariant time @xmath126 which we shall call @xmath127 . the feynman propagator is then given by the path integral g(x| x ) & = & dx + & = & _ 0^ d()^e^-(+ ) , [ e2 ] where @xmath128 and @xmath127 should be integrated over positive values . evaluating the gaussian path integrals is straightforward , with the only unusual factor being the prefactor of @xmath129 in the second line , which arises from the functional integral over @xmath130 , which has the `` wrong sign '' kinetic term so that the overall phase factor contributed is @xmath131 rather than the usual @xmath132 . the second line of eq . ( [ e2 ] ) is , of course , just the familiar schwinger representation of the feynman propagator , in which the exponent is the classical action evaluated on a solution of the equations of motion @xmath133 , satisfying the correct boundary conditions , _ i.e. _ , @xmath134 , and the prefactor is given by the usual ( regularized ) functional determinant . note that this solution is only the saddle point for the functional integral over paths @xmath135 , at fixed @xmath127 . the constraint @xmath136 arises subsequently , as the condition for a saddle point in the exponent of the @xmath127 integral . in fact , once the saddle point is chosen , the integration contour is then fixed ( up to an equivalence class of contours yielding the same result ) as the complete extension of the corresponding steepest descent contour . integrating over negative proper time in eq . ( [ e2 ] ) would reverse the notion of time ordering , whereas integrating over both positive and negative @xmath127 would lead to a symmetrized two - point function in which one sums over both time - orderings , _ i.e. _ , the hadamard propagator . for @xmath137 , the @xmath127 integral in eq . ( [ e2 ] ) has a potential divergence at @xmath138 . in fact , the integral converges at all real values of @xmath139 except @xmath140 . that divergence is real : the feynman propagator is singular for null - separated points . for other real values of @xmath139 , given that the integral converges for all @xmath139 in the lower - half @xmath139-plane , one may define the feynman propagator as the boundary value of the function defined by the integral , which is analytic in the lower - half @xmath139-plane . traditionally , the mass @xmath74 is also taken to have a small negative imaginary part , in order to make the @xmath127 integral absolutely convergent at large positive values ( feynman s @xmath141 " prescription ) . equivalently , one may distort the @xmath127-contour to run to infinite values below the real axis . the integral ( [ e2 ] ) may be directly expressed in terms of a hankel function , whose properties confirm these general arguments ( see appendix ) . it is instructive , however , to evaluate the @xmath127 integral in eq . ( [ e2 ] ) in the saddle - point approximation . first , consider timelike separations , @xmath142 . the exponent in the @xmath127 integral ( [ e2 ] ) is stationary at @xmath143 and @xmath144 , but only the former saddle point is relevant to the contour we want , which is deformable into the positive @xmath127-axis . the saddle point at @xmath143 gives rise to a `` positive frequency '' result , @xmath145 at large @xmath146 . the integration contour for @xmath127 may then be taken to be the corresponding steepest descent contour , shown as the solid line in fig . [ conts ] . now consider analytically continuing @xmath146 through the lower right quadrant to the negative imaginary axis , @xmath147 . it follows that @xmath0 converges as @xmath148 at large @xmath149 . correspondingly , this continuation implies that @xmath139 runs _ below _ the origin in the complex @xmath139-plane to negative values . the corresponding saddle point in @xmath127 moves as shown in fig . [ conts ] , passing below the origin in the complex @xmath127-plane and down the imaginary @xmath127-axis . at spacelike separations , @xmath150 , the saddle point is at @xmath151 , and the propagator falls exponentially with spacelike separation . notice that although the classical constraint @xmath136 remains satisfied at the saddle point , the saddle point value for @xmath127 is imaginary , and hence classically disallowed . hence , the propagation of a massive relativistic particle in spacelike directions may be viewed as a semiclassical quantum tunneling process , mediated by a complex classical solution . -plane , for the relativistic massive propagator , defined in eq . ( [ e2 ] ) . as @xmath152 is varied , from timelike values @xmath153 with @xmath146 real , to spacelike values @xmath154 , with @xmath149 real , by passing beneath the origin in the complex @xmath139-plane , the saddle point in @xmath127 , shown by the black point , moves correspondingly . in each case , the integral is defined by the associated steepest descent contour running from @xmath155 to @xmath156 , also shown . ] in order to match the path integral definition of the feynman propagator to its definition as a green s function , it is convenient to use a time - slicing with maximal spatial symmetry . here , the trivial time - slicing defined by @xmath130 is spatially homogeneous , so one can fourier transform in the spatial coordinates and reduce the problem to a single timelike dimension . defining g(x|x)= e^(- ) g_k(x^0,x^0 ) , [ e6 ] one finds that @xmath157 is given by g_k(x^0,x^0 ) = _ 0^ de^-(+ ) [ fourierint ] where @xmath158 . by considering the saddle - point approximation to eq . ( [ fourierint ] ) , we see that the fourier - transformed feynman propagator asymptotically satisfies g_k(x^0,x^0)&~ & e^-_k x^0,x^0 + , x^0 , [ asymp1 ] + g_k(x^0,x^0)&~ & e^+_k x^0,x^0 - , x^0 . [ asymp2 ] such asymptotic expressions can be used to fix boundary conditions for the corresponding wave ( wheeler - dewitt ) equation , as we will do shortly . formally , @xmath159 is the matrix element @xmath160 , where we again assume the integral converges at infinite @xmath127 . hence , suitably defined , @xmath161 should obey h_x g(x| x)=-^m+1(x - x ) , [ e3 ] where @xmath162 is the hamiltonian in the @xmath163-representation , @xmath164 . we can check eq . ( [ e3 ] ) is indeed satisfied by applying @xmath162 to the last line of eq . ( [ e2 ] ) and using the fact that the integrand is a product of free - particle quantum mechanical propagators , & & ( -_x+m^2)g(x|x ) + & = & _ 0^ d \ { ( ) ^e^(- ) } + & = & _ 0 ( ) ^e^ ( ) , [ e5 ] where the limit should be taken along the appropriate contour in the complex @xmath127-plane . the last line of eq . ( [ e5 ] ) is a representation of the @xmath30-dimensional delta function : separating it into a product of similar terms for each coordinate @xmath165 , we determine the coefficient of the corresponding delta function by fourier transforming with respect to @xmath165 , and then taking the limit @xmath166 . for the timelike coordinate we obtain @xmath167 , whereas for the spacelike coordinates we obtain @xmath168 . together , these results verify eq . ( [ e3 ] ) . the point is now that the feynman propagator can also be computed by directly solving eq . ( [ e3 ] ) in terms of mode functions , again because the fourier transform allows reduction of the problem to one dimension . writing both the delta function and the propagator in eq . ( [ e3 ] ) as fourier transforms , one sees that @xmath161 clearly satisfies eq . ( [ e3 ] ) as long as ( _ 0 ^ 2 + _ k^2)g_k(x^0,x^0)=-2 m ( x^0-x^0 ) . this equation is solved by g_k(x^0,x^0)&=&- ( ^k_1(x^0)^k_2(x^0 ) ( x^0-x^0 ) . + ^k_1(x^0)^k_2(x^0 ) ( x^0-x^0 ) ) , [ e7 ] where @xmath169 and @xmath170 are two independent solutions to the homogeneous equation @xmath171 , and @xmath172 is the natural conserved ( _ i.e. _ , @xmath130-independent ) inner product , or wronskian . the dependence of the feynman propagator at large positive and negative times now determines the appropriate choices for @xmath173 and @xmath174 : comparing eq . ( [ asymp1])-([asymp2 ] ) with eq . ( [ e7 ] ) we infer that , up to irrelevant constants , @xmath175 and @xmath176 . inserted into eq . ( [ e6 ] ) and eq . ( [ e7 ] ) , these give the usual expression for the feynman propagator in `` time - ordered '' form . this shows how , in the example of the relativistic particle , the correct boundary conditions that define the feynman propagator as one particular solution of eq . ( [ e3 ] ) can be obtained from the asymptotic behavior of its path integral definition . we will now proceed similarly to define the feynman propagator for general frw universes . for our cosmological model , the feynman propagator can be defined through a phase - space path integral , taking into account the integration over the lapse @xmath62 @xcite , g(x , m| x,m ) = x^p_m p_mn ( _ -1/2 ^ 1/2 dt(^p_+p_m - n(+ ( x^x_+ 1 ) ) ) ) . [ phsppathint ] as in the previous example , due to the reparametrization invariance of the theory the parameter time ( specified by @xmath60 ) between the initial and final configurations is arbitrary , and we choose it to run from @xmath177 to @xmath46 . in order for the path integral to be well - defined , the gauge invariance under time reparametrizations generated by the hamiltonian constraint must be broken by fixing a specific gauge . one simple gauge - fixing , @xmath178 , can be obtained by introducing a new field @xmath179 and adding the term @xmath180 to the action ; we refer to ref . @xcite for details . integrating over the field @xmath179 then reduces the integration over @xmath62 to an ordinary integral over the total conformal time between the initial and final configurations ; we make this explicit by again writing @xmath62 as @xmath127 . the remaining path integrals may be computed exactly . path integration over @xmath74 and @xmath181 simply gives a delta function in @xmath74 , as expected since @xmath74 has trivial dynamics constraining it to be constant . one can then integrate over @xmath182 which yields g(x , m| x,m ) & & = ( m - m)[eq3a ] + & & dx corresponding to @xmath183 decoupled harmonic oscillators . for @xmath70 , apart from the overall delta function , this is exactly the expression eq . ( [ e2 ] ) . accordingly , the path integral over @xmath163 is just that of a free relativistic particle and the @xmath127 integral can be evaluated exactly ; the result is g^0(x , m| x,m ) = ( m - m ) ( -m)^m ( 2s)^ h_^(2)(s ) , [ eq4a ] with @xmath184 , where @xmath185 is a hankel function of the second kind ( see appendix ) . the @xmath186 in its argument indicates the expression is the boundary value of a function which is analytic in the lower half @xmath187-plane . as we have emphasized , we have derived this definition from the path integral , and the requirement that the integral over proper time @xmath127 converges . in order to understand the more involved case of spatial curvature @xmath71 , it is again helpful to recall how eq . ( [ eq4a ] ) can be obtained from the wronksian method ; for simplicity , let us set @xmath50 and label @xmath188 which is our scale factor . then the feynman propagator is a solution to ( + ) g^0(a , m| a,m ) = -(m - m)(a - a ) and can be written in the form g^0(a , m|a,m)&=&-2m(m - m)((a - a ) . + & & + .(a-a ) ) [ analyticgreens ] where @xmath189 is again the ( @xmath4-independent ) wronskian and @xmath190 and @xmath191 are two appropriate independent solutions to the homogeneous equation @xmath192 , found by matching eq . ( [ analyticgreens ] ) with the asymptotic behavior of eq . ( [ e2 ] ) at infinity , with @xmath193 ( and there are no spacelike directions to be considered ) . as explained below eq . ( [ fourierint ] ) , ( [ e2 ] ) asymptotes to @xmath194 for large positive @xmath4 at fixed @xmath195 , and to @xmath196 for large negative @xmath195 at fixed @xmath4 ; this fixes the modes in ( [ analyticgreens ] ) as @xmath197 and @xmath198 ( up to a normalization that is irrelevant for @xmath199 ) . thus , one finds g^0(a , m|a,m)=(m - m)e^-m|a - a| , in agreement with eq . ( [ eq4a ] ) for @xmath50 . with this in mind , we can now go beyond the simplest flat case , and consider @xmath71 , where the dynamics of the universe corresponds to those of a relativistic oscillator or `` upside - down '' oscillator . the path integral over @xmath163 in eq . ( [ eq3a ] ) is easily calculated : the classical path which fixes the exponent generalizes to x(t)= , [ class1 ] which is unique for all @xmath163 , @xmath200 and @xmath127 ( where we exclude special cases for which @xmath201 ) , and the prefactor is given by the usual regularized functional determinant for the harmonic oscillator , so that g(x , m| x,m ) = ( m - m)_0^ d()^. [ oscpathint ] the overall factor of @xmath129 arises just as it did for the free relativistic particle , discussed in the previous subsection . as there , we are left with an ordinary integral over @xmath127 , and need to establish the appropriate integration contour . the resulting integral is difficult to do directly but we can use its behavior at large positive @xmath4 and large negative @xmath195 to fix the mode functions @xmath202 and @xmath203 appearing in the wronskian representation . as a consistency check , we compare the resulting green s function to a numerical evaluation of the @xmath127 integral in eq . ( [ oscpathint ] ) along a suitable contour , finding perfect agreement in all cases . in this numerical evaluation , we choose @xmath204 and @xmath205 , so that any classical real solution has to pass through the singularity @xmath6 at least once , which is the situation of main relevance for our study . for ease of comparison , we plot the flat case @xmath70 , with @xmath50 , _ i.e. _ , @xmath206 , with @xmath207 , in fig . [ flatpropplot ] ( here and in the following we are of course plotting the function multiplying @xmath208 ) . , for @xmath207 , showing real part ( blue ) , imaginary part ( dashed ) and absolute value ( black ) which is constant here . ] consider the saddle points in the @xmath127 integral for the curved - space propagator , and the associated steepest descent contour . the condition for the exponent to be stationary with respect to @xmath127 is precisely the hamiltonian constraint ( friedmann equation ) @xmath209 , with @xmath135 given by eq . ( [ class1 ] ) . real saddle points of the full functional integral , when they exist , are real solutions of the classical equations of motion , including the constraints . given such saddle points , one defines the associated @xmath127 integration cycle as the complete extension of the steepest descent contour . if this cycle can be deformed to the real @xmath127-axis while maintaining the convergence of the integral , then the saddle point contribution is relevant to the final result . we start with the case of negative @xmath210 , where , just as in the flat case , there is always a unique classical solution : for timelike separated @xmath163 and @xmath200 , the saddle point in @xmath127 is located on the real axis , and the steepest descent contour is the solid curve in fig . [ taucontour ] . the singular behavior of the integrand at @xmath138 ( cf . ( [ e5 ] ) ) then ensures , just as in the argument leading to eq . ( [ e5 ] ) , that eq . ( [ oscpathint ] ) is a green s function for the wheeler - dewitt equation , ( -+(x^2 + 1))g = -(m - m)^m+1(x - x ) . -plane for @xmath211 ( solid line ) and for @xmath212 ( dashed line ) , for the case where @xmath204 and @xmath205 . ] once more we set @xmath50 for simplicity , and obtain the green s function from the wronskian method , with the modes determined from their behavior at large argument . the wheeler - dewitt equation , at fixed @xmath74 , is ( + m^2(1-a^2))(a ) = 0 , [ webereq ] and is solved by parabolic cylinder functions @xcite , denoted by @xmath213 . in order to find the modes that generalize the plane waves @xmath214 used in the @xmath70 case , we can again study the asymptotic limits of eq . ( [ oscpathint ] ) using the saddle point approximation , finding that we must have ( with @xmath85 ) _ 3(a)&~ & |a|^- e^-a^2,a- , + _ 4(a)&~ & |a|^- e^-a^2,a+ , [ asymptotics ] for the mode functions @xmath215 and @xmath216 appearing in the analog of eq . ( [ analyticgreens ] ) . this asymptotic behavior is also consistent with the requirement that , as eq . ( [ oscpathint ] ) is invariant under @xmath217 and @xmath218 , @xmath215 and @xmath216 must satisfy _ 3(-a)=_4(a ) . two independent solutions to eq . ( [ webereq ] ) are given by ( a)&=&d_-((1-)(-)^1/4a ) and its complex conjugate , which asymptotically become pure negative and positive frequency modes as @xmath219 but are a mixture as @xmath220 . we therefore set _ 4(a)=d_--((1+)(-)^1/4a ) and @xmath221 . by computing their wronskian we obtain the green s function g(a , m|a,m)&&=(+)(m - m ) + & & ( _ 3(a)_4(a)(a - a)+(aa ) ) . [ paragreens ] as we have said , this result can also be obtained from numerical evaluation of eq . ( [ oscpathint ] ) . again we choose @xmath204 and @xmath205 and also fix @xmath222 , @xmath50 and @xmath207 . the resulting function of @xmath146 is plotted in fig . [ openprop ] . notice that the resulting propagator resembles the flat - space ( @xmath70 ) expression for small @xmath146 , and the effects of spatial curvature become relevant only at scales @xmath223 . , for @xmath207 and @xmath222 , showing real part ( blue ) , imaginary part ( dashed ) and absolute value ( black ) . ] for positive @xmath210 , the behavior is rather different from @xmath224 in that for positive @xmath210 the real , classical solutions are periodic in @xmath127 ; for given @xmath163 and @xmath200 , when one classical solution exists there will be an infinite number , and in general they should all contribute to the propagator . again for consistency with the @xmath225 limit , we can choose the @xmath127 integration contour such that it only picks out the simplest saddle point , where the classical solution interpolating between @xmath163 and @xmath200 has no turning points . the corresponding saddle point and steepest descent contour , indicated by the dashed curve in fig . [ taucontour ] , goes over to the unique @xmath70 saddle point and steepest descent contour in fig . [ conts ] in the flat limit @xmath225 . , for @xmath207 and @xmath226 , showing real part ( blue ) , imaginary part ( dashed ) and absolute value ( black ) . as discussed in the text , for @xmath227 the semiclassical interpretation fails . ] another issue is that for large timelike @xmath163 and @xmath200 there is _ no _ real classical solution at all ; for large timelike arguments , the saddle point for @xmath127 becomes imaginary and , as explained above , we choose the one on the negative imaginary axis . by the same saddle point approximation as above , one then determines the asymptotic behavior of the relevant mode functions @xmath228 and @xmath229 , _ 5(a)&~ & |a|^-- e^+a^2,a- , + _ 6(a)&~ & |a|^-- e^+a^2,a+ , again consistent with @xmath230 . these results , as well as the form of the propagator , can in fact be obtained by replacing @xmath231 in the expressions for the open case . ( the factor @xmath232 was dropped in the expressions above since it was a subleading oscillatory factor @xmath233 . ) it is straightforward to obtain a complete analytic expression for the @xmath86 propagator from parabolic cylinder functions by solving the homogeneous equation ( [ webereq ] ) . two independent solutions with @xmath86 are _ 5(a)&=&d_--(-^1/4a ) , + _ 6(a)&=&d_--(^1/4a ) . [ parabolic ] these are again complex conjugates of each other , and here also already satisfy @xmath230 , unlike for the open case @xmath85 . on the other hand , they are not asymptotic positive or negative frequency modes , but blow up exponentially both at positive and at negative infinity . at small @xmath4 , up to corrections that vanish as @xmath225 they reduce to plane waves @xmath234 . from eq . ( [ parabolic ] ) , the wronskian method gives the green s function g(a , m|a,m)&&=(+)(m - m ) + & & ( _ 5(a)_6(a)(a - a)+(aa ) ) . [ greensclosed ] as before , we have verified that this expression agrees with the result of a numerical integration of the @xmath127 integral along the chosen contour . with @xmath204 , @xmath205 , as well as @xmath226 , @xmath50 and @xmath207 , the resulting function of @xmath146 is plotted in fig . [ propfig ] . again , it reduces to the @xmath70 expression @xmath235 for small @xmath146 . the integration contour in fig . [ taucontour ] is chosen in such a way that its main contribution , for small enough @xmath146 , comes from the lowest positive real saddle point in @xmath127 , corresponding to the real classical solution that takes the smallest amount of proper time . as the arguments of the feynman propagator approach @xmath236 and @xmath237 , this saddle point moves towards @xmath238 where it eventually merges with another saddle point approaching @xmath238 from above , corresponding to two classical solutions that become indistinguishable in this limit . our choice of integration contour then becomes ambiguous and is no longer defined by consistency with the @xmath225 limit . as we extend the arguments to @xmath239 , where there is no longer a real solution , these two saddle points separate again and start moving up and down the imaginary axis this is akin to the situation for spacelike separations for the relativistic particle , and means that our saddle point needs to be replaced by a saddle point on the line @xmath240 parallel to the negative imaginary @xmath127-axis . for the purposes of this paper , we are mainly interested in studying the propagator with arguments for which there is a classical solution , so that a semiclassical picture of the propagator as given by these solutions is meaningful . the exponential blowup of the feynman propagator for large @xmath146 follows from the asymptotic behavior of the integral ( [ oscpathint ] ) for large timelike @xmath163 and @xmath200 . the corresponding mode functions increase exponentially for @xmath239 when there are no classical solutions , as can be verified explicitly from the asymptotics of the parabolic cylinder functions ( [ parabolic ] ) . the feynman propagator is hence pathological for large timelike separations , and does not define a suitable two - point function on the entire superspace , because positive curvature forces classical solutions to recollapse . an asymptotic description in terms of well - defined states that can be used to formulate a quantum theory of expanding universes does not exist for positive spatial curvature , and this case does not consistently describe the type of quantum bounce we are interested in . of course , this situation could be altered by the inclusion of a positive cosmological constant , as we mention later . for @xmath85 , classical solutions with pure radiation are well - behaved , expanding to infinite volume in the future and past and leading to a well - behaved feynman propagator , eq . ( [ asymptotics ] ) . however , as we mentioned in sec . [ friedbounce ] , when conformally coupled scalars are introduced ( @xmath110 ) , the general solution x^(t)&= & ( _ 0^t dtn(t ) ) + & & + ( -_0^t dtn(t ) ) , with @xmath241 , has both spacelike `` antigravity '' and timelike `` gravity '' solutions : choosing spacelike @xmath242 and @xmath243 that satisfy the constraint , one finds a universe that comes in from one `` antigravity '' direction , turns around before entering `` gravity '' and then disappears into a different ( or the same ) `` antigravity '' direction . such spacelike solutions are far enough in the `` antigravity '' region that the curvature term dominates over the positive mass in the potential @xmath244 , leading to their acceleration towards spacelike infinity . even though there are no real classical solutions that connect incoming `` gravity '' solutions to these far `` antigravity '' regions , and starting in a gravity region one is guaranteed to asymptote into the other gravity region , quantum - mechanically one expects the spacelike solutions to determine the behavior of the feynman propagator for spacelike separations . this is indeed confirmed by finding the saddle point approximation to eq . ( [ oscpathint ] ) for large spacelike separations , _ e.g. _ , for @xmath245 at fixed @xmath200 , g(x , m|x,m)~|x|^-1/2e^x^2 . the propagator becomes oscillatory at spacelike separations , so that a given initial state , _ e.g. _ , a wave packet centered around an initial state in the `` gravity '' region @xmath52 , is propagated to large spacelike distances into the `` antigravity '' region . in this sense , the quantum theory is even more pathological for open than for closed universes , where one finds , again for @xmath245 at fixed @xmath200 , g(x , m|x,m)~|x|^-- e^-x^2 , , exponential fall - off for large spacelike separations . this is because for @xmath86 , both timelike and spacelike classical solutions are bounded due to the potential , and never reach ( timelike or spacelike ) infinity . neither @xmath85 nor @xmath86 can lead to a viable `` perfect bounce '' picture in terms of a transition between incoming and outgoing `` gravity '' states with @xmath246 , while the @xmath70 case leads directly to a `` perfect bounce . '' we conclude that , at least for the theories considered here , only flat frw universes lead to a consistent quantum theory , able to account for an expanding universe . the inclusion of a positive cosmological constant could rescue positively curved universes from this conclusion , provided the curvature is too small to cause a recollapse . nevertheless , the quantum pathology we have identified for negatively curved frw universes is intriguing , because it raises the possibility that the observed ( nearly flat ) universe lives on the corresponding critical boundary . this would be the case , for example , if we could identify the correct quantum measure on the space of closed universes , with sufficiently large cosmological constant to prevent recollapse , and if this measure favoured the flat case . we shall explore this possibility in future work . for the remainder of this paper , however , we shall ignore spatial curvature . we now extend the treatment to anisotropic cosmologies , choosing the simplest form of anisotropies , the bianchi i model : we still require the metric to be spatially homogeneous , with an abelian group of isometries acting on constant time hypersurfaces , but no longer impose isotropy . the most convenient parametrization of such a metric employs misner variables @xcite , ds^2&=&a^2(t)(-n^2(t)dt^2+e^2_1(t)+2_2(t)dx_1 ^ 2 . + & & .+e^2_1(t)-2_2(t)dx_2 ^ 2+e^-4_1(t)dx_3 ^ 2 ) . [ bianchimetric ] the ricci tensor , and hence the einstein tensor , for this metric are diagonal , which by the einstein equations forbids any anisotropy in the fluid , manifest in a velocity @xmath247 . we hence continue to assume that the fluid moves with the cosmological flow , @xmath248 . we can then again exploit the conformal freedom to set @xmath64 to one . the ricci scalar of ( [ bianchimetric ] ) is then r=6 , giving the correct canonical normalization of the anisotropy variables @xmath249 in the symmetry - reduced action , s = v_0dt . [ symraction ] in terms of the variables @xmath165 and @xmath74 defined in eq . ( [ newvariables ] ) , this action reads s= dt . [ bianchiaction ] as for the flat frw universe which the bianchi i universe generalizes , this is the action of a free massive relativistic particle . however , here the particle is not moving through a flat minkowski spacetime but through a curved superspace , with metric ds^2=_dx^dx^-x^2(d_1 ^ 2+d_2 ^ 2 ) or , if we again use the parametrization @xmath250 with @xmath251 to separate the scale factor @xmath4 , introducing coordinates @xmath33 on the hyperboloid @xmath32 , ds^2=-da^2+a^2g_h^m+a^2(d_1 ^ 2+d_2 ^ 2 ) where @xmath112 is a constant negative curvature metric on @xmath32 , as in sec . [ friedbounce ] . the geometry of superspace at fixed @xmath4 corresponds to the maximally symmetric space @xmath252 ; in the absence of anisotropies , the last term would vanish and one would simply use milne coordinates for flat minkowski spacetime . it is well known that the dynamics of anisotropies in the bianchi i model are equivalent to minimally coupled free scalar fields in a flat frw universe . to see this , we momentarily switch to einstein gauge , where a flat frw universe has metric ds^2=a^2(t)(-n^2(t)dt^2+h_ijdx^idx^j ) . the action of a free scalar field in this background is -d^4 x()^2 = v_0dta^2 . [ scalaraction ] to see that this reduces to the kinetic terms for the anisotropies @xmath249 in eq . ( [ symraction ] ) , we note that since the scale factor ( [ scalefactor ] ) is weyl - invariant , one can express it both in weyl and einstein gauge , a^2=(^2-^2)|_weyl=|_einstein with @xmath253 in einstein gauge ( in weyl gauge , @xmath254 is constant ) . to change gauges , one hence has to replace a^2|_einstein ( ^2-^2)|_weyl ; the factor @xmath255 can be absorbed in the normalization of the scalar fields , : = [ normalize ] ( the anisotropy variables are dimensionless while a scalar field has dimensions of mass ) , showing the equivalence . hence , we obtain a simple generalization of the theory we have discussed by also adding an arbitrary number of minimally coupled free scalar fields , which can represent either physical scalar fields or anisotropy degrees of freedom of the bianchi i model . one has to `` lift '' the free scalar fields to a weyl - invariant theory by -d^4 x()^2 -d^4 x(^2-^2)()^2 [ scalarlift ] where @xmath256 is again dimensionless and conformally invariant . in einstein gauge , eq . ( [ scalarlift ] ) clearly reduces to eq . ( [ scalaraction ] ) . going back to weyl gauge , the total action is then s= dt , [ generalaction ] which is a simple generalization of eq . ( [ bianchiaction ] ) . the @xmath257 variables @xmath249 , @xmath258 , can now correspond to anisotropy variables or minimally coupled scalar fields with the unusual normalization ( [ normalize ] ) . ( [ generalaction ] ) is now the action of a particle moving in an @xmath259-dimensional superspace with curved metric ds^2&=&_dx^dx^-x^2_i=1^k d_i^2 + & = & -da^2+a^2g_h^m+a^2_i=1^k d_i^2 . [ supermetric ] by an elementary generalization of the procedure described in sec . [ canonical ] , eq . ( [ generalaction ] ) gives a hamiltonian constraint c:=g^(x,)p_p_+ 0 [ generalconstraint ] where @xmath260 is the inverse metric on superspace , and @xmath261 includes conjugate momenta for both the variables @xmath165 and the new degrees of freedom @xmath249 ; more concretely , c=(-p_a^2+g^ij_h^m()_i_j + ^ijk_i k_j)+ [ constraint ] in terms of the momentum @xmath262 conjugate to @xmath4 , momenta @xmath263 conjugate to the conformally coupled scalar field variables @xmath33 living on @xmath32 , and momenta @xmath264 conjugate to the free scalar fields and anisotropy variables . when quantizing this hamiltonian constraint in order to obtain the wheeler - dewitt equation , there is now an ambiguity , the well known quantization ambiguity for a particle moving on a curved manifold @xcite : if the ricci scalar for the superspace metric ( [ supermetric ] ) is @xmath265 , the general expression for the quantum hamiltonian is h=(-+)+ [ quantham ] where @xmath266 is the laplace - beltrami operator for the curved metric ( corresponding to the operator ordering that ensures that the hamiltonian is independent of the choice of coordinates on superspace ) and @xmath98 is , in general , a free parameter . halliwell @xcite has given the following strong argument for fixing @xmath98 : the ( classical ) hamiltonian of minisuperspace models is really @xmath267 ( see sec . [ friedbounce ] ) where the lapse function @xmath62 is arbitrary , and in particular can be redefined arbitrarily , @xmath268 , where @xmath269 is any function on minisuperspace . under such a redefinition , the constraint ( [ generalconstraint ] ) becomes : = ^(x,)p_p_+ 0 with @xmath270 and @xmath271 , leading by the same argument as above to a quantum hamiltonian = ( -+)+ , [ qhricc ] where now @xmath272 and @xmath273 are the laplace - beltrami operator and ricci scalar for the conformally rescaled metric @xmath274 on superspace . halliwell now asks that , since redefining the lapse is always possible classically , the solutions @xmath275 and @xmath276 to @xmath277 and @xmath278 be related by a conformal transformation , @xmath279 for some @xmath280 , and finds that this is only possible if one fixes @xmath98 to be the conformal coupling , = [ xivalue ] ( recall that the dimension of our superspace manifold is @xmath281 ; ref . @xcite gives an overall minus sign for @xmath98 , presumably due to a different sign convention for the ricci curvature ) . demanding covariance under field redefinitions of the lapse function hence fixes @xmath98 uniquely . special cases are @xmath282 where there is no conformal coupling that can restore covariance under lapse redefinitions , and @xmath283 where the laplace beltrami operator is conformally covariant and @xmath100 . the wheeler - dewitt equation corresponding to the classical constraint ( [ constraint ] ) then becomes ( + -_h^m^k . & & + .++m^2)&(a,,,m)=&0with = . as in sec . [ friedbounce ] , one can simplify the wheeler - dewitt equation by fourier transforming on @xmath284 from @xmath285 and @xmath256 to the momenta @xmath109 and @xmath286 . one then has ( + -+m^2)(a,,k , m)=0 [ wdwbianchi ] with c=-(m-1)^2+_m,0-^2-^2-k ( 2m+k-1 ) , [ constant ] where we have explicitly included also the case @xmath50 through the kronecker delta . this is precisely the same functional form as the wheeler - dewitt equation for frw universes , eq . ( [ wdwfrw ] ) , and so the extension of our formalism from frw symmetry to the bianchi i model and the inclusion of minimally coupled scalars are completely straightforward . the constant @xmath111 now gets contributions from the eigenvalues of the laplacian on @xmath284 , as well as from the curvature on superspace . we can now obtain the general solution to eq . ( [ wdwbianchi ] ) in the usual way , by setting ( a,,k , m)=a^-(m+k)/2(a,,k , m ) [ psichi ] to eliminate the first derivative . @xmath287 then satisfies the differential equation ( -+m^2)(a,,k , m)=0 [ schrodinger ] where @xmath288 , which has two independent solutions in terms of bessel functions of the first and second kind , _ 1=j_(ma),_2=y_(ma ) . a more convenient basis is given by the hankel functions @xmath289 of the first and second kind ( which are just linear combinations of the bessel functions ) , so that two linearly independent solutions of eq . ( [ wdwbianchi ] ) , for fixed @xmath109 , @xmath286 and @xmath74 , are finally given by _ + , -(a)=a^-(m+k-1)/2h_^(2,1)(ma ) . [ plusminus ] as indicated by the subscript @xmath290 , these functions represent positive- and negative - frequency modes for the wheeler - dewitt equation . indeed , when extended to negative @xmath4 through the analytic continuation ( see , _ e.g. _ , ref . @xcite ) @xmath291 and @xmath292 , @xmath293 have the interesting property of corresponding to pure positive and pure negative frequency , respectively , both at positive and negative infinite @xmath4 , _ + ( a)&~ & a^-(m+k)/2e^-m a , a , + _ -(a)&~ & a^-(m+k)/2e^+m a , a . [ hankelasymptotics ] that is , for the wheeler - dewitt equation ( [ wdwbianchi ] ) one finds that an incoming positive - frequency mode simply continues to an outgoing positive - frequency mode , with the potential at @xmath6 not even leading to a phase shift . this complete invisibility of the @xmath294 potential is a direct consequence of the symmetry of eq . ( [ wdwbianchi ] ) under @xmath295 and @xmath296 , which forbids any phase shift . these special properties of a @xmath297 potential , and its invisibility in a scattering process , are well - known in quantum mechanics . in the context of our `` perfect bounce '' scenario , they imply that the universe can go through the singularity @xmath6 without any noticeable impact on its evolution , when viewed asymptotically . this is already true classically , where the classical solutions bounce without any net time delay or advance : the classical hamiltonian is equal to the constraint ( [ constraint ] ) times a lapse function , = n((-p_a^2+g^ij_h^m()_i_j + ^2)+ ) the terms multiplying @xmath294 are again conserved and can be replaced by a constant , @xmath298 with @xmath299 ; classically the effect of anisotropies and momenta in the scalar fields always leads to an attractive potential for @xmath4 , centered on the singularity at @xmath6 . the classical solutions to the equations of motion including the constraint are then a^2=+n^2(t - t_0)^2=+(-_0)^2 [ solutions ] in terms of proper time @xmath300 . these solutions are singular at @xmath6 and perform an excursion into the `` antigravity '' region of imaginary @xmath4 , just as the generic flat frw solutions described in sec . [ friedbounce ] which would be of the exact same form . the attractive potential at @xmath6 speeds up the trajectory as it heads toward the singularity , but this time advance is canceled by the additional time it takes to cross `` antigravity . '' indeed , both at large positive and negative @xmath4 we have simply @xmath301 . in the quantum theory , ordering ambiguities in the hamiltonian constraint can alter the coefficient of the @xmath294 potential , making it repulsive in some cases . indeed , the relevant coefficient of the potential is the one appearing in eq . ( [ schrodinger ] ) , c&=&-(m-1)^2+_m,0-^2-^2 + & & + [ cprime ] if we use the value ( [ xivalue ] ) for @xmath98 , that is , we fix the ordering ambiguities by demanding coordinate covariance on superspace and covariance under redefinitions of the lapse function , giving a purely quantum contribution in the second line of eq . ( [ cprime ] ) . if we ignore the trivial case @xmath302 , we can rewrite eq . ( [ cprime ] ) as c = -^2- & m1,k=0 , -^2- & k1,m=0 , -^2-^2- & k 1,m=1 , -^2-^2-+ & k 1,m > 1 . [ cpp ] this is an intriguing result . the contributions coming from anisotropy or scalar field momenta are both negative . the numerical term is fixed by covariance . the first line corresponds to the situation of sec . [ friedbounce ] , where no anisotropies or minimally coupled scalars are present ( from eq . ( [ wdwfrw ] ) , removing the first derivative term changes @xmath111 in eq . ( [ cpminimal ] ) to @xmath303 given here ) . the similarity of the first three lines is not a coincidence ; for @xmath304 , the superspace metric ( [ supermetric ] ) is conformally flat . as we have imposed conformal coupling to the ricci scalar on superspace in eq . ( [ qhricc ] ) and eq . ( [ xivalue ] ) , the dynamics must be equivalent to the flat superspace case of sec . [ friedbounce ] . the value @xmath305 is well - known as a critical value in the quantum mechanics of an inverse square potential . if @xmath306 , the negative classical potential is outweighed by the kinetic energy due to the heisenberg uncertainty principle , rendering the energy spectrum strictly positive . there are various infrared regularized versions of the theory in which the spectrum is made discrete by including a positive harmonic potential @xcite , with @xmath4 is taken on the infinite line , or by imposing periodicity in @xmath4 , in which case the model becomes the calogero - sutherland model ( see , _ e.g. _ , ref . these are well - defined , exactly solvable models which exhibit , among other interesting phenomena , anomalous dimensions in the operator product expansion @xcite . if , however , @xmath307 , any finite energy wavefunction has an infinite number of oscillations on the way to @xmath6 . in quantum mechanics , standard arguments would then imply an infinite number of lower energy states , and hence a spectrum which is unbounded below . it has been claimed that the theory is nevertheless renormalizable , although the renormalization group displays a limit cycle @xcite . ( there is a large literature on inverse square potentials in quantum mechanics , and even some experimental tests . e.g. _ , ref . @xcite for a recent discussion and further references . ) at the minisuperspace level discussed here , negative energy states are irrelevant because we are only interested in solutions of the wheeler - dewitt equation with positive energy , defined by @xmath308 . however , when we include interactions with other modes , such as the inhomogeneous modes of gravitons or scalars , then for @xmath307 it is possible that the negative energy states for the scale factor @xmath4 would become excited , potentially signifying strong backreaction as the universe passes through the quantum bounce . the problem may be avoided in two ways . for @xmath50 or @xmath309 one can restrict consideration to background cosmologies for which the zero - mode momenta of the anisotropy and scalar fields are strictly zero , in which case the quantum mechanics for @xmath4 lies on the critical boundary where it ( just ) makes sense . or , one can include additional conformally coupled scalars , taking @xmath310 so that , from the last line of eq . ( [ cpp ] ) , the quantum mechanics of @xmath4 is well - defined for a range of classical anisotropy and scalar field momenta . for @xmath311 ( _ i.e. _ , only anisotropies but no minimally coupled scalars ) and @xmath312 , the numerical contribution can be large enough to make the potential repulsive at small momenta . if we consider classical solutions with this ( order @xmath313 squared ) potential , an isotropic universe with no scalar momenta would bounce off the repulsive potential and avoid the singularity altogether . quantum mechanically , however , if we extend the range of @xmath4 to negative values , then @xmath4 tunnels through the barrier in a process which may be described with complex classical solutions , as we explained in ref . @xcite . the conclusion is that when anisotropy and scalar field degrees of freedom are included , then for small numbers of conformal scalars , the isotropic cosmology with no scalar momenta is a special case , poised on the edge of a qualitatively different ( and perhaps ill - defined ) phase . on the positive side , this finding may turn out to be a selection principle , telling us that anisotropic or kinetic - dominated singularities should be excluded from the theory whereas isotropic universes with zero scalar momenta are allowed . if so , this would imply that black hole singularities , which locally resemble strongly anisotropic cosmological singularities , do not correspond to a bounce " ( contradicting the interpretation given by ref . @xcite , for example ) ; there would be no born again " universe on the other side of the black hole singularity . on the negative side , one may wonder whether the inclusion of inhomogeneities could lead to problems even for the isotropic , non - kinetic cosmological bounce . we emphasize that , for @xmath50 or @xmath309 , _ any _ amount of classical momentum in the zero modes of the anisotropy or scalar degrees of freedom would take the quantum mechanics of @xmath4 into the subcritical regime . perhaps it will be essential to work at @xmath310 for the theory to make sense . clearly , we have only scratched the surface with this discussion , and there is a great deal to explore further . for the remainder of the paper , we shall _ assume _ that the quantum mechanics for @xmath4 makes sense . as explained in ref . @xcite , this allows us to calculate the propagation of the universe , and all inhomogeneous modes in it , by solving the theory on complex trajectories which bypass @xmath6 in the complex @xmath4-plane . remarkably , as was also explained in ref . @xcite , due to its scale - invariant property , the inverse square potential , if present , is actually _ invisible _ in our final results for in - out " amplitudes . having defined positive- and negative - frequency modes by their asymptotics , given in eq . ( [ hankelasymptotics ] ) ( and _ without _ using any boundary condition at @xmath6 ) , it is easy to obtain the feynman propagator for the anisotropic case as a green s function for the wheeler - dewitt equation , by using the wronskian method as before . with the quantum hamiltonian given by eq . ( [ quantham ] ) , the feynman propagator satisfies & & ( -++m^2)g(x,,m|x,,m ) + & = & -2m(-g)^-^m+1(x - x)^k(-)(m - m)where we must introduce a factor @xmath314 for the nontrivial metric determinant on superspace . again switching to the scale factor coordinate @xmath4 , this is equivalent to & & ( + -_h^m^k++m^2)g + & = & -2m(m - m)with @xmath315 , and the metric determinant on superspace is now made explicit . again , we can now go to fourier space on @xmath284 introducing momenta @xmath316 and @xmath317 ; the feynman propagator in fourier space satisfies & & ( + -+m^2)g(a,,k , m|a,,k , m ) + & = & -2ma^-(m+k)(a - a)(m - m ) [ newwdweq ] with @xmath111 as in eq . ( [ constant ] ) . since we have already identified the positive- and negative - frequency solutions ( [ plusminus ] ) of the corresponding homogeneous equation , it is immediate to write down the solution to eq . ( [ newwdweq ] ) with the correct boundary conditions , g(a , m|a,m)&=&-2 m a^-(m+k)(m - m ) + & & w(_-,_+)^-1(_-(a)_+(a ) ( a - a ) . + & & . + _ -(a)_+(a ) ( a-a ) ) , where the wronskian is w(_-,_+)= and no longer constant in @xmath4 , as is consistent with the appearance of a first derivative in eq . ( [ wdwbianchi ] ) . the wronskian takes care of the factors of @xmath4 appearing in the elimination of the first derivative , eq . ( [ psichi ] ) , and cancels the determinant factor @xmath318 . the final result is g(a , m|a,m)&&=(m - m)(aa)^-(m+k-1)/2 + & & ( h_^(1)(ma)h_^(2)(ma)(a - a)+(aa))with @xmath319 , which is consistent with the results of ref . @xcite ( with @xmath320 as only the @xmath321 anisotropy degrees of freedom of a @xmath322-dimensional universe were considered there ) . one can check that in the absence of anisotropies or minimally coupled scalar fields , @xmath323 , this result reduces to the expression obtained in sec . [ friedbounce ] , _ i.e. _ , the propagator for a free massive particle in @xmath30-dimensional minkowski spacetime . by our remarks below eq . ( [ cpp ] ) the same should be true for @xmath50 or @xmath309 and general @xmath257 , where the superspace metric is conformally flat . in this section , we extend our analysis to inhomogeneous cosmology , treated perturbatively at both linear and nonlinear order . we aim to solve the following problem : given an incoming state at large negative @xmath4 consisting of a flat , frw , radiation - dominated classical background universe with perturbations in their local adiabatic vacuum state , what is the outgoing quantum state at large positive @xmath4 , as defined by our analytic continuation prescription ? this question can be answered , in the semiclassical limit , by using complex solutions of the classical einstein - matter field equations . if one sends in any combination of linearized positive- ( negative-)frequency modes then , even after including the effects of nonlinearities in the field equations , it turns out that one finds only positive- ( negative-)frequency linearized modes coming out . as we now explain , this is sufficient to show , semiclassically , that the outgoing quantum state is also the local adiabatic vacuum . hence , at a semiclassical level , there is no particle production across the bounce . let us see this in detail . consider a classical time - dependent background solution of the einstein - matter equations . if the matter is a perfect fluid , the only propagating degrees of freedom are scalar density perturbations and tensor gravitational wave modes . at the linearized level , we can decouple the modes by exploiting the homogeneity and isotropy of the background : for a flat background , every mode is a sum of plane waves @xmath324 , with @xmath325 , with the coefficients decomposed into irreducible representations of the little group of rotations about @xmath326 . now consider the action for the perturbations . at leading order , it is quadratic and it is diagonalized by the above mode decomposition . after a suitable time - dependent rescaling of the perturbations , the kinetic terms can always be brought to canonical form in which the action reads ( see , _ e.g. _ , ref . @xcite , p.269 , eq . ( 10.59 ) ) ^(2)=_*k*,a d(|_*k*^a|^2-w_k^2,a ( ) |v_*k*^a|^2 ) , [ pert1 ] where the index @xmath4 labels the independent modes ( here , scalar and tensor ) , and w_k^2,a()= ( k c_s^a)^2 + m^2,a_eff ( ) where @xmath327 is the speed of sound , @xmath328 for the scalar acoustic modes and unity for the tensor modes . in general , the time - dependent effective mass " introduces a nontrivial @xmath1-dependence . however , in our chosen background , the effective mass vanishes for both the scalar and tensor modes so @xmath329 in both cases . we now make the assumption that the perturbations are well - described by linear theory for wide intervals of conformal time @xmath1 well before and well after the bounce . as we shall see later , we can not actually take the limit of infinite positive and negative conformal time because of the effect of nonlinearities in the fluid . nevertheless , in the semiclassical approximation , and for modes whose wavelength is longer than the thermal wavelength of the fluid , the periods of incoming and outgoing conformal time during which linear theory remains valid are very large . we define our incoming and outgoing states during these intervals . when linear theory is valid , and when the frequencies @xmath330 change adiabatically , @xmath331 , the quantum states of the system are well - described by those of a set of decoupled harmonic oscillators . let us denote the corresponding real coordinates , _ i.e. _ , the real and imaginary parts of the @xmath332 , by the coordinates @xmath333 , where the single index @xmath74 runs over all of the real , independent modes . each of the coordinates @xmath333 contributes an action @xmath334 , and the adiabatic vacuum state is just the product of the corresponding harmonic oscillator ground states , _ 0(,q ) = _ m ( _ m /)^1/4 e^-_m q_m^2 /(2 ) . [ pert2 ] this state is uniquely defined by @xmath335 for all @xmath74 , for the annihilation operator a_m ( + _ m q_m ) . let us assume that the incoming state of the perturbations is @xmath336 at some large negative @xmath337 , for which linear theory is valid . the quantum fluctuations in the fluid density may be shown to be small compared to the background density provided the wavelength of the modes is longer than the thermal wavelength , a condition which is in any case required in order for the fluid description to hold . the outgoing quantum state , at some large positive time @xmath1 , is then given by propagating the incoming vacuum @xmath338 to large positive times @xmath1 , for which linear theory is once again valid , using the path integral , _ out(,q ) q e^(q , ; q, ) _ m dq_m _ 0(,q ) , [ pert3 ] where @xmath339 is the full , nonlinear einstein - matter action taken with boundary conditions @xmath340 , @xmath341 , @xmath342 indicates the complete path - integral measure and @xmath343 is a normalization constant . we compute eq . ( [ pert3 ] ) in the semiclassical approximation , by finding the appropriate complex classical solution @xmath344 @xmath345 , which is a stationary point of the combined exponent . substituting eq . ( [ pert2 ] ) for @xmath346 and varying the exponent with respect to @xmath347 yields , using the hamilton - jacobi relation , the initial condition for the classical solution @xmath348 : ( p^c_m+_m q^c_m)()=0 , [ pert4 ] where @xmath349 is the canonical momentum . the initial condition ( [ pert4 ] ) specifies that @xmath350 is pure negative - frequency at @xmath351 , a large negative time . the final boundary condition is just @xmath352 , where @xmath1 is a large positive time . we shall solve the classical einstein - matter equations with these two boundary conditions in linear perturbation theory . at linear order , the solution satisfying the boundary conditions is @xmath353 . below , we give the complete solution for generic perturbation modes at linear and nonlinear order . we find that the solution is well - described by linear perturbation theory at large negative and large positive times , with small nonlinear corrections , and that an incoming positive ( negative ) frequency mode evolves to an outgoing positive ( negative ) frequency mode which directly implies that the outgoing quantum state is the local adiabatic vacuum . to verify this , we need only apply the annihilation operators @xmath354 to @xmath355 as given in eq . ( [ pert3 ] ) . using the hamilton - jacobi equation , the result is proportional to @xmath356 , which vanishes if the solution is pure negative - frequency . hence the incoming adiabatic vacuum evolves to the outgoing adiabatic vacuum , and there is no particle production across the bounce . we wish to study perturbations about a flat ( @xmath70 ) radiation - dominated frw universe in a perturbation expansion . we shall go to nonlinear order but , for simplicity , restrict consideration to planar symmetry so that the metric depends only on conformal time @xmath1 and one spatial coordinate @xmath163 , with two orthogonal spatial directions @xmath357 . to keep the calculations manageable , we do not introduce conformally or minimally coupled scalar fields , so @xmath302 . we work in einstein gauge , _ i.e. _ , in the usual formulation of general relativity coupled to a radiation fluid . the general form of the metric compatible with our assumed symmetry would be ds^2=a^2 ( ) -1+g_(,x ) & g_x(,x ) & & + g_x(,x ) & 1 + g_xx(,x ) & & + & & 1+g_yy(,x ) & g_yz(,x ) + & & g_yz(,x ) & 1+g_zz(,x ) . we can still apply coordinate transformations that leave this form of the metric invariant . a coordinate transformation @xmath358 will change the metric coefficients as & & g_=-2(g+ ) , g_x = -2 g , + & & g_xx = g_yy = g_zz=2 g where here and in the remainder of this section @xmath359 is derivative with respect to @xmath1 and @xmath360 denotes derivative with respect to @xmath163 . we use this freedom to eliminate @xmath361 and introduce a different notation for the metric perturbation functions ( note that in this section @xmath362 denotes a scalar metric perturbation , not a solution to the wheeler - dewitt equation as in earlier sections ) : ds^2&=&a^2 ( ) . [ comov ] the form ( [ comov ] ) is still left invariant by a transformation of the form & & = + ( g()+^ dx(x , ) ) , + & & x=+f ( , ) , [ cotra2 ] which we will use to simplify the matter variables . the energy - momentum tensor for radiation is t_=u_u_+g_;u^u_=-1 . the density @xmath363 and four - velocity @xmath364 can also be written in terms of background and perturbation as ( , x)&=&_0()(1+_r(,x ) ) , + u^(,x)&=&(v^0(,x),v(,x),0,0 ) . the constraint @xmath365 can be solved for @xmath366 . under a coordinate transformation ( [ cotra2 ] ) , we have @xmath367 , so that we can set @xmath368 everywhere , _ i.e. _ , adopt a coordinate system in which the radiation is at rest everywhere ( _ comoving gauge _ ) . the remaining gauge freedom is then under transformations & & = + g(),x=+f(),[gaugef ] + & & y=+(a + c + y_0),z=+(b + d + z_0 ) where @xmath369 and @xmath370 are arbitrary constants and @xmath0 and @xmath371 are free functions . under such a transformation , @xmath372 , @xmath373 , @xmath374 , @xmath375 and @xmath376 , and so functions of this form in the perturbations are to be considered pure gauge . we will solve the einstein equations in fourier space , where the gauge freedom for the functions @xmath8 , @xmath362 , @xmath377 and @xmath378 is somewhat hidden as it only becomes apparent for @xmath379 . we are left with five free functions for the metric ( @xmath380 ) and the density perturbation @xmath381 . as we will see , there are also six nontrivial einstein equations relating these . to proceed , we assume that all of the perturbation functions can further be expanded as a power series in @xmath382 , ( , x)=_n1^n-1_n(,x ) , the idea is now to solve the einstein equations @xmath383 order by order in @xmath382 ; the einstein equations also imply energy - momentum conservation @xmath384 for the fluid . first , for the background ( at order @xmath385 ) we have the equations _ 0 + 4_0 = 0,()^2 = . the first one tells us that @xmath386 for some constant @xmath7 ; the friedmann equation then gives @xmath2 , as we have already discussed in the introduction to this paper . it follows that @xmath387 , and that analytic continuation in the scale factor @xmath4 ( as we have discussed in previous sections ) is equivalent to analytic continuation in the conformal time coordinate @xmath1 , which we will use in this section . at order @xmath388 in the perturbation expansion , the six nontrivial einstein equations are _ n + 2 _ n - _ n-_n & = & j_1,n , [ einstnl1 ] + _ n+_n & = & j_2,n , [ einstnl2 ] + _ r , n - _ n + 2 _ n & = & j_3,n , [ einstnl3 ] + ^t_n + ^t_n - ( h^t_n ) & = & j_4,n , [ einstnl4 ] + ^_n + ^_n - ( h^_n ) & = & j_5,n , [ einstnl5 ] + -_r , n + _ n + _ n-_n & & + - _ n- _ n - _ n - _ n - 2 _ n & = & j_6,n [ einstnl6 ] for some `` source terms '' @xmath389 that are nonlinear combinations of the lower - order perturbations . we first note that eqs . ( [ einstnl4 ] ) and ( [ einstnl5 ] ) that govern the tensor modes @xmath390 and @xmath391 are already decoupled from the others . for the scalars , eq . ( [ einstnl1 ] ) and eq . ( [ einstnl2 ] ) can be solved for @xmath381 and @xmath8 directly . from eq . ( [ einstnl2 ] ) we get _ n(,x)=-_n(,x)+f_n()+^x dxj_2,n(,x ) [ phi ] where @xmath392 is a free function ; then eq . ( [ einstnl1 ] ) implies that _ r , n(,x)&=&-^2_n+_n+2f_n+j_1,n + & & + 2^x dxj_2,n . [ delta ] substituting these relations into eq . ( [ einstnl3 ] ) and eq . ( [ einstnl6 ] ) and taking linear combinations one obtains _ n&=&_n-6_n-3_n - j_1,n-3^x dxj_2,n + & & -3^x dx_2,n+j_3,n [ gammeq ] and _ n+_n-_n&=&----[psieq ] + & & + j_2,n+j_3,n + _ 3,n + + & & -^x dx(+2_2,n + _ 2,n).eq . ( [ psieq ] ) can now be solved for @xmath393 using green s functions ; eq . ( [ gammeq ] ) then gives @xmath280 by a single integration over @xmath1 , and from eq . ( [ phi ] ) and eq . ( [ delta ] ) one can obtain explicit expressions for @xmath394 and @xmath395 at each order . at each order in @xmath382 , this provides an explicit algorithm for solving the system of einstein equations ( [ einstnl1])-([einstnl6 ] ) . the equations ( [ einstnl4])-([einstnl5 ] ) are easily solved . first , consider the homogeneous equation solved by the first - order perturbation , ^t_1 + ^t_1 - ( h^t_1)=0 . we can easily find the general solution in fourier space , for @xmath396 , h^t_1(,x)&=&e^k xh^t_1(,k ) , + h^t_1(,k)&=&b_1(k)+b_2(k ) . for @xmath379 , the two independent solutions are @xmath397 and @xmath398 . we can write the general solution as h^t_1=d_1++e^k x(b_1(k)+b_2(k ) ) where @xmath399 is an arbitrary momentum scale to make @xmath400 dimensionless . @xmath401 satisfies the same differential equation , its general solution is h^_1=e_1++e^k x(c_1(k)+c_2(k ) ) . for a real solution we need @xmath402 , @xmath403 and similar for @xmath404 and @xmath405 . we recognize @xmath406 and @xmath407 as gauge modes corresponding to coordinate transformations ( [ gaugef ] ) , whereas @xmath400 and @xmath408 are physical @xmath379 modes the free functions @xmath409 and @xmath405 are the physical gravitational degrees of freedom . now consider the general inhomogeneous equation , ^t_n + ^t_n - ( h^t_n)=j_4,n . [ inhomo ] again , we go to fourier space and first consider @xmath396 . using the usual wronskian method to determine the green s function , we find that one particular solution to eq . ( [ inhomo ] ) is h^t_n(,k)=^d(k(-))j_4,n(,k ) , [ htfourier ] while for @xmath379 we find h^t_n(,0)=^d(-)j_4,n(,0 ) , [ htzero ] which is just the limit @xmath410 of eq . ( [ htfourier ] ) . expressions for @xmath391 are analogous . clearly , at each order @xmath388 one can also add a solution of the homogeneous equation to this solution for @xmath411 . this can however be absorbed into the linear perturbation @xmath412 . we hence set these arbitrary solutions to the homogeneous equations to zero for @xmath413 . for the scalar perturbation functions @xmath414 and @xmath381 , we proceed analogously . for clarity , we first derive the general solutions for the first order perturbations , for which there are no sources and the general solution is obtained straightforwardly . the equation for @xmath415 is eq . ( [ psieq ] ) with the sources set to zero , _ i.e. _ , _ 1+_1-_1=-- where @xmath416 is a free function of @xmath1 . going into fourier space , the general solution for @xmath396 , where @xmath416 does not contribute , is _ 1(,x)&=&e^k x_1(,k ) , + _ 1(,k)&=&a_1(k)+a_2(k ) . the fourier mode @xmath379 is a gauge mode ( see the discussion below eq . ( [ gaugef ] ) ) , with general solution _ 1(,0)=-+c_2- ; since @xmath416 is arbitrary , we can set @xmath417 with no loss of generality . putting this together , we have _ 1(,x)&=&e^k x(a_1(k)+a_2(k ) ) + & & - , where for a real solution we need @xmath418 and @xmath419 . as said , from this expression we can determine the other scalar functions @xmath420 and @xmath381 . 1(,x)&=&a_3(x)+e^k x(a_1(k)e^-(-- ) . + & & .+a_2(k)e^(-+ ) ) , + _ 1(,x)&=&f_1()+ _ 1()+e^k x , + _ r,1(,x)&=&2f_1()+e^k x(a_1(k)e^-(+ ) . + & & .+a_2(k)e^(- ) ) , where we recognize @xmath421 and @xmath422 as encoding the remaining gauge freedom in comoving gauge ( [ gaugef ] ) . @xmath423 and @xmath424 correspond to the scalar degrees of freedom of the radiation fluid . in order to obtain the solutions for higher order perturbations , we derive the green s function for the @xmath362 equation ( [ psieq ] ) , which has the general form _ n+_n-_n=_n . we find , for @xmath396 , _ n(,k)=^ d()_n(,k ) , [ psifourier ] and for @xmath379 the same as for the tensors , _ n(,0)=^d(-)_n(,0 ) . [ psizero ] again , once the solution for @xmath393 is found , the other perturbation functions @xmath425 , @xmath395 and @xmath394 can be obtained easily . from these expressions , we can now work out the nonlinear solution for all metric perturbation functions and the density perturbation order by order in @xmath382 ; all we need to do is to expand einstein equations up to any given order to find the sources @xmath389 and then compute the integrals ( [ htfourier ] ) , ( [ htzero ] ) , ( [ psifourier ] ) and ( [ psizero ] ) to find the perturbations at the next order . to be more specific , we are now interested in the nonlinear extension of linear positive frequency modes at a given wavenumber @xmath399 . ( for incoming negative frequency modes we simply take the complex conjugate of all expressions below . ) we choose these to be _ 1(,x)&=&a(k_0 x ) , + h^t_1(,x)&=&b(k_0x ) . as seen before , the expression for @xmath202 then determines @xmath426 and @xmath427 . the scalar quantities are all gauge - dependent but one may compute the `` gauge - invariant '' newtonian potentials first introduced by bardeen @xcite and given by ( in fourier space for @xmath396 ) = -++,=-- . we find that for the linear perturbations @xmath428 and @xmath275 are equal and fall off as @xmath429 at large @xmath430 , _ 1(,k_0)=_1(,k_0)=- . [ newt1 ] the explicit form of the sources at order @xmath431 is , in terms of the linear perturbations , j_1,2 & = & ^2 + ( ( h^t))^2 + ( ( h^))^2 + 2 + 3()^2 + h^t(h^t)+h^(h^)+4 + 8 - + & & + - -h^t^t-(^t)^2 -h^^-(^)^2 -+ -+ 2 + 3 ^ 2 , + j_2,2 & = & - + + + ( h^t)^t + ( h^)^- + 2 + h^t(^t) + h^(^) + & & + 2 + 4 , + j_3,2 & = & ^2 - ( ( h^t))^2 - ( ( h^))^2 - 2 + ( )^2 + h^t^t + ( ^t)^2 + h^^+ ( ^)^2 - - + & & + - 2 + ^2 + h^t^t+h^^-4 + 4 , + j_4,2 & = & -(h^t) - ( h^t) - 3 ( h^t) - 2 ( h^t ) - 4(h^t ) - 2 h^t -^t + ^t -^t - ^t+ h^t+ ^t + & & - 2 ^t + 2^t + 2 h^t , + j_5,2 & = & -(h^) - ( h^) - 3 ( h^)- 2 ( h^ ) - 4(h^ ) - 2h^ -^+ ^-^- ^+ h^+ ^ + & & -2^+ 2 ^+ 2 h^ , + j_6,2 & = & -^2 + ( ( h^t))^2 + ( ( h^))^2 - + ( )^2 + + 2()^2 + h^t(h^t ) + h^(h^ ) -2 + 2 + & & - 2 + 2 + 4 -+ --^2 - h^t^t - ( ^t)^2 - h^^- ( ^)^2 + + + & & - + - -+ 2- ^2 -2 + 2 -2- h^t^t - h^^- 2 + 4 - 4 , where we omit the subscripts @xmath432 on the first - order perturbations on the right - hand side of these equations . for simplicity , we also set the second tensor mode @xmath378 to zero from now on ( its dynamics are analogous to that of @xmath377 ) . we now compute the second - order perturbations from eqs . ( [ htfourier ] ) , ( [ htzero ] ) , ( [ psifourier ] ) and ( [ psizero ] ) . for @xmath433 , we find h^t_2&=&ab((1+(2k_0x ) ) . + & & -(2k_0x ) + & & + + ( 0,(1+)k_0 ) + & & + ( 2k_0x)&&.-(2k_0x)).[htexpr ] here @xmath434 are incomplete gamma functions . their asymptotic expansion for large arguments is ( 0,z)~e^-z(-+o ( ) ) . using this expansion , we see that as @xmath435 , @xmath433 has the asymptotic behavior h^t_2 & & ~abe^-(1+)k_0 ( + & & + + o()).the asymptotic expansion shows in particular that all the terms in eq . ( [ htexpr ] ) oscillate as @xmath436 for large @xmath437 , and decay exponentially for large negative imaginary @xmath1 . we can obtain expressions for the scalar perturbations in exactly the same way . the expressions are similar to those for @xmath438 but involve more terms ( 15 in total ) , as there can be contributions of order @xmath439 and @xmath440 , corresponding to two tensor modes or two scalar modes combining to give a scalar . just as the second order tensors , they contain incomplete gamma functions , but there is also a term involving a logarithm , -a^2e^-k_0 . these terms are potentially problematic when the perturbation functions are extended to the complex @xmath1-plane as the logarithms and incomplete gamma functions have branch cuts . however , all we require for positive - frequency modes is analyticity in the lower - half @xmath1-plane , where these modes extend to euclidean , asymptotically decaying modes . this can be achieved by defining all the branch cuts to be along the positive imaginary axis . the analytic continuation of these modes that avoids the singularity at @xmath5 is then defined by choosing any contour that remains in the lower - half complex @xmath1-plane . asymptotically , we find that at large @xmath437 , _ 2 & ~ & -e^-2k_0 + e^-k_0 a^2(+(2k_0 x ) . + & & .-)+o(),and one can check that all terms , including all subleading ones , oscillate at positive frequencies asymptotically ( either at @xmath441 or at @xmath442 ) . the nonlinear modes again decay exponentially as @xmath443 , and indeed define nonlinear positive frequency modes . from the general structure of the equations ( [ einstnl1])-([einstnl6 ] ) , one can see that the same property should hold to all higher nonlinear orders : the `` source terms '' , being nonlinear in lower - order perturbations , always decay exponentially sufficiently fast in imaginary time that integration with a green s function that has an exponentially growing and an exponentially decaying part , as in eq . ( [ psifourier ] ) , gives again an exponentially decaying next - order perturbation . the method we have described then allows a general definition of positive frequency modes in the complex @xmath1-plane , to all orders in perturbation theory . the other perturbations are determined by eqs . ( [ phi ] ) , ( [ delta ] ) and ( [ gammeq ] ) . for completeness , we give their asymptotic expressions for large @xmath437 , _ 2 & ~ & a^2e^-k_0 ( - . + & & .-1-(2k_0x)(+3(k_0 ) ) ) + o ( ) , + _ r,2 & ~ & a^2e^-k_0 ( + & & -7-(2k_0x)(7 - 12(k_0 ) ) ) + o ( ) , + _ 2 & ~ & e^-2k_0 + a^2e^-k_0 ( . + & & .+-(2k_0 x)(-(k_0)))+o().to verify the validity of our solution method , we have checked explicitly that the second - order perturbations solve einstein s equations up to order @xmath431 . we see that none of the scalar perturbation functions decay at real infinity @xmath444 , and some even blow up , indicating a breakdown of perturbation theory at large times . again , to get gauge - invariant statements about this behavior , we can compute the newtonian potentials , and find that they fall off as @xmath445 , _ 2(,2k_0 ) ~-e^-k_0 + o ( ) with similar behavior for @xmath275 . this compares with @xmath446 in eq . ( [ newt1 ] ) , which still indicates that the perturbation expansion breaks down when @xmath447 . this physical behavior is due to the nonlinear evolution in the fluid , as shown by analytical and numerical studies in ref . when we go down the imaginary axis , _ i.e. _ for @xmath448 with @xmath449 , all perturbation functions fall off exponentially , with exponential terms of the form @xmath450 dominating any polynomially growing terms . as we have argued , this behavior persists for higher orders in the @xmath382 expansion , and defines these modes by regularity for large negative imaginary @xmath1 ; the blowup of scalar perturbations along the real axis due to nonlinearities in the fluid does not prevent us from defining nonlinear asymptotic positive - frequency modes . we have given an algorithm for solving the einstein - matter equations order by order in perturbation theory , and exhibited explicit results at second order that show in detail how the positive - frequency incoming modes match only to positive - frequency outgoing modes , and similarly for negative - frequency modes ( where our results trivially extend by taking complex conjugates ) . we have argued that this behavior should extend to all orders in perturbation theory , as the nonlinear extension of linear positive - frequency modes leads to perturbation functions that decay exponentially for large negative imaginary times , and branch cuts can be restricted to the positive half - plane for positive - frequency solutions , so that the nonlinear metric perturbation satisfies a nonlinear notion of positive frequency . we identified some subtleties , namely that the perturbation expansion fails at late times @xmath451 , where @xmath382 is the perturbation amplitude , meaning that one has to restrict attention to an annulus in the complex plane , @xmath452 , in which the @xmath382 expansion can be trusted and nonlinearities are not yet dominant @xcite . this paper represents a detailed study of a very simple cosmological model , based on the principle of conformal symmetry for matter and gravity and the observed fact that the early universe was dominated by radiation . classical cosmological solutions of this model describe a bounce , with a big bang / big crunch singularity , but the singularity can be avoided by going into the complex plane . while this `` singularity avoidance '' seems ad hoc in classical gravity , we have shown its meaning in the quantum theory where , similar to quantum tunneling , the complexified solutions represent legitimate saddle points to the path integral . the picture that emerges for quantum cosmology is based on modes that are asymptotically purely positive frequency at early and late times when the universe is large and classical , corresponding to a positive expansion rate of the universe , as we observe . we have shown that the addition of a positive radiation density makes a crucial difference , as it leads to classical solutions which connect asymptotic contracting and expanding lorentzian regions , and which are represented by the positive - frequency modes defined by the feynman propagator . we do not impose any boundary conditions for the wavefunction at @xmath6 , and accept that some modes may even diverge there : all that is required is a consistent evolution from an asymptotic contracting to an asymptotic expanding universe , through or `` around '' the bounce , as this allows a calculation of transition amplitudes and hence , ultimately , predictions for the transition of a given state in the contracting phase to a state in the expanding phase . this formalism appears much more natural than an imposition of a boundary condition at @xmath6 , where quantum effects are large and where classical notions of singularity avoidance " may cease to have any relevance . in practical terms , the fact that our wavefunctions and propagators admit a semiclassical wkb description in which high - curvature regions near @xmath6 can be avoided gives hope that a semiclassical approach to the quantum cosmology of bouncing scenarios can be used for predictions , even in the absence of a complete theory of quantum gravity . some features we are exploiting are clearly restricted to homogeneous cosmological models such as the frw and bianchi i universes we have studied explicitly . it is therefore vital to check that the formalism can be extended consistently to generic perturbations around homogeneity , and ultimately to fully nonlinear solutions of gr . we have developed a systematic perturbative treatment that shows how this question can be attacked , at linear and nonlinear order , and given evidence for a consistent nonlinear extension of positive - frequency modes to the complex @xmath4-plane . again , one is interested in the transition of incoming asymptotic positive - frequency modes to outgoing modes which are , in general , a mixture of positive and negative frequency and which signal particle production ( and potential divergencies ) at the bounce . we have shown that an incoming positive - frequency mode can be continued `` around '' the singularity , and unambiguously matches to an outgoing positive - frequency solution . so the incoming adiabatic vacuum state is stable across the bounce and no divergencies arise . our calculations have been limited to pure radiation and planar symmetry , and one focus of future work will be to extend these results to more general cases . the present results already indicate that a consistent semiclassical picture exists for nonlinear perturbations of cosmological models , and that this picture can be used for calculations of the cosmological phenomenology of bounce scenarios of the type we consider . thus , our results show how classical singularities do not necessarily prevent a consistent quantum description of bouncing cosmologies . the inclusion of quantum effects into the big bounce seems a natural and simple alternative to the development of more complicated bounce scenarios @xcite . there are many avenues for further exploration . in sec . [ anisosec ] , we began to explore the quantum theory on the real @xmath4-axis around @xmath6 . in some cases , it may be that the attractive inverse square potential in the wheeler - dewitt operator may lead the quantum theory to fail when further ( inhomogeneous ) degrees of freedom are included , but in others the quantum theory seems to be healthy . the quantum dynamics of more general bianchi models also deserve to be understood ; for these , the `` invisibility '' of the singularity that we have observed for bianchi i will presumably be replaced by nontrivial scattering matrix between in " and out " asymptotic states . the pathologies we have identified in the feynman propagator for curved frw universes should be revisited with the inclusion of a positive cosmological constant . more basic conceptual questions concerning the interpretation of the propagator and the determination of probabilities need to be investigated . ultimately , we need to find a compelling measure on the space of quantum universes . there are hints that the present flat , isotropic universe lies on a critical boundary in the quantum theory , and these may point to novel resolutions of the classic flatness and isotropy puzzles . this research was supported in part by perimeter institute for theoretical physics , in particular through the mike and ophelia lazaridis niels bohr chair . research at perimeter institute is supported by the government of canada through the department of innovation , science and economic development canada and by the province of ontario through the ministry of research , innovation and science . the work of s.g . was supported in part by the people programme ( marie curie actions ) of the european union s seventh framework programme ( fp7/2007 - 2013 ) under rea grant agreement n@xmath453 622339 . in this appendix , we calculate the massive relativistic propagator given in eq . ( [ e2 ] ) exactly . first , we note that g(x| x ) = _ 0^ d()^e^-(+ ) , is a convergent integral when @xmath139 is positive . the @xmath127 integral may be taken along the positive real axis @xmath454 . next , we set @xmath455 , with @xmath456 , so that the integral becomes & & _ -^ du ( ) ^ ( ) ^ e^ -m u - u + & = & ( -m)^m ( 2 m ) ^ h_^(2)(m ) , where we have used the standard integral representation of the hankel function of the second kind , h_^(2)(z)=_-^due^-z u - u , and for positive real argument the function is defined as the boundary value of a function in the lower - half complex @xmath457-plane where the integral converges . i. bars , s. h. chen , p. j. steinhardt , and n. turok , `` antigravity and the big crunch / big bang transition , '' _ phys . b _ * 715 * ( 2012 ) , 278281 , http://arxiv.org/abs/1112.2470[arxiv:1112.2470 ] ; i. bars , p. j. steinhardt , and n. turok , `` local conformal symmetry in physics and cosmology , '' _ phys . rev . d _ * 89 * ( 2014 ) , 043515 , http://arxiv.org/abs/1307.1848[arxiv:1307.1848 ] j .- l . lehners , `` classical inflationary and ekpyrotic universes in the no - boundary wavefunction , '' _ phys . d _ * 91 * ( 2015 ) , 083525 , http://arxiv.org/abs/1502.00629[arxiv:1502.00629 ] ; 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the initial singularity is the most troubling feature of the standard cosmology , which quantum effects are hoped to resolve . in this paper , we study quantum cosmology with conformal ( weyl ) invariant matter . we show it is natural to extend the scale factor to negative values , allowing a large , collapsing universe to evolve across a quantum bounce " into an expanding universe like ours . we compute the feynman propagator for friedmann - robertson - walker backgrounds exactly , identifying curious pathologies in the case of curved ( open or closed ) universes . we then include anisotropies , fixing the operator ordering of the quantum hamiltonian by imposing covariance under field redefinitions and again finding exact solutions . we show how complex classical solutions allow one to circumvent the singularity while maintaining the validity of the semiclassical approximation . the simplest isotropic universes sit on a critical boundary , beyond which there is qualitatively different behavior , with potential for instability . additional scalars improve the theory s stability . finally , we study the semiclassical propagation of inhomogeneous perturbations about the flat , isotropic case , at linear and nonlinear order , showing that , at least at this level , there is _ no _ particle production across the bounce . these results form the basis for a promising new approach to quantum cosmology and the resolution of the big bang singularity .

the existence of anapole moment was theoretically predicted by zeldovich fifty years ago @xcite . the anapole moment arises in the system where currents or magnetic moments of particles create a ring - like closed distribution of magnetic field lines . a classic example of such distribution can be a magnetic field inside the toroidal solenoid over the surface of which poloidal currents flow . a less trivial example is an atomic nucleus in which spins of nucleons compose a ring with forming the corresponding configuration of the magnetic field . the great interest to the anapole is related to fundamental investigations on the parity nonconservation in atomic - nuclear interactions @xcite . in 1997 the anapole moment of the nucleus @xmath3cs was discovered just in the experiment on parity nonconservation in the atomic transition @xmath4 of cs @xcite . now the anapole is regarded as a dipole moment of the fundamental family of toroid moments @xcite which naturally arise when currents on a torus surface are described . toroid moments are now used in problems of current parametrization and of radiation theory @xcite , in investigations of topological effects in quantum mechanics ( the aharonov - bohm effect @xcite ) , in elementary particle physics ( toroid dipole momentum of neutrino @xcite and @xmath5-scattering @xcite for example ) , in the theory of anomalous internal conversion @xcite , in atomic physics ( anapole moments of atoms @xcite , atomic emission in a condensed medium @xcite ) , in the physics of nanostructures ( carbon toroids @xcite ) , in the physics of spin - ordered crystals @xcite etc . thus the physics of toroid moments is a wide area of scientific activity ranging from elementary particles to condensed matter . at the same time , the nucleus together with the atomic shell remain one of the most suitable quantum object for probing the toroid moments . the reason is as follows . the electronic wave functions for @xmath1 and @xmath6 states have large amplitudes at the origin . as a consequence , the electronic current at such states effectively penetrates the nucleus and interacts with the toroid moment , whose magnetic field does not exceed the boundary of the nucleus . ( this interaction mechanism is a direct analogy of a thought experiment offered in ref . @xcite for a toroidal solenoid immersed into the electrolyte . ) today the situation is . the static toroid dipole moment has discovered @xcite . as regards the toroid dipole moment of transition , there are evidences @xcite that this moment results in known anomalies in the internal conversion coefficients for @xmath7 transitions in nuclei @xcite and in the process of nuclear excitation by electron transition in the atomic shell @xcite . thus , more detailed and precise `` conversion '' experiments are needed to detect the toroid dipole moment of transition . in the present work we consider , on the example of the nucleus atomic shell system , two new effects dealt with the toroid moments . first of all , we prove that the anomalies mentioned above for @xmath0 transitions result from a `` cyclo - toroid moment '' . this moment arises when the toroid dipole moments are arranged in a ring . secondary , we demonstrate a possibility of experimental investigation of the existence of the cyclo - toroid moment by measuring of the energy shift in atomic @xmath1 levels . the results obtained here would be useful for more fundamental understanding of the nontrivial distribution of the currents inside nucleus and nucleons , and for the processes of the interaction between nucleus and atomic shell . anomalous internal conversion of @xmath8-rays in deformed nuclei arises because of the penetration of the electron current @xmath9 into the nucleus `` beneath '' the nuclear current @xmath10 , i.e. when the current coordinates satisfy the condition @xmath11 . the reason which changes the probability of the mentioned atomic - nuclear processes originates from to the additional selection rules @xcite . nuclear and atomic matrix elements which determine the process of de - excitation ( excitation ) of deformed nuclei through the atomic shell for @xmath11 are different from those for @xmath12 . in some cases the additional selection rules allow the nuclear transition for @xmath11 and forbid a @xmath8-radiative transition @xcite with nuclear matrix element @xmath13 entering the probability formula for @xmath12 . ( here and further @xmath14 are the standard electric / magnetic multipoles according to the gauge of @xmath15 ( see in ref . @xcite ) , and @xmath16 are current densities . we call @xmath16 `` currents '' for short . ) at the beginning of 80s it was found out that the real cause of the mentioned anomaly in the processes of an electric - dipole ( @xmath7 ) interaction of the nucleus with the atomic shell results from the dipole toroid moment of the transition @xcite . toroid moments are the components of electric moments @xcite . moreover , the anomaly also exists in conversion magnetic - dipole ( @xmath0 ) transitions @xcite . let us consider the nature of such @xmath0 anomaly . the nucleus matrix element corresponding to the anomalous part of the magnetic - dipole process of the nuclear interaction with the atomic shell is as follows @xcite @xmath17 where @xmath18 @xcite , @xmath19 is the energy of a nuclear transition , @xmath20 , @xmath21 are the spherical bessel functions , @xmath22 are the vector spherical harmonics from ref . @xcite , @xmath23 is the nucleus radius . we use in this paper the system of units @xmath24 . the operator structure of @xmath25 is well known . if the nuclear transition current in eq ( [ eq : n - an ] ) is the sum of convection and spin terms @xmath26 , where @xmath27 and @xmath28 ( we consider one - nucleon current for simplicity ) then it is easy to get the following expression for the anomalous nuclear matrix element @xcite @xmath29 \right ) \varphi_i(r ) . \label{eq : operat - an}\end{aligned}\ ] ] in formula ( [ eq : operat - an ] ) and in the expression for the transition current the following standard symbols were used : @xmath30 $ ] is the operator of the angular momentum , @xmath31 are the spherical functions @xcite , @xmath32 , @xmath33 and @xmath34 are the charge , the mass , and the wave functions of the nucleon , accordingly , @xmath35 is the operator of the magnetic moment of the nucleon : @xmath36 , where @xmath37 are the pauli spin matrices , @xmath38 is the nuclear magneton , @xmath39 is the empirical magnetic moment of the nucleon @xmath40 for the proton and -1.91 for the neutron . the spin term of the current @xmath41 in the matrix element @xmath25 in eq ( [ eq : n - an ] ) corresponds to the operator in eq ( [ eq : operat - an ] ) in square brackets under the integral @xmath42 $ ] ( here @xmath43 is the density of the magnetic moment @xmath44 ) . let us compare this operator with a known density operator of the dipole toroid moment @xmath45/10 $ ] @xcite , that is created by the convection current @xmath46 . operators in square brackets have different parity and are transformed into each other by exchanging @xmath46 and @xmath43 . taking into account this fact let us introduce the new operator @xmath47 \label{eq : ct-1}\ ] ] and find out what geometrical pattern corresponds to @xmath48 . using the spherical functions it is easy to rewrite eq ( [ eq : ct-1 ] ) in the form : @xmath49 then let us remember that the following objects possess the toroid moment : ( a ) a toroidal solenoid with a current @xmath46 ; ( b ) a ring formed by magnetic moments @xmath43 @xcite . for case ( b ) the following relationship is true : @xmath50 , besides that @xmath51 due to helmholtz theorem @xcite . substituting @xmath52 into eq ( [ eq:<ct > ] ) instead of @xmath43 , we get the following relation @xmath53 . a sub - integral expression can be easily transformed to the vector production ( see for example , in ref . @xcite ) . as a result , the operator @xmath48 can be written in as follows : @xmath54 $ ] , in full accordance with similar expressions for the density of a current magnetic moment @xmath55 $ ] and for the toroid moment formed by the ring - like composed magnetic dipoles @xmath56 $ ] @xcite . expression @xmath57 $ ] results in @xmath58 . the geometrical image corresponding to the operator @xmath48 , is the ring - like composed dipole toroid moments @xmath59 . therefore @xmath48 can be called the density of cyclo - toroid moment , and @xmath60 the cyclo - toroid moment . the properties of a cyclo - toroid are shown by the torus whose surface is formed by either ring - like composed magnetic moments @xmath43 , or by poloidal lines of the magnetic field ( fig . [ fig1]a ) . it is also possible to consider the cyclo - toroid as a sequence of toroidal solenoids all together forming again a toroidal solenoid ( such objects were considered for the first time in ref . @xcite ) . in this case the equal currents flow in opposite directions on the surface of two toruses ( one of them is embedded into another ) as it is shown in fig . [ fig1]b . zeldovich s anapole @xcite in the static case interacts with the external current @xmath61 only . the energy of this interaction is @xmath62 . taking also into account the equality @xmath63 , we arrive straightforwardly to the hamiltonian of the interaction of the cyclo - toroid with the external current : @xmath64 that is , the cyclo - toroid interacts locally ( only inside the nucleus ) with the vortex part of penetrating external current . let us determine now the role of a cyclo - toroid in the anomalous conversion . consider the internal electron conversion from one of the @xmath1 states of an atom and show first of all that @xmath65 during the @xmath0 transition of an electron to the @xmath66 state of the continuous spectrum . we write the electron current in a common way @xmath67 , where @xmath68 , @xmath69 and @xmath70 are the dirac matrixes @xcite , @xmath71 is the proton charge , @xmath72 are the electron wave functions . let us write these wave functions in the form of @xmath73 , where @xmath74 and @xmath75 are correspondingly the large and the small components of radial wave functions , @xmath76 are the spinor spherical harmonics @xcite . for the bound states in the atom the normalization condition is as follow : @xmath77 . the wave function of the final state is considered as a superposition of the plane wave and the converging spherical wave . for the states with @xmath78 , @xmath79 and @xmath80 the angular part @xmath81 is very simple , and the components of the bispinor can be written in the following way : @xmath82 , @xmath83 and @xmath84 . within the spherical coordinate system the current is as follows @xmath85 for @xmath86 correspondingly . we can see that the existence of the @xmath87 transition electron current itself is a totally relativistic effect . the current disappears ( as it should be ) when the small parts of the dirac wave functions @xmath75 tend to zero . the interaction of the current with the cyclo - toroid does not occur beyond the nucleus range . therefore , for the radial components of the @xmath88 states one can use the expressions which are true for small values of arguments : @xmath89 , @xmath90 , and @xmath91 , @xmath92 , where @xmath93 is the bohr radius , @xmath94 and @xmath95 are the coefficients of decomposition . ( here the potential inside the nucleus corresponds to the nuclear charge uniformly distributed over the spherical volume of radius @xmath23 @xcite . ) using the expansion , we can get from eq ( [ eq : j ] ) for @xmath96 the following @xmath97 where the @xmath96 vector components are given in the polar system @xcite and correspond to transitions @xmath98 and @xmath99 accordingly . since @xmath100 and @xmath101 for @xmath102 states , then @xmath103 . as an example we consider the known anomaly in the conversion @xmath0 transition with the energy of @xmath104 kev in @xmath105ta nucleus . the experimental magnitude of the @xmath106 shell conversion coefficient is 3 times as great as the so - called normal theoretical magnitude @xcite . the magnitude of the penetration parameter @xmath107 equals to 150 @xcite . the transition occurs between the states with quantum numbers in the nilsson model being as follows : @xmath108\sigma = 5/2^+5/2[402]\uparrow$ ] and @xmath109\downarrow$ ] @xcite . the radiation nuclear matrix element of this transition is forbidden by asymptotic quantum numbers , while the anomalous one is allowed @xcite . however , the selection rules for the operator @xmath110 in eq ( [ eq : operat - an ] ) forbid the anomaly nuclear transition in @xmath105ta @xcite . therefore we can infer that the anomaly results just from the interaction of the transition cyclo - toroid moment with the vortex part of the penetrating electron current . in order to determine @xmath60 let us use the standard view for the radiation nuclear matrix element @xcite : @xmath111 , where @xmath112 are the klebsch - gordan coefficients . the reduced matrix element @xmath113 in the nuclear spectroscopy is usually related to the experimentally measured reduced probability of the nuclear transition latexmath:[$b(e / ml;j_i\rightarrow{}j_f ) = reduced probability of the @xmath0 transition in the single - particle weisskopf model is @xmath115 @xcite . as a rule , the value of the experimental probability is given in weisskopf units @xmath116 . for the considered transition in @xmath105ta it is @xmath117 @xcite . let us substitute operator in square brackets in eq ( [ eq : operat - an ] ) to operator @xmath118 and then , using the definitions for @xmath119 and @xmath120 , derive the expression for the reduced matrix element of the cyclo - toroid moment of the transition through the parameters measured in the experiment : @xmath121 we introduced here @xmath122 as the `` unit '' for measurement of the cyclo - toroid moment . for @xmath105ta nucleus the following is true : @xmath123 @xmath124/gev if the radius of a nucleus with atomic number @xmath125 is @xmath126 fm . using eq ( [ eq : ct - reduced ] ) one can estimate the value @xmath127 for the anomalous conversion @xmath0(482 kev ) transition : @xmath128 . the cyclo - toroid moment is a pseudovector . atomic nuclei , like some other objects , for example , nucleons , can have a static cyclo - toroid moment in the ground state . the value of a @xmath48 for nucleus should not depend on the fermi coupling constant @xmath129 of the weak interaction , unlike the static toroid moment ( the latter as a rule arises due to the parity violation for the nuclear forces and contains @xmath129 @xcite ) . another positive aspect is the geometric factor similar to the one considered for toroid moments in ref . the cyclo - toroid moment @xmath60 is proportional to the nucleus volume , that is , to the atomic number @xmath125 . as for the interaction of the cyclo - toroid moment with an atom electron , this interaction is of the electromagnetic nature and , therefore , is proportional to the fine structure constant @xmath130 . besides , the additional smallness of @xmath131 is produced by the small component of the dirac wave function @xmath75 . the interaction of the atomic @xmath132-electron with the cyclo - toroid moment of a nucleus results in the contribution to the atomic level energy already in the first order of the perturbation theory . to demonstrate this , let us estimate the shift of the @xmath133 level in @xmath3cs . the dependence of the energy on the electron spin projection @xmath134 and on the value of the cyclo - toroid moment @xmath135 ( here and further @xmath135 is measured in @xmath136 units ) can be found from the following formula : @xmath137 that can be obtained from eqs ( [ eq : hint ] ) and ( [ eq : curlj ] ) , if one uses the @xmath138 wave function for the initial and the final state simultaneously , and takes into account the relation @xmath139 , where @xmath140 is the electron mass . we have @xmath141 ev when @xmath142 , @xmath143 . hydrogen - like ions in the @xmath2 state are perspective objects for such investigation . we give here the qualitative estimations for the h - like ions of two heavy nuclei : @xmath144cs@xmath145 ev and @xmath146u@xmath147 ev . the proton constituted of quarks can also possess a cyclo - toroid moment . in this case the shift of @xmath148 level of a hydrogen atom as a function of @xmath135 is @xmath149 ev ( the calculation was performed according to formula ( [ eq : deltae ] ) with the following parameters : @xmath150 , @xmath151 if @xmath152 fm , @xmath153 ) . it should be noted that the magnitude of @xmath154 for @xmath155 is at present close to the accuracy of the measurement of the lamb shift for the @xmath148 level of hydrogen @xcite . in conclusion it is important to note the following . the system depicted in fig . [ fig1 ] has no charges . therefore , for all the charge moments there is @xmath156 ( where @xmath157 is the charge density ) . for all the magnetic moments of the system there is also @xmath158 , since all the elementary magnetic moments are ring - like composed and can be written in the following way : @xmath159 , and @xmath160 . the same is also true for the toroid moment @xmath161 @xcite , because for the object in fig . [ fig1 ] there is @xmath162 . thus , the system has no toroid moments . in spite of the fact that the mentioned electromagnetic moments are equal to zero , the interaction energy of the system with the external current has a nonzero value . so , the cyclo - toroid moment can be the single non - vanishing moment of the quantum object . during recent years the author discussed some problems considered in sec . 2 of this paper with dr . m.a . listengarten . without his benevolent interest , constructive advices and persistent wish to see work finished , this paper would be hardly written . this work was partially supported by the istc , project n2651 , and by the leading science school grant n2078.2003.2 .

we offer the hypothesis that atomic nuclei , nucleons , and atoms possess a new type of electromagnetic moment , that we call a `` cyclo - toroid moment '' . in nuclei , this moment arises when the toroid dipole ( anapole ) moments are arrayed in the form of a ring , or , equivalently , when the magnetic moments of the nucleons are arranged in the form of rings which , in turn , constitute the surface of a torus . we establish theoretically that the cyclo - toroid moment plays a role in the processes of the atomic shell nucleus interaction . the existence of this moment would explain known anomalies in the internal conversion coefficients for @xmath0 transitions in nuclei . we show also that the static cyclo - toroid nuclear moment interacts locally inside the nucleus with the vortex part of the atomic electron currents and this leads to an energy shift in atomic @xmath1 states . for the hydrogen atom the value of this shift may be comparable in order of magnitude to the present accuracy of measurements of the lamb shift for the @xmath2 level .

adequate hemodynamic management using well - defined perioperative goal - directed therapy ( gdt ) is a corner - stone of tissue perfusion and oxygenation that can improve outcome . the aim of gdt is to prevent tissue oxygen debt and energy crisis by maintaining adequate tissue perfusion and oxygenation in relation to increased metabolic demand during major surgery . in an elegant study in the previous issue of critical care , jhanji and the authors showed that stroke volume - targeted colloid administration coupled with a fixed infusion rate of dopexamine improved oxygen delivery ( do2 ) , central venous oxygen saturation ( scvo2 ) , micro - vascular blood flow , and tissue oxygenation and that fluid therapy alone led to additional modest improvements . these data echo previous findings that optimizing do2 improves outcome [ 2 - 5 ] and that microvascular flow abnormalities could be a key point in determining postoperative complications following high - risk surgery . these results were consistent with those of lobo and colleagues , who compared the use of fluids and dobutamine and fluids alone in high - risk surgical patients . the use of fluids and dobutamine to achieve a do2 goal ( of greater than 600 ml / min per m ) determined better postoperative outcomes than fluids alone did . the study of hanja and colleagues , however , raises several important questions that might deserve future clinical trials . first , we have to ask whether the hemodynamic optimization should be performed postoperatively or , more logically , once the surgical trauma is induced . in the three study groups , it is clear that baseline postoperative inflammatory markers were largely elevated , rendering the hemodynamic optimization less able to reduce complications that appear to be present at a very high rate regardless of the intervention protocol ( between 58% and 69% of the patients ) . indeed , several pieces of evidence suggest that the timing of therapeutic intervention during gdt could be a critical issue , and most studies predominantly performed gdt starting intraoperatively . second , one may question the use of a fixed low infusion rate of dopexamine ( 0.5 g / kg per minute ) without targeting any specific goals for cardiac output or do2 . although the use of a low dose of dopexamine demonstrated benefits in terms of survival and reduction in hospital stay in a previous small- scale study , this was not observed here by jhanji and colleagues in this randomized trial on a larger scale . in the latter context , it seems important to emphasize that the serum lactate concentration and the base deficit remained a bit higher ( though not significantly so ) during the first 4 hours of treatment in the fixed - dose dopexamine treatment group . therefore , two important complementary questions remain : do we need , as for fluids , an individualized approach to deliver inotrope during gdt ? what should be the goal to address the adequacy of inotrope infusion ? from an ' energy debt ' perspective , it is certainly much more important to consider the do2-to - o2 consumption ( vo2 ) relationship than to indicate a specific value of do2 as a goal . to this end , donati and colleagues demonstrated improved outcome in patients treated with individualized gdt using fluids and dobutamine titrated to maintain o2 extraction ( ero2 , the ratio of vo2 to do2 ) at less than 27% ( corresponding approximately to an scvo2 of greater than 73% ) . an increase in vo2 without a corresponding increase in do2 , or a decrease in do2 and no change in o2 requirements , results in an increase in ero2 , rendering scvo2 an interesting contributor to patient monitoring . in critical illness , however , the ability of tissue to increase ero2 might be impaired , and ' normalized scvo2 ' would lose its ability to guide fluid or inotrope therapy . this constitutes the third important remaining issue raised by this study : should we systematically integrate other markers of cellular energy adequacy ( besides scvo2 ) such as serum lactate , base deficit , or tissue hypercarbia ? in any case , these markers deserve further investigations in gdt - based protocols , as has been done in critical illness such as severe sepsis , before being considered eligible tools for high - risk surgery . in total , we believe it would be more rational to apply gdt according to individual patients ' targets based on their specific physiological profile , whether it pertains to fluid loading or dopexamine titration . it is obvious that the use of inotropes should be cautious in patients with high risk of ischemic cardiovascular events , in which beta stimulation may be harmful . in a previous study of 122 high - risk patients ( 81% with an american society of anesthesiologists score of at least 3 ) , pearse and colleagues reported a 13% rate of adverse events ( tachycardia and myocardial ischemia ) using mean doses of dopexamine of 0.75 g / kg per minute ( interquartile range of 0.5 to 1.0 g / kg per minute ) whereas 24% of patients did not achieve the do2 goal despite receiving the maximum therapy allowed . inotrope titration should integrate the relationship of o2 needs to the o2 costs to be delivered . finally , we feel that gdt must be applied at the time of injury ( that is , intraoperatively ) and not after inflammation has already started . such an approach , applied in further clinical trials , might provide us with responses to our yet unanswered questions . do2 : oxygen delivery ; ero2 : oxygen extraction ; gdt : goal - directed therapy ; scvo2 : central venous oxygen saturation ; vo2 : oxygen consumption .

there is substantial evidence to demonstrate the benefits of goal - directed hemodynamic optimization using fluid loading or inotropic support or both to improve outcome during major surgery . however , until now , only limited pathophysiological data have been available to explain this benefit . the maintenance of adequate tissue perfusion and global oxygen delivery is an essential goal for therapy . in an interesting study , jhanji and colleagues provided additional data that emphasize the roles of optimization of intravascular fluid status and low doses of inotropes to improve microvascular blood flow and tissue oxygenation . this commentary aims to highlight some issues raised by this important study and provides additional elements to further position these results .

motion of a test particle around a black hole is a very old topic of investigation to know the behavior of the gravitational field around black hole(for example [ 1 - 3 ] and any other book on general relativity ) . such investigation was started long back when within a year of publication of general theory of relativity by einstein(1915)[4 - 7 ] , schwarzchild [ 8 ] gave a vacuum solution to the einstein field equations . the solution describes the geometry of vacuum space - time outside a spherical massive body and is known today as schwarzchild black hole solution . at present in all text books on general relativity there is an exhaustive study of the motion of a test particle around the schwarzchild black hole(see for example [ 1 - 3 ] ) . in the present work , an investigation of the motion of a test particle is done around a general static non - rotating black hole . a general formula for determining bending of light is evaluated and is tested for schwarzchild black hole.gravitational field outside the black hole is approximated by pseudo - newtonian(pn ) gravitational potential and is compared with the corresponding effective potential for test particle motion . finally all results are verified for reissner - nordstrm black hole solution . + the paper is organized as follows : section ii deals with the motion of a massive test particle around a general spherically symmetric non - rotating black hole . also effective potential , energy and condition for circular orbit are determined for the black hole . further some comments are presented point wise . in section iii trajectory of a photon and bending of light is studied . pseudo - newtonian gravitational potential is determined and it is compared with effective potential in section iv . as an example all results are deduced for reissner - nordstrm black hole in section v. the paper ends with a short conclusion in section vi . the line element of a static spherically symmetric space time which describes a black hole can be written as , @xmath0 where @xmath1 is at least a @xmath2 function and it should satisfy the following conditions so that line element ( eq.1 ) describes a black hole solution : i ) @xmath1 must have a zero at some positive r ( say @xmath3 ) so that time dilation is infinite at @xmath3 , ii ) the kretschmann scalar ( @xmath4 ) should be finite at @xmath5 but it diverges at @xmath6 i.e. the space time described by equation ( 1 ) has curvature singularity only at @xmath6 . here @xmath7is the metric on unit two sphere . suppose we consider the motion of a test particle of rest mass m around the black hole . the corresponding lagrangian will be @xmath8 where @xmath9 is any affine parameter . + as the lagrangian has two cyclic co - ordinates @xmath10 and @xmath11 so the corresponding momenta must be constant . this leads to @xmath12 a constant and @xmath13 is also a constant . as the space - time is spherically symmetric so the motion is always confined to a plane which for convenience chosen to be the equatorial plane @xmath14 . the explicit form of the momentum components are @xmath15 @xmath16 @xmath17 @xmath18 using the above expressions for momentum components in the energy momentum conservation relation @xmath19 we obtain @xmath20 where @xmath21 is called the ( square of the ) effective potential . + now differentiating both sides of equation ( 7 ) we have @xmath22 also from ( 5 ) the momentum in the @xmath11 direction gives @xmath23 so eliminating the affine parameter between @xmath24 and @xmath25 the differential equation of the trajectory of the particle in the equatorial plane is given by @xmath26\ ] ] which can be written as @xmath27 where @xmath28 we can make the following conclusions on the trajectory of the particle : + @xmath29 the energy of the particle should not be less than the potential @xmath30 i.e. for a given @xmath31 the trajectory should be such that the radial range is restricted to those radii for which @xmath32 is smaller than @xmath31 . + @xmath29 if @xmath33 for all values of @xmath34 then the particle comes from infinity and moves directly to the origin . this is called the terminating escape orbit . + @xmath29 if @xmath35 has one positive zero then the particle either starts from finite distance moves directly to the origin ( known as terminating bound orbit ) or it may move on an escape orbit with a finite impact parameter @xmath36 . if @xmath35 has two positive zeros then we have two possible cases : i. if @xmath33 between the two zeros then the trajectory is called periodic bound orbit like planetary orbit or ii . if @xmath37 between these two zeros then the trajectory is either an escape orbit or a terminating bound orbit . + @xmath29 the points where @xmath38 are known as turning points of the trajectory i.e. the value of r which satisfies @xmath39 are turning points and eq.(13 ) determines the potential curves . + @xmath29for circular orbit @xmath40 we have from ( 9)@xmath41 i.e. circular orbits are possible for those radial co ordinates which correspond to maximum ( unstable ) or minimum(stable ) of the potential . thus for circular orbit we must have @xmath42 to determine the photon trajectory we shall proceed as before . here from the energy momentum conservation relation we have @xmath43 i.e. @xmath44 is the ( square of the ) effective potential . so differentiating both sides we get@xmath45 thus the differential path of a light ray is given by @xmath46}}\ ] ] where @xmath47 . now for photon circular orbit we have @xmath48 i.e. the radius of the circular orbit satisfies @xmath49 one may note that the radius of photon circular orbit is independent of the angular momentum of photon . in particular , for a schwarzchild black hole the radius of photon circular orbit is @xmath50 .for an ingoing photon choosing @xmath51 we have @xmath52}}\ ] ] where @xmath53 . + note that if @xmath54 is a constant then @xmath55 has the solution @xmath56 ( choosing the constant to be unity ) a straight line . this is expected as f(r)=constant means the space time is minkowskian ( having no gravitational effect ) and photon trajectory will be straight line . further we see that at large distance ( small @xmath57 ) the gravitational field due to the black hole will be negligible so we may expand @xmath54 in a power series of u i.e. @xmath58 so keeping up to first order in @xmath57 we have from @xmath55@xmath59}}\ ] ] let @xmath60 then @xmath61 . then the above differential equation becomes @xmath62 so on integration , @xmath63 if we choose @xmath64 as the initial incoming direction of light i.e. @xmath65 as @xmath66 and as in the approximation @xmath67 corresponds to the smallest @xmath34 that photon can travel then @xmath68 so the angle of deflection is @xmath69 , as the photon comes from infinity to the point of closest approach . hence the total deflection would be @xmath70 . therefore , considering the straight line path the net amount of deflection will be @xmath71 if we take schwarzschild solution then we have @xmath72 and @xmath73 . further , if it so happen that @xmath74 then we choose @xmath75 . using the transformation @xmath76 the net amount of deflection will be given by @xmath77 based on a general heuristic method([9 ] ) , the pn gravitational potential can be defined as @xmath78 where , r is the usual radial co - ordinate and @xmath79 is the general relativistic specific angular momentum i.e. @xmath80 is the ratio of the conserved angular momentum and energy per particle mass , related to the circular geodesic in the equatorial plane . + in newtonian theory , the gravitational potential @xmath81 is given by @xmath82 with @xmath83 , the newtonian angular momentum per mass of the particle moving in the circular orbit . the motivation of choosing pn potential ( 27 ) is to match the newtonian angular momentum per particle mass on a circular orbit with the general relativistic angular momentum . in the present study , the general relativistic conserved angular momentum and energy per particle mass for circular orbit are given by ( from equations ( 13 ) and ( 14 ) ) @xmath84^{\frac{1}{2}}\ ] ] and @xmath85}}\ ] ] i.e. @xmath86 hence from ( 27 ) the pn gravitational potential is @xmath87 where the constant of integration c is determined from the known result of the schwarzchild black hole as follows:(note that c has no physical meaning ) + for schwarzchild black hole , the well known paczyski - witta gravitational potential([10 ] ) is @xmath88 substituting in eq.(31 ) we get @xmath89 and hence the pn gravitational potential for a general spherically symmetric black hole described by eq.(1 ) is @xmath90\ ] ] as for static radius @xmath91 gravitational potential should be zero so from ( 33 ) we have @xmath92 . hence from equations ( 28),(29 ) the circular orbit of the test particle exist for radius @xmath93 in the range([11 ] ) @xmath94 where @xmath95 satisfies @xmath96 i.e. @xmath95 is the photon circular orbit . thus all circular orbits of the test particle are lower bounded by the photon circular orbit and are extended upto the static radius . + further , from eq.(33 ) we see that the pn potential diverges at the event horizon ( i.e.@xmath97 ) reaches its maximum value at @xmath98 ( where@xmath99 ) and then decreases for @xmath100 i.e. the gravitational field corresponding to pn potential become repulsive for @xmath100 . also if the metric(1 ) becomes asymptotically flat(i.e . @xmath101 as @xmath102 ) then @xmath103 asymptotically([11],[12 ] ) . moreover , for central gravitational fields , if we assume that the motion of the test particle is confined to the equatorial plane then for keplarian motion along the radial direction gives @xmath104 where e stands for total pn energy per particle mass and @xmath105 stands for pn effective potential per particle mass having explicit form ( [ 13 ] ) @xmath106 where @xmath107 is the pn gravitational potential given by eq.(33 ) and @xmath108 is the pn angular momentum per particle mass . thus circular keplarian orbits are characterized by the extrema of @xmath105(i.e.@xmath109 ) and we have @xmath110^{2}}\ ] ] which can be written as ( using eq.s ( 28 ) and ( 29 ) ) @xmath111 the corresponding expression for energy is @xmath112\ ] ] using @xmath113 it can be written as @xmath114\ ] ] it is to be noted that angular momentum per particle mass is same for both general relativity as well as for pn effective potential theory . + we shall now examine the stability of circular orbits studied above . as stability criteria is determined by the extrema of the effective potential @xmath105 , so we have @xmath115 for stable circular orbit and @xmath116 for unstable circular orbit . due to identical nature of @xmath79 both gr and pn potential theory have same criteria for stability . further , inner and outer marginally stable circular orbits corresponds to extrema of @xmath117 and we have @xmath118^{2}=f(r)\left[3f'(r)+rf''(r)\right]\ ] ] hence for stability one should have @xmath119^{2}<f(r ) \left[3f'(r)+rf''(r ) \right]\ ] ] finally , from the above expressions ( eq.s ( 36 ) and ( 38 ) ) of @xmath117 and @xmath120 we have the following observations : + @xmath121 at the event horizon(@xmath97 ) both @xmath117 and @xmath120 diverge while @xmath113 and @xmath122 exist if @xmath123 $ ] is positive definite . for example in case of schwarzchild - de sitter space time([11 ] ) they become finite while for our reissner - nordstrm black hole ( see next section ) they do not exist . + @xmath121 at the static radius ( @xmath124 ) both @xmath117 and @xmath120 vanish while @xmath113 and @xmath122 depend on choice of @xmath1 . + @xmath125 at the photon circular orbit ( @xmath126 ) both @xmath122 and @xmath113 diverge while @xmath127 and @xmath79 is finite there . + thus we conclude that both in pn approach and in relativistic approach the circular orbits are bounded from above by static radius while bound from below by event horizon in pn approach and that by the radius of photon orbit in relativistic approach . this is due to the fact that we do not get photon circular orbit in pn approach([11 ] ) . for reissner - nordstrm(r - n ) black hole solution we have @xmath128 where m being the mass and q the charge of black hole . so for horizon we have @xmath97 i.e. @xmath129 black hole solution exists for @xmath130 and we have event horizon at @xmath131 and @xmath132 corresponds to black hole cauchy horizon . when @xmath133 then both the horizons coincide and it is the case of extremal black hole . the static radius is given by ( @xmath124 ) @xmath134 the radius at which @xmath135gives the solution@xmath136 one may note that @xmath137 so both the static radius and @xmath138 lie inside the event horizon . hence they have no physical significance for r - n black hole . also the radius of photon circular orbits are given by @xmath139\ ] ] * relativistic theory * : + for circular orbit the conserved angular momentum and energy per particle mass are @xmath140 variation of @xmath122 with respect to the variation of @xmath141 and @xmath34 for @xmath142 has been shown in figure 1 [ variables in the figures are in any standard units ] . figure 1 figure 1 : the figure shows the variation of relativistic conserved angular momentum @xmath122 with respect to variation of q and r for the choice @xmath142 . @xmath143}{\sqrt{r^{2}-3mr+2q^{2}}}\ ] ] @xmath144 with effective potential @xmath145}\ ] ] * pseudo - newtonian theory * : + pn gravitational potential and effective potentials are @xmath146}\ ] ] the graph of @xmath107 for variation of both q and r with @xmath142 is presented in figure 2 . also in figure 3 , we have shown the dependence of @xmath107 by drawing the graphs of @xmath107 for three different values of q. figure 2 figure 2 : here variation of pn gravitational potential @xmath107 with variation of both q and r for @xmath142 is shown . figure 3 figure 3:here pn gravitational potential @xmath107 is drawn for three different values of q. the upper one for @xmath147 , middle one for @xmath148 and the lower one for @xmath149 . @xmath150}+\frac{l^{2}}{2r^{2}}\ ] ] also we have @xmath151 the graphical presentation of @xmath79 for the variation of both q and r with @xmath142 has been shown in figure 4 . also graphically a comparative study of @xmath122(given by eq.(46 ) ) and @xmath79(given by eq.(52 ) ) has been presented in figure 5(a ) and 5(b ) for two different values of q. figure 4 figure 4:the figure shows the graphical representation of pn angular momentum per particle mass @xmath79 for variation of both q and r with @xmath142 figure 5(a ) figure 5(b ) figure 5(a ) and 5(b ) show the comparative study of the variation of relativistic angular momentum @xmath122(given by eq.(46 ) ) and pn angular momentum per particle mass @xmath79(given by eq.(52 ) ) for @xmath148 and @xmath152 respectively.where upper one gives @xmath122 and lower one @xmath79 @xmath153^{2}}\ ] ] the marginally stable circular orbits are given by the positive root of the equation @xmath154 if the cubic eq has three positive real roots(@xmath155)then @xmath156 and @xmath157 are respectively the radii of the outer and inner marginally stable circular orbits . finally , for stable circular orbit we have @xmath158 in this work we give a general formulation of the trajectory of a test particle ( or a photon ) around any spherically symmetric black hole in four dimensional space time . we also classify the trajectories by studying the possible positive zeros of the function @xmath28 so once @xmath1 is given for a given black hole we can immediately tell the trajectories of a test particle or a photon around it . in the pn approach physical parameters for circular orbits are evaluated and are compared with the corresponding quantities in relativistic treatments . stability condition for the circular orbits are determined and bounds of the marginally stable circular orbits are compared in both formalism . as an example we have applied our results for r - n black hole solution . + it is to be noted that the above analysis of the trajectory is not restricted to einstein gravity , it can also be applied to any black hole solution in a modified gravity theory . further our analysis can be extended to any higher dimension . for example , the metric ansatz for a @xmath159 dimensional black hole is written in the form @xmath160 where @xmath161 is the metric on unit @xmath162 sphere and is given by @xmath163 @xmath164 then due to spherical symmetry of the space time the motion of a test particle can be restricted to the equatorial plane defined by @xmath165 . as before energy @xmath31 and the angular momentum @xmath166 are two conserved quantities and the differential equation for the path of the test particle becomes @xmath167\ ] ] where @xmath168 or @xmath169 for photon or massive particle . finally , one may note that throughout our calculations we have not used any specific gravity theory . so if we have a black hole solution given by equation ( 1 ) not only in einstein gravity but also in any other gravity theory , the above analysis of the trajectory of a test particle is valid . moreover from equations ( 56 ) and ( 57 ) , we may conclude that above analysis of particle trajectory can be extended to any dimension of space time . + for future work , an extension of the above approach to non - spherical systems ( particularly axi - symmetric ) would be interesting . + * acknowledgement : * + the first author is thankful to dr.prabir kr . mukherjee , department of physics , presidency college , kolkata , for valuable help in preparing the manuscript.the first author is also thankful to dst , govt.of india for awarding kvpy fellowship.the authors greatly acknowledge the warm hospitality at iucaa , pune where apart of the work has been done . + + * references : * + @xmath170 $ ] . narlikar.j.v _ lectures on general relativity and cosmology _ ( the macmillan company of india ) ( 1978 ) + @xmath171 $ ] schutz.bernerd _ a first course in general relativity _ ( cambridge university press)(1995 ) + @xmath172 $ ] ray.d.inverno _ introducing einstein s general theory of relativity _ ( clarenden press , oxford)(2003 ) + @xmath173 $ ] einstein.a _ preuss , akad.wiss.berlin , sitzber , _ * 778*,*799*,*831 * and * 844 * ( 1915 ) + @xmath174 $ ] einstein.a _ preuss , akad.wiss.berlin , sitzber , _ * 142 * ( 1917 ) + @xmath175 $ ] einstein.a _ the meaning of relativity_(methuen , london ) ( 1951 ) + @xmath176 $ ] einstein . relativity : the special and general theory _ ( methuen , london ) ( 1920 ) + @xmath177 $ ] schwarzchild.k _ sitzber , deut.akad.wiss.berlin.ki.math-phys . * 189 * ( 1923 ) + @xmath178 $ ] mukhopadhyay.b _ astrophysical journal _ * 581 * ( 2002 ) 427 . + @xmath179 $ ] paczyski.b and witta.p _ astron.astrophys . _ * 88 * ( 1980 ) 23 . + @xmath180 $ ] stuchlk.z and kov.j _ int.j.mod.phys.d _ * 17 * ( 2008 ) 2089 . + @xmath181 $ ] stuchlk.z , slan and kov.j _ class.quantum.grav _ * 26 * ( 2009 ) 215013 . + @xmath182 $ ] minser.c.w , thorne.k.s and wheeler.j.a , _ gravitation _ ( freeman , san francisco , 1973 ) .

trajectory of a test particle or a photon around a general spherical black hole is studied and bending of light trajectory is investigated . pseudo - newtonian gravitational potential describing the gravitational field of the black hole is determined and is compared with the related effective potential for test particle motion . as an example , results are presented for reissner - nordstrm black hole .

the identification of individuals with influential positions in a network is of outmost importance for a number of problems in economics and beyond , as for instance regarding the diffusion of epidemics @xcite , the stability of systems of interconnected banks @xcite and the development of criminal networks @xcite . different contexts often lead to different measures of _ centrality _ that capture the level of the said influence more appropriately . degree centrality is found to be important in problems of adoption with word of mouth communication @xcite and biases in the perception of social norms @xcite . bonacich centrality @xcite is found to be crucial in problems related to criminal behavior @xcite , whereas eigenvector centrality is found to be important in diffusion processes @xcite . in this article we focus on _ decay centrality_. this is a measure of centrality in which a node is rewarded for how close it is to other nodes , but in a way that very distant nodes are weighted less than closer ones ( see * ? ? ? it is defined as @xmath0 , where @xmath1 is a decay parameter and @xmath2 is the geodesic distance between nodes @xmath3 and @xmath4 . for low values of @xmath5 decay centrality puts much more weight on closer nodes , thus becoming proportional to degree centrality , whereas for high values of @xmath5 it measures the size of the component a node lies in it is considered to be richer than other distance related measures , because it captures the idea that the importance of a node for another is proportional to their distance ( see for instance * ? ? ? it has been considered important in problems of optimal targeting selection in networks ( see * ? ? ? * ; * ? ? ? * ; * ? ? ? in particular , @xcite and @xcite find decay centrality to be the measure that helps selecting the node that can lead to the maximum diffusion of a given action in a social network . nevertheless , its use is cumbersome for two main reasons . first , except in very simple structures , the nodes with maximum decay centrality can not be easily identified , since the measure depends vastly on the exact network topology and the value of the decay parameter . second , calculating the decay centrality of all nodes and subsequently choosing the one that maximizes it might be computationally costly , since it requires calculating the geodesic distance between each pair of nodes and subsequently summing a function of them . nodes , the time complexity for calculating degree and closeness centrality are in @xmath6 and @xmath7 respectively ( see * ? ? ? * ) , where for the calculation of shortest paths that is necessary for closeness centrality is used the simple dijkstra algorithm ( see * ? ? ? once the shortest paths have been calculated , decay centrality requires the calculation of @xmath8 for each pair of nodes @xmath9 . hence , the time complexity of calculating decay centrality is in @xmath10 . ] the aim of this article is to show the close connection between decay centrality and two well studied and computationally cheaper measures , namely degree and closeness centrality . the relations are established both analytically and numerically and suggest that the nodes with maximum decay centrality usually belong either to the set of nodes with maximum degree or to the set of nodes with maximum closeness . in particular , focusing on connected networks , we show that for sufficiently low values of the decay parameter the nodes that maximize decay centrality belong to the set of nodes with maximum degree , whereas for sufficiently high values of the decay parameter the nodes that maximize decay centrality maximize closeness as well . the first proposition is not surprising as it is already known that for low values of @xmath5 decay centrality is proportional to degree . however , the second proposition establishes a novel relationship between decay and closeness centrality for high values of @xmath5 , for which so far decay centrality was associated only with the size of the component a node lied in . furthermore , we provide two conditions that are sufficient to order a pair of nodes with respect to their decay centrality for all values of the decay parameter . the conditions depend , in an intuitive way , on the distances between the nodes under comparison and all other nodes in the network . finally , we provide a more general relation between decay centrality , degree and closeness that extends to intermediate values of the decay parameter . in particular , we provide sufficient conditions for a node with higher degree than another node to also have higher decay centrality for all @xmath11 and similarly for a node with higher closeness to also have higher decay centrality for all @xmath12 . based on those theoretical findings , we attempt to obtain a better understanding on these relations for intermediate values of the decay parameter via numerical simulations . we find that in the vast majority of cases the nodes with maximum decay centrality belong either to the set of nodes with maximum degree or to the set of nodes with maximum closeness . when the two sets intersect a node that belongs to their intersection almost always maximizes decay centrality as well , whereas when the two sets do not intersect for low values of @xmath5 decay centrality is maximized by nodes with maximum degree and as @xmath5 increases there is a threshold above which decay centrality is maximized by nodes with maximum closeness . the threshold varies with the network parameters , however a rule of thumb with a threshold at @xmath13 is sufficient to ensure that the chosen node is ranked among the top nodes in terms of decay centrality , with high probability . the relation between different measures of centrality has attracted research interest over the years ( see * ? ? ? * and references therein ) . for instance , @xcite found strong correlation among centrality measures that included degree and closeness , but not decay centrality , in a network of relations between ceos . similarly , @xcite found strong concordance in the ranking of individuals across different network centrality measures in a network of individuals who participated in activities with the risk of hiv transmission . finally , @xcite find similar results , although not as strong correlation coefficients as the previous studies , for a variety of networks corresponding to different process . all of these studies show particularly strong connection between degree and closeness , but do not consider decay centrality . more recently , and closer to the flavor of our analysis , @xcite provided an axiomatization of several centrality measures , including decay centrality , and showed that all of them can be described using the same set of axioms . given these axioms , the measures differ only in that they consider different vectors of data that describe the position of nodes in the network . the authors also provide correlation coefficients between different measures in simulated networks and their results are in line with our findings . the simulations report results on correlation coefficients , similarly to the previously mentioned articles , whereas the emphasis of our analysis is put particularly on nodes that are highly ranked in different measures . to some extent our analysis is related to the problem of identifying networks for which different centrality measures generate the same ranking , which remains largely unexplored for non tree networks . for degree and closeness centrality @xcite show that this is indeed the case for nested split graphs . finally , there is a broad connection with the literature related to the axiomatization of centrality measures , although not decay centrality per se , and other related problems ( see * ? ? ? * ; * ? ? ? consider a set of nodes @xmath14 , with cardinality @xmath15 , which are connected through a network . a network is represented by a family of sets @xmath16 , with @xmath17 denoting the set of nodes that are directly connected with @xmath3 . @xmath17 is called @xmath3 s neighborhood and has cardinality , @xmath18 . we focus on undirected networks , where @xmath19 if and only if @xmath20 . a path in a network between nodes @xmath3 and @xmath4 is a sequence @xmath21 such that @xmath22 , @xmath23 and @xmath24 for @xmath25 . the _ geodesic distance _ , @xmath2 , between two nodes is the length of the shortest path between them . two nodes are connected if there exists a path between them . the network is connected if every pair of nodes is connected . our analysis focuses on connected networks . for a given network @xmath26 , a _ centrality measure _ is a function that maps from the set of nodes to the real numbers , i.e. @xmath27 , where @xmath28 is the centrality of node @xmath3 in the network @xmath26 . the _ degree centrality _ ( or simply _ degree _ ) maps from each node to the cardinality of its neighborhood , i.e. @xmath29 . we also define the set of nodes with maximum degree , i.e. @xmath30 . similarly to this , denote by @xmath31 the number of nodes that have geodesic distance @xmath32 from node @xmath3 , i.e. @xmath33 where @xmath34 . the superscript @xmath32 will often be omitted when referring to @xmath35 ( degree ) . also , for connected networks it holds by definition that @xmath36 . the _ closeness centrality _ ( or simply _ closeness _ ) maps from each node to the inverse of the sum of the geodesic distances from each other agent in the network , i.e. @xmath37 . notice that closeness centrality measures how easily a node can reach all other nodes in the network . according to this definition , we define the set of nodes with maximum closeness centrality , i.e. @xmath38 . for some of the analytical results we focus on the inverse of closeness , which is known as _ farness _ and is defined as @xmath39 . this is essentially a measure of discentrality , as it measures how far a node is from all other nodes . obviously the order of nodes with respect to closeness is the reverse of that with respect to farness , hence central nodes are going to be considered those that minimize farness . finally , given a decay parameter @xmath40 , _ decay centrality _ is a measure that maps from each node to the sum of distances from each other node in the network , adjusted by a decay parameter that makes distant nodes count less than closer ones , i.e. @xmath41 . as in the previous two cases , for each value of @xmath5 , we define the set of nodes with maximum decay centrality , i.e. @xmath42 . [ proplowdelta ] exists @xmath43 such that for all @xmath44 and @xmath45 , if @xmath46 then @xmath47 . the proposition states that for low values of the decay parameter a node with higher degree than another will necessarily have higher decay centrality as well . this result implies immediately corollary [ corlowdelta ] which states that for sufficiently low values of the decay parameter the set of nodes with maximum of decay centrality will be a subset of the set of nodes with maximum degree . [ corlowdelta ] exists @xmath43 such that for all @xmath44 holds that @xmath48 . the reason why the two sets may not be identical is that two nodes with the same degree might have different decay centralities . when the degrees of two nodes are equal , differences arise from the factors corresponding to more distant nodes , which previously had a negligible effect . in fact , again for low values of @xmath5 , between two nodes with equal degrees , higher decay centrality has the node with higher number of nodes at distance equal to 2 , i.e. @xmath49 . if these quantities are also equal then we move to @xmath50 etc . in order to state this result formally we need an additional definition . given two vectors of real numbers @xmath51 and @xmath52 the first vector is larger than the second one according to the _ lexicographic order _ , i.e. @xmath53 , if @xmath54 for the first @xmath32 for which @xmath55 and @xmath56 differ . the two vectors are equal according to the lexicographic order , i.e. @xmath57 , if @xmath58 for all @xmath59 . it is apparent that two vectors that are equal according to the lexicographic order , i.e. @xmath60 for all @xmath32 , will also have equal decay centralities . the following result covers the remaining cases . [ proplowdeltageneral ] exists @xmath43 such that for all @xmath44 and @xmath45 , if @xmath61 then @xmath47 , where @xmath62 propositions [ proplowdelta ] and [ proplowdeltageneral ] allow the comparison of decay centralities between any pair of nodes for low values of @xmath5 . we proceed in a similar way to obtain the respective results for high values of @xmath5 . [ prophighdelta ] exists @xmath63 such that for all @xmath64 and @xmath45 , if @xmath65 then @xmath47 . proposition [ prophighdelta ] establishes a relation between the order of nodes with respect to decay centrality and closeness for high values of the decay parameter . this also implies immediately corollary [ corhighdelta ] which states that for sufficiently high values of the decay parameter the set of nodes with maximum decay centrality will be a subset of the set of nodes with maximum closeness . [ corhighdelta ] exists @xmath63 such that for all @xmath64 holds that @xmath66 . similarly to the previous case , proposition [ prophighdelta ] does not allow the comparison between nodes with equal closeness centralities . in order to do so it is necessary to define for each node the vector @xmath67 , with typical element @xmath68 , where @xmath69 by definition . observe that @xmath70 , i.e. the _ farness _ of node @xmath3 . note that , the rest of the terms of vector @xmath71 are related to the derivatives of farness , which is a different interpretation compared to @xmath72 . continuously differentiable functions in @xmath73 such that @xmath74 , @xmath75 for all @xmath76 and @xmath77 . then , there is @xmath78 such that for all @xmath79 it holds that @xmath80 if @xmath81 is even and @xmath82 if @xmath81 is odd . @xmath83 denotes @xmath32-th order derivative of @xmath84 . ] based on this definition , one can also define the vector @xmath85 , where @xmath86 if @xmath87 and @xmath88 if @xmath89 for all @xmath90 . note that @xmath91 corresponds to the closeness centrality , thus the overscript will often be omitted , and the following equivalence relations hold always . [ remarkfarclos ] @xmath92 and @xmath93 . it is important to underline that such an equivalence does not hold for all orders . for instance , it does not hold for the _ unsorted dominance order _ that is defined and used later in the article . having said that , we are ready to provide a result that determines the complete order among nodes in terms of decay centrality . [ prophighdeltageneral ] exists @xmath63 such that for all @xmath64 and @xmath45 , if @xmath94 then @xmath47 , where @xmath95 the results so far have established a clear relation between decay centrality , degree and closeness , in the two limits , which provides a more intuitive picture of the characteristics of nodes with high decay centrality for some values of the decay parameter . however , the established relations still leave unanswered what happens for intermediate values of @xmath5 . given two vectors of real numbers @xmath51 and @xmath52 the first one is larger than the second one according to the _ unsorted dominance order _ , i.e. @xmath96 , if @xmath97 for all @xmath90 and at least one of the inequalities is strict . [ defunsorteddominance ] we use the term _ unsorted _ because the standard definition of dominance order considers vectors whose elements are already sorted in decreasing order , which is not the case here . moreover , notice that _ unsorted dominance _ is a partial order , thus it may not allow the comparison between all nodes . finally , observe that , under certain assumptions on the vectors under comparison , the unsorted dominance order can be seen as a deterministic analog of _ first order stochastic dominance_. definition [ defunsorteddominance ] allows us to establish the following result : for @xmath45 , if @xmath98 then @xmath47 for all @xmath40 . [ propintermediatedeltadomdeg ] despite not providing a complete order , the result grasps the important relation between degree and closeness in the calculation of decay centrality . on one hand a high degree is beneficial as it is included in all sums @xmath99 , on the other hand , high closeness implies , though indirectly , that a higher number of nodes will be in a shorter distance from @xmath3 , thus boosting all relevant sums upwards . a similar result can be established using the relation between @xmath100 and @xmath101 as follows : for @xmath45 , if @xmath102 then @xmath47 for all @xmath40 . [ propintermediatedeltadomfar ] observe that the subscripts in the first relation are reversed compared to proposition [ propintermediatedeltadomdeg ] , meaning that lower values of the elements of @xmath100 are associated with higher decay centrality . additionally , as it has already been mentioned , there is no equivalence relation between @xmath71 and @xmath103 with respect to _ unsorted dominance _ , thus the result needs to be stated using the vector associated with farness , rather than the one associated with closeness . the next result , builds upon propositions [ proplowdelta ] and [ proplowdeltageneral ] , as it provides several sufficient conditions that characterize nodes with high decay centrality for values of @xmath104 . namely , [ propdeltalowerhalf ] consider two distinct nodes @xmath45 and let @xmath105 and @xmath106 for all @xmath107 . then , if @xmath108 either of the following four conditions is sufficient to ensure that @xmath47 for all @xmath109 $ ] . 2 1 . @xmath110 2 . @xmath111 3 . @xmath112 4 . @xmath113 the essence of all conditions is that as long as node @xmath3 has sufficiently many more immediate neighbors than node @xmath4 ( high @xmath114 ) then node @xmath3 has higher decay centrality not only very close to the limit , but for a large range of values of @xmath5 . the first two conditions provide also a simple illustration of the higher relative importance of closer neighbors compared to more distant ones , which is essential for decay centrality . a closer look at the proof of proposition [ propdeltalowerhalf ] reveals that the conditions are relatively demanding and the bounds are not tight , which is to be expected given that they hold for any potential network structure . the next result establishes similar conditions for high values of @xmath5 , where high decay centrality is more closely associated with low farness . namely , [ propdeltaupperhalf ] consider two distinct nodes @xmath45 and let @xmath115 and @xmath116 for all @xmath107 . then , if @xmath117 either of the following two conditions is sufficient to ensure that @xmath47 for all @xmath118 . 2 1 . @xmath119 2 . @xmath120 propositions [ propdeltalowerhalf ] and [ propdeltaupperhalf ] provide a connection between decay centrality , degree and closeness for values that extend away from the limits . an important observation is that @xmath121 is the maximum upper bound for which conditions 3 and 4 of proposition [ propdeltalowerhalf ] guarantee the order of decay centralities , given that the remaining conditions hold . similarly , @xmath121 is also the minimum lower bound for which conditions 1 and 2 of proposition [ propdeltaupperhalf ] guarantee the order of decay centralities , given that the remaining conditions hold . this last observation provides a natural motivation for the rule of - thumb that is proposed in the next section . the theoretical results have provided several conditions that support the relation between decay centrality , degree and closeness . nevertheless , some of these conditions may not be easily satisfied in certain networks . for this reason , we perform an extensive set of simulations that intends to identify how strong this relation is in general networks . in particular , we focus on analyzing the extent to which the set of nodes with maximum decay centrality , @xmath122 , coincides with either @xmath123 or @xmath124 ( or both ) for different values of the decay parameter @xmath5 . we simulate undirected rdos - renyi networks @xcite , @xmath125 , where @xmath15 is the network size and @xmath126 is the link probability . the networks are required to be connected so that geodesic distances are well defined . we consider five network sizes , @xmath127 and ten link probabilities @xmath128 and perform 10000 trials for each combination @xmath129 . , some additional figures and some extensions . additional figures are available upon request . ] the first question is how often @xmath122 , i.e. the set of nodes with maximum decay centrality , intersects with either @xmath123 , i.e. the set of nodes with maximum degree , or with @xmath124 , i.e. the set of nodes with maximum closeness . we find that in the vast majority of the cases @xmath130 for almost all values of @xmath5 and not only for the limit values . it is important to mention that @xmath123 intersects with @xmath124 quite often for random networks . the reasons why this occurs are outside the scope of this paper , however it has an apparent effect on our results as it provides a natural connection between the two limit cases explored by theory . in fact , in `` almost all '' cases where there are nodes that belong both to @xmath123 and @xmath124 , those nodes also belong to @xmath122 . this result can not be generalized as there are cases in which , for some values of @xmath5 , the nodes with maximum decay centrality do not belong to either @xmath123 or @xmath124 . nevertheless , as it becomes apparent from tables [ table::coinciding ] and [ table::coincidingandintermediate ] the frequency with which such cases arise is practically negligible . .frequency of occassions where @xmath131 . [ cols="^,^,^,^,^,^,^,^,^,^,^",options="header " , ] we turn our attention to the case where @xmath123 and @xmath124 do not intersect . in this case , we expect from theory a transition in the nodes that belong to @xmath122 as @xmath5 increases . it turns out that most of the times the transition is immediate , meaning that any node in @xmath122 belongs to either @xmath123 or @xmath124 . this can become apparent in figure [ fig::frequency ] , which contains the percentage frequencies with which @xmath132 , @xmath133 and @xmath134 . for each value of @xmath5 the frequencies correspond to the fraction of the simulated networks in which each of the three conditions held true . the fact that in the left subfigure @xmath123 and @xmath124 can intersect means that the sum of the frequencies may exceed 100% , which seems to be the case rather often . this is no longer possible in the right subfigure , where we include only the cases where @xmath123 and @xmath124 do not intersect , therefore the three conditions are mutually exclusive . note that , observing a node that maximizes decay centrality without belonging either to @xmath123 or @xmath124 is never observed in more than a 2% of the trials , with the percentage becoming much lower away from @xmath13 . this suggests that for most networks there is a threshold value of @xmath5 below which @xmath132 and above which @xmath133 . + figures [ fig::histpernet_prob05_to10 ] and [ fig::histpernet_prob15_to20 ] contain the three percentage frequencies of interest for all network sizes and values of @xmath135 , focusing on networks where @xmath123 and @xmath124 do not intersect . the results are qualitatively similar in all configurations , presenting an inverted s - shaped curve for the frequency of @xmath132 , an s - shaped curve for @xmath133 and an inverted bell curve for @xmath134 . + + + + the latter one never exceeds 10% , with this being the case only for @xmath136 and values of @xmath5 close to 0.5 . we also observe the transition of maximizers of decay centrality from belonging to the set of nodes with maximum degree to that of nodes with maximum closeness occurs for lower values of @xmath5 as networks become larger , with the result being more prevalent for low values of @xmath126 ; as @xmath126 increases we observe a sharp transition occurring for @xmath5 around 0.5 . there are very few observations where @xmath123 and @xmath124 do not intersect . ] at this point one might wonder what is the rank in terms of decay centrality of nodes with maximum degree and closeness , when they are not ranked first ? figures [ fig::rank_degree_p05_allnets ] and [ fig::rank_closeness_p05_allnets ] show the average rank , as well as the 5th and 95th percentiles of rank distribution in decay centrality of nodes with maximum degree and closeness respectively . it turns out that nodes belonging to @xmath123 or @xmath124 are highly ranked in terms of decay centrality for all values of @xmath5 , even when they are not ranked first . the result is similar if we exclude the networks in which @xmath123 and @xmath124 intersect . 0.63 0.63 0.63 0.63 0.63 0.63 nevertheless , focusing only on degree or only on closeness leads to increasingly suboptimal choices as @xmath5 moves towards the extremes . hence , it remains unclear which of the two sets would provide better candidates depending on the value of @xmath5 . ideally , we would like to have a simple rule of thumb that would facilitate this choice . a natural rule would be to choose a node from @xmath123 for @xmath137 and a node from @xmath124 for @xmath138 . given that the two sets usually contain few nodes , it should not be too costly to calculate the decay centrality of each of these nodes and pick the one that maximizes it . it turns out that this rule of thumb is sufficient to ensure that the chosen node will be highly ranked in terms of decay centrality . figure [ fig::rank_combined_p05_allnets ] shows the same statistics as figures [ fig::rank_degree_p05_allnets ] and [ fig::rank_closeness_p05_allnets ] for @xmath136 and all network sizes , in which it can be seen that in all networks a node chosen according to this rule will be ranked in terms of decay centrality among the top three with probability 95% . additional figures in the online appendix suggest that the result is robust to different parameter values and even for networks with 1000 nodes . 0.625 0.625 0.625 we have established , both analytically and numerically , a relation between decay centrality , degree and closeness , showing that nodes that maximize one of the two measures are natural candidates for maximizing decay centrality as well . in fact , the majority of networks has a threshold value of @xmath5 below which maximum decay centrality coincides with maximum degree and above which it coincides with maximum closeness . we show that a simple rule of thumb that considers a common threshold at @xmath13 performs particularly well . it still remains rather unexplored whether there are particular characteristics of the network that can allow the accurate characterization of this threshold value with some accuracy . finally , simulations are limited to networks of small to medium size . in the online appendix we provide some additional support in favor of our results by considering networks with 1000 nodes , however a more systematic extension of the analysis to large networks would ensure their applicability to problems where decay centrality has been shown to play an important role . ballester , c. , calv armengol , a. and zenou , y. 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( 2008 ) . how correlated are network centrality measures . _ connect ( tor ) _ , 28 , 1626 . notice that decay centrality can be rewritten as @xmath139 and consider the limit @xmath140 , where the last inequality is implied by @xmath46 . the expression that appears inside the limit is continuous in @xmath5 , therefore exists @xmath43 such that for all @xmath44 it holds that @xmath141 or equivalently @xmath47 . if @xmath46 then the result holds immediately by proposition [ proplowdelta ] . otherwise , let @xmath142 be the first instance such that @xmath143 . in this case , the difference between decay centralities can be written as @xmath144 , because all previous terms of the sum are equal to zero . hence , @xmath145 and by continuity with respect to @xmath5 , there is @xmath43 such that for all @xmath44 it holds that @xmath146 or equivalently @xmath47 . we need three direct observations to obtain the result . first , note that @xmath147 . second , recall the alternative formulation of decay centrality as @xmath139 and third to observe that @xmath148 . therefore , @xmath149 where the last inequality is implied by @xmath65 . hence , by continuity with respect to @xmath5 , exists @xmath63 such that for all @xmath64 holds that @xmath150 or equivalently @xmath47 . if @xmath65 the result holds immediately by proposition [ prophighdelta ] . otherwise , let @xmath142 be the first instance such that @xmath151 , hence also the first instance in which @xmath152 . hence : @xmath153 and by continuity with respect to @xmath5 , there is @xmath63 such that for all @xmath64 it holds that @xmath154 or equivalently @xmath47 . @xmath139 , which gives @xmath155 for all @xmath3 . therefore , the polynomial @xmath156 has a root for @xmath157 and another for @xmath158 , for any pair @xmath45 . having observed that , we obtain the following expression . @xmath159=\\ & = \delta(1-\delta)\left[-\sum\limits_{l=2}^{n-1}a_l-\sum\limits_{l=3}^{n-1}a_l\delta-\dots-(a_{n-1}+a_{n-2})\delta^{n-4}-a_{n-1}\delta^{n-3}\right]\end{aligned}\ ] ] where @xmath105 and @xmath106 for @xmath107 , with the crucial observation being that @xmath160 . this last equation allows us to rewrite the above expression as follows : @xmath161 \label{dcdifa}\ ] ] from the last expression is apparent that a sufficient condition , though not necessary , to satisfy @xmath47 is that @xmath162 for all @xmath90 , with at least one inequality being strict . this in turn is equivalent to @xmath163 for all @xmath81 , which by definition means that @xmath164 . let @xmath165 and restate decay centrality as follows : @xmath166 which gives @xmath167 for all @xmath3 . therefore , the polynomial @xmath168 has a root for @xmath169 ( equivalent to @xmath158 ) and another for @xmath170 ( equivalent to @xmath157 ) , for any pair @xmath45 . in addition to this , we consider the binomial identity : @xmath171 , which allows us to rewrite @xmath168 as follows : @xmath172=\\ & = -\epsilon\left[b_1+b_2\epsilon+\dots+b_{n-1}\epsilon^{n-2}\right]\end{aligned}\ ] ] where @xmath115 and @xmath116 for @xmath107 . having observed that and knowing that @xmath169 is also a root of the polynomial , we obtain the following expression via euclidean division : @xmath173\ ] ] with the crucial observation being that @xmath174 , which is the remainder of the division of the polynomial by @xmath175 , which we know that it should be equal to zero . hence , similarly to proposition [ propintermediatedeltadomdeg ] , we obtain the following expression : @xmath176 \label{dcdifb}\ ] ] it is apparent from the last expression that a sufficient condition , though not necessary , to satisfy @xmath177 for all @xmath178 , hence equivalently for all @xmath40 , is that @xmath179 for all @xmath90 , with at least one inequality being strict . this in turn is equivalent to @xmath180 for all @xmath81 , which by definition means that @xmath181 . the result can also be implied by rouch s theorem , but it is presented here with an independent proof , which follows a similar process to the one used for obtaining cauchy s bound of polynomial roots . more specifically , observe that by proposition [ proplowdelta ] together with @xmath108 it must hold true that @xmath186 for @xmath5 close to zero and obviously has a root for @xmath158 . we also know that it has another root for @xmath157 . then it is sufficient to show that @xmath156 has no other root for @xmath187 as long as @xmath188 for all @xmath107 . to prove this , it is sufficient to focus on the term @xmath189 . @xmath190 therefore , the polynomial has the same number of roots in @xmath191 as @xmath192 , which by descartes rule of signs has either zero or two positive roots . one of them is obsviously for @xmath157 and and the other is for some @xmath193 , because the polynomial has a unique minimum for some @xmath194 and is positive for @xmath158 . moreover , note that @xmath195 for any @xmath15 , and in fact @xmath196 as @xmath197 . hence , the expression is always positive in @xmath198 $ ] , which turn means that @xmath199 has no root for @xmath109 $ ] and in fact it is always positive in that region , by continuity . consider again the reformulated expression with @xmath165 , for which we know that @xmath200 $ ] , for which it is sufficient to show that it has no root for @xmath201 $ ] as long as @xmath202 for all @xmath107 . this is proven identically to condition 3 of proposition [ propdeltalowerhalf ] . the obtained result , together with the fact that @xmath117 ensures that @xmath177 for all @xmath201 $ ] , which is identical to saying that @xmath203 for all @xmath118 .

we establish a relationship between decay centrality and two widely used and computationally cheaper measures of centrality , namely degree and closeness . we show that for low values of the decay parameter the nodes with maximum decay centrality also have maximum degree , whereas for high values of the decay parameter they also maximize closeness . for intermediate values , we provide sufficient conditions that allow the comparison of decay centrality of different nodes and we show via numerical simulations that in the vast majority of networks , the nodes with maximum decay centrality are characterized by a threshold on the decay parameter below which they belong to the set of nodes with maximum degree and above which they belong to the set of nodes with maximum closeness . we also propose a simple rule of thumb that ensures a nearly optimal choice with very high probability . * jel classification : * c15 , c63 , d85 + * keywords : * decay centrality , centrality measures , networks

Advertisement Slate media critic and Press Box columnist Jack Shafer lost his job on Wednesday. He was, along with three others, part of a round of layoffs at the online news magazine. The news was met with much consternation. Just that day, an article praising Shafer as a "fearless media critic" was published on the website of the American Journalism Review, and that praise was echoed by his readers and peers, who turned to Twitter to express shock, dismay, and a little outrage. Adweek spoke with Shafer shortly after the news broke and found him in good spirits. Adweek: How are you doing? Shafer: I’m picking ‘em up and laying ‘em down. You’ve got a lot of support on Twitter right now. I tweeted out that it was a bit like reading short and kind obituaries, and that being dead has never felt so good. So I’m grateful for the reaction, obviously. But I have to imagine you’re not dead. Do you have something else in mind? I was thinking of becoming an alcoholic. Because one of the things I’ve always prided myself in, in these first 59 years of my life, is being a controlled drinker. I think now is the time to throw off the training wheels and see if maybe in the last decade and a half of my life, I can be an accomplished, functional alcoholic. And that’s starting tonight. What are you drinking? I’m just drinking some cheap red. Some cheap, Argentinian Malbec. Because it’s one thing to be an alcoholic; it’s another thing to be a bankrupt alcoholic. So you have to drink the cheap stuff. But you’re going to keep contributing to Slate? Yes, Slate is paying me a severance and has kindly asked me to continue writing for them, and I’ve accepted. And will it be Press Box? No, it won’t be press coverage. I’ll stir up the press animals in another venue. Do you know what that venue might be? No, because the news was only made public today, so I haven’t approached anybody. I haven’t phoned up Rupert Murdoch and asked him if he wants another columnist at The Wall Street Journal. I’m sure there’d be a lot of people who would take you, based on what your colleagues in media are saying on Twitter. They’re all great Americans. So what happened at Slate? The best guys to ask that question would be [chairman] Jake [Weisberg] and [editor] David [Plotz]. Since I’ve not been a manager, which is practically a decade now, I’ve not been privy to the real hard-core financials. I’m not the only one who has been let go by Slate. Slate has expanded ambitiously, and right now it’s responding to the industry-wide recession in a sensible fashion by cutting some costs—and I’m one of those costs. But based on the response to this news, I’d say you’re an incredible asset to Slate. I’m flattered. But that’s somebody else’s call. That’s not mine to make. So if you won’t be writing about media for Slate, what are you going to turn your attention to? I don’t have any preconceived notions. I’ve only known this week that I’m being let go. So I haven’t done a lot of thinking about what columns I’m going to write and what topics I’m going to attack. It’s a long way of saying, “I don’t know.” I’m just recently among the unemployed. I’ll probably have a better idea once my column starts. Are you confident about what happens next? Are you at all concerned or worried, given the climate we’re in? I’m simultaneously never worried and always concerned, as everybody in our business should be. You are moments from being fired—or from being hired by The New York Times to replace David Carr. That is just the state of our business. I’m a great fan of journalistic history. It doesn’t matter where you drop the plumb line in the time line, you find these upheavals in journalism all the time. I don’t think that these times are completely unique. So . . . this is the wine talking. I’ve lost my train of thought. There was a piece about you in the American Journalism Review today, describing how you write for everyone, not just the guy in the next cubicle. Do you agree with that portrayal? I got into the press criticism racket because as the editor of Washington City Paper in 1985, I couldn’t get anybody to write press criticism. As strange as this may seem, in 1985 everyone was worried that if they wrote negatively about The Washington Post and The New York Times and Time and Newsweek and the dominant publications of that time, that they’d screw themselves out of a job. I think what the writer of the AJR piece accurately described was that I started writing about the press and continued to write about the press as if I have no career—that I shouldn’t worry, and that no one should worry if they’re writing about the press. They should write about the press the same way they write about GE, or President Obama, or the New York Yankees. They shouldn’t be thinking about their next job. The piece was very flattering. It was my ambition to write that way, but I leave it to the readers of the piece and you and others to decide whether I’ve accomplished that. You know, when you read a flattering piece about yourself . . . I mean, have you ever read a flattering piece about yourself? I got a good report card once. I got a report card in first grade that said, “Jack excels in his studies and really enjoys math and English, but he starts fights on the playground that he brings back into the classroom.” I’ve tried to make that my operating premise: Let’s start some fights and see who wins. I assume that won’t go away. Not if I survive this first bout of alcoholism. ||||| Here's something for media critics. Last night AdWeek broke the news that Slate had laid off Jack Shafer "and several others." I'd known this for a few hours; I walked up to Shafer's office earlier in the day to beg him for inspiration on a story that was going poorly, and saw a stack of cardboard boxes, one already full of books about Rupert Murdoch and the 1930s and boozy detectives. AdWeek's story went up only an hour or so after the news became official. I braced myself for phone calls and e-mails from reporters asking for details: Who were these "others"? ||||| Slate has laid off longtime media columnist Jack Shafer as well as other staffers and contractors. The news, first reported by AdWeek, prompted a quick and dumbfounded reaction on journo-infested Twitter. this is preposterous RT @DylanByers Jack Shafer, others laid off at Slate http://t.co/Iedi38y Felix Gillette felixgillette Preposterous, sure, when considering that Shafer is among the country’s leading writers on media, a favorite of anyone who values original, uncorrupted thinking on how journalists and news outlets operate. Not so preposterous when considering that Shafer occupies a senior post at a magazine whose owner, The Washington Post Co., recently announced a bad quarterly earnings report that included a 13 percent drop in online publishing revenues, a basket that includes the flagship newspaper’s Web site as well as Slate. When asked about the reasons behind Slate’s cost reductions, Editor David Plotz handled the question in the manner of many newsroom executives over the past decade. “We made several cuts to our full-time staff as well as to contractors. It was painful and we think that Slate has to be a flexible place and has worked to be an agile and innovative Web magazine. These are not cuts that we want to make,” says Plotz. As for Shafer, well, his beat prepared him for this day. “Everybody in our business has to see this coming,” he says, noting that journalists should be “looking both ways when they cross the street.” What did Slate’s bosses tell him? “What they told me was that they needed to economize and got rid of several positions,” he says and points out that he has “no reason to distrust” that rationale. Slate, it appears, just couldn’t afford its well-regarded editor-at-large. “It was a decision made for financial and editorial future reasons,”says Plotz. “Jack is obviously a brilliant journalist.” The journalism, says Shafer, wasn’t an issue with his supervisors. “There were no tensions about my performance and my [publishing] frequency,” says Shafer. Asked about his exit package, Shafer said he was “delighted with the way they treated me.” He’ll be writing for the magazine on a freelance basis. Which leaves a gap in the magazine’s day-to-day coverage of the media. Plotz didn’t respond to a question about plans to fill that slot, and Shafer had no information either. “When you’re given your walking papers, you’re not asking a lot of questions about what the publication is going to be after you leave,” he says. Slate has lived a privileged existence as a media property, a place where newsmaking layoffs are covered, not experienced. The property launched with a small staff in 1996 under the leadership of Michael Kinsley. First under the ownership of Microsoft and under The Washington Post Co. starting in late 2004, Slate has followed a steady growth curve on ambition, topical breadth and staffing. The magazine’s “Who We Are” page now lists about 70 contributors and full-timers. Plotz declined to address staffing history and other corporate matters. Again, like any editor called upon to account for cutbacks, Plotz contends that the present changes are designed to “strengthen us in the long run.” If that means improving upon the brand of media coverage supplied by Shafer, Slate readers will be elated. Shafer’s departure from Slate is more than an industry story; it’s a personal one as well. Shafer was editor of the Washington City Paper in 1993 when he hired David Plotz onto his staff. Plotz had written a paper on Marion Barry at Harvard University, an opus that impressed Shafer, who solicited unconventional clips from job applicants. Plotz didn’t disappoint, producing a number of excellent news and feature pieces before moving on to an editing position. With each edition of the alt-weekly, Plotz learned a bit more about the Shafer doctrine, including how not to get spun by sources and public officials; how to use muscular, transitive verbs in your copy; how to use concepts to toy with the news; how to delete vast fields of copy in the editing process. The Shafer-Plotz relationship at City Paper was memorialized in this Shafer piece from December 1994, which recounts how linguistics guru Deborah Tannen had evaluated the interactions between the two men. Tannen drilled in on a stunted exchange between Plotz and Shafer over the functionality of the former’s computer. Plotz complained that the machine was inadequate: Shafer: Why? Plotz: I--’Cause it doesn’t-- Shafer: Why, it’s slow? Plotz: No, it’s not that. It’s just like there are all sorts of keys that don’t work and stuff. Shafer: What do you mean keys that don’t work? Plotz: Like the caps lock doesn’t work. Shafer: It can. You want it to? Plotz: No, it doesn’t. Shafer: You want it to? Plotz: OK. Shafer: All right. What else would you like? Plotz: Um, I don’t know. It was just sort of-- Shafer: No no no, come on. Plotz: Like I can’t turn it off because-- Shafer: You would like--you’d like to be able to turn it off? Why? ‘Cause it bothers you? Plotz: And it’s--it’s frozen up on me like three times. Shafer: Yeah? Plotz: Yeah. Shafer: Like is there a pattern? Plotz: No, I mean maybe there is, I haven’t noticed it. I--I don’t know. It hasn’t done it for about a week or so, so don’t worry. I’m just griping. I’m just griping. I’ve never--I’ve got no particular complaints because it--all I need to--I’m not--I’m not a computer junkie so I don’t really care. Shafer: So if you want your caps-lock key to work, there’s no problem. I can come in and do that. Plotz: No, I don’t really need a caps lock. Shafer: It’ll take me twenty-five seconds. Aside from shedding light on how newsies speak to each other, the piece conveyed the mutual respect between boss and up-and-coming journalist. Shafer writes in the piece: “Plotz is among the proudly computer illiterate. But that’s OK with me. I pay him because he knows how to write great stories on deadline, not because he knows when to give his computer the three-finger salute when he flummoxes it.” (Both Plotz and Shafer edited my work when I contributed to City Paper, and I consider both of them friends.) Both editors took separate paths to Slate, where Shafer vied for a repeat term as Plotz’s top boss. He and Jacob Weisberg competed in the legendary “bake-off,” wherein the two took turns editing Slate in a bid to succeed founding editor Kinsley. Shafer lost that contest after publishing a fictitious 2001 story on fishing for monkeys. A role reversal occurred when Plotz subsequently became Shafer’s editor. One easy way to get both of these fellows to shut up is to ask them to talk about all their years bossing each other around. Plotz says that Shafer has been a “great colleague and great friend over many years” but clams up when probed for something more. And Shafer says that he was “happy for David to be my boss, and he’s been a good boss” but clams up when probed for something more. Neither is much for sentimentality. Perhaps that explains why there won’t be one of those “so long” pieces when Shafer finishes up at Slate on Sept. 2. “Farewell columns are bush league,” he says.

– Slate co-founder Jack Shafer, who has been with the online magazine since before its official launch in 1996, is being laid off, it was announced yesterday. The media critic is one of four staff members being let go; Timothy Noah, June Thomas, and Juliet Lapidos are the others, reports the Washington Post. (The Washington Post Co. bought Slate in 2004 from Microsoft.) Some reactions: "If you weren't reading [Jack, Tim, June, and Juliet's] stuff, you're in luck—it'll be online 'til the Internet dies," writes Slate colleague David Weigel. "If you write, you should study it, because these people think and write circles around most everyone in the job-formerly-known-as-the-Life-of-Kings." The move is "preposterous, sure, when considering that Shafer is among the country’s leading writers on media, a favorite of anyone who values original, uncorrupted thinking on how journalists and news outlets operate," writes Erik Wemple in the Washington Post. Wemple also notes that the news "prompted a quick and dumbfounded reaction on journo-infested Twitter." Among those: Jonah Goldberg, who wondered, "Slate laid off Jack Shafer? Good lord, who did they keep?" Click to read Shafer's candid post-mortem interview with AdWeek, in which he declares, "I was thinking of becoming an alcoholic."

A photo series on the popular Humans of New York Facebook page may have went viral and captured the nation’s attention last Tuesday, but for Daniel Kang, the post really hit home. When Kang, a junior studying computer science at the University of Michigan, heard that the refugee pictured and his family were relocating to his hometown of Troy, Mich., he said he knew he had to help. “I was really inspired by how intelligent he was and I knew a lot of people wanted to welcome him, so I thought, why not it be me?” he said. On the Humans of New York Facebook page with over 16 million likes — including comments from President Obama — the seven-part picture series’ captions detail one Syrian scientist and his family’s tale of loss after a missile strike destroyed their home, forcing them to to flee to Turkey, now with plans of coming to the United States. “Everything ended for us that day. That was our destiny. That was our share in life,” the scientist said. Battling stomach cancer, the loss of a home, career and seven family members, the man, whose name remains confidential to protect his identity as a refugee, expressed his hope for a new life in the United States. “I learned today that I’m going to Troy, Michigan,” he said. “I know nothing about it. I just hope that it’s safe and that it’s a place where they respect science. I just want to get back to work. I want to be a person again. I don’t want the world to think I’m over. I’m still here.” Knowing that refugees come to the United States with little more than they can carry, Kang quickly organized a crowdfunding campaign to help establish the man in his new home. In four days, the GoFundMe page has raised over $16K in donations from over 700 people. On Saturday afternoon, actor Edward Norton also began a fundraiser for the scientist, raising even more for the refugee who says he “just wants to be a person again.” “The response has been overwhelmingly positive,” said Kang. “A lot of people thanked me for doing a nice thing but I really feel like I was doing what anyone else would have done.” Kang said he’s received many messages from people expressing their gratitude, those who want to reach out to the man personally, as well local companies interested in working with the scientist. This includes invitations to lecture at local colleges, research job opportunities and potential help from local medical facilities in treating the man’s stomach cancer. “There’s definitely a lot of interest in helping him out,” he said. The biggest concern, said Kang, are those skeptical of how the money will reach the man. Kang, who has successfully crowdfunded in the past, is working closely with GoFundMe, the local refugee relocation agency Lutheran Social Services of Michigan, and is in communication with the Humans of New York staff to make sure all funding goes to the scientist. In the end, Kang said he just hopes the scientist receives the welcome he deserves. “If I could talk to him right now, I’d just tell him how sorry I am for everything he’s been through and that he’s coming to a great place. One of the things he said that resonated with me the most is that ‘I hope Troy is a place that appreciates science.’ I’d say out of all the cities in Michigan, Troy is the best place to raise a family, be a scientist and we can’t wait to have him.” Oona Goodin-Smith is a student at Oakland University and a member of the USA TODAY College contributor network. ||||| I saw this story on one of my favorite sites, Humans of New York, and it moved me to tears. This man has suffered profound loss that would crush the spirit of many people and yet he still passionately wants a chance to contribute positively to the world. If we don’t welcome people like this into our communities and empower his dream of making an impact with his life, then we’re not the country we tell ourselves we are. Let’s reject the 'anti-human’ voices that tell us to fear refugees and show this man and his family what Americans are really made of. Let’s show that a country built by the energy and dreams of immigrants still believes in brave people who come here with hope for better life. Everything we raise here will go to help this family so that the father can get the medical treatment he needs to live and pursue his work, and his family can build a new stable life after their tragedy, and…as the Scientist beautifully expresses…to support his dream of contributing to the world. Thanks to Humans of New York for sharing these stories. Thanks to the team at CrowdRise for putting this together and figuring out how to get even the credit card transaction fees covered so we can get the maximum to the family. Thanks to everyone who rallies together to create the power of the crowd. If enough of us kick in the price of two frappucinos, we can probably transform the experience of this family and show them that life can deliver healing and kindness, not just heartbreak. Thanks to Benevolent, all donations are tax-deductible. We will work with Benevolent to use all donated funds to help this family and will seek to use any excess or unused funds to help the other 11 profiled in the HONY ‘Syrian American’ series. Edward Norton ||||| DETROIT, MI -- Moved to tears by a Humans of New York feature on a Syrian refugee fleeing to Metro Detroit, Hollywood actor Edward Norton launched an online fundraiser that had raised nearly $450,000 for the widower and his four children as of Thursday afternoon. "I didn't hear about it, but I want to thank him very much from the humanity perspective," the man told NBC News after hearing about the fundraiser's success. "There are people outside who need that money much more than me." The man asked NBC to refer to him as "Abu Ammar," a fake named used to protect his relatives who remain in Syria. He's known to many on the Internet simply as "The Scientist," which is also his profession. The refugee's family was scheduled to arrive in Troy, a Detroit suburb, Thursday. He and four surviving children spent the last two years in Instanbul, Turkey. They fled civil-war-torn Syria after the man's wife and one of his daughters were killed in a missile attack on April 6, 2013. His is one of 12 families featured by Humans of New York and cleared to resettle in the U.S. "I learned today that I'm going to Troy, Michigan," the man told Humans of New York. "I know nothing about it. I just hope that it's safe and that it's a place where they respect science. I just want to get back to work. I want to be a person again. I don't want the world to think I'm over. I'm still here." The story made rounds throughout the Internet and even garnered a response from President Barack Obama's official Facebook page: As a husband and a father, I cannot even begin to imagine the loss you've endured. You and your family are an inspiration. I know that the great people of Michigan will embrace you with the compassion and support you deserve. Yes, you can still make a difference in the world, and we're proud that you'll pursue your dreams here. Welcome to your new home. You're part of what makes America great. ,Norton, known for his roles in movies like "Fight Club" and "Birdman," wrote in the description of his online fundraiser: If we don't welcome people like this into our communities and empower his dream of making an impact with his life, then we're not the country we tell ourselves we are. Let's reject the 'anti-human' voices that tell us to fear refugees and show this man and his family what Americans are really made of. Let's show that a country built by the energy and dreams of immigrants still believes in brave people who come here with hope for better life. (6/7) “I had no problems before the bombing. I think the cancer came from my sadness and my stress. It’s in my... Posted by Humans of New York on Tuesday, December 8, 2015 ||||| ISTANBUL — The grieving refugee who touched hearts as "The Scientist" on the Humans of New York blog only mustered a brief smile when told that a Hollywood star had helped raise $450,000 for him. Hours before flying to Michigan to start a new life in the U.S. on Thursday, the cancer-stricken Syrian civil engineer glanced down. "I didn't hear about it, but I want to thank him very much from the humanity perspective," he said after NBC News revealed the crowdfunding appeal. Oscar-nominated actor Edward Norton was moved to tears after reading the refugee's biography on the photography site last week and launched the fundraiser. "There are people outside who need that money much more than me," The Scientist said, displaying the sort of compassion and humility that helped his story go viral. The Scientist, who asked NBC News to refer to him as "Abu Ammar" to protect family in Syria, said his life was shattered by a bomb that killed his wife and daughter just under three years ago. He was later diagnosed with stomach cancer, and has had to care for five remaining children. They include a teenage son, who is still reeling after watching his mother die, and a daughter who carries inside of her shrapnel from the attack on April 6, 2013. "When a bomb drops you don't know where it comes from," he said. "There is no question our lives changed after that ... 180 degrees. I am mentally tired, in overwhelming sadness." “ As long as there are good people in the world … then we can stop this bloodshed” On Thursday, Abu Ammar and four of his children flew to Troy, Michigan, as part of a United Nations refugee resettlement program. For about two years, the family had been living close to destitution in Turkey. But the drive to succeed still lingers, Abu Ammar said. "I've had ambitions since I was a child, and right now I'm still that same child with the same ambitions," he said. "But I still have a message — sometimes when I'm talking to myself I say, 'No, I'm not supposed to die. I need to live long enough to realize my message to humanity.'" Abu Ammar's story on Humans of New York, a popular blog started in 2010 that spawned a bestselling book, prompted an outpouring of compassion. Even President Barack Obama contributed, calling Abu Ammar and his family an "inspirations" on HONY's Facebook page. "Yes, you can still make a difference in the world, and we're proud that you'll pursue your dreams here." Obama wrote. "Welcome to your new home. You're part of what makes America great." Last night President @BarackObama wrote a very sweet welcome note to the scientist in Tuesday's story. pic.twitter.com/ZGrn3gOdR7 — Brandon Stanton (@humansofny) December 10, 2015 Norton, who starred in "Birdman," "Fight Club" and "American History X," set out to help pay The Scientist's medical expenses. "This man has suffered profound loss that would crush the spirit of many people and yet he still passionately wants a chance to contribute positively to the world," Norton wrote. The resettlement of Syrian and Muslim refugees in the United States is controversial, especially in the aftermath of attacks by Islamic extremists in Paris and San Bernardino. Some politicians — notably GOP presidential hopeful Donald Trump — have called for a ban on Muslims entering the country. Abu Ammar told NBC News he didn't know anything about the debate over Muslims and immigration raging in the U.S. He also didn't have a solution to the war raging in his home country. "I don't like to get into politics because I am a man of science, and I can separate science and politics completely," he said. "But as long as there are good people in the world, and everyone looks into his or her conscience, then we can stop this bloodshed." Abu Ammar added: "No one benefits from people dying, and wars overall never benefit anybody — so let's hope God can help everyone and put out this fire."

– A Syrian refugee whose moving story went viral earlier this month starts his new life in Troy, Michigan, on Thursday, NBC News reports. The refugee—who wants to keep his real name out of the media to protect family members still in Syria—is known as "The Scientist" on the blog Humans of New York, where he was first profiled. "I learned today that I’m going to Troy, Michigan," The Scientist told HONY. "I know nothing about it. I just hope that it’s safe and that it’s a place where they respect science." According to MLive, The Scientist left Syria in 2013 after a bomb killed his wife and one of his daughters. Since then, he's been diagnosed with stomach cancer and was barely scraping by in Turkey. Despite being "in overwhelming sadness," he and his surviving children are hoping for a new start in the US, he tells NBC. Thanks to his story—which even got the attention of President Obama—The Scientist will have some help to get that new start. NBC reports actor Edward Norton was moved to tears after reading The Scientist's story and started a crowdfunding page that has raised nearly $450,000. "I didn't hear about it, but I want to thank him very much from the humanity perspective," The Scientist says. "There are people outside who need that money much more than me." A Michigan college student was also inspired to help after hearing The Scientist would be moving to his hometown, according to USA Today. His fundraising page has raised more than $16,000. "I’d say out of all the cities in Michigan, Troy is the best place to raise a family, be a scientist, and we can’t wait to have him," Daniel Kang says.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Homeowners' Assistance Act of 2007''. SEC. 2. TAX-FAVORED WITHDRAWALS FROM RETIREMENT PLANS FOR MORTGAGE RELIEF. (a) In General.--Section 72(t) of the Internal Revenue Code of 1986 shall not apply to any qualified mortgage relief distribution. (b) Aggregate Dollar Limitation.-- (1) In general.--For purposes of this section, the aggregate amount of distributions received by an individual which may be treated as qualified mortgage relief distributions for any taxable year shall not exceed the excess (if any) of-- (A) $25,000, over (B) the aggregate amounts treated as qualified mortgage relief distributions received by such individual for all prior taxable years. (2) Treatment of plan distributions.--If a distribution to an individual would (without regard to paragraph (1)) be a qualified mortgage relief distribution, a plan shall not be treated as violating any requirement of the Internal Revenue Code of 1986 merely because the plan treats such distribution as a qualified mortgage relief distribution, unless the aggregate amount of such distributions from all plans maintained by the employer (and any member of any controlled group which includes the employer) to such individual exceeds $25,000. (3) Controlled group.--For purposes of paragraph (2), the term ``controlled group'' means any group treated as a single employer under subsection (b), (c), (m), or (o) of section 414 of such Code. (c) Amount Distributed May Be Repaid.-- (1) In general.--Any individual who receives a qualified mortgage relief distribution may, at any time during the 5-year period beginning on the day after the date on which such distribution was received, make one or more contributions in an aggregate amount not to exceed the amount of such distribution to an eligible retirement plan of which such individual is a beneficiary and to which a rollover contribution of such distribution could be made under section 402(c), 403(a)(4), 403(b)(8), 408(d)(3), or 457(e)(16) of the Internal Revenue Code of 1986, as the case may be. (2) Treatment of repayments of distributions from eligible retirement plans other than iras.--For purposes of such Code, if a contribution is made pursuant to paragraph (1) with respect to a qualified mortgage relief distribution from an eligible retirement plan other than an individual retirement plan, then the taxpayer shall, to the extent of the amount of the contribution, be treated as having received the qualified mortgage relief distribution in an eligible rollover distribution (as defined in section 402(c)(4) of such Code) and as having transferred the amount to the eligible retirement plan in a direct trustee to trustee transfer within 60 days of the distribution. (3) Treatment of repayments for distributions from iras.-- For purposes of such Code, if a contribution is made pursuant to paragraph (1) with respect to a qualified mortgage relief distribution from an individual retirement plan (as defined by section 7701(a)(37) of such Code), then, to the extent of the amount of the contribution, the qualified mortgage relief distribution shall be treated as a distribution described in section 408(d)(3) of such Code and as having been transferred to the eligible retirement plan in a direct trustee to trustee transfer within 60 days of the distribution. (d) Definitions.--For purposes of this section-- (1) Qualified mortgage relief distribution.--Except as provided in subsection (b), the term ``qualified mortgage relief distribution'' means any distribution from an eligible retirement plan made on or after the date of the enactment of this Act and before January 1, 2010, if-- (A) such distribution is made during any 90-day period beginning on the date of any increase which occurs under the terms of the loan in the interest rate applicable to acquisition indebtedness (as defined in section 163(h)(3)(B) of the Internal Revenue Code of 1986, without regard to clause (ii) thereof) with respect to the principal residence of the taxpayer, and (B) the adjusted gross income (as defined in section 62 of the such Code) of the taxpayer for the taxable year of such distribution does not exceed $114,000 ($166,000 in the case of a joint return under section 6013 of such Code). For purposes of subparagraph (A), any increase in interest rate which occurs after May 31, 2005, and before the date of the enactment of this Act shall be treated as occurring on such date of enactment. (2) Eligible retirement plan.--The term ``eligible retirement plan'' shall have the meaning given such term by section 402(c)(8)(B) of such Code. (3) Principal residence.--The term ``principal residence'' has the same meaning as when used in section 121 of such Code. (e) Income Inclusion Spread Over 5 Year Period for Qualified Mortgage Relief Distributions.-- (1) In general.--In the case of any qualified mortgage relief distribution, unless the taxpayer elects not to have this subsection apply for any taxable year, any amount required to be included in gross income for such taxable year shall be so included ratably over the 5-taxable year period beginning with such taxable year. (2) Special rule.--For purposes of paragraph (1), rules similar to the rules of subparagraph (E) of section 408A(d)(3) of the Internal Revenue Code of 1986 shall apply. (f) Special Rules.-- (1) Exemption of distributions from trustee to trustee transfer and withholding rules.--For purposes of sections 401(a)(31), 402(f), and 3405 of the Internal Revenue Code of 1986, qualified mortgage relief distributions shall not be treated as eligible rollover distributions. (2) Qualified mortgage relief distributions treated as meeting plan distribution requirements.--For purposes of such Code, a qualified mortgage relief distribution shall be treated as meeting the requirements of sections 401(k)(2)(B)(i), 403(b)(7)(A)(ii), 403(b)(11), and 457(d)(1)(A) of such Code. (g) Provisions Relating to Plan Amendments.-- (1) In general.--If this subsection applies to any amendment to any plan or annuity contract, such plan or contract shall be treated as being operated in accordance with the terms of the plan during the period described in paragraph (2)(B)(i). (2) Amendments to which subsection applies.-- (A) In general.--This subsection shall apply to any amendment to any plan or annuity contract which is made-- (i) pursuant to any amendment made by this section, or pursuant to any regulation issued by the Secretary of the Treasury or the Secretary of Labor under this section, and (ii) on or before the last day of the first plan year beginning on or after January 1, 2010, or such later date as the Secretary of the Treasury may prescribe. In the case of a governmental plan (as defined in section 414(d) of the Internal Revenue Code of 1986), clause (ii) shall be applied by substituting the date which is 2 years after the date otherwise applied under clause (ii). (B) Conditions.--This subsection shall not apply to any amendment unless-- (i) during the period-- (I) beginning on the date the legislative or regulatory amendment described in subparagraph (A)(i) takes effect (or in the case of a plan or contract amendment not required by such legislative or regulatory amendment, the effective date specified by the plan), and (II) ending on the date described in subparagraph (A)(ii) (or, if earlier, the date the plan or contract amendment is adopted), the plan or contract is operated as if such plan or contract amendment were in effect; and (ii) such plan or contract amendment applies retroactively for such period.

Homeowners' Assistance Act of 2007 - Exempts any qualified mortgage relief distribution from the 10% additional tax imposed by the Internal Revenue Code on early distributions from qualified retirement plans. Provides that the aggregate amount of distributions received by an individual which may be treated as qualified mortgage relief distributions for any taxable year shall not exceed the excess (if any) of $25,000, over the aggregate amounts treated as qualified mortgage delinquency relief distributions received by such individual for all prior taxable years. Defines such distributions as those made from an eligible retirement plan between the enactment of this Act and January 1, 2010, if: (1) the distribution is made during any 90-day period beginning on the date of any increase in the interest rate applicable to the acquisition indebtedness of the taxpayer's principal residence; and (2) taxpayer's adjusted gross income for the taxable year of such distribution does not exceed $114,000 ($166,000 in the case of a joint return).

SECTION 1. SHORT TITLE. This Act may be cited as the ``Independent Ethics Commission Act of 2007''. SEC. 2. ESTABLISHMENT OF INDEPENDENT ETHICS COMMISSION. (a) Establishment.--There is established an independent ethics commission within the House of Representatives to be known as the Independent Ethics Committee (in this Act referred to as the ``Commission''). (b) Membership and Terms of Office.--(1) The Commission shall consist of 9 commissioners, 4 appointed by the Speaker and 4 by the minority leader of the House, and one selected by the affirmative vote of two-thirds of the 8 appointed commissioners for a term of 5 years. No commissioner may serve for more than 5 years. (2) Commissioners shall be appointed for terms of 5 years, except that of the commissioners first appointed, 2 appointed by the Speaker and 2 by the minority leader shall be for 3-year terms and 2 appointed by the Speaker and 2 by the minority leader shall be for 4-year terms as designated by the Speaker and the minority leader at the time of appointment. (c) Qualifications.--Only former Federal judges shall be eligible for appointment to the Commission. (1) Disqualifications for appointments.-- (A) Lobbying.--No individual who has been a lobbyist registered under the Lobbying Disclosure Act of 1995 or engages in, or is otherwise employed in, lobbying of the Congress or who is an agent of a foreign principal registered under the Foreign Agents Registration Act within the 4-year period immediately preceding appointment shall be eligible for appointment to, or service on, the Commission. (B) Incompatible office.--No member of the Commission appointed under subsection (b) may be a Member of the House of Representatives or Senator. (2) Vacancies.--A vacancy on the Commission shall be filled in the manner in which the original appointment was made. (d) Compensation.--Members shall each be entitled to receive the daily equivalent of the maximum annual rate of basic pay in effect for Level III of the Executive Schedule for each day (including travel time) during which they are engaged in the actual performance of duties vested in the Commission. (e) Quorum.--A majority of the members of the Commission shall constitute a quorum. (f) Meetings.--The Commission shall meet at the call a majority of its members. SEC. 3. DUTIES OF COMMISSION. (a) Duties.--The Commission is authorized-- (1) to receive, monitor, and oversee financial disclosure and other reports filed by Members of the House and officers and employees of the House under the Ethics in Government Act of 1978, and reports filed by registered lobbyists under the Lobbying Disclosure Act of 1995; (2) to investigate any alleged violation, by a Member, officer, or employee of the House of Representatives, of any rule or other standard of conduct applicable to the conduct of such Member, officer, or employee under House rules in the performance of his duties or the discharge of his responsibilities; (3) to present a case of probable ethics violations to the Committee on Standards of Official Conduct of the House of Representatives; (4) to make recommendations to the Committee on Standards of Official Conduct of the House of Representatives that it report to the appropriate Federal or State authorities any substantial evidence of a violation by a Member, officer, or employee of the House of Representatives of any law applicable to the performance of his duties or the discharge of his responsibilities, which may have been disclosed in an investigation by the Office; (5) to provide information and informal guidance to Members, officers and employees of the House of Representatives regarding any rules and other standards of conduct applicable to such individuals in their official capacities, and develop and carry out periodic educational briefings for Members, officers, and employees of the House of Representatives on those laws, rules, regulations, or other standards; and (6) to give consideration to the request of any Member, officer, or employee of the House of Representatives for a formal advisory opinion or other formal ruling, subject to the review of the Committee on Standards of Official Conduct of the House of Representatives, as applicable, with respect to the general propriety of any current or proposed conduct of such Member, officer, or employee and, with appropriate deletions to assure the privacy of the individual concerned, to publish such opinion for the guidance of other Members, officers, and employees of the House of Representatives. SEC. 4. POWERS OF COMMISSION. (a) Hearings and Evidence.--The Commission may for the purpose of carrying out this Act-- (1) hold such hearings and sit and act at such times and places, take such testimony, receive such evidence, administer such oaths; and (2) subject to subsection (b), require, by subpoena or otherwise, the attendance and testimony of such witnesses and the production of such books, records, correspondence, memoranda, papers, and documents, as the Commission may determine advisable. (b) Subpoenas.--A subpoena may be issued only with a majority of the Commission. (c) Obtaining Information.--Upon request of the Commission, the head of any agency or instrumentality of the Government shall furnish information deemed necessary by the Commission to enable it to carry out its duties. (d) Referrals to the Department of Justice.--Whenever the Commission has reason to believe that a violation of the Lobbying Disclosure Act of 1995 may have occurred, that matter may be referred to the Department of Justice for it to investigate. (e) General Audits.--The Commission shall have the authority to conduct general audits of filings under the Lobbying Disclosure Act of 1995. SEC. 5. INVESTIGATIONS AND INTERACTION WITH THE HOUSE COMMITTEE ON STANDARDS OF OFFICIAL CONDUCT. (a) Notification.--Whenever the Commission determines that there are sufficient grounds to conduct an investigation-- (1) the Commission shall notify the Committee on Standards of Official Conduct of this determination; (2) the applicable committee may overrule the determination of the Commission if, within 10 legislative days-- (A) the committee by an affirmative, roll-call vote of two-thirds of the full committee votes to overrule the determination of the Commission; (B) the committee issues a public report detailing its reasoning for overruling the Commission; (C) the vote of each member of the committee on such roll-call vote is included in the report; (D) dissenting members are allowed to issue their own report detailing their reasons for disagreeing with the majority vote; and (E) if the committee votes to overrule the determination of the Commission pursuant to subparagraph (B), the Commission may publish and make available to the general public a report detailing the reasons that the Commission concluded there were sufficient grounds to conduct an investigation. (b) Conducting Investigations.--(1) If the Commission determines that there are sufficient grounds to conduct an investigation and his determination is not overruled under subsection (a)(5), the Commission shall conduct an investigation to determine if probable cause exists that a violation occurred. (2) As part of an investigation, the Commission may-- (A) administer oaths; (B) issue subpoenas; (C) compel the attendance of witnesses and the production of papers, books, accounts, documents, and testimony; and (D) take the deposition of witnesses. (3) If a person disobeys or refuses to comply with a subpoena, or if a witness refuses to testify to a matter, he may be held in contempt of Congress. (c) Presentation of Case to House Committee on Standards of Official Conduct.--(1) If the Commission determines, upon conclusion of an investigation, that probable cause exists that an ethics violation has occurred, the Commission shall notify the Committee on Standards of Official Conduct of the House of Representatives of this determination. (2) The committee may overrule the determination of the Commission if, within 10 legislative days-- (A) the committee by an affirmative, roll-call vote of two- thirds of the full committee votes to overrule the determination of the Commission; (B) the committee issues a public report detailing its reasoning for overruling the Commission; (C) the vote of each member of the committee on such roll- call vote is included in the report; and (D) dissenting members are allowed to issue their own report detailing their reasons for disagreeing with the majority vote. (3) If the committee votes to overrule the determination of the Commission pursuant to paragraph (2), the Commission may publish and make available to the general public a report detailing the reasons that he concluded there were sufficient grounds to present such case to the committee. (4)(A) If the Commission determines there is probable cause that an ethics violation has occurred and the Commission's determination is not overruled, the Commission shall present the case and evidence to the Committee on Standards of Official Conduct of the House of Representatives to hear and make a determination pursuant to its rules. (B) The committee shall vote upon whether the individual who is the subject of the investigation has violated any rules or other standards of conduct applicable to that individual in his official capacity. Such votes shall be a roll-call vote of the full committee, a quorum being present. The committee shall issue a public report which shall include the vote of each member of the committee on such roll-call vote. Dissenting members may issue their own report detailing their own reasons for disagreeing with the majority vote. (d) Sanctions.--Whenever the Committee on Standards of Official Conduct of the House of Representatives finds that an ethics violation has occurred the Commission shall recommend appropriate sanctions to the committee and whether a matter should be referred to the Department of Justice for investigation. SEC. 6. PROCEDURAL RULES. (a) Majority Approval.--No report or recommendation relating to the official conduct of a Member, officer, or employee of the House of Representatives shall be made by the Commission, and no investigation of such conduct shall be undertaken by the Commission, unless approved by the affirmative vote of a majority of the members of the Commission. (b) Investigations.--Except in the case of an investigation undertaken by the Commission on its own initiative, the Commission may undertake an investigation relating to the official conduct of an individual Member, officer, or employee of the House of Representatives only-- (1) upon receipt of a complaint, in writing and under oath, made by or submitted to a Member of the House of Representatives and transmitted to the Commission by such Member, or (2) upon receipt of a complaint from the chairman of the Committee on Standards of Official Conduct of the House of Representatives, in writing and under oath, made by that committee. (c) Prohibition of Certain Investigations.--No investigation shall be undertaken by the Commission of any alleged violation of a law, rule, regulation, or standard of conduct not in effect at the time of the alleged violation. (d) Disclosure.--No information or testimony received, or the contents of a complaint or the fact of its filing, shall be publicly disclosed by any member of the Commission or staff of the Commission unless specifically authorized in each instance by a vote of the Commission. SEC. 7. STAFF OF COMMISSION. The Commission may appoint and fix the compensation of such staff as the Commission considers necessary to perform its duties. The Commission shall be appointed jointly by the Speaker and minority leader and shall be paid at a rate not to exceed the rate of basic pay payable for Level III of the Executive Schedule. SEC. 8. AMENDMENTS TO THE RULES OF THE HOUSE TO CHANGE THE DUTIES OF THE COMMITTEE ON STANDARDS OF OFFICIAL CONDUCT. (a) House Rules Amendments.--Clause 3 of rule XI of the Rules of the House of Representatives is amended as follows: (1) In paragraph (a), strike subparagraphs (1), (2), and (3), and redesignate subparagraphs (4), (5), and (6), as subparagraphs (1), (2), and (3), respectively. (2)(A) Paragraph (b)(1) is amended by striking ``(A)'', by striking ``a resolution, report, recommendation, or'' and inserting ``an'', and by striking ``, or, except as provided in subparagraph (2), undertake an investigation'', and by striking subdivision (B). (B) Paragraph (b) is further amended by striking subparagraphs (2), (3), (4), and (5) and by redesignating subparagraphs (6) and (7) as subparagraphs (2) and (3), respectively. (3) Strike paragraphs (j) (k), (l), (m), (n), (o), (p), and (q). (b) Conforming Amendments.--Section 803 of the Ethics Reform Act of 1989 (2 U.S.C. 29d) is amended by striking subsections (c) and (d). SEC. 9. ACTION ON COMMISSION RECOMMENDATIONS. (a) Printing of Reports in Congressional Record.--Upon receipt by the Committee on Standards of Official Conduct of the House of Representatives of any report of the Commission, the Speaker of the House of Representatives shall have the report printed in the Congressional Record. (b) House Consideration of Independent Ethics Commission Recommendations.--Within 14 calendar days after a report referred to in subsection (a) is printed in the Congressional Record, that portion of the report recommending action by the House of Representatives respecting any alleged violation, by a Member, officer, or employee of the House of Representatives, of any law, rule, regulation, or other standard of conduct applicable to the conduct of such Member, officer, or employee in the performance of his duties or the discharge of his responsibilities shall be introduced (by request) in the House by the Speaker of the House, for himself and the minority leader of the House in the form of a resolution. This resolution shall constitute a question of privilege under rule IX of the Rules of the House of Representatives. Any Member favoring the resolution may call it up as a question of privilege but only on the third day after the calendar date upon which such Member announces to the House his intention to do so. SEC. 10. EFFECTIVE DATE. This Act shall take effect upon the date of its enactment, except that sections 3, 4, and 8 shall not take effect immediately prior to noon January 3, 2009.

Independent Ethics Commission Act of 2007 - Establishes within the House of Representatives an Independent Ethics Commission composed only of former federal judges.

orthodontic force application to the teeth is responsible for a series of biological responses in the bone tissue , which lead to bone modeling and remodeling , allowing tooth movement . the resulting neoformed bone has a low degree of mineralization , with short - term reduction of the mineral density of the tooth - surrounding alveolar bone , which may impair its structural resistance . besides causing obvious structural changes in the bone tissue , animal studies have shown orthodontic movement to have effects on the dental tissue , causing odontoblast activation and increased dentin mineralization . such tissue reactions maybe due to the presence of specific proteins ( dentin matrix protein 1 dmp1 , and dentin sialophosphoprotein - dspp ) , which have their levels upregulated by mechanical stress . once such proteins are present in dentin and bone , mineralization of these 2 tissues may be likewise influenced by mechanical perturbations . alveolar bone mineral density is already associated with the formation of areas of hyalinization and root resorption units during orthodontic treatment . although this process might also be influenced by the degree of mineral density of the roots , there is a lack of studies investigating this issue . computed tomography ( ct ) and cone beam computed tomography ( cbct ) scanners are the most frequently used instruments to assess the mineral density of craniofacial bone structures [ 4,1519 ] . however , because the intensity values of cbct images are influenced by the scanning device , image - acquisition settings and positioning , these variables should be controlled for in order to guarantee the reliability of the results . the purpose of this controlled study was to assess the degree of mineral density of the apical third of the roots of upper central incisors and of the periapical bone , through cbct images , comparing orthodontically treated and untreated subjects . they were consecutively selected from a postgraduate orthodontic program of the juiz de fora federal university . they were divided into 2 groups : the untreated group ( 15 males , 15 females ; mean age 23.1 years ) , which had not undergone orthodontic treatment ; and the treated group ( 7 males , 8 females ; mean age 22.8 years ) , which had finished their orthodontic treatment at least 1 year ( mean time 6.52 years ) prior to the study . all had full permanent dentition ( with the exception of the 3 molars ) and no endodontic treatment in the teeth examined , root resorption , history of injury to the upper central incisors , or any kind of bone pathology . this study was approved by the human research ethics committee of the juiz de fora federal university . mineral density of the roots of the upper central incisors and the alveolar bone was calculated from cbct images . the cbct images were obtained with i - cat ( imaging sciences international inc . , hatfield , usa ) , using a 160 mm diameter and 100 mm height field of view ( fov ) . the nominal beam was 120 kv and 38 ma , with 26.9 s rotation time . the individual s head was aligned with a chin rest and laser lines , with the frankfurt plane parallel to the floor and the median sagittal plane perpendicular to the floor . as for fov positioning , the occlusal plane was positioned in its vertical center and the anterior nasal spine 35 mm from its anterior surface . the images were analyzed with the i - cat vision ( imaging sciences international inc . , hatfield , usa ) software , with 0.5 mm - thick slices . at mpr viewing modality , each upper central incisor was positioned vertically , so that the intersection of the sagittal and coronal sections coincided with its long central axis , with the coronal section parallel to the incisal border ( figure 1 ) . in the sagittal section , the root length was measured as the distance between the most apical point of the root and the middle point of the vestibular and lingual cementum - enamel junctions . one calibrated investigator ( b.p . ) randomly and blindly assessed the cbct images of all patients , and determined the bone and root mineral densities . the rmd was determined as the mean of 4 regions of interest ( roi ) within the apical third of the roots , 2 areas in the coronal section ( right and left figure 2 ) and 2 areas in the sagittal section ( vestibular and lingual figure 3 ) , encompassing as large an area as possible , but without impinging on the images corresponding to the periodontal ligament and the pulp . bmd was determined in the same sagittal section used for rmd assessment for each tooth . bmd was determined as the mean density of 4 regions of interest ( roi ) at the alveolar bone , 3 11 mm areas located on the lingual side of the apical third of the root ( superior , middle and inferior ) and another 1 mm - high supra - apical area , localized above the root apex , extending from the vestibular cortical wall to 2 mm lingual to the apex center ( figure 4 ) . although this was a controlled study , palatal bone areas were assessed in order to compare the md of similar structures not affected by orthodontic movement , in both groups , as well as to assess the reliability of the measurements of symmetrical areas from the same individuals . likewise , the md of bone areas not influenced by tooth movement or occlusal stress were assessed in order to compare similar structures of the 2 groups , as well as to assess the reliability of the measurements of symmetrical areas of the same individuals . the bmd of 8 reference areas in the maxilla , 4 on each side , symmetrically positioned in the anteroposterior and mediolateral directions , was assessed . the maxilla was initially positioned with the axial and sagittal planes intersecting the anterior and posterior nasal spines . afterwards , the lowermost axial section , where the posterior wall of the incisal foramen could be visualized , was selected . coronal views of the maxilla were selected at 4 and 6 mm posterior to the distal wall of the incisal foramen , and the bmd was measured in 4 3 mm - wide areas in each coronal views , 1.5 and 4.5 mm lateral to the midline , on both sides ( figure 5 ) . intra - rater agreement values of bmd of alveolar and reference areas and rmd measurements were examined by intraclass correlations ( icc ) , being based on 15 randomly chosen incisors , which were measured twice , with an interval of 15 days . due to the different size of the 2 groups , the normality of the variables was tested with the shapiro - wilks test for the treated group and with kolmogorov - smirnov test for the untreated group . additionally , the homoscedasticity of the variables was tested with levene s test for the treated and the untreated groups . comparison of the bmd values of reference and alveolar areas between left and right sides , for each group , was undertaken with student s dependent t test , the independent t test being used for between - group comparison . for rmd values , student s dependent t test was used to compare the left and right sides , the independent t test being used for between - group comparison . the mann - whitney test was used to confirm the results of the parametric test for between - group comparison . the statistical analysis was made with =.05 significance level and processed with spss statistics 17.0.0 ( spss inc . , the rmd was determined as the mean of 4 regions of interest ( roi ) within the apical third of the roots , 2 areas in the coronal section ( right and left figure 2 ) and 2 areas in the sagittal section ( vestibular and lingual figure 3 ) , encompassing as large an area as possible , but without impinging on the images corresponding to the periodontal ligament and the pulp . bmd was determined in the same sagittal section used for rmd assessment for each tooth . bmd was determined as the mean density of 4 regions of interest ( roi ) at the alveolar bone , 3 11 mm areas located on the lingual side of the apical third of the root ( superior , middle and inferior ) and another 1 mm - high supra - apical area , localized above the root apex , extending from the vestibular cortical wall to 2 mm lingual to the apex center ( figure 4 ) . although this was a controlled study , palatal bone areas were assessed in order to compare the md of similar structures not affected by orthodontic movement , in both groups , as well as to assess the reliability of the measurements of symmetrical areas from the same individuals . likewise , the md of bone areas not influenced by tooth movement or occlusal stress were assessed in order to compare similar structures of the 2 groups , as well as to assess the reliability of the measurements of symmetrical areas of the same individuals . the bmd of 8 reference areas in the maxilla , 4 on each side , symmetrically positioned in the anteroposterior and mediolateral directions , was assessed . the maxilla was initially positioned with the axial and sagittal planes intersecting the anterior and posterior nasal spines . afterwards , the lowermost axial section , where the posterior wall of the incisal foramen could be visualized , was selected . coronal views of the maxilla were selected at 4 and 6 mm posterior to the distal wall of the incisal foramen , and the bmd was measured in 4 3 mm - wide areas in each coronal views , 1.5 and 4.5 mm lateral to the midline , on both sides ( figure 5 ) . intra - rater agreement values of bmd of alveolar and reference areas and rmd measurements were examined by intraclass correlations ( icc ) , being based on 15 randomly chosen incisors , which were measured twice , with an interval of 15 days . due to the different size of the 2 groups , the normality of the variables was tested with the shapiro - wilks test for the treated group and with kolmogorov - smirnov test for the untreated group . additionally , the homoscedasticity of the variables was tested with levene s test for the treated and the untreated groups . comparison of the bmd values of reference and alveolar areas between left and right sides , for each group , was undertaken with student s dependent t test , the independent t test being used for between - group comparison . for rmd values , student s dependent t test was used to compare the left and right sides , the independent t test being used for between - group comparison . the mann - whitney test was used to confirm the results of the parametric test for between - group comparison . the statistical analysis was made with =.05 significance level and processed with spss statistics 17.0.0 ( spss inc . , chicago , usa ) software . intra - rater agreement values of bmd ( reference and alveolar areas ) and rmd from the cbct measurements were over 0.9 , showing excellent agreement . the bmd mean values of the reference areas of treated and untreated individuals , and the comparison between the right and left sides and between the groups , are shown in table 1 . the reference bone areas in the maxilla showed a significant difference ( p=.010 ) only between the 4.5 mm right and left areas in the 6 mm section of the untreated group . for all the other comparisons , between right and left sides and treated and untreated groups , there was no statistically significant difference . table 2 shows the mean values of bmd and rmd of treated and untreated individuals , and the comparison between groups . the mean values for bmd and rmd were 674.84 and 1282.26 for the untreated group and 630.28 and 1370.29 for the treated group , respectively . a significant difference was observed between the groups only for rmd values ( p<.05 ) . descriptive statistics suggested that bmd and rmd variances might differ between the groups , levene s test being necessary for homoscedasticity verification . the groups did not significantly differ in bmd variance ( p=.754 ) , whereas there was a significant difference in rmd variance ( p=.037 ) . when the mann - whitney non - parametric test was used to verify the between - group rmd difference , the result was similar to that obtained with the t test ( p=0.002 ) , thus indicating a significant difference between the groups . the forces resulting from the action of orthodontic appliances move irregular teeth to better positions and produce mechanical stimuli that trigger biological responses which , in turn , lead to bone modeling and remodeling . while modeling is the sculpting mechanism that uses the raw materials of bone growth to shape structures , remodeling is the mechanism involving lifelong skeletal turnover and maintenance . because such bone responses are difficult to observe , few experimental studies in animals [ 10,2225 ] and clinical short - term studies are available , pointing to the need for greater investigation of the effects of tooth movement on the alveolar bone . hsu et al . and chang et al . found a 24% bmd reduction around the teeth of the anterior maxilla in 8 patients investigated 7 months after orthodontic treatment . the results of this study indicated that the bmd of the closely root - associated alveolar bone of the orthodontically - moved upper central incisors did not differ from the bmd of the untreated group . this difference may be related to the post - treatment assessment time ( mean 6.52 years ) , because a long period is necessary for bone recovery and mineralization after tooth movement , which allows the bmd to return to baseline ( before tooth movement ) values . the fact that the groups did not have a significant difference in the bmd of the maxillary reference areas suggests that the influence of tooth movement on bone quality is limited to a certain period of time after treatment . in contrast with the bmd , the patients who had undergone orthodontic treatment had significantly higher rmd values than untreated patients . although orthodontics - related alterations in the dentin surface , with increased mineralization rate , have already been reported , effects on the dentin matrix have not . dentin matrix has a peculiar morphology , being composed of 12 m diameter tubules surrounded by a hyper - mineralized layer called peritubular dentin , and of a softer intertubular matrix , where the organic material concentrates as collagen fibrils and noncollagenous proteins . two proteins , dmp1 and dspp , are responsible for similar structural alterations in the dentin matrix and surface , being present in predentin , odontoblasts and dentinal tubules . these proteins are thought to play key biological roles in the mineralization of dentin because they are prominent in this mineralized tissue and are secreted into the extracellular matrix of dentin during formation and mineralization . dmp1 and dspp expression and levels are increased by mechanical stress , which may account for not only the increased dentin mineralization rate , but also for the increased mineral density of the peritubular extracellular matrix during tooth movement , because of acceleration of dentin mineralization . such structural alteration enhances biomechanical function , allowing a tougher foundation that helps to prevent propagation of cracks from the brittle enamel . dmp1 and dspp are also expressed by osteocytes , being involved in the development and/or maintenance of bone tissue and responding to mechanical stress as occurs in dentin . however , significant bmd increases were not observed , probably due to the complete bone renewal during tooth movement , with resorption alongside the movement direction and deposition in the opposite direction . mineral density determination is the best indicator for the quality of mineralized tissues , and cbct has been proposed as a low - radiation - dose method for achieving such a purpose , because the density evaluated shows a linear relationship with the attenuation coefficients of the materials and hu values obtained with medical ct and dexa . however , the arbitrary gray levels and artifacts displayed in cbct systems do not allow the assessment of bone quality , which can be performed with hu in medical ct . such instability of grey levels was associated with different imaging devices , image - acquisition settings , positioning of the object in the fov , the mass presented outside the fov ( dubbed the exo - mass ) [ 3739 ] , the mass in the slice ( inside and outside the fov ) and the size of fov . controlling for these variables has thus become essential for measurements of mineral density in cbct images . all patients , treated and untreated , were scanned with the same large - volume cbct scan , which may yield more consistent density values than limited - volume cbct scans , and under the same exposure conditions , which eliminated equipment and image - acquisition setting - related variations . according to araki et al . , in a cbct system designed to scan a large fov with large - sized detectors , the influence of artifacts might be small and the hu application is possible . in spite of the disagreement on the correlation between the cbct and hu md values , we used the hu values as a comparative rather than an absolute measurement . in cbct images , the ct number of the same material tends to increase ( brighter in gray scale ) as the roi approximates the to exo - mass , and/or the exo - mass increase and/or the mass in slice increase , resulting in varied readings of the mineral density of a given structure . in the assessment of adults , standardization of the head orientation and its position in the fov and the use of a standardized fov size allowed the control of variables related to the structure mass , as the mass in slice ( estimated as 7 g for each 0.4 mm slice of the adult head ) , localization of the exo - mass and positioning of the upper incisors in the fov were similar across the patients , resulting in the same distortion of the gray levels in the areas of interest assessed in this study . the object position inside the fov modifies the relation between the roi and the exo - mass and influences mineral density determination , as reported by nackaerts et al . , who demonstrated a significant variation when the object was repositioned in fov between acquisitions . these authors used a fov with a volume 35 times greater than ours , which may have influenced the results . nevertheless , no conclusive information on the influence of fov size on md determination has been reported to date . katsumata et al . described the possible influence of fov size on md , reporting a 381 hu ( 266647 ) bmd variation in a half - mandible , in 51 , 102 , 153 and 200 mm diameter fovs . yet , these authors did not eliminate the exo - mass ( present in the 51 mm fov ) and roi positioning inside the fov , adding the influence of other variables to their results , and leaving the issue of the influence of fov size on md determination in large - volume cbct images unresolved . in spite of the number of possibly influential variables of md values in cbct images this may be verified by analysis of the maxillary reference areas , where no significant differences between treated and untreated individuals were observed . a significant difference was only verified between the right and left sides in the 4.5 mm lateral area in the 6 mm section of the untreated group , with 3 patients presenting discrepantly reduced bmd values on the right , with no apparent reason . individuals who had finished an orthodontic treatment at least 1 year previously had higher root mineral density means , compared with untreated individuals . on the other hand ,

summarybackgroundorthodontic force application to the teeth is responsible for a series of biological responses in the bone and dentin , which lead to some alterations of the mineral density of the tissues . our objective was determine , through cone - beam computed tomography ( cbct ) , the mineral density of the apical third of the roots of the upper central incisors and of the periapical bone portion surrounding these teeth , in patients submitted to orthodontic treated and untreated individuals.material/methods30 untreated individuals and 15 treated ones ( treatment cessation at least 1 year before the study ) underwent cbct . mineral density was assessed in the apical third of the root of the upper central incisors and in the alveolar bone in the periapical region of these teeth . in order to reduce cbct - related mineral density variability , we standardized the cone - beam tomography device , the image - acquisition settings and the field of view positioning and size . student s t test was used for the analyses.resultsbone mineral density ( bmd ) and root mineral density ( rmd ) , in hounsfield units , were 674.84 and 1282.26 for the untreated group and 630.28 and 1370.29 for the treated group , respectively . the differences between the group means were statistically significant for rmd ( p<0.05).conclusionsuntreated individuals had a significant lower mean rmd in comparison with those submitted to orthodontic treatment .

age - related declines in muscle mass and strength , known as sarcopenia , are often an important antecedent of the onset of disability in older adulthood . although the term is applied clinically to denote loss of muscle mass , sarcopenia is often used to describe both a set of cellular processes ( denervation , mitochondrial dysfunction , and inflammatory and hormonal changes ) and a set of outcomes such as decreased muscle strength , decreased mobility and function , increased fatigue , a greater risk of falls , and reduced energy needs . lean muscle mass generally contributes up to ~50% of total body weight in young adults but declines with aging to be 25% at 7580 years old [ 3 , 4 ] . the loss is most notable in the lower limb muscle groups , with the cross - sectional area of the vastus lateralis being reduced by as much as 40% between the ages of 20 and 80 yr . several possible mechanisms for age - related muscle atrophy have been described ; however , the precise contribution of each is unknown . age - related muscle loss is a result of reductions in the size and number of muscle fibers possibly due to a multifactorial process that involves physical activity , nutritional intake , oxidative stress , and hormonal changes [ 2 , 7 ] . the specific contribution of each of these factors is unknown , but there is emerging evidence that the disruption of several positive regulators ( akt and serum response factor ) of muscle hypertrophy with age is an important feature in the progression of sarcopenia [ 810 ] . in contrast , many investigators have failed to demonstrate an age - related enhancement in levels of common negative regulators ( atrogin-1 , myostatin , and calpain ) in senescent mammalian muscles . several lines of evidence point to inflammation being associated with loss of muscle strength and mass with aging . animal studies have shown that the administration of interleukin ( il)-6 or tumor necrosis factor ( tnf)- increases skeletal muscle breakdown , decreases the rate of protein synthesis , and reduces plasma concentrations of insulin - like growth factor [ 12 , 13 ] . in older men and women , higher levels of il-6 and c - reactive protein ( crp ) were associated with a two- to threefold greater risk of losing more than 40% of grip strength over 3 years . on the other hand , several studies have indicated age - related endocrine defects such as decreases in anabolic hormones ( testosterone , estrogen , growth hormone ( gh ) , and insulin - like growth factor - i ( igf - i ) ) [ 1518 ] . although hormonal supplementation for the elderly has been conducted on a large scale , it was found not to be effective against sarcopenia and to have minor side effects [ 9 , 10 , 15 , 16 , 19 , 20 ] . in this paper , we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on practical hormonal intervention for the elderly . inflammation may negatively influence skeletal muscle through direct catabolic effects or through indirect mechanisms ( i.e. , decreases in gh and igf - i concentrations , induction of anorexia , etc . ) . there is growing evidence that higher levels of inflammatory markers are associated with physical decline in older individuals , possibly through the catabolic effects of these markers on muscle . in an observational study of more than 2000 men and women , tnf- showed a consistent association with declines in muscle mass and strength . the impact of inflammation on the development of sarcopenia is further supported by a recently published animal study showing that a reduction in low - grade inflammation by ibuprofen in old ( 20 months ) rats resulted in a significant decrease in muscle mass loss . an age - related disruption of the intracellular redox balance appears to be a primary causal factor for a chronic state of low - grade inflammation . more recently , chung et al . hypothesized that abundant nuclear factor-b ( nf-b ) protein induced age - related increases in il-6 and tnf-. moreover , reactive oxygen species ( ros ) also appear to function as second messengers for tnf- in skeletal muscle , activating nf-b either directly or indirectly . indeed , marked production of ros has been documented in muscle of the elderly [ 26 , 27 ] . despite some evidence supporting enhanced nf-b signaling in type i fibers of aged skeletal muscle , direct evidence for increased activation and dna binding of nf-b is lacking [ 28 , 29 ] . for example , phillips and leeuwenburgh found that neither p65 protein expression nor the binding activity of nf-b was significantly altered in the vastus lateralis muscles of 26-month - old rats despite the marked upregulation of tnf- expression in both blood and muscle . upregulated tnf- expression in serum and muscle seems to enhance apoptosis through increased mitochondrial defects resulting in a loss of muscle fibers [ 2931 ] . it has been shown that tnf- is one of the primary signals inducing apoptosis in muscle . myostatin was first discovered during screening for new members of the transforming growth factor- ( tgf- ) superfamily and shown to be a potent negative regulator of muscle growth . like other family members , myostatin is synthesized as a precursor protein that is cleaved by furin proteases to generate the active c - terminal dimer . most , if not all , of the myostatin protein that circulates in blood also appears to exist in an inactive complex with a variety of proteins , including the propeptide . the latent form of myostatin seems to be activated in vitro by dissociation from the complex with either acid or heat treatment [ 33 , 34 ] or by proteolytic cleavage of the propeptide with members of the bone morphogenetic protein-1/tolloid family of metalloproteases . studies indicate that myostatin inhibits cell cycle progression and reduces levels of myogenic regulatory factors ( mrfs ) , thereby controlling myoblastic proliferation and differentiation during developmental myogenesis [ 3537 ] . myostatin binds to and signals through a combination of actriia / b receptors on the cell membrane but has higher affinity for actriib . on binding to actriib , myostatin forms a complex with either activin receptor - like kinase ( alk ) 4 or alk5 to activate ( phosphorylate ) the smad2/3 transcription factors . then smad2/3 are translocated and modulate the nuclear transcription of genes such as myod via a tgf--like mechanism . more recently , the igf - i - akt - mtor ( mammalian target of rapamycin ) pathway , which mediates both differentiation in myoblasts and hypertrophy in myotubes , has been shown to inhibit myostatin - dependent signaling . blockade of the akt - mtor pathway , using sirna to raptor , a component of torc1 ( tor signaling complex 1 ) , facilitates myostatin 's inhibition of muscle differentiation because of an increase in smad2 phosphorylation . several researchers have investigated the effect of inhibiting myostatin to counteract sarcopenia using animals [ 41 , 42 ] . lebrasseur et al . found that treatment with a mouse chimera of antihuman myostatin antibody ( 24 mg / kg , 4 weeks ) , a drug for inhibiting myostatin , elicited a significant increase in muscle mass and in running performance probably due to decreased levels of phosphorylated smad3 and muscle ring finger-1 ( murf-1 ) . more recently , murphy et al . showed , by way of once weekly injections , that a lower dose of this anti - human myostatin antibody ( 10 mg / kg ) significantly increased the fiber cross - sectional area ( by 12% ) and in situ muscle force ( by 35% ) of aged mice ( 21 mo old ) . these findings highlight the therapeutic potential of antibody - directed myostatin inhibition for sarcopenia by inhibiting protein degradation . although many researchers expect myostatin levels to be increased not only in muscle but also in serum , blood myostatin levels have not been shown to increase with age . glucocorticoid - associated atrophy appears to be specific to type ii or phasic muscle fibers . in a study of controlled hypercortisolaemia in healthy men , experimental inactivity increased the catabolic effect of glucocorticoids , suggesting that an absence of mechanical signals potentiates the effect . the mechanism of glucocorticoid - induced atrophy may involve upregulated expression of myostatin and glutamine synthetase , the latter via the glucocorticoid receptor 's interaction with the glutamine synthetase promoter . glucocorticoids inhibit the physiological secretion of gh and appear to induce igf - i activity in target organs . changes in steroid - induced glutamine synthetase represent a potential mechanism of action , and dose - dependent inhibition of glutamine synthetase by igf - i was observed in rat l6 cells . the increased incidence of various diseased states during aging is associated with the hypersecretion of glucocorticoids [ 47 , 48 ] . in addition , when adult ( 7-month - old ) and aged ( 22-month - old ) rats received dexamethasone ( approximately 500 g / kg body weight / day ) in their drinking water for 5 - 6 days , muscle wasting was much more rapid in aged animals . furthermore , glucocorticoids induced prolonged leucine resistance to muscle protein synthesis in old rats . still , it remains to be directly elucidated , using pharmacological inhibitors for glucocorticoids , whether age - related increases in serum glucocorticoid levels actually inhibit protein synthesis and/or enhance protein degradation . il-6 and crp , known as geriatric cytokines , are multifunctional cytokine produced in situations of trauma , stress , and infection . during the aging process , the natural production of cytokines is likely beneficial during inflammation , but overproduction and the maintaining of an inflammatory state for long periods of time , as seen in elderly individuals , are detrimental [ 50 , 51 ] . a number of authors have demonstrated that a rise in plasma levels of proinflammatory cytokines , especially il-6 , and proteins under acute conditions is associated with a reduction in mobility as well as a reduced capacity to perform daily activities , the development of fragility syndrome , and increased mortality rates [ 5052 ] . in older men and women , higher levels of il-6 and crp were associated with a two- to threefold greater risk of losing more than 40% of grip strength over 3 years . in contrast , there were no longitudinal associations between inflammatory markers and changes in grip strength among high functioning elderly participants from the macarthur study of successful ageing . more recently , hamer and molloy demonstrated , in a large representative community - based cohort of older adults ( 1,926 men and 2,260 women ( aged 65.3 9.0 years ) ) , that crp was associated with poorer hand grip strength and chair stand performance in women but only chair stand performance in men . in addition , haddad et al . demonstrated atrophy in the tibialis anterior muscle of mice following the injection of relatively low doses of il-6 . in a recent randomized trial that employed aerobic and strength training in a group of elderly participants , significant reductions in various inflammatory markers ( il-6 , crp , and il-18 ) were observed for aerobic but not strength training . in contrast , combined resistance and aerobic training that increased strength by 38% resulted in significant reductions in crp . more descriptive data appears to be needed whether il-6 and crp have an actual catabolic effect in sarcopenic muscle . in males , levels of testosterone decrease by 1% per year , and those of bioavailable testosterone by 2% per year from age 30 [ 16 , 58 , 59 ] . in women , testosterone increases muscle protein synthesis , and its effects on muscle are modulated by several factors including genetic background , nutrition , and exercise . numerous studies of treatment with testosterone in the elderly have been performed over the past few years [ 6366 ] . in 1999 , snyder et al . suggested that increasing the level of testosterone in old men to that seen in young men increased muscle mass but did not result in functional gains in strength . systemic reviews of the literature have concluded that testosterone supplementation attenuates several sarcopenic symptoms including decreases in muscle mass [ 6466 ] and grip strength . for instance , a recent study of 6 months of supraphysiological dosage of testosterone in a randomized placebo - controlled trial reported increased leg lean body mass and leg and arm strength . although there are significant increases in strength among elderly males given high doses of testosterone , the potential risks may outweigh the benefits . risks associated with testosterone therapy in older men include sleep apnea , thrombotic complications , and the increased risk of prostate cancer . novel , nonsteroidal compounds , called selective androgen receptor modulators , have shown tissue - selective activity and improved pharmacokinetic properties . dehydroepiandrosterone ( dhea ) is marketed as a nutritional supplement in the usa and is available over the counter . unlike testosterone and estrogen , dhea is a hormone precursor which is converted into sex hormones in specific target tissues . however , supplementation of dhea in aged men and women resulted in an increase in bone density and testosterone and estradiol levels , but no changes in muscle size , strength , or function [ 72 , 73 ] . it has been hypothesized that menopause transition and the subsequent decline in estrogen may play a role in muscle mass loss [ 7 , 18 ] . van geel et al . reported a positive relationship between lean body mass and estrogen levels . observed that muscle mass is correlated significantly with plasma estrone and estradiol levels in women . however , baumgartner et al . reported that estrogen levels were not associated with muscle mass in women aged 65 years and older . the mechanisms by which decrease in estrogen levels may have a negative effect on muscle mass are not well understood but may be associated with an increase in proinflammatory cytokines , such as tnf- and il-6 , which might be implicated in the apparition of sarcopenia . furthermore , estrogen could have a direct effect on muscle mass since it has been shown that skeletal muscle has estrogen beta - receptors on the cell membrane . therefore , a direct potential mechanistic link could exist between low estrogen levels and a decrease in protein synthesis . further studies are needed to investigate this hypothesis . nevertheless , before reaching a conclusion on the contribution of estrogens to the onset of sarcopenia , it would be important to measure urinary estrogen metabolites since a relationship between breast cancer and urinary estrogen metabolites has been shown . growth hormone ( gh ) is a single - chain peptide of 191 amino acids produced and secreted mainly by the somatotrophs of the anterior pituitary gland . gh secretion occurs in a pulsatile manner with a major surge at the onset of slow - wave sleep and less conspicuous secretory episodes a few hours after meals and is controlled by the actions of two hypothalamic factors , gh - releasing hormone ( ghrh ) , which stimulates gh secretion , and somatostatin , which inhibits gh secretion . the secretion of gh is maximal at puberty accompanied by very high circulating igf - i levels , with a gradual decline during adulthood . indeed , circulating gh levels decline progressively after 30 years of age at a rate of ~1% per year . in aged men , the age - dependent decline in gh secretion is secondary to a decrease in ghrh and to an increase in somatostatin secretion . with respect to the somatomedin hypothesis , the growth - promoting actions of gh are mediated by circulating or locally produced igf - i . gh - induced muscle growth may be mediated in an endocrine manner by circulating igf - i derived from liver and/or in an autocrine / paracrine manner by direct expression of igf - i from target muscle via gh receptors on muscle membranes . the effects of gh administration on muscle mass , strength and physical performance are still under debate . in animal models , gh treatment is very effective at inhibiting sarcopenic symptoms such as muscle atrophy and decreases in protein synthesis particularly in combination with exercise training . some groups demonstrated an improvement in strength after long - term administration ( 311 months ) of gh . in contrast , many researchers have found that muscle strength or muscle mass did not improve on supplementation with gh [ 19 , 89 ] . one recent study reported a positive effect for counteracting sarcopenia after the administration of both gh and testosterone . several reasons may underlie the ineffectiveness of gh treatment in improving muscle mass and strength in the elderly , such as a failure of exogeneous gh to mimic the pulsatile pattern of natural gh secretion or the induction of gh - related insulin resistance . in addition , reduced mrna levels of the gh receptor in skeletal muscle have been observed in older versus younger healthy men , exhibiting a significant negative relationship with myostatin levels . it should also be considered that the majority of the trials conducted on gh supplementation have reported a high incidence of side effects , including soft tissue edema , carpal tunnel syndrome , arthralgias , and gynecomastica , which pose serious concerns especially in older adults . therefore , one should pay very careful attention when administering gh to the elderly . there is evidence that the age - associated decline in gh levels in combination with lower igf - i levels contributes to the development of sarcopenia . igf - i is perhaps the most important mediator of muscle growth and repair possibly by utilizing akt - mtor - p70s6k ( p70 ribosomal protein s6 kinase ) signaling . although the transgenic approach of upregulating igf - i expression in skeletal muscle would be appropriate for inhibiting sarcopenia , the administration of igf - i to the elderly has resulted in controversial findings on muscle strength and function . the ineffectiveness may be attributable to age - related insulin resistance to amino acid transport and protein synthesis or a marked decrease in igf - i receptors [ 96 , 97 ] and receptor affinity for igf - i in muscle with age . . demonstrated a reduced effect of insulin on protein breakdown in the legs in older versus younger subjects probably due to the blunted activation of akt by insulin . ghrelin is a 28-amino - acid peptide mainly produced by cells in the stomach , intestines , and hypothalamus . ghrelin is a natural ligand for the gh - secretagogue receptor ( ghs - r ) , which possesses a unique fatty acid modification , an n - octanoylation , at ser 3 . ghrelin plays a critical role in a variety of physiological processes , including the stimulation of gh secretion and regulation of energy homeostasis by stimulating food intake and promoting adiposity via a gh - independent mechanism . in contrast , ghrelin inhibits the production of anorectic proinflammatory cytokines , including il-1 , il-6 , and tnf- . because of their combined anabolic effects on skeletal muscle and appetite , ghrelin and low - molecular - weight agonists of the ghrelin receptor are considered attractive candidates for the treatment of cachexia . for example , nagaya et al . gave human ghrelin ( 2 g / kg twice daily intravenously ) for 3 weeks to cachexic patients with chronic obstructive pulmonary disease in an open - label study . after ghrelin therapy , significant increases from baseline measurements were observed for body weight , lean body mass , food intake , hand grip strength , maximal inspiratory pressure , and karnofsky performance score . in another unblinded study , the same group demonstrated that treatment with human ghrelin ( 2 g / kg twice daily intravenously , 3 weeks ) significantly improved several parameters ( eg . , lean body mass measured by dual - energy x - ray absorption and left ventricular ejection fraction ) in 10 patients with chronic heart failure . in a 1-year placebo - controlled study in healthy older adults over the age of 60 years given an oral ghrelin - mimetic ( mk-677 ) , an increase in appetite was observed . the study did not show a significant increase in strength or function in the ghrelin - mimetic treatment group , when compared to the placebo group ; however , a tendency was observed . as pointed out in a recent review by nass et al . , the use of this compound induces the potential deterioration of insulin sensitivity and development of diabetes mellitus in older adults with impaired glucose tolerance . figure 1 provides an overview of several regulators for muscle mass in both young and sarcopenic mammalian muscles . vitamin d has been traditionally considered a key regulator of bone metabolism and calcium and phosphorus homeostasis through negative feedback with the parathyroid hormone [ 107 , 108 ] . it is also well established that vitamin d deficiency causes rickets in children and osteomalacia and osteoporosis in adults . a large and growing body of evidence suggests that vitamin d is not only necessary for bone tissue and calcium metabolism but may also represent a crucial determinant for the development of major ( sub)clinical conditions and health - related events [ 107 , 109 ] . today , approximately 1 billion , mostly elderly people , worldwide have vitamin d deficiency . the prevalence of low vitamin d concentrations in subjects older than 65 years of age has been estimated at approximately 50% [ 110112 ] , but this figure is highly variable because it is influenced by sociodemographic , clinical , therapeutic , and environmental factors . similarly there is an age - dependent reduction in vitamin d receptor expression in skeletal muscle . prolonged vitamin d deficiency has been associated with severe muscle weakness , which improves with vitamin d supplementation . the histological examination of muscle tissue from subjects with osteomalacia is characterized by increased interfibrillar space , intramuscular adipose tissue infiltrates , and fibrosis . interestingly , muscle biopsies performed before and after vitamin d supplementation have documented an increased number and sectional area of type ii ( or fast ) muscle fibers [ 113 , 116 ] . a large body of evidence currently demonstrates that low vitamin d concentrations represent an independent risk factor for falls in the elderly [ 117119 ] . supplementation with vitamin d in double - blind randomized - controlled trials has been shown to increase muscle strength and performance and reduce the risk of falling in community - living elderly and nursing home residents with low vitamin d levels [ 120124 ] . in contrast , several groups found no positive effect of vitamin d supplementation on fall event outcomes [ 125127 ] . cesari et al . attributed these contradictory findings to the selection criteria adopted to recruit study populations , adherence to the intervention , or the extreme heterogeneity of cut - points defining the status of deficiency . a more comprehensive knowledge on vitamin - d - related mechanisms may provide a very useful tool preventing muscle atrophy for older persons ( sarcopenia ) . given the current and future demographic age shift in the world 's population , intense research in this area is imperative . decreases in muscle mass have been shown to be a key element in the development of frailty . currently , resistance training combined with amino - acid - containing supplements would be the best way to prevent age - related muscle wasting and weakness . comprehensive trials have demonstrated that supplementation with gh , igf - i , or estrogen has a minor sarcopenia - inhibiting effect . testosterone supplementation in large amounts improves muscle defects with aging but has several side effects . ghrelin - mimetics which have the ability to increase caloric intake as well as to increase lean body mass in the older population could be potentially beneficial and reverse the catabolic state associated with sarcopenia . myostatin inhibition seems to be an intriguing strategy for attenuating sarcopenia as well as muscular dystrophy .

sarcopenia , the age - related loss of skeletal muscle , is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement , a decline in strength and power , and an increased risk of fall - related injuries . since sarcopenia is largely attributed to various molecular mediators affecting fiber size , mitochondrial homeostasis , and apoptosis , numerous targets exist for drug discovery . in this paper , we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects . myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation . testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects . although igf - i is a potent regulator of muscle mass , its therapeutic use has not had a positive effect probably due to local igf - i resistance . treatment with ghrelin may ameliorate the muscle atrophy elicited by age - dependent decreases in growth hormone . ghrelin is an interesting candidate because it is orally active , avoiding the need for injections . a more comprehensive knowledge of vitamin - d - related mechanisms is needed to utilize this nutrient to prevent sarcopenia .

seizures lie among prevalent diseases of childhood and occur in 10% of children . in the emergency setting , the intravenous route is considered as the most suitable method , delivering adequate quantities of benzodiazepines in a short time . however , when intravenous administration is not available , other forms of benzodiazepine administration such as rectal diazepam or buccal midazolam may offer an alternative way of drug administration . benzodiazepines contain an imidazole ring which is highly water soluble and is rapidly absorbed from rectal , nasal , and buccal mucosa . the ring is also highly lipophilic at physiologic ph , a characteristic that facilitates its rapid effect on the central nervous system . a few studies have confirmed both efficacy and safety of buccal midazolam as well as rectal diazepam[610 ] . meanwhile , few studies have reported severe respiratory depression following buccal midazolam administration ; a fact that might have resulted from using high doses of the medication[6 , 8 ] . in the study conducted by thomas marshal , buccal midazolam was found effective in seizure attacks but it was mentioned that the medication was unlicensed for such a purpose . these findings shed light on the necessity to perform further studies to evaluate the efficacy and potential side effects of buccal midazolam . the purpose of this study was to determine whether buccal midazolam is efficient in control of convulsive episodes in children irrespective of the etiology of the seizure in comparison with intravenous diazepam , namely , the best accepted way of acute seizure episodes therapy[1 , 2 , 9 ] . this study was approved by the clinical ethics committee of shahid beheshti university of medical sciences . 271 children , aged 6 months to 14 years , admitted to the pediatric emergency ward of mofid children 's hospital due to seizure diagnosis between october 2007 and september 2008 . mofid children 's hospital has full - time medical and nursing staff on site . the inclusion criteria dictated that the patients needed to fulfill the following criteria : ( 1 ) documented seizure persisting at the time of administration of anticonvulsant ; ( 2 ) types of atonic , tonic and tonic - clonic seizures ; ( 3 ) seizure lasting for more than 5 min . the exclusion criteria were : ( 1 ) patients who received intravenous diazepam or other benzodiazepines within 24 hours prior to presentation of the seizure ; ( 2 ) previous history of narrow angle acute glaucoma ; ( 3 ) doubt about the historical information given by patient 's family . after history taking and physical examination , 46 patients had conditions that mimicked seizure like drugs side effects ( e.g. extrapyramidal movement due to metoclopramide ) , movement disorders ( like myoclonic jerks ) , etc . so , 92 children ( 51 boys , 41 girls ) were enrolled in the study ( fig 1 ) . flow diagram of patients consecutive patients were enrolled and were randomized to receive either buccal midazolam or intravenous diazepam . if the seizure was not controlled within five minutes of administration of buccal midazolam or intravenous diazepam , the second dose of the same drug was given to patient . in the event that the seizure remained uncontrolled within ten minutes after the first buccal midazolam or intravenous diazepam administration , either phenobarbital or phenytoin buccal midazolam ( epistatus , midazolam buccal liquid , and midazolam maleate ) was used with following doses : 2.5 mg for children aged 6 - 12 months , 5 mg for 1 - 4 years , 7.5 mg for 5 - 9 years , and 10 mg for 10 years or older . children received buccal midazolam by placing the syringe between their teeth and cheek , and after drug administration the cheek was gently massaged . intravenous diazepam was administered in a dosage of 0.3 mg / kg / dose and through an intravenous line as usual . all the nurses and doctors of the emergency ward were aware of the study and helped our team for administration of drugs as well as follow up of the patients and completing the information sheet . in case the patient fulfilled the inclusion criteria , an informed consent was provided after a parent or legal guardian was briefed about the study purpose and procedures . in the next step , the patient was randomly assigned into one of the two treatment groups , either buccal midazolam ( first group ) or intravenous diazepam ( second group ) . in order to record the underlying causes of convulsions , patient 's history , physical examination , and laboratory evaluations including determination of electrolytes and glucose were considered for all patients . heart rate , respiratory rate , blood pressure , and hemoglobin oxygen saturation were monitored continuously all through the procedure . during the seizure patients were followed up for 24 hours after drug administration . any side effects including apnea , hypotension , bradycardia , due to drug administration were also recorded . the duration of seizures before buccal midazolam or intravenous diazepam therapy was approximate , based on the history obtained from the patient 's attendants and other family members . for each patient , the time of noticing the first convulsion at the arrival in emergency , the time of administrating the drugs and the time of cessation of all motor seizure activity were recorded . the drug administration was considered as failed in case the convulsive motor activities did not stop within 10 minutes of administration . nobody was lost to follow up in both groups , because the results of intervention were recorded on site and all patients were admitted for at least 24 hours . every patient included in the study , was assigned by a number in series and the numbering was based upon differences between proportions were statically tested by chi - square or fisher 's exact test . all other numerical or quantitative comparisons were performed using student 's unpaired t - test . this study was approved by the clinical ethics committee of shahid beheshti university of medical sciences . 271 children , aged 6 months to 14 years , admitted to the pediatric emergency ward of mofid children 's hospital due to seizure diagnosis between october 2007 and september 2008 . mofid children 's hospital has full - time medical and nursing staff on site . the inclusion criteria dictated that the patients needed to fulfill the following criteria : ( 1 ) documented seizure persisting at the time of administration of anticonvulsant ; ( 2 ) types of atonic , tonic and tonic - clonic seizures ; ( 3 ) seizure lasting for more than 5 min . the exclusion criteria were : ( 1 ) patients who received intravenous diazepam or other benzodiazepines within 24 hours prior to presentation of the seizure ; ( 2 ) previous history of narrow angle acute glaucoma ; ( 3 ) doubt about the historical information given by patient 's family . after history taking and physical examination , 46 patients had conditions that mimicked seizure like drugs side effects ( e.g. extrapyramidal movement due to metoclopramide ) , movement disorders ( like myoclonic jerks ) , etc . so , 92 children ( 51 boys , 41 girls ) were enrolled in the study ( fig 1 ) . flow diagram of patients consecutive patients were enrolled and were randomized to receive either buccal midazolam or intravenous diazepam . if the seizure was not controlled within five minutes of administration of buccal midazolam or intravenous diazepam , the second dose of the same drug was given to patient . in the event that the seizure remained uncontrolled within ten minutes after the first buccal midazolam or intravenous diazepam administration , either phenobarbital or phenytoin was used as the second line antiepileptic . buccal midazolam ( epistatus , midazolam buccal liquid , and midazolam maleate ) was used with following doses : 2.5 mg for children aged 6 - 12 months , 5 mg for 1 - 4 years , 7.5 mg for 5 - 9 years , and 10 mg for 10 years or older . children received buccal midazolam by placing the syringe between their teeth and cheek , and after drug administration the cheek was gently massaged . intravenous diazepam was administered in a dosage of 0.3 mg / kg / dose and through an intravenous line as usual . all the nurses and doctors of the emergency ward were aware of the study and helped our team for administration of drugs as well as follow up of the patients and completing the information sheet . in case the patient fulfilled the inclusion criteria , an informed consent was provided after a parent or legal guardian was briefed about the study purpose and procedures . in the next step , the patient was randomly assigned into one of the two treatment groups , either buccal midazolam ( first group ) or intravenous diazepam ( second group ) . in order to record the underlying causes of convulsions , patient 's history , physical examination , and laboratory evaluations including determination of electrolytes and glucose were considered for all patients . heart rate , respiratory rate , blood pressure , and hemoglobin oxygen saturation were monitored continuously all through the procedure . during the seizure , oxygen was administered by nasal prongs . patients were followed up for 24 hours after drug administration . any side effects including apnea , hypotension , bradycardia , due to drug administration were also recorded . the duration of seizures before buccal midazolam or intravenous diazepam therapy was approximate , based on the history obtained from the patient 's attendants and other family members . for each patient , the time of noticing the first convulsion at the arrival in emergency , the time of administrating the drugs and the time of cessation of all motor seizure activity were recorded . the drug administration was considered as failed in case the convulsive motor activities did not stop within 10 minutes of administration . nobody was lost to follow up in both groups , because the results of intervention were recorded on site and all patients were admitted for at least 24 hours . every patient included in the study , was assigned by a number in series and the numbering was based upon table of random sampling for grouping them in case and control groups . differences between proportions were statically tested by chi - square or fisher 's exact test . all other numerical or quantitative comparisons were performed using student 's unpaired t - test . fifty - one ( 55.4% ) out of 92 participants were male and 41 ( 44.6% ) female . in the buccal midazolam group , 14 patients were male and 18 were female while in the intravenous diazepam group , 37 were male and 23 were female ( p=0.1 ) . the median age in buccal midazolam group was 18.410.3 and in the other group was 17.110.1 . 82% of patients age was equal or less than 24 months with mean weight of 10.62.73 kg ( 6 to 18 kg ) . twenty ( 21.8% ) patients had tonic seizure , 58 ( 63% ) had tonic - clonic seizures and others ( 15.2% ) had atonic seizure . in the buccal midazolam group , 9 patients had tonic seizures , 18 had tonic - clonic and 5 had atonic seizures . in intravenous diazepam group , 11 had tonc seizures , 40 had tonic - clonic and 9 had atonic seizures . there was no statistically significant difference in the seizure types between the two groups ( p=0.5 ) . the etiologies included idiopathic epilepsy 64 ( 70% ) , febrile seizure 9 ( 10% ) , and cryptogenic or symptomatic epilepsy 19 ( 20% ) . underlying disorders associated with the symptomatic or cryptogenic seizure episodes has been shown in table 1 . in our study , 32 ( 34.8% ) of patients received buccal midazolam and 60 ( 65.2% ) intravenous diazepam . comparison of the two treatment responses is illustrated in table 2 and fig 2 . in the first group , the first administration was effective in controlling the seizures in 13 ( 40% ) whereas in the second , seizures were completely controlled after the first dosage in 24 ( 40% ) ( p=0.9 ) . overall , 22 ( 68.7% ) of the patients in the first group were relieved from seizures after the first or the second dosage whereas the applied medication controlled seizures in 42 ( 70% ) patients of the second group ( p=0.9 ) . box and whisker plots of time from drug administration up to the end of seizure underlying disorders associated with the symptomatic or cryptogenic seizure episodes control of seizures and seizure control time in two groups significant adverse effects included agitation observed in 11 and 25 patients , and mild hypotension in 7 and 9 patients in the first and second group , respectively . in the second group , 4 patients experienced apnea ; there was no statistically significant difference in the side effects between the two groups ( agitation p=0.5 , hypotention p=0.4 , apnea p=0.2 ) . the mean time for medication effect was not significantly shorter with intravenous diazepam as compared to buccal midazolam ( p=0.09 ) , but the mean time for control of patients in the first or the second administration drug dose was significantly shorter with intravenous diazepam than with buccal midazolam ( fig . 2 and table 2 ) . according to our results , administration of intravenous diazepam or buccal midazolam resulted in cessation of convulsions similarly . the overall rate of response in both groups was similar and this suggests that buccal midazolam is effective in controlling acute convulsions of generalized tonic , tonic - clonic , or atonic type . so far there has been a few study comparing intravenous diazepam and buccal midazolam[4 , 13 ] . in that study the rate of controlled seizures was similar in both groups , but the overall frequency of control of convulsive episodes by buccal midazolam was 85% . in ashrafi 's et al study , midazolam ceased all of the seizures with 5 min and diazepam ceased 82% of patient 's seizures with 5 min of drug administration . in another study from iran javadzadeh et al showed the time needed to control seizure by intranasal midazolam was shorter than intravenous diazepam . in other researches such as our study , efficacy of buccal midazolam was confirmed[3 , 5 , 810 ] . our results showed the time of seizure control in both groups of patients in the first five minutes or the second five minutes after administration of drugs was not significantly different . in the previous study , the results of the mean time for controlled seizure in the two groups was similar to our study , and the time for seizure cessation with intravenous diazepam was less than buccal midazolam . in another study , mean time for seizure cessation with buccal midazolam was reported to be 3.892.22 minutes . these differences of overall control and the time required to complete the control should be subject to further investigation . there is increasing evidence that the longer seizures persist , the more difficult they will be to stop . a previous study showed that first line therapy stopped seizures in 80% of patients when administered within 2 hours after the onset of the seizures , but less than 40% of patients were controlled if the treatment started after 2 hours . the results of the present study manifest that buccal midazolam efficacy is similar to intravenous diazepam for seizure cessation and because buccal midazolam administration is very easy and fast , it can prevent status epilepticus . so far , no serious adverse effects have been reported in most cases of buccal midazolam administration[4 , 7 , 15 , 16 ] , but in some of the studies respiratory depression has been observed[6 , 8 ] . probably , this complication is a result of high dosage of buccal midazolam ( 0.5 mg / kg / dose ) . administration of buccal midazolam with a dose of 0.3 mg / kg / dose does not seem to cause side effects . in our study , respiratory depression with buccal midazolam was not seen ; some patients experienced mild hypotension and agitation whereas patients who took intravenous diazepam showed respiratory depression , mild hypotension , and agitation . this study was not blinded and placebo was not administered , although placebo administration in these situations may not be ethical . another limitation of our study was small numbers of patients , so we suggest this study must be repeated with more patients . our results suggest that buccal midazolam at a dose of 0.3 mg / kg may be as effective as intravenous diazepam for the treatment of acute convulsive seizures in children and it is safer than intravenous diazepam , so buccal midazolam can be used at home very easy , safe and effective .

objectivethe purpose of the present study is to compare efficacy and safety of buccal midazolam with intravenous diazepam in control of seizures in iranian children.methodsthis is a randomized clinical trial . 92 patients with acute seizures , ranging from 6 months to 14 years were randomly assigned to receive either buccal midazolam ( 32 cases ) or intravenous diazepam ( 60 cases ) at the emergency department of a children 's hospital . the primary outcome of this study was cessation of visible seizure activity within 5 minutes from administration of the first dosage . the second dosage was used in case the seizure remained uncontrolled 5 minutes after the first one.findingsin the midazolam group , 22 ( 68.8% ) patients were relieved from seizures in 10 minutes . meanwhile , diazepam controlled the episodes of 42 ( 70% ) patients within 10 minutes . the difference was , however , not statistically significant ( p=0.9 ) . the mean time required to control the convulsive episodes after administration of medications was not statistically significant ( p=0.09 ) . no significant side effects were observed in either group . nevertheless , the risk of respiratory failure in intravenous diazepam is greater than in buccal midazolam.conclusionbuccal midazolam is as effective as and safer than intravenous diazepam in control of seizures .

metrology has fundamental implications in science and technology . it is concerned with the largest possible precision achievable in various parameter estimation tasks and frame measurement schemes to achieve that precision . in metrology quantum fisher information ( qfi ) plays central role @xcite and its inverse provides the lower bound on the error in statistical estimation of an unknown parameter @xcite . hence , the ways to increase qfi become an intriguing question in quantum metrology . in particular , if the quantum entanglement present in a system can be used as a resource . a substantial amount of effort has been put forward in this context @xcite and it has been proven that entanglement does play a positive role to enhance precision in metrology . even entanglement can be exploited as the quantum resource to go beyond standard quantum limit ( sql ) and attain heisenberg limit ( hl ) @xcite . this fact gives rise to an important question , whether such increase in qfi can be used as the signature of quantum entanglement . further , if it would be possible to relate and quantify quantum entanglement in terms of qfi . recently several studies have been carried out in this direction @xcite . a quantum correlation measure has been introduced , recently , based on quantum fisher information and the measure has been shown to set the minimum precision achievable in `` black - box '' quantum metrology @xcite . however , the understanding on the role of quantum correlation in quantum metrology , in particular to attain larger precision , is far from complete . in this paper , we address two intriguing questions , relating general ( pure and mixed ) quantum states . first , if the quantum correlation other than entanglement can be the resource to enhance the precision in metrology by increasing qfi . and , if so , how do quantum correlations play role in it . second , if it is possible to provide tighter bounds on the metrological precision in the presence of quantum correlations . we give affirmative answers to above questions . we observe , for given quantum correlated state , that not only entanglement but also quantum correlation is a resource in quantum metrology and we uncover the role behind . we demonstrate that , even in the absence of quantum entanglement , quantum correlation is capable of playing constructive role to beat sql and attain hl . we also provide , solely quantum state dependent , tighter bounds on the metrological precision in the presence of quantum correlations . the paper is organized as follows . in sec . [ sec : qfi ] , we introduce quantum fisher information and how it is connected to quantum speed of evolution . sec . [ sec : lqfi ] is dedicated to local quantum fisher information and the quantum correlation measure based on it . we revisit the properties of the quantum correlation measure proposed in @xcite , but from a slightly different approach . the role of quantum correlations in quantum metrology is studied in sec . [ sec : metro ] and finally we conclude in sec . [ sec : concl ] . our whole analysis is centralized on the qfi which is a riemannian metric in quantum geometry of state space @xcite . the geometric distance between two arbitrary quantum states , in the projective hilbert space , using bures distance @xcite , is given by @xmath0 , where @xmath1 , the uhlmann fidelity . now consider a smooth dynamical process in the hilbert space of density matrix following unitary evolution , parametrized by time @xmath2 . that leads to an evolution of the quantum state from @xmath3 to @xmath4 such that the @xmath5 is a piecewise smooth function of @xmath6 and @xmath7 . for an infinitesimal time evolution from @xmath2 to @xmath8 with a given unitary @xmath9 $ ] , the distance between the initial and final states , becomes @xmath10 where we ignore @xmath11 . the @xmath12 is the qfi @xcite . note that @xmath13 is the instantaneous speed , @xmath14 , of quantum evolution due to the hamiltonian , @xmath15 , in the projective hilbert space and vanishes iff @xmath16=0 $ ] . without loss of generality we assume @xmath17 in the following . qfi is defined as @xmath18 where @xmath19 is the symmetric logarithmic derivative ( sld ) operator which can be expressed as @xmath20=\frac{1}{2 } ( l\rho + \rho l ) $ ] . qfi , based on sld operator , has several important properties @xcite inheriting from bures distance @xcite . these properties such as convexity , invariance under the unitaries on both initial and final states , and monotonicity under completely positive trace preserving ( cptp ) maps , establish qfi as the fundamental quantity in quantum geometry , quantum information and quantum metrology . for a given quantum state @xmath21 with @xmath22 and @xmath23 , the qfi reduces to @xcite @xmath24 the summation is carried out under the condition @xmath25 . henceforth , whenever there appears summation with @xmath26 in the denominator , we assume that the sum is taken under the condition @xmath25 with @xmath21 , unless otherwise stated . ( color online ) . the quantum fisher information represents the quantum speed of evolution when it is driven with a unitary . the schematics depicts a special case , when one party of a bipartite quantum state , @xmath27 , is driven with a local unitary @xmath28 $ ] . the resultant global quantum speed we call as the local quantum fisher information . , scaledwidth=45.0% ] in this section we review the quantum correlation measure based on qfi originally introduced in @xcite . let us consider an @xmath29 bipartite quantum state @xmath21 in the hilbert space @xmath30 . in the case , as shown in fig . [ fig : speedmeter ] , where the first party , say @xmath27-party , is driven with the hamiltonian @xmath31 the local quantum fisher information ( lqfi ) reduces to : @xmath32 after simple manipulation of eq . ( [ eq : qfi ] ) . our goal is to quantify quantum correlation in terms of lqfi and for that we define the minimum of lqfi , @xmath33 , over all local hamiltonians @xmath34 on @xmath27-party , as @xmath35 the @xmath36 represents the minimal quantum speed of evolution , in projective space of @xmath30 , when the party-@xmath27 is driven with the local hamiltonian @xmath37 . following the properties of qfi @xcite , the @xmath38 acquires several interesting properties : it is nonnegative ; invariant under local unitary operations ; convex i.e. , non increasing under classical mixing and monotonically decreasing under local completely positive trace preserving ( cptp ) maps on b - party ; and in general @xmath39 except for symmetric quantum states . all these important properties indulge us to avow that the _ @xmath40 is the measure of quantum correlation _ and hence , we introduce the following theorem . * theorem i : * _ @xmath40 vanishes iff the bipartite states are either classical - quantum ( cq ) i.e. , @xmath41 where @xmath42 and @xmath43 for @xmath44 or classical - classical ( cc ) i.e. , @xmath45 where @xmath46 for @xmath44 . _ * proof : * let us consider a bipartite quantum state @xmath47 represented in terms of arbitrary bases of hermitian operators @xmath48 and @xmath49 where @xmath50 and @xmath51 . the real valued @xmath52 correlation matrix @xmath53_{mn}=\gamma_{mn}$ ] can be diagonalized , using singular value decomposition ( svd ) , to @xmath54 $ ] where @xmath55 and @xmath56 are the @xmath57 and @xmath58 orthogonal matrices , respectively . accordingly , the local bases transform to @xmath59 and @xmath60 and the state , in this new basis , becomes @xmath61 where @xmath62 . for vanishing @xmath40 the necessary and sufficient condition is @xmath63=0 $ ] or equivalently @xmath64=0 \ \forall m$ ] . therefore , the @xmath65 and @xmath66 shares common eigenbasis and that is achievable if and only if @xmath67=0 $ ] for @xmath68 . so , the states with vanishing @xmath40 , assumes the form @xmath69 where @xmath70 are orthonormal eigenvectors in @xmath71 . @xmath72 vanishing @xmath40 highlights the fact that there exists at least one local hamiltonian @xmath66 for which the quantum speed of evolution is zero . on the other hand , if the bipartite state is either qc or quantum - quantum ( qq ) , it is impossible to find a local hamiltonian @xmath66 with which the quantum states remain stationary in the projective space of @xmath73 and thus , the @xmath40 acquires non - zero value . note that , for pure quantum states the @xmath40 reduces to the minimal variance over the local unitaries and it is an entanglement monotone @xcite . for a bipartite quantum state of @xmath74 dimension the @xmath40 can be calculated easily . we note that the maximally informative hamiltonians on the @xmath27-party are the traceless hermitian operators with non - degenerate spectrum . so it is sufficient to consider the hamiltonian as @xmath75 where @xmath76 , i.e. , @xmath77 and @xmath78 are the pauli matrices . now the minimum of lqfi @xmath40 , which is solely the property of the quantum state , can be calculated analytically as @xmath79 where @xmath80 is the largest eigenvalue of the real symmetric matrix @xmath81_{ij}= \sum_{m\neq n}\frac{2 \lambda_m \lambda_n}{\lambda_m+\lambda_n } \langle m | \sigma_i \otimes \mathbb{i } | n \rangle \langle n | \sigma_j \otimes \mathbb{i } | m \rangle$ ] . here to minimize @xmath82 , we maximize @xmath83 over all unit vectors @xmath84 for the real symmetric matrix @xmath85 and the maximum value equals to the largest eigenvalue of @xmath81_{ij}$ ] @xcite . note that an equivalent formula of @xmath40 , for @xmath74 bipartite quantum states , is also derived in @xcite . the @xmath40 can be compared with other measures of quantum correlation of a bipartite quantum state @xmath86 which are based on various geometric distances such as hilbert - schmidt @xcite and hellinger @xcite distances ( see fig . [ fig : qcs ] ) . these measures can again be interpreted as the minimum quantum speed , quantified with the corresponding geometric distances @xcite , of local unitary evolutions with the local hamiltonian @xmath87 with @xmath76 and @xmath88 are the pauli matrices . the measure based on the hilbert - schmidt distance , also known as geometric quantum discord @xcite , is given by @xmath89 . the local uncertainty measure of quantum correlation , based on helligner distance @xcite , is written as @xmath90 . from the expression of qfi , we have @xmath91 . in fig . [ fig : qcs ] we consider an example of a two - qubit werner state @xmath92 , where @xmath93 and compare the quantum correlation measures , with respect to the state parameter @xmath94 . the solid ( black ) , dashed ( blue ) and dotted ( red ) traces correspond to the quantum correlation measures @xmath95 , @xmath96 and @xmath97 respectively . the state is entangled for @xmath98 while it is quantum correlated for @xmath99 . the measure @xmath100 can reliably quantify it along with other two measures . though @xmath100 is appeared to be a variant of discord - like quantifier of quantum correlation along with @xmath96 and @xmath97 , it establishes its precedence over the others in the context of quantum metrology . the intimate connection of qfi with quantum metrology and quantum correlation present in a system entices one to ask the question , we pose in this paper , on the role of quantum correlation in quantum metrology . in quantum parameter estimation , a quantum state @xmath101 , which acts as a probe , undergoes a unitary transformation ( in general a shift in phase ) so that the evolved state becomes @xmath102 , where @xmath15 is the hamiltonian assumed to have non - degenerate spectrum . the parameter @xmath103 is encoded in the state @xmath104 and the task is to estimate the unobservable parameter @xmath103 . interestingly , the lower bound on the error ( or variance , @xmath105 ) , in estimating @xmath103 , is independent of the choice of the measurements ( povms ) performed after the unitary evolution and solely determined by the dependence of the output state on the parameter @xmath103 . for a single shot experiment , it is given by the celebrated quantum cramr - rao ( qcr ) bound @xcite as @xmath106 . ( color online ) . the variation quantum correlation measures based on lqfi @xmath107 ( black solid trace ) , hilbert - schmidt distance @xmath96 ( blue dashed trace ) and hellinger distance @xmath97 ( red dotted trace ) for two - qubit werner state @xmath92 where @xmath93 , with respect to the state parameter @xmath94 . , scaledwidth=45.0% ] for simplicity here we consider a bipartite state @xmath101 of @xmath108 dimension and the parameter estimation process with local unitary evolution . though our analysis can easily be extended to the systems with arbitrary @xmath109 dimensions . hence , @xmath110 , where @xmath111 and @xmath66 is the local hamiltonian acting on the @xmath27-party . in the presence of quantum correlation , we have non - zero @xmath40 and lqfi is lower bounded as @xmath112 . the upper bound of lqfi can also be derived and it is the maximal @xmath113 over all possible @xmath37 and can be calculated analytically as @xmath114 where @xmath115 is the smallest eigenvalue of the real symmetric matrix @xmath81_{ij}= \sum_{m , n}\frac{2 \lambda_m \lambda_n}{\lambda_m+\lambda_n } \langle m | \sigma_i \otimes \mathbb{i } | n \rangle \langle n | \sigma_j \otimes \mathbb{i } | m \rangle$ ] . the maximization of @xmath113 is carried out using the same logic as in eq . ( [ eq : wmax ] ) except that here we consider the smallest eigenvalue of @xmath85 . the @xmath116 possesses all the good properties as of @xmath117 . now the bounds on the lqfi becomes @xmath118 . hence in the presence of quantum correlation @xmath119 , the error on the estimated parameter , in a single shot experiment , is given by @xmath120 remarkably the quantum correlated states have intrinsic precision in metrology with local unitaries that is inverse to the quantum correlation present in the system , while it is absent for the cq states . this intrinsic precision is also tested experimentally @xcite . on the other hand the maximum metrological precision achievable , given all choices of local unitaries , is determined by the inverse of @xmath121 . ( color online ) . a schematic of a quantum metrological experiment with n - party quantum state @xmath122 , which acts as a probe . the @xmath122 is driven with local unitaries and as a result it encodes the unobservable parameter , say @xmath103 ( in general a shift in phase ) , which is to be estimated with measurements ( povms ) . , scaledwidth=35.0% ] it is known that the qfi is additive quantity on product states and in particular @xmath123 . thus , the qcr bound becomes @xmath124 . the term @xmath125 in the denominator may be equivalently interpreted as due to @xmath126 independent repetitions of an experiment with a state @xmath101 or a single shot experiment ( see fig . [ fig : metrology ] ) with a multi - party state @xmath127 . the corresponding scaling of metrological error @xmath128 is referred to as the sql . the situation becomes very different when the system @xmath122 is quantum correlated . the @xmath126-party state @xmath122 is referred to as the _ genuinely quantum correlated _ ( gqc ) state if @xmath129 . now we show that for a gqc state , @xmath122 , the @xmath130 . consider an @xmath131 bipartite system @xmath101 is driven with the hamiltonian @xmath132 . in such case , the global ( or joint ) quantum fisher information ( gqfi ) becomes @xmath133 where the third term ( also called the interference term ) @xmath134 vanishes for arbitrary @xmath37 and @xmath135 . _ * proof : * to prove the above theorem it is sufficient to show that every non - diagonal ( @xmath136 ) elements @xmath137 , of @xmath138 in eq . ( [ eq : gqfi ] ) , is vanishing as long as it is a non - gqc state . let us consider an @xmath29 bipartite non - gqc state , say cq state @xmath139 with @xmath140 . here @xmath141 , where @xmath142 @xmath143 and @xmath144 for @xmath145 and @xmath146 only . now in the new basis the non - diagonal terms become @xmath147 . to assure @xmath148 , we are left with three choices . first , @xmath149 but @xmath150 . second , @xmath151 but @xmath152 and finally , @xmath151 but @xmath153 . interestingly , in all three cases the @xmath154 and thus the @xmath155 , for arbitrary @xmath37 and @xmath135 . similarly , it is straightforward to show that the @xmath138 also vanishes for qc and cc states . @xmath72 ( color online ) . the figure displays the role of _ genuine quantum correlation _ , other than entanglement , in increasing quantum fisher information . the figure is calculated for the bipartite quantum state , the werner state @xmath156 where @xmath157 ) and @xmath158 , which has zero entanglement . the parameters @xmath103 and @xmath159 belong to the local hamiltonians @xmath160 , where @xmath77 and @xmath78 are the pauli matrices . the vertical axis ( the z - axis ) represents the quantum fisher information . the flat surface ( in blue ) represents lqfi ( which is independent of @xmath103 and @xmath159 ) @xmath161 . the curved surface ( in yellow ) corresponds to the gqfi . for @xmath162 , gqfi vanishes due to destructive interference while for @xmath163 , it acquires maximum value @xmath164 due to constructive interference between the local unitary evolutions.,scaledwidth=47.0% ] it is clear from theorem ii that for non - gqc states , the gqfi is , just , simple algebraical sum of the lqfis , as the interference term becomes zero . while for gqc states the interference term @xmath138 , is non - vanishing and can acquire both positive and negative values . so it reveals that genuine quantum correlation plays a pivotal role to increase as well as to reduce gqfi than that of the sum of lqfis ( e.g. , see fig . [ fig : interfare ] ) . therefore for the gqc states , we have @xmath165 . as a result the gqfi is upper and lower bounded as @xmath166 , where the equalities can be achieved for certain choices of @xmath37 and @xmath135 depending on the state @xmath101 . this particular feature can be adjusted to attain better metrological precision beyond sql , even to reach hl . in fig . [ fig : interfare ] , we consider an example of werner state with zero entanglement , @xmath156 , where @xmath157 ) and @xmath158 . it is a symmetric state and @xmath167 for @xmath168 . for the hamiltonian @xmath160 , where @xmath77 and @xmath78 the pauli matrices , gqfi vanishes for @xmath162 . the lqfi is independent of @xmath103 and @xmath159 , i.e. , @xmath169 . while for @xmath163 , the gqfi becomes maximum and @xmath170 . for arbitrary bipartite states and hamiltonians , the tighter bounds on gqfi can be provided since @xmath171 and @xmath172 . as a result the bounds on the error in parameter estimation , with gqc states , is @xmath173 for n - party symmetric gqc states and identical local hamiltonians , i.e. , @xmath174 , the @xmath175 @xmath176 . similarly , @xmath177 and @xmath178 @xmath176 . it is straightforward to see that for n - party symmetric gqc states @xmath122 , gqfi is @xmath179 for the particular choice of quantum states and the local hamiltonians , which is not the case otherwise . note , here we need quantum correlation , which may not include entanglement , to attain hl with the scaling @xmath180 . further , the tighter qcr bound , independent of the local unitaries , can be given in terms of solely a state dependent quantity as @xmath181 it is interesting to note that for a class of gqc states with arbitrary @xmath174 , the interference term , in eq . ( [ eq : gqfi ] ) , reduces to @xmath182 and consequently gqfi vanishes arbitrarily , e.g. , the werner state of the form @xmath183 where @xmath184 . hence , these quantum states are useless from the perspectives of quantum metrology . in this paper we investigate the role of quantum correlation in quantum metrology . the best suited measure of quantum correlation , which laid the basis of investigation , is the one based on quantum fisher information originally introduced in @xcite . as the quantum fisher information represents the quantum speed of evolution , when the geometric distance in the quantum state space is expressed in terms of bures metric , the quantum correlation can be interpreted from quantum dynamical perspective . thus the measure of quantum correlation becomes identified with the minimal speed of evolution over all possible local unitaries . this dynamical approach to quantify quantum correlation provides us the premise to study quantum metrology in the presence of quantum correlation . the quantum correlation measure gives the lowest bound on the error in quantum metrology , when the experiment is performed on one of the sub - systems . an upper bound on the error is also derived analytically . for quantum metrology with multi - party quantum systems , we show that not only the entanglement but also the quantum correlation plays important roles in enhancing precision in quantum metrology . even in the absence of entanglement , quantum correlation can be exploited to go beyond sql and attain hl . the very reason for better precision is the constructive interference between the local unitary evolutions , resulting in larger quantum fisher information and that happens only in the presence of quantum correlation . it is also possible to have destructive interference , in the presence of quantum correlation , to make the resultant quantum fisher information very small or even zero . we have derived the tighter bounds on the metrological error in the presence of quantum correlation in multiparty scenario . * acknowledgement * the author thanks prof . arun k. pati and himadri s. dhar for carefully reading the manuscript . the author also gratefully acknowledges the useful comments by gerardo adesso and davide girolami . 99 a. monras , phys . a * 73 * , 033821 ( 2006 ) ; 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quantum metrology is studied in the presence of quantum correlation . the quantum correlation measure based on quantum fisher information enables us to gain a deeper insight on how quantum correlations are instrumental in setting metrological precision . our analysis shows that not only the entanglement but also the quantum correlation plays important roles to enhance precision in quantum metrology . even in the absence of entanglement , quantum correlation can be exploited as the resource to beat standard quantum limit and reach heisenberg limit in metrology . clearly unraveling the role of quantum correlations , the tighter bounds on the metrological precision are derived .

a 63 year old caucasian high school graduated man , who has been a known case of alzheimer 's disease according to dsm - iv - tr and criteria of national institute of neurological and communicative disorders and stroke and alzheimer 's disease and related disorders association ( nincds / adrda ) ( 1 ) since 3 years ago , was visited in february 2012 . at the time of diagnosis , his past medical history was otherwise unremarkable . with worsening of his cognitive functional state , the patient was treated with 10 mg / day donepezil . on the next day , the patient appeared delirious and was referred to our center due to agitation and confusion . based on reports by family members , following the dosage increase of the medication , the patient was unable to recognize family members consistently , showed difficulty in awareness of time , acted aimlessly , and became emotionally irritable and violent with the family member attempts to assist him . at the time of referral , his mmse score was 8/30 . upon general and neurologic examination , routine laboratory examinations , serum creatinine and ammonia as well as liver and thyroid function tests were in normal limits . after withdrawing donepezil , patient 's symptoms improved gradually in course of one day . patient became alert and returned to his baseline cognitive functional state although he was unaware of his previous delirious behaviors . at 6 months follow - up , the patient demonstrated no delirious behavior and his mild cognitive impairments have not progressed substantially . to the best of our knowledge , this is the second reported case of delirium in a patient upon treatment with donepezil . in 2003 , kawashima and yamada reported a patient with alzheimer 's disease who was presented with delirium three days after increasing the dosage of donepezil from 3 mg / day to 5 mg / day ( 2 ) . this patient also recovered in two days following withdrawal of the medication and his recovery was maintained at 5 months follow - up . two months subsequent to donepezil discontinuation based on a decision by family members , patient 's aggressive behaviors disappeared and no similar event was repeated . along the same line , emergence of violent actions during treatment with donepezil and disappearance of symptoms with medication withdrawal is reported by bouman and pinner in a patient with dementia in 1998 ( 3 ) . similarly , in 2003 , bianchetti and trabucchi presented a patient suffering from alzheimer 's with mild cognitive impairments that demonstrated aggressive and agitated behaviors toward relatives and attempted self - harm following increase in starting dose of 10 mg / day donepezil from 5 mg / day ( 4 ) . in line with these cases , lo coco and cannizzaro described a patient who showed inappropriate sexual behaviors during treatment with donepezil ( 5 ) . notably , in 1996 , traepacz et al . reported a patient with alzheimer 's disease who showed signs of neurotoxicity and cholinergic delirium following dosage increase of tacrine , another member of acetylcholinesterase inhibitors which is not currently widely used due to its associated adverse events , to 160 mg / day ( 6 ) . this patient also recovered to a great extent although he did not return to his baseline function after 5 months of tacrine withdrawal . although this case does not prove donepezil as a cause of delirium , incidence of delirium following treatment with this medication and spontaneous recovery of the patient subsequent to its withdrawal , suggest physicians should be cautious in prescribing acetylcholinesterase inhibitors .

donepezil , a member of the acetylcholinesterase inhibitor family , is approved for management of cognitive impairments as well as behavioral complications in patients with neurodegenerative alzheimer 's disease . generally , donepezil is regarded as a safe medication in patients with alzheimer 's disease although there have been reports of several minor adverse events including gastrointestinal disturbances . herein we describe a patient with alzheimer 's disease who demonstrated delirious behavior upon treatment with donepezil .

SECTION 1. SHORT TITLE; TABLE OF CONTENTS. (a) Short Title.--This Act may be cited as the ``Depleted Uranium Munitions Suspension and Study Act of 2001''. (b) Table of Contents.--The table of contents of this Act is as follows: Sec. 1. Short title; table of contents. Sec. 2. Findings. Sec. 3. Purposes. Sec. 4. Suspension of use of depleted uranium munitions. Sec. 5. Suspension of sale and export of depleted uranium munitions. Sec. 6. Comptroller general investigation of plutonium contamination. Sec. 7. Study of health effects of depleted uranium. Sec. 8. Epa studies of environmental contamination by depleted uranium. Sec. 9. Environmental mitigation and cleanup requirements. SEC. 2. FINDINGS. Congress makes the following findings: (1) The highest regard should be given to the health and safety of the Nation's military personnel. (2) Among the characteristics of depleted uranium munitions are that (A) they are pyrophoric, resulting in the munition burning upon impact with a target, and (B) the impact of a depleted uranium munition on a target creates aerosol particles, which can be inhaled. (3) Depleted uranium munitions were used by the United States in 1991 during the Persian Gulf War in Southwest Asia and during the conflicts in the former Federal Republic of Yugoslavia (Bosnia, Kosovo, Serbia, and Montenegro) during the 1990s, with approximately 300 metric tons of depleted uranium being used during the Gulf War, three metric tons being used in Bosnia, and over nine metric tons being used in Kosovo, Serbia, and Montenegro. (4) The United States has provided or sold depleted uranium and depleted uranium munitions to allied nations, and the United Kingdom used depleted uranium munitions during the Persian Gulf War. (5) Depleted uranium munitions have been used at numerous United States military installations, proving grounds, and testing facilities. (6) The Yugoslav and Iraqi Governments have claimed that depleted uranium is affecting the health of their people, although such claims have yet to be independently verified. (7) No definitive cause has been established for the various illnesses (commonly referred to as ``Gulf War Syndrome'') that currently affect approximately 130,000 United States servicemembers and veterans who served in Southwest Asia during the Persian Gulf War. (8) The British Royal Navy, Canadian Navy, and United States Navy have all announced that they would phase out use of depleted uranium munitions. (9) It has been reported that depleted uranium munitions use has proliferated to more than 20 nations. (10) Crash investigators of the Federal Aviation Administration are instructed, in FAA Advisory Circular 20-123, dated December 20, 1984, to ``handle with caution'' any depleted uranium that they encounter in crash investigations, and are instructed that ``the main hazard associated with depleted uranium is the harmful effect the material could have if it enters the body,'' and that ``[i]f particles are inhaled or digested, they can be chemically toxic and cause a significant and long-lasting irradiation of internal tissues,''. (11) The 1949 Geneva Convention specifically outlines the precautions warring nations must take to avoid harming civilian populations, and it would be a violation of the 1977 Protocol to that Convention to cause superfluous injury or unnecessary suffering to civilians, as depleted uranium has the potential to cause. (12) The Department of Defense has acknowledged that stocks of depleted uranium munitions have been contaminated with transuranic elements, including plutonium. (13) Plutonium is an extremely toxic, carcinogenic, and radioactive material with a half-life of 4.5 billion years. SEC. 3. PURPOSES. The purposes of this Act are the following: (1) To eliminate health threats from depleted uranium munitions to-- (A) United States military personnel and United States civilian employees; (B) military personnel and employees of NATO member nations; and (C) civilian populations in regions where such munitions were used (whether in conflict, training, or development) or produced. (2) To provide for studies of-- (A) the level and scope of contamination of depleted uranium munitions by plutonium and other transuranic elements; (B) the health effects resulting from exposure by inhalation, ingestion, or injection to depleted uranium munitions; and (C) environmental contamination caused by depleted uranium at sites where depleted uranium was used in conflict, development, testing, or training and at sites where depleted uranium and depleted uranium munitions were produced. (3) To require the Administrator of the Environmental Protection Agency to issue regulations and requirements, based upon Environmental Protection Agency studies, concerning the cleanup and mitigation of depleted uranium contamination at sites of depleted uranium munition use and production in the United States. SEC. 4. SUSPENSION OF USE OF DEPLETED URANIUM MUNITIONS. (a) Suspension of Use.--Effective no later than 90 days after the date of the enactment of this Act, the Secretary of Defense shall direct that all elements of the Department of Defense suspend use of depleted uranium munitions. (b) Duration.--(1) The suspension of use of depleted uranium munitions required by subsection (a) shall remain in effect until the Secretary of Health and Human Services, based upon the results of the study under section 7(a), certifies to the committees specified in paragraph (2) that use of depleted uranium munitions in future conflicts-- (A) will not pose a likely long-term or residual threat to the health of United States or NATO military personnel; and (B) will not jeopardize the health of civilian populations in the area of such use. (2) The committees referred to in paragraph (1) are the following: (A) The Committee on Armed Services and the Committee on Government Reform of the House of Representatives. (B) The Committee on Armed Services and the Committee on Governmental Affairs of the Senate. (c) Future Use Limited to Stocks Free of Transuranic Matter.--Upon a certification by the Secretary of Health and Human Services described in subsection (b), the Secretary of Defense shall limit any subsequent use of depleted uranium munitions to stocks of such munitions that the Secretary certifies to be free of plutonium and other transuranic matter. SEC. 5. SUSPENSION OF SALE AND EXPORT OF DEPLETED URANIUM MUNITIONS. (a) Suspension of Sale and Export.--Upon the enactment of this Act, all elements of the Government with responsibility for approving the foreign sale or export of munitions shall suspend the approval of the sale and export of munitions containing depleted uranium. (b) Duration.--The suspension required by subsection (a) of approval of the foreign sale and export of depleted uranium munitions shall remain in effect until the Secretary of Health and Human Services makes a certification described in section 4(b). (c) Future Exports To Be Limited to Stocks Free of Transuranic Matter.--Upon a certification by the Secretary of Health and Human Services described in section 4(b), any subsequent foreign sale or export of depleted uranium munitions or preproduction depleted uranium may be made only from stocks of such munitions or preproduction depleted uranium that the Secretary of Defense certifies to be free of plutonium and other transuranic matter, excluding depleted uranium. SEC. 6. COMPTROLLER GENERAL INVESTIGATION OF PLUTONIUM CONTAMINATION. (a) Investigation.--The Comptroller General of the United States shall conduct a full investigation into the contamination of stocks of depleted uranium munitions with transuranic elements, including plutonium, neptunium, americium, and other forms of uranium. The investigation shall include-- (1) determination of when such contamination occurred; (2) identification of the manufacturing or refining facilities at which such contamination occurred; (3) identification of the quantity, by volume and percentage, of the material by which such contamination occurred; (4) identification of when such contamination was first realized by Department of Defense personnel and when such contamination was brought to the attention of senior Department of Defense management; (5) identification of persons responsible for monitoring the quality of such production; (6) identification of the time when notification of such contamination was made to NATO-member nations; and (7) determination of whether any law or treaty was broken by any such contamination or by any failure to provide timely notice of such contamination to any affected party. (b) Report.--Upon completion of the investigation under subsection (a), the Comptroller General shall submit to the committeed specified in section 4(b)(2) a report on the investigation. SEC. 7. STUDY OF HEALTH EFFECTS OF DEPLETED URANIUM. (a) Study.--The Director of the Agency for Toxic Substances and Disease Registry and the Director of the Center for Disease Control and Prevention shall jointly conduct a comprehensive study of the health effects of exposure to depleted uranium munitions on uranium-exposed veterans and on their children who were born after their respective exposures to uranium. (b) Uranium-Exposed Veterans.--For purposes of this section, the term ``uranium-exposed veteran'' means a member or former member of the Armed Forces who while on active duty handled, came in contact with, or had the likelihood of contact with depleted uranium munitions, including members and former members who while on active duty-- (1) were exposed to smoke from fires resulting from the burning of vehicles uploaded with depleted uranium munitions or fires at depots at which depleted uranium was stored; (2) worked within environments containing depleted uranium dust or residues from depleted uranium fires; (3) were within a structure or vehicle while it was struck by a depleted uranium munition; (4) climbed on or entered equipment or structures struck by depleted uranium; or (5) were medical personnel who provided near-term treatment to members of the Armed Forces described in paragraph (1), (2), (3), or (4). (c) Public Health Assessment.--The Director of the Agency for Toxic Substances and Disease Registry shall conduct a public health assessment of persons who are thought to have an epidemiological link to any United States military installation or facility at which depleted uranium munitions have been or currently are used or any production facility at which depleted uranium or depleted uranium munitions are currently, or have been, produced. (d) Report.--The Directors shall submit to Congress a report on the results of the study under subsection (a) and the assessment under subsection (c). The report shall be submitted not later than two years after the date of the enactment of this Act and shall include the findings of the Directors on the matters covered by the report. The Directors shall include in the report a list of diseases or conditions that are found to exist within the populations specified in subsection (a) and their rate of occurrence compared to the general population. SEC. 8. EPA STUDIES OF ENVIRONMENTAL CONTAMINATION BY DEPLETED URANIUM. (a) List of Locations in United States.--Not later than 180 days after the date of the enactment of this Act, the Secretary of Defense shall provide to the Administrator of the Environmental Protection Agency a list of all sites in the United States where depleted uranium munitions have been used or produced and a site-specific map of each such site. (b) EPA Studies.--After receipt of the list and maps under subsection (a), the Administrator shall, for each site specified on the list, conduct a comprehensive environmental study of the possible contamination of the soil, air, water, and vegetation by depleted uranium at that site. (c) Report.--Not later than two years after the date of the enactment of this Act, the Administrator of the Environmental Protection Agency shall submit to the Secretary of Defense and the Committee on Armed Services and the Committee on Government Reform of the House of Representatives and the Committee on Armed Services and the Committee on Governmental Affairs of the Senate a report-- (1) describing the extent of contamination by depleted uranium at each site studied by the Administrator pursuant to subsection (b); (2) providing site-specific recommendations for the mitigation and cleanup of each such site; and (3) providing general recommendations regarding the cleanup of sites where depleted uranium has been used on foreign lands. SEC. 9. ENVIRONMENTAL MITIGATION AND CLEANUP REQUIREMENTS. (a) Department of Defense Cleanup Plan.--Not later than one year after receiving the report under section 8(c), the Secretary of Defense shall develop a plan for mitigation and cleanup at each site and a prioritized list for such cleanups. The Secretary shall submit a copy of the plan to the Committee on Armed Services and the Committee on Government Reform of the House of Representatives and the Committee on Armed Services and the Committee on Governmental Affairs of the Senate. (b) Report.--The Secretary shall submit a report to those committees and the Administrator of the Environmental Protection Agency each year before commencement of the mitigations and cleanups until those projects are complete. (c) Cleanup.--After filing of such plans, the Secretary shall commence, or contract for, the mitigation and cleanup of each site for which the Administrator of the Environmental Protection Agency has recommended such mitigation and cleanup and in the manner and scope that the Administrator's report specifies. (d) Applicability of NEPA.--Notwithstanding any other provision of law, the cleanup and mitigation required by subsection (c) shall be carried out in a manner consistent with the provisions of the National Environmental Policy Act of 1969, without regard to any exemption to any of the provisions of that Act for the Department of Defense or any element thereof.

Depleted Uranium Munitions Suspension and Study Act of 2001 - Directs the Secretary of Defense and other Federal entities to suspend the use and approval for foreign sale or export of depleted uranium munitions until the Secretary of Health and Human Services certifies to specified congressional committees that studies indicate such munitions will not jeopardize the health of U.S. or NATO military personnel or civilian populations if used in future conflicts.Limits subsequent use, foreign sale, or export to stocks certifiably free of plutonium and other transuranic matter.Directs the Comptroller General to investigate the contamination of stocks of depleted uranium munitions with transuranic elements.Requires the Directors of the Agency for Toxic Substances and Disease Registry and the Center for Disease Control and Prevention to jointly and comprehensively study the health effects of exposure to such weapons on veterans and their children, as well as a public health assessment of persons with an epidemiological link to military installations or production facilities where such munitions have been used or produced. Directs the Administrator of the Environmental Protection Agency to conduct a comprehensive study of possible environmental contamination at these installations or facilities. Requires the Secretary of Defense to: (1) furnish to the Administrator with a list of sites; and (2) develop a plan for their mitigation and cleanup (consistent with the National Environmental Policy Act of 1969).

cloud computing is a disruptive technology that has already changed the way many people live and conduct business . clearly , individuals , organizations , and businesses in developing countries are also adopting services such as reliable data storage , webmail , or online social networks . however , according to a report by the united nations conference on trade and development ( unctad ) , the rate at which this adoption takes place is much slower @xcite . in western countries the increasing demand by users is met by creating ever - larger data centers and upgrading and extending high - speed communication networks . in developing countries the picture looks different . the unctad report goes on saying that missing infrastructure is a major obstacle for the uptake of cloud computing in these regions @xcite : _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ [ ] whereas there were in 2011 more than 1000 secure data servers per million inhabitants in high - income economies , there was only one such server per million in [ the least developed countries ( lcds ) ] . _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ we argue that trying to copy the infrastructure of western countries is neither feasible nor meets the requirements of developing countries , since setting up and maintaining a number of large data centers can easily cost hundreds of millions of dollars . just using the infrastructure provided by the large multinational corporations that create such data centers is also not an ideal situation . handing over data to foreign entities raises all kinds of issues ranging from privacy and data protection ( the local laws and regulations may not match those of the hosting country ) to national security and industrial espionage . additionally , due to network outages it may be difficult to establish reliable access to these remote servers , which is an even more acute problem for rural areas . then moving to the cloud to gain a reliable storage solution would be negated by not being able to access it at all times . consequently , we advocate the use of small , distributed data centers that can be adapted to the local needs in a bottom - up , community - based fashion . these can serve as hubs and relays for ( large - scale ) remote cloud services or as facilities for local community services . pushing some of the data storage and computation to the client side is known as a _ architecture @xcite , and is done to improve the availability and durability of stored data , as well as to lower network latencies in mobile devices . figure [ fig : cloudlet ] shows a typical cloudlet architecture : the clients are not directly connected to the cloud but via cloudlet servers . it is important that the design of cloudlet data centers considers the specific requirements of developing countries . first of all , it has to use low - cost components that are readily available . second , low power consumption is a crucial criterion . due to unreliabilities in the provision of electricity , the data center may have to be run on solar power or batteries for considerable stretches of time . third , we need a robust and sustainable system than can be operated in a harsh environment ( in terms of temperatures and weather ) . finally , the data center should be based on open platforms and standards and avoid proprietary technology as much as possible . this will make it easier to deploy , maintain , and repair the hardware . additionally , an open system allows users to adapt , extend , and scale it to their particular needs . interestingly enough , even a big player like facebook is advocating the use of open hardware in their open compute project initiative @xcite . here we illustrate how single - board computers , such as the raspberry pi ( rpi ) , can serve as building blocks for computing platforms that meet the requirements described above . originally developed to spark the interest of school children in computer science , it has also been discovered by hobbyists worldwide , who use it for a wide range of projects . we have been building raspberry pi clusters and experimenting with them for more than two years now . a while ago we have started using them for teaching and training purposes and even as a testbed for research . we believe that this technology has a lot of potential and can make an impact on the lives of many more people by serving as a low - cost data storage and computing platform . the remainder of the paper is structured as follows . we discuss related work in the next section and then describe our hardware design in section [ sec : hardware ] , followed by a brief discussion of software aspects in section [ sec : software ] . section [ sec : discussion ] highlights and explains some of our design decisions in more detail and also sketches use cases and application domains . finally , in section [ sec : concl ] we conclude with a brief summary . there are many studies investigating the adoption of cloud computing , for some overview and survey papers , see @xcite . however , most of these studies highlight the topic from the point of view of well - developed countries . while some inhibitors , such as security and privacy concerns , hold universally @xcite , others are predominantly found in developing countries and play almost no role in western countries @xcite . predominant among these are unstable power grids and inadequate internet connectivity , translating into more or less frequent outages . this calls for a different approach to cloud computing : before cloud services can take off , a reliable infrastructure has to be put in place . there are numerous publications on connectivity , communications networks , and bandwidth , see @xcite for a few examples . while the networking aspect is very important , the storage and computational aspects should not be neglected ; especially since getting the infrastructure for widespread broadband connectivity into place will still take considerable time . consequently , there is a need for local data centers that can bridge the communication gaps . tesgera et al . propose a cloudlet - based approach to tackle network issues in emerging regions , but do so very briefly on a very abstract level , identifying research challenges , but not proposing any implementation @xcite . we agree with hosman and baikie @xcite that the western `` bigger is better '' approach for building large - scale data centers is bound to fail in developing countries , due to the particular constraints . furthermore , in a study hosman identifies the main challenges faced by hardware deployers in these regions @xcite : energy consumption , cost , environment - related issues , connectivity , and maintenance and support . these are all crucial aspects we cover by relying on inexpensive , low - power , rugged platforms , such as micro - computers , to build micro - data centers . there are various groups already working on developing raspberry pi clusters and similar architectures @xcite , the challenge is to adapt these designs to the conditions found in developing countries . in the following we give an overview of the hardware employed in our design : in particular the casing , network architecture , electronic components , power supply , and cooling . at the core of our design are modular wooden stackable boxes of size 40 x 40 x 25 cm ( shown in figure [ fig : box ] ) , offering several advantages . the boxes can be assembled and disassembled with a simple screw driver and for transport the individual parts can even be stored in ( hand ) luggage . once set up , the contents of a box can be accessed without the need for any tools . the front plate is fixed with wing screws , which can be opened with bare hands . the boxes also feature handles , which allows their transport in assembled state . additionally , the electronic components are not soldered to the casing , but fixed on shelves with screws . consequently , the devices inside of a box can be easily accessed , repaired , substituted , maintained , and updated , even by a person with minimal technical skill . for the casing we have chosen wood , because it is an environmentally friendly material that can be found around the world . however , this can be replaced with material that is readily available locally . the default network architecture consists of two subclusters connected via two switches , which in turn can be connected to an external network . figure [ fig : network ] shows a schematic diagram of the architecture . ( we use 8-port switches with two additional uplink ports ; poe stands for power over ethernet and will be discussed later ) . a subcluster , which fits into one box , comprises two control and five data storage / computational raspberry pis , to which solid state disks are connected . by running two subclusters each containing multiple rpis , we avoid a single point of failure , in case of a breakdown the data center can be kept up and running , albeit at reduced performance . this design is also scalable : we do not need to connect both switches to the external network , one of them can also be connected to one or more other subclusters . in our current design we use the new raspberry pi 2 , model b , with a 900 mhz quad - core armv7 cpu and 1gbyte ram , as it exhibits a higher performance than its predecessor , the raspberry pi b+ . however , it has a slightly higher power consumption than the b+ model , even in single - core mode . thus , if power consumption is a crucial issue , the pi 2 can be swapped for the pi b+ . in terms of costs , the difference between the two models is about $ 10 , the raspberry pi 2 currently sells for around $ 35 , the b+ model for $ 25 . in fact , we are not restricted to raspberry pi boards , other single - board computers , such as banana pi , odroid or any other device with a cpu of the arm family would also work . with some tinkering it would even be possible to make use of old smart phones . using the power over ethernet ( poe ) technology simplifies the assembly , as we do not need separate sets of cables for communication and power supply . additionally , it eliminates the need for separate power supply sockets for the raspberry pis , although a poe adapter is necessary on the rpi side . the main advantage , though , is the provision of smart power management and monitoring techniques integrated into the system . for example , when using the hp 2530 - 8-poe+ switch , poe operation can be disabled and enabled ( at different levels of priority ) for each individual port . clearly , this configuration has a price tag attached to it : a solution relying on poe will add to the costs of the system . we can make a marginal saving by connecting the two controller rpis of a subcluster via a single poe adapter for supplying them with power . the power supply , which requires a separate box , comprises four 12v lithium or lead - acid batteries configured in series with a total capacity of 200 ah . the batteries , whose task it is to provide a constant source of energy , can be charged via solar panels or any other source of electricity that is available . the lead batteries have the advantage of being cheaper than the lithium ones . however , the lithium batteries are much better suited to higher temperatures and will degrade much more slowly under these conditions . the lead batteries should not be ruled out completely , though . in a high - altitude environment , such as the andes or the himalayas , we may run into problems with lithium batteries and low temperatures , as they can not be charged at temperatures below freezing . thus , lead batteries would be a better choice for these regions . the power management is controlled by a power inverter and battery charging regulator . in our prototype , a 220v ac 300w sine wave power inverter ( studer aj-400 - 48 ) and a lithium battery charger is used . when using lead batteries , we can replace this with the aj-400 - 48-s model , which also integrates a 10a 48v dc lead - acid battery charging regulator . the ac output socket from the power inverter can be extended by a three - way power strip to supply a laptop or other external diagnosis tool . an important design decision is to use only passive cooling techniques , so that we do not incur any additional power consumption and that there are no moving parts that can break down . we created a set of holes on two opposite sides of the casing to make use of the stack effect for cooling . one set of holes is found in the upper part of one side , while the opposite set is located in the lower part . the warm air flows out through the upper set , drawing in cooler outside air through the lower set . for protection , the holes can be covered with anti - insect and anti - dust nets . depending on the placement of the boxes , additional cooling mechanisms can be put into place , such as solar chimneys , windcatchers , or making use of the cooler temperature underground by installing additional heat sinks . in our group we developed tools to set up and maintain the operating system installed on the individual nodes of the data center . we do this in an efficient and automated manner with scripts that install a minimal version of debian or archlinuxarm on a node , register a node in the cluster , and then update the node to fully integrate it into the cluster . we can also monitor the activity of each node by installing our monitoring panel . this covers the basic infrastructure , but is not enough yet . a cluster in which software is deployed in a bare - metal fashion on individual nodes is not attractive for potential users , some form of middleware is needed . however , most off - the - shelf solutions , such as openstack or similar frameworks , are usually too heavyweight for raspberry pi clusters . the storage manager component of openstack , swift , is relatively lightweight compared to other components , such as nova ( computing ) and neutron ( networking ) . we have successfully deployed it on a raspberry pi cluster , making the cluster usable as a data storage platform with data replication , meaning that we do not lose data in case of ( partial ) hardware failure . currently , we are working on extending this solution to other aspects of cloud computing . in the following we provide more details and motivate some of the particular design decisions we made . we also discuss application domains of our server architecture . while we were designing our data center we realized that it would be crucial to already anticipate some of the future requirements or changes that users would make to the system to adapt it to their needs . that is the reason why we went for a flexible design around the core of wooden boxes housing the electronic devices . depending on the specific requirements in terms of power consumption , redundancy , and computational power , a suitable number of boxes containing electronics and power supplies can be selected and stacked on top of each other . in a test run , we measured the power consumption of one box , i.e. one subcluster with seven raspberry pis , a switch , and five ssds . generating a stress test under archlinux with two cpu processes , one io load , and one ram load with 128 mb malloc as a benchmark , one subcluster consumed 48w running the benchmark . we specified the capacity of the batteries assuming a load that continuously consumes 96w ( for the two subclusters ) . the goal was to keep the discharge rate at 50% for a duration of twelve hours . regularly discharging down to low levels has a detrimental effect on the life of the batteries . a duration of twelve hours was chosen to be able to run the data center over night , during which there is no sunlight for solar panels . nevertheless , the capacity of the batteries can be adapted to the local circumstances . our goal is not to compete with the high - tech environment usually found in large cities and metropolitan areas , but to provide an alternative for more rural areas . the proposed approach allows users to set up local servers which can be used as components of a private or community cloud network . this is especially important when it comes to handling sensitive data in domains such as health care and governance , as it gives full ownership of the data and services to the persons running the data center . other important use cases are education and research . as we have experienced with our own students , it is an ideal platform for teaching practical skills in the area of distributed systems . the acquired knowledge ranges from hardware all the way to protocols synchronizing nodes in a network . due to its mobility it can also be used to set up field labs for processing data , which , for example , is generated by sensor networks monitoring the environment . beyond these applications , the platform may even help in sparking entrepreneurial activity , as the initial investment is not large and the system can be scaled out when and if the need arises . moreover , upgrading the system with more efficient boards as they become available can be done gradually , i.e. , this does not have to be done in one go , making it possible to achieve the upgrade with a number of smaller investments rather than one big one . even though cloud computing and similar services are also expanding in developing countries , they are still far from being widely spread . while there are also discussions about factors inhibiting the adoption of cloud computing in western countries , there are factors which are unique to the developing world , so trying to apply the western approach to cloud computing is very likely bound to fail . two crucial factors , which were also identified in a report by the world economic forum @xcite , are the lack of both infrastructure and a skilled workforce . we believe that our micro - data center architecture can start filling these gaps by providing an open , inexpensive , adaptable , and extendible platform with a low power consumption , empowering communities to take matters into their own hands . due to these features , it can also be rolled out in schools and universities to teach and grow the next generation of engineers and computer scientists . we hope that in the near future the digital divide will not widen , as it is currently doing in the area of cloud computing , but become narrower . however , we believe that in order for this to happen , it is not sufficient for developing countries to just import information technology . ultimately , a lot of the needed infrastructure should be developed and produced in the countries themselves . in that light , we see our cluster as a starting point for many more creative and innovative solutions .

instead of relying on huge and expensive data centers for rolling out cloud - based services to rural and remote areas , we propose a hardware platform based on small single - board computers . the role of these micro - data centers is twofold . on the one hand , they act as intermediaries between cloud services and clients , improving availability in the case of network or power outages . on the other hand , they run community - based services on local infrastructure . we illustrate how to build such a system without incurring high costs , high power consumption , or single points of failure . additionally , we opt for a system that is extendable and scalable as well as easy to deploy , relying on an open design .

the z(2 ) symmetric quantum field theory of a single scalar field with @xmath0 interaction is the number one textbook prototype model for all kinds of field theoretic methods . at the same time , with its possibility of spontaneous symmetry breaking , it may be viewed as the crudest caricature of the higgs sector of the standard model . in this context the strongly conjectured triviality of the model in four space time dimensions is of physical interest as it leads to upper bounds on the higgs mass . this is so because triviality means that the cutoff can not be removed from the regularized theory without ending in a free gaussian theory . the model is then interpreted as an effective theory in which an upper limit on tolerable unphysical cutoff effects implies an upper bound on the interaction strength which in turn is responsible for mass generation by the higgs field . unfortunately in the four dimensional case , we still have to rely on numerical methods to demonstrate triviality beyond the perturbative regime . such studies in the lattice regularization have been strongly boosted by a series of papers by lscher and weisz ( lw ) , of which the first two have dealt with the one component model in the symmetric @xcite and in the broken @xcite phase . here control over the lattice theory was gained by combining large orders in the hopping parameter expansion with careful perturbative renormalization group evolution.@xcite these studies were in addition corroborated by some early monte carlo simulations as for example @xcite , @xcite . in these cases the ising model was considered as the limit of @xmath0 theory at infinite bare coupling . barring a complicated non - monotonic relation between bare and ( natural ) renormalized couplings on the lattice , this limit is the most interesting case for questions concerning triviality . in recent years one of the authors has taken up the subject again after some progress had been made in monte carlo methods which allow to achieve a new level of precision in this context with only moderate investments in compute power . the main new ingredients are on the one hand the use of so - called worm algorithms @xcite , @xcite to simulate arbitrary order contributions of a hopping parameter expansion for observables on finite lattices instead of generating field configurations . the second ingredient is the use of finite volume renormalization schemes as in @xcite . as triviality is an ultraviolet renormalization effect , more compute power can be devoted in this way to closely approaching the continuum limit as the thermodynamic limit does not have to be taken . in other words , the manageable ratios @xmath1 between lattice size and spacing is used to achieve a significant range of small @xmath2 and not for large @xmath3 in physical units . in @xcite , @xcite , @xcite such a strategy has been explored for the symmetric phase of the model . in this publication we now offer a finite size scaling study on the other side of the critical line . in section 2 . we define our renormalization scheme , followed by basic definitions of @xmath0 theory . in section 4 . the numerical method and achieved results are described followed by a brief summary . this work is based on the master thesis of the first author at humboldt university , berlin 2013 . at first glance the title of this subsection might look paradoxical as there is no symmetry breaking in a finite volume . if we define however an order parameter @xmath4 by the large distance behavior of the z(2 ) symmetric fundamental two point correlation ( @xmath5 is the correlation length ) , @xmath6 then this definition has a smooth thermodynamic limit . to define definite renormalization conditions we employ the fourier transform @xmath7 and extract @xmath8 from @xmath9 where we have assumed a torus of extent @xmath3 in each direction and @xmath10 is the varying part of the correlation ( ` connected ' , although we here avoid the one - point function ) . we now complete our renormalization scheme by singling out two small torus momenta @xmath11 beside zero momentum . we match @xmath12 to the form @xmath13 which simultaneously fixes the wave function renormalization factor @xmath14 , a renormalized expectation value @xmath15 and the renormalized mass @xmath16 . by solving these conditions we obtain @xmath17 and @xmath18 where we have introduced the dimensionless finite size scaling quantities @xmath19 and @xmath20 and the usual lattice momentum @xmath21 it is not difficult to see that in the thermodynamic limit @xmath22 our definitions of @xmath16 and @xmath15 approach those of @xmath23 and @xmath24 in @xcite . apart from this limit however , each fixed value of @xmath19 defines a different renormalization scheme and the perturbative coefficients of the continuum perturbative callan symanzik @xmath25 function , for instance , will depend on @xmath19 beyond the scheme independent one and two loop terms . as usual in the spontaneously broken theory we define the renormalized coupling constant in terms of @xmath15 by setting @xmath26 the action in the lattice form is given by @xmath27 - 2 \kappa \sum_{x \mu } \varphi \left ( x \right ) \varphi \left ( x + \hat{\mu } \right)\ ] ] with all dimensionless quantities . this is equivalent to the field theoretic form @xmath28 with mass dimension one field corresponds to @xmath29 in the lw papers . ] @xmath30 if we match @xmath31 classically , the symmetric phase arises for @xmath32 where @xmath33 fluctuate around zero with a bare mass given by @xmath34 for @xmath35 the field fluctuates around one of two equivalent nonzero values @xmath36 . the quadratic fluctuations around either constant field are now controlled by the bare mass @xmath37 note that in lw @xmath38 does not appear , as in @xcite it is replaced by @xmath39 while in @xcite the action in terms of @xmath30 is not written and only the @xmath39 for the broken phase appears . consequently the relations between @xmath39 and @xmath40 differ in the two papers as emphasized in a footnote in @xcite . following lw we explore the plane of bare parameters by approaching the critical line ( continuum limit ) on trajectories at fixed @xmath41 and define the @xmath25-function @xmath42 this definition entails the following tree level lattice artefact contributions @xmath43 and ( @xmath44 ) @xmath45 although these artefacts are small they may be avoided by switching to modified couplings @xmath46 the perturbative continuum @xmath25 function for the coupling @xmath47 of the previous subsection and also @xmath48 formed from it is given by @xmath49 while the first two coefficients are scheme independent , the three loop term @xmath50 is at the moment not known for our present scheme at finite @xmath19 . the infinite volume case is found in @xcite , @xmath51 the renormalization scheme of section [ scheme ] is defined entirely in terms of the two point correlation . worm simulations are ideally suited for its numerical computation in the ising limit @xmath52 . the worm ensemble is given by the partition function @xmath53 . \label{zens}\ ] ] in this formula we sum over link variables @xmath54 and @xmath55 $ ] enforces the constraint that is most easily described in words : each site except @xmath56 must be surrounded by an even number of @xmath57 links while at @xmath56 ( unless @xmath58 ) this number must be odd . the fugacity is @xmath59 . the @xmath60 configurations are in one - to - one correspondence with strong coupling graphs with lines drawn on links with @xmath61 . at the same time we have the connection with the spin formulation @xmath62 where for the ising limit the sum is over @xmath63 and @xmath64 is a normalization factor . in @xcite a lot more details about this reformulation and the efficient simulation of ( [ zens ] ) can be found . it is obvious now that the two point function is given by @xmath65 with the double angles referring to expectation values with respect to ( [ zens ] ) . the required fourier transforms can be directly accumulated from @xmath66 for the last step we have used the invariance under individual reflections along each direction . note that with the small momenta of interest we do not expect very rapid oscillations . as only ratios of @xmath67 , where the wave function renormalization cancels , are of interest , the denominator @xmath68 ( inverse susceptibility ) is never really needed here . at first we have explored how @xmath19 depends on the hopping parameter for lattice sizes @xmath69 . the results are shown in fig.[zkappa ] . we are here just above the infinite volume critical point which is known @xcite to occur close to @xmath70 . each data point in the plot corresponds to @xmath71 iterations , where an iteration @xcite consists of one worm move per site . from these results we have decided to adopt in the following the target value @xmath72 for our study . our results are summarized in table [ tabg ] . .simulation results to determine the renormalized coupling in the continuum limit ( growing @xmath1 ) for fixed @xmath72.[tabg ] [ cols="<,<,<,<,<",options="header " , ] each line corresponds to a statistics of @xmath73 iterations . by some tuning we found values of @xmath74 that lead to @xmath72 within errors . the directly measured couplings ( [ gdef ] ) are given in the fourth column while the rightmost column differs by two tiny corrections . by the first order reweighting technique described in @xcite the value is adjusted to @xmath72 exactly and then the cutoff correction ( [ gtildedef ] ) is applied . the first correction is clearly only a change within the error bars , but , although to a much lesser degree than in @xcite , it in addition lowers the statistical error slightly . these data are plotted in fig.[figg ] . the dotted ( blue ) , dashed ( red ) and solid ( black ) curves derive from integrating the callan symanzik equation @xmath75 with the continuum @xmath25-function at 1,2,3 loop perturbative precision . beside the universal coefficients ( [ betaf ] ) we here use the infinite volume value ( [ beta2 ] ) for the three loop coefficient . as discussed before this is only indicative with the presently unknown coefficient for @xmath72 certainly being slightly different . the experience in the symmetric phase has been , however , that at this size the difference may not be very sizeable . we have defined a finite size renormalization scheme for @xmath0 theory , which in the infinite volume limit goes over into the one that is standard in the broken phase of the model . in the ising limit of infinite bare coupling , we have numerically generated values of the renormalized coupling as a function of the lattice cutoff . using novel simulation techniques we computed precise values which turn out to closely follow the perturbative renormalization group . the data points are nicely sandwiched between the one and two loop trajectories . the three loop curve falls in between and is only about two sigma ( 2 % ) away from our data , although the three loop coefficient is taken for @xmath76 rather than @xmath72 studied here . if we conclude agreement with perturbation theory in the range studied then this should be even better justified for larger @xmath1 and @xmath48 tends to zero in the continuum limit at a logarithmic rate . this supports the triviality scenario once more by combining numerical and perturbative methods . we would like to thank tomasz korzec and peter weisz for very helpful discussions and comments on the manuscript . 10 u. m. heller , m. klomfass , h. neuberger , and p. m. vranas , _ regularization dependence of the higgs mass triviality bound _ , _ nucl.phys.proc.suppl . _ * 30 * ( 1993 ) 685 , [ http://xxx.lanl.gov/abs/hep-lat/9210026 [ ] ] .

we study the standard one - component @xmath0-theory in four dimensions . a renormalized coupling is defined in a finite size renormalization scheme which becomes the standard scheme of the broken phase for large volumes . numerical simulations are reported using the worm algorithm in the limit of infinite bare coupling . the cutoff dependence of the renormalized coupling closely follows the perturbative callan symanzik equation and the triviality scenario is hence further supported . hu - ep-14/08 sfb / ccp-14 - 18

SECTION 1. DEPARTMENT OF DEFENSE PAYMENT FOR CONTINUATION OF NON- TRICARE HEALTH BENEFITS COVERAGE FOR CERTAIN MOBILIZED RESERVES. (a) Payment of Premiums.-- (1) Requirement to pay premiums.--Chapter 55 of title 10, United States Code, is amended by inserting after section 1078a the following new section: ``Sec. 1078b. 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Upon such a revocation, the member's dependents shall become eligible for TRICARE as provided for under this chapter. ``(j) Regulations.--The Secretary of Defense shall prescribe regulations for carrying out this section. The regulations shall include such requirements for making an election of payment of applicable premiums as the Secretary considers appropriate.''. (2) Clerical amendment.--The table of sections at the beginning of such chapter is amended by inserting after the item relating to section 1078a the following new item: ``1078b. Continuation of non-TRICARE health benefits plan coverage for certain Reserves called or ordered to active duty and their dependents.''. (b) Applicability.--Section 1078b of title 10, United States Code (as added by subsection (a)), shall apply with respect to calls or orders of members of reserve components of the Armed Forces to active duty as described in subsection (b) of such section, that are issued by the Secretary of a military department on or after the date of the enactment of this Act.

Directs the Secretary of the military department concerned to pay the applicable premium to continue in force during the duty period any qualified health benefits plan coverage of a member of the reserves who is called or ordered to active duty for more than 30 days during a war or national emergency. Prohibits the private health insurance issuer of such a member from declining coverage or re-enrollment, imposing re-enrollment exclusions, or increasing premiums during such benefits coverage continuation period.

Any mention of an Iranian nuclear weapon is taboo in the Islamic Republic, which insists that its nuclear programme is entirely for peaceful, civil purposes. So it is remarkable, to say the least, that an article has appeared on the Gerdab website, run by Iran's Revolutionary Guards, anticipating the day after Iran's first test of a nuclear warhead. Here is a translation of the text: The day after Iran's first nuclear test is a normal day. The day after Islamic Republic of Iran's first nuclear test will be an ordinary day for us Iranians but in the eyes of some of us there will be a new sparkle. It's a good day. It's seven in the morning. The sun is not fully up yet but everywhere is bright. In the northern hemisphere many countries are beginning the day... The day before, probably in central deserts of Iran, where once Americans and some other Western countries wanted to bury their nuclear waste, an underground nuclear explosion has taken place. The strength of the explosion was not so great as to cause severe damage to the region nor so weak that Iranian scientists face any problems in running their tests. Today is a normal day like any other. Like 90% of the year, there is news about Iran, and these are the headlines which can be seen on foreign news sites: Reuters: Iran detonated its nuclear bomb CNN: Iran detonated nuclear bomb Al-Jazeera: The second Islamic nuclear bomb was tested Al-Arabia: The Shia nuclear bomb was tested Yahoo! News: Nuclear explosion in Iran Jerusalem Post: Mullahs obtained nuclear weapon Washington Post: Nuclear explosion in Iran, Shock and despair in Tel Aviv Meanwhile, the domestic media will offer many congratulations to the Hidden Imam and the Supreme Leader: Keyhan: Iran's first nuclear bomb was tested Jomhoori-e-eslami: Iran successfully carried out a nuclear test Iran: By order of the president, Iran's 100% homemade nuclear bomb was tested Ettela'at: Iran's much anticipated nuclear bomb exploded This strange, hypothetical, article, which first appeared on April 24, hammers home again and again the message that an Iranian nuclear test will not lead to disaster. On the contrary, life will go as before except that Iranians will feel better about themselves. The news commotion will not knock life in Iran off balance. Civil servants will punch in at work on time as always, while some will be late as always. ...The day after the Islamic Republic of Iran's first nuclear test will be an ordinary day for us Iranians but in the eyes of some of us there will be a new sparkle. A sparkle of national pride and strength. This has the look of a kite being flown, but for whom? It could be intended to get Iranians used to the idea of a nuclear test, and less fearful of international reaction. It could be a gesture of defiance to the world by hardline elements - according to independent experts, Gerdab is run by the Revolutionary Guards' cyber defence command, which is presumably still smarting from the Stuxnet attack. Opposition websites describe it as an enforcement tool for the regime, identifying and threatening independent bloggers inside Iran. The article comes during a period when Tehran's official stance is particularly defiant and assertive, announcing today that it will triple its production of 20% enriched uranium and shift it to the underground Fordow site, near Qom. Meir Javedanfar, an Iranian-Israeli expert on the Tehran regime currently lecturing in Colombia, described the Gerdab article as "unbelievable". ||||| An article praising the idea of Iran testing a nuclear bomb on a Revolutionary Guard website is raising alarms in western intelligence circles, which interpret it as evidence of strong backing in the Islamic Republic for such a move. Iranian President Mahmoud Ahmadinejad waves to the media, as he arrives for his press conference, in Tehran, Iran, Tuesday, June 7, 2011. Ahmadinejad says the U.N. nuclear watchdog agency chief has discredited... (Associated Press) Iranian President Mahmoud Ahmadinejad speaks with media, during his press conference in Tehran, Iran, Tuesday, June 7, 2011. Ahmadinejad says the U.N. nuclear watchdog agency chief has discredited the... (Associated Press) Entitled "The Day After the First Iranian Nuclear Test _ a Normal Day," the article coincides with other public or suspected activities that the United States and its allies see as indications that Tehran wants to possess atomic arms. "The day after the first Iranian nuclear test for us Iranians will be an ordinary day, but in the eyes of many of us, it will have a new shine, from the power and dignity of the nation," says the article published on the Gerdab site run by the Revolutionary Guard. A translation that was vetted by The Associated Press was provided by a Western official who asked for anonymity because of the nature of his information. Iran denies nuclear weapons intentions _ while moving consistently closer to such a capacity. An International Atomic Energy Agency report last month listed "high-voltage firing and instrumentation for explosives testing over long distances and possibly underground" as one of seven "areas of concern" that Iran may be conducting clandestine nuclear weapons work. Adding to concerns Wednesday, the country's nuclear chief announced that his country will soon install more advanced equipment at a fortified underground site to allow it to enrich uranium faster and to higher levels. Iran says it wants to enrich only to power a future network of reactors. But over the past two years it has started to enrich uranium to a level higher than what is needed for nuclear fuel and closer to the grade used to make the fissile core of nuclear warheads. On Wednesday, Vice President and nuclear head Fereidoun Abbasi announced Iran would increase its capacity to enrich to that higher level _ near 20 percent _ by installing more efficient centrifuges and would triple the output of the higher grade material. The move comes despite four rounds of U.N. Security Council sanctions over Tehran's refusal to halt enrichment. Abbasi said that the new generation centrifuges would be set up at the Fordo site near the holy city of Qom in central Iran. Built next to a military complex to protect it in case of an attack, Fordo was long kept secret and was only acknowledged by Iran shortly before Western intelligence agencies went public with it in September 2009. The area is heavily protected by the powerful Revolutionary Guard. Low-enriched uranium _ at around 3.5 percent _ can be used to fuel a reactor to generate electricity. But if uranium is further enriched to around 90 percent purity, it can be used to develop a nuclear warhead _ and enriching to 90 percent can be done much more quickly from near 20 percent than from low-enriched material. Iran has been producing low-enriched uranium for years and began higher enrichment in February 2010, asserting it needs the higher grade material to produce fuel for a Tehran reactor that makes medical radioisotopes needed for cancer patients. David Albright, whose Institute for Science and International Security tracks suspected proliferators, said it was unrealistic for Tehran to accelerate production of 20-percent uranium to the degree stated by Abbasi for that one research reactor. "It doesn't make any sense for civil research purposes," he said. "They are not going to build for or five research reactors." The article on the website _ along with Wednesday's announcement on enrichment and the IAEA suspicions about secret experiments _ strengthens concerns that "they are moving toward nuclear weapons," he said. The article ends with an Arabic quote from the Quaran: "And prepare against them whatever you are able of power and of steeds of war by which you may terrify the enemy of Allah and your enemy." The official said that the article was first posted in April. The Farsi version was still on the website late Wednesday. Albright speculated that its publication reflected that at least some powerful Revolutionary Guard factions supported such a test, even if the article did not express the position of the Iranian leadership as a whole. "This could be reflecting an internal debate," he said. ___ George Jahn is at http://twitter.com/georgejahn ___ Associated Press writer Ali Akbar Dareini contributed from Tehran.

– “The day after Iran’s first nuclear test is a normal day.” So begins a strange article posted on the Iranian Revolutionary Guards’ Gerdab website that has set off alarms in the West. Originally posted in April, the hypothetical article waxes poetic about how great it will be when Iran successfully tests a nuclear weapon. “In the eyes of some of us there will be a new sparkle. A sparkle of national pride and strength,” it promises, according to the Guardian’s translation. The post is startling because Iran is usually careful to toe the official line that its nuclear activities are purely peaceful. “I have never seen anything like this report. It’s breaking a major taboo,” says one Iranian-Israeli expert from Colombia University. Iran also raised some eyebrows yesterday when it announced that it would be installing more advanced equipment in one fortified underground nuclear site to speed up its enrichment activities, the AP reports.

the dynamics of magnetic flux propagation in a long josephson junction ( ljj ) has been and continues to be a subject of strong theoretical and practical interest during the last three decades @xcite . the magnetic flux quantum in a ljj is a soliton ( also known as _ fluxon _ ) governed by the well - known sine - gordon ( sg ) equation . the convenient way to prepare a junction with the required properties is to install various inhomogeneities into it . up to now the substantial theoretical work has been devoted to the study of the fluxon motion in the one - dimensional ( 1d ) ljjs with point - like @xcite and spatially extended @xcite inhomogeneities . experimental results on the fluxon scattering on impurities are reported in @xcite spatially inhomogeneous josephson systems with trapped fluxons have been discussed as prospective applications , such as fluxon - based information devices @xcite . real ljjs are always two - dimensional ( 2d ) , or , more precisely , quasi - one - dimensional ( q1d ) , in the sense that they have a finite width in the direction perpendicular to the direction of fluxon propagation . up to now the fluxon dynamics in q1d junctions has been scarcely investigated as compared to the pure 1d case . most of attention has been focused on the various isotropic 2d structures like oscillons and ring kinks @xcite . it is worth mentioning also the case of window junctions @xcite , which can be called inverse in some sense : it studies point or rectangular junctions embedded in a larger two - dimensional superconduncting sample . quasi - one - dimensional solitons , or , in other words , solitonic fronts in infinite ( in both @xmath1 and @xmath2 directions ) samples have been studied in detail by malomed @xcite . several interesting results in the absence of dissipation have been reported including the waves in the q1d sine - gordon equation , travelling along the soliton line @xcite and skyrmion scattering on impurities in the 2d baby scyrme model @xcite . however , in the case of the fluxon dynamics in a ljj the presence of dissipation is unavoidable . it is of interest to investigate the q1d fluxon dynamics in the presence of spatial inhomogeneities when the junction width is finite . we expect that the fluxon transmission in this case will be significantly enhanced comparing to the pure 1d case . for example , in the previously studied case of the lattice acoustic soliton front interaction with mass impurities @xcite it has been shown that the front can _ round _ the point impurity while a 1d lattice soliton gets reflected from it . moreover , the soliton front can overcome even the impurity of the infinite mass . to our knowledge the fluxon interaction with spatial inhomogeneities has not been studied except in @xcite , however this paper deals only with the infinite sample width . thus , in this letter we aim at studying the q1d fluxon interaction with impurities and finding out how this interaction depends on the junction width and other system parameters . in particular , it is planned to find how the retrapping current ( e.g. , the minimal bias current for which the fluxon propagation is still possible ) depends on the junction width . the paper is organized as follows . in the next section , the model is described . section [ sec3 ] is devoted to the fluxon transmission through impurities . in the last section discussion and conclusions are presented . we consider the q1d long josephson junction ( ljj ) subjected to the external time - independent bias . the main dynamical variable is the difference between the phases @xmath3 of the macroscopic wave functions of the superconducting layers of the junction . the time evolution of the phase difference is governed by the perturbed sine - gordon ( sg ) equation of the form @xmath4\sin \phi=-\alpha \phi_t-\gamma,\ ] ] where @xmath5 and the indexes @xmath6 stand for the respective partial derivatives . in this dimensionless equation the spatial variables @xmath1 and @xmath2 are normalised to the josephson penetration depth @xmath0 , the temporal variable @xmath7 is normalised to the inverse josephson plasma frequency @xmath8 @xcite . the bias current @xmath9 is normalised to the critical josephson current of the junction and @xmath10 is the dimensionless dissipation parameter . the function @xmath11 describes the spatial inhomogenity . in the case of point impurities in the general form it reads @xmath12 it is supposed that there are @xmath13 impurities in this junction , positioned at the points @xmath14 , @xmath15 , @xmath16 , with @xmath17 being the `` strength '' or the amplitude of the impurity . only the microshorts ( @xmath18 ) , i.e. , a narrow regions of locally enhanced critical density of the tunnelling superconctucting current will be investigated in this article . however , the size an inhomogeneity in experimental samples is finite @xcite . therefore , we consider also the case of the line microshort of width @xmath19 , stretched along the @xmath2 direction : @xmath20 \,.\ ] ] here @xmath21 is the heavyside function . and finally , the rectangular impurity of the finite size in both @xmath1 and @xmath2 directions @xmath22 \left [ \theta\left ( y+\frac{d_y}{2}\right ) + \theta \left ( \frac{d_y}{2}-y\right ) \right ] \ ] ] will be considered as well . it should be noted that the impurity strength @xmath17 has different meanings in all three cases ( [ 2])-([4 ] ) . for the point impurity ( [ 2 ] ) setting @xmath23 does not automatically yield the pure 1d case studied before in @xcite . this case can be retained in the strip impurity case if @xmath24 . the 1d finite - size impurity case @xcite is retained in the same way . we choose the boundary conditions along the @xmath2 direction in the von neumann form : @xmath25 the boundary conditions along the @xmath1 axis are periodic : @xmath26 , where @xmath27 is the junction length , @xmath28 . in order to get an idea about the character of the fluxon dynamics , the numerical integration of the q1d sg equation ( [ 1 ] ) has been performed . the josephson phase and its space derivatives are discretized in the following way : @xmath29 , + @xmath30 , while the @xmath31-function is approximated by the kronecker @xmath31-symbol . the resulting set of ode s with the boundary conditions were integrated using the 4th order runge - kutta scheme . details of the fluxon propagation through the two identical point impurities ( [ 2 ] ) placed along the @xmath2 axis at @xmath32 and @xmath33 are given in fig . it is important to mention that the dissipation in eq . ( [ 1 ] ) is crucial and the soliton interaction with impurities differs from the dissipationless case where the complex resonant behaviour occurs either for the @xmath31-like @xcite or for the finite - size @xcite obstacles . far away from the impurities the fluxon exists as only one attractor of the system with the velocity , predefined by the damping parameter and external bias . therefore , contrary to the non - dissipative case , the transmission consists of only two possible scenarios : trapping and passage . for the sake of better visualization the derivative @xmath34 is plotted on the @xmath35 plane for the different time moments and for three different dissipation values : @xmath36 , @xmath37 and @xmath38 . without loss of generality the topological charge is assumed to be @xmath39 ( soliton ) throughout the paper . the initial conditions are taken in the form of the approximate ( invariant in the @xmath2 direction ) soliton solution , placed at the beginning of the junction and having with the equilibrium velocity . the fluxon interaction with the rectangular impurity is presented in fig . [ fig2 ] for @xmath36 and @xmath38 . in this case , the countour plot of the function @xmath34 is plotted on the @xmath35 plane . the fluxon retrapping current was computed numerically as well , showing its steady decay when the junction width was increased . these results will be discussed in detail in the next subsection . the following conclusions can be drawn from these results . the fluxon shape experiences certain changes after passing the impurities , namely the redistribution of the josephson phase along the fluxon line in the @xmath2 direction , as well as the slight bending of the fluxon shape in the same direction . these distortions eventually die out after some time , for @xmath37 and @xmath36 this happens quite soon after the passage through the impurity . for smaller dissipation ( @xmath38 , as shown in figs . [ fig1]i - l ) the oscillations of the josephson phase along the @xmath2 direction seem to survive for much longer time , comparable with the fluxon propagation time along the junction . the numerical simulations for thinner junctions , @xmath40 ( not shown in the paper ) , demonstrate that these shape distortions are much weaker and are hardly noticeable . thus , when studying the q1d fluxon interaction with impurities one can assume with the high degree of certainty that the fluxon is an almost hard rod at least if @xmath41 . due to finiteness of the junction in the @xmath2 direction and the boundary conditions ( [ 5 ] ) , the straight soliton front is the energetically most favourable solution and thus it is not possible to observe the arc - like solitons reported in @xcite . similarly to fluxon propagation in the 1d ljj @xcite , there must exist two characteristic values of the bias current , @xmath42 and @xmath43 , @xmath44 . moreover , the current - voltage characteristics of the ljj with impurities have hysteretic nature @xcite . if @xmath45 , the pinning on the impurity is not possible and there exists only one attractor that corresponds to fluxon propagation . this happens because the bias current is too strong for the fluxon to get trapped on the impurity . in the interval @xmath46 , at least two attractors coexist : one corresponds to fluxon pinning on the impurity ( there can be several different pinned fluxons if the impurity has finite length @xcite ) and another one to fluxon propagation . if @xmath47 , the only possible regime is fluxon pinning on the impurity . the value of @xmath42 is defined only by the properties of the impurity , and can be obtained directly from the 1d analog . contrary , for the retrapping current the dimensionality of the junction and its width are crucial . far from the impurity , the fluxon kinetic energy is proportional to the junction width and equals @xmath48 $ ] . here , @xmath49^{-1/2}$ ] is the equilibrium fluxon velocity in the spatially homogeneous ljj @xcite . in the non - relativistic fluxon case ( @xmath50 ) , one gets @xmath51 . by substituting the ansatz + @xmath52/\sqrt{1-v^2}\}$ ] into eq . ( [ 1 ] ) , where @xmath53 is the coordinate of the fluxon center of mass , one can obtain the newtonian equation of motion for the fluxon center . since the fluxons under consideration are extended objects in the @xmath2 direction , the equation for the center of mass dynamics as well as the impurity potential should depend on @xmath2 . taking into account the numerical simulation in the previous section , we consider the fuxon as an absolutely rigid rod . we also mention that the impurity function @xmath11 can be factorised in the cases ( [ 3])-([5 ] ) , therefore its center of mass dynamics can be effectively projected on the @xmath1 axis and the respective equation of motion can be written as @xmath54 where the center of mass coordinate @xmath55 depends only on time . the impurity potential @xmath56 now can be calculated from the respective 1d problem by simply taking away the @xmath2-dependent part in eqs . ( [ 2])-([4 ] ) . the fluxon mass @xmath57 has to be rescaled depending on the type of the impurity . in the pure 1d case @xmath58 . this assumption works well only if the impurity is consists of lines and/or rectangles . if it has a more complex shape , for example , like triangle , the projection on the 1d problem becomes more complicated . * point impurity . * in the point impurity case ( [ 2 ] ) , we consider the line of @xmath13 identical equidistant impurities with @xmath59 , @xmath16 which are placed symmetrically with respect to the central line @xmath60 . each impurity creates the potential @xmath61 . in order to project the problem on the 1d picture it is necessary to rescale the fluxon mass from @xmath58 to @xmath62 , thus within the kinematic approach the retrapping current can be found as a root of the energy balance equation @xmath63 , where @xmath64\simeq 4wv_\infty^2/n+{\cal o}(v_\infty^4)$ ] is the fluxon kinetic energy . in the non - relativistic case one gets @xmath65 . the correction of the order @xmath66 can be taken into account with the help of the method , developed in @xcite . the modification of this method for the q1d case is straightforward , therefore we describe only the main steps . the improved energy balance relation equates the fluxon energy at @xmath67 and its losses due to the dissipation , @xmath68 , with the maximal height of the potential barrier @xmath69 : @xmath70 where @xmath71 , @xmath72 are the extrema of the potential @xmath69 , @xmath73 , @xmath74 . equation ( [ en - bal ] ) is universal and will be used for all types of impurities . the energy loss due to the dissipation equals + @xmath75 . inserting this correction term @xmath68 into the improved energy balance equation and keeping the terms up to the order @xmath66 , one gets the final corrected expression for the retrapping current : @xmath76 it appears that the @xmath77 relation is obtained simply by dividing the impurity strength by the factor @xmath78 , moreover , the @xmath66 correction does not depend on the junction width at all . from this expression one can clearly see that if only the @xmath79 term is taken into account , the retrapping current disappears as @xmath80 , thus , in the infinitely wide junction a fluxon always passes the impurity . the second term in eq . ( [ 4a ] ) does not depend on @xmath81 , and , therefore it may lead to the wrong conclusion that @xmath43 does not tend to zero as @xmath80 . however , it should be noted that this term has been derived under the assumption of @xmath81 being finite . the numerical simulations confirm the main suggestion of this letter : the retrapping current decays with the growth of the junction width . the approximate expression ( [ 4a ] ) appears to be in good agreement with the numerical data for smaller values of @xmath81 , while for larger @xmath81 the numerical and analytic data diverge ( however , the agreement remains to be satisfactory ) . all this is presented in fig . [ fig1]a where the analytic results are given by solid lines and the numerical data are shown by markers . in the case of two and three impurities , placed along the line in the @xmath2 direction , the retrapping current virtually does not depend on the distance @xmath82 between them . for instance , the markers that correspond to @xmath83 ( @xmath84 ) , @xmath85 ( @xmath86 ) , @xmath87 ( @xmath88 ) at @xmath89 and @xmath90 are almost indistinguishable . one may consider the excentrically placed ( i.e. , lying away from the @xmath91 axis ) impurity . the kinematic approach does not distinguish the impurities , placed at the different positions . the numerical simulations show that the difference between the retrapping currents in both the cases is very small . for example , @xmath92 for the centrally placed impurity , @xmath93 , at @xmath94 ( the rest of the parameters are as in fig . [ fig1]a ) and @xmath95 for the impurity at @xmath96 , @xmath97 . * line impurity . * in the case of the impurity line ( [ 3 ] ) , the same energy balance expression holds as for the point impurity but the fluxon mass is assumed to be @xmath98 . the rest of the calculation procedure for the retrapping current is the same as for the point impuritiy . as a result , we obtain the the final expression for the retrapping current : @xmath99 numerically computed @xmath43 appears to be in good correspondence with the approximate expression ( [ 4b ] ) as shown in fig . similarly to the point impurity case , the discrepancy between the analytical and numerical results increases at larger @xmath81 . in the limit @xmath100 , the effective 1d picture is restored because the impurity strip crosses the whole junction in the @xmath2 direction . thus , the retrapping current attains the value @xmath101 for the 1d soliton case ( shown by the thick horizontal line in fig . [ fig3]b ) . thus , we observe that if the strip impurity consitutes , for example , about @xmath102 of the junction width , the retrapping current is about @xmath103 less than the respective 1d value . * rectangular impurity . * finally , we consider the rectangular impurity ( [ 4 ] ) . in the point - particle description , the fluxon `` feels '' this impurity as the potential @xmath104 $ ] @xcite . in this case , the energy balance reads @xmath105=4\mu d_y \tanh ( d_x/2)$ ] , from which the expression for the threshold current can be easily computed . for large @xmath106 it can be complemented by the correction @xmath66 computed for the 1d case in @xcite . the fluxon mass should be renormalized as @xmath107 . in this limit it is assumed that the impurity creates the step - like potential @xmath108 $ ] , which has a minimum at @xmath109 and a maximum at @xmath110 . the energy losses due to the dissipation @xmath111+{\cal o}(1)\}$ ] should be substituted in the energy balance equation ( [ en - bal ] ) . the final approximation reads @xmath112.\ ] ] note that at variance with the point and line impurities , the second correction depends on the both junction and the impurity width . in the 1d limit ( @xmath100 ) , the formula ( [ 9 ] ) retains the form , found in @xcite . in the limit @xmath113 , the second term decays to zero , but much slower than the decay law @xmath114 of the first term . once again , the second term is a correct approximation only for finite values of @xmath81 . in the opposite limit , @xmath115 , one can use the following approximation : @xmath116\simeq d_x \mbox{sech}^2 x + { \cal o}(d_x^2)$ ] . thus , the effective potential @xmath69 is approximately the same as for the line impurity up to the coefficient @xmath117 . therefore the formula ( [ 4b ] ) can be modified accordingly and finally the retrapping current reads @xmath118.\ ] ] the results of numerical simulations given in fig . [ fig4 ] demonstrate satisfactory correspondence with the analytical approximations ( [ 9])-([10 ] ) . the deviations from the numerical results appear to be stronger as compared to the point and line impurities , mostly because we were unable to provide the @xmath66 correction that works equally well in both limits @xmath119 and @xmath120 and also due to higher degree of the fluxon deformation during the interation with the impurity . it should be mentioned that even for @xmath121 one can consider the `` long '' @xmath106 limit and it works fairly well . indeeed , the markers that correspond to @xmath122 ( @xmath123 ) , @xmath124 ( @xmath125 ) and @xmath126 ( @xmath88 ) seem to be almost indistinguishable in fig . to summarize , we have shown that quasi - one - dimensional fluxon passage across microshorts is significantly enhanced in comparison with the purely one - dimensional case . the retrapping threshold current decays with the junction width approximately as @xmath127 , according to the kinematic approach . the numerical simulations support this dependence for intermediate ( several @xmath0 ) values of @xmath81 . with the increase of @xmath81 , the discrepancy between the numerical results and the kinematic approximation becomes more distinct . the reason of this discrepancy lies in the fact that for @xmath128 the fluxon can not be longer considered as an completely rigid object and its deformation the @xmath2 direction should be taken into account . one can formulate the following simple argument that explains the enhanced fluxon transmission across the obstacle of the width @xmath19 in the q1d case . the obstacle can be described as a localized ( both in the @xmath1 and @xmath2 directions ) potential barrier . only the central part ( @xmath129 ) of the initially homogeneous in the @xmath2 direction fluxon takes part in the interaction process , while the marginal areas @xmath130 do not . thus , if the energy in the tails is sufficient enough to overcome the barrier , the fluxon will pass . if @xmath113 , the energy in the non - interacting part of the fluxon tends to infinity , and , consequently , it will overcome any localized obstacle . finally , we would like to outline the future research directions . in our opinion they lie beyond the rigid rod approximation used in this letter . in this case the fluxon center of mass depends also on the transverse coordinate @xmath2 and the effective equations of motion are pde s and not ode s , like eq . ( [ 7 ] ) . accounting for the dependence on @xmath2 becomes important in the following cases : ( i ) the junction width is too large and the flexural oscillations along the fluxon line appear ; ( ii ) the dissipation is rather small and/or the junction length is @xmath131 , thus the spatial distortions of the fluxon line do not have enough time to die out . these cases are also interesting in connection with the arc - like fluxons found in the infinitely wide junction @xcite and the variety of the excitations that travel along the fluxon crest in the dissipationless 2d junctions @xcite . the combined effect of the dissipation and the finite junction width makes the transverse - invariant fluxon front the energetically most favourable solution . however , other attractors of the system which are non - transverse - invariant may exist as suggested by figs . [ 1]j - l , especially when dissipation is small . finding them and investigating how they will manifest themselves on the junction current - voltage dependence is an important problem . authors are indebted to dffd ( project f35/544 - 2011 ) for financial support . s. sakai , h. akoh and h. hayakawa , japan . ( 1985 ) l771 ; h. akoh , s. sakai , a. yagi and h. hayakawa , ieee trans . ( 1985 ) 737 ; i.l . serpuchenko and a.v . ustinov , pisma zh . 46 ( 1987 ) 435 [ sov jetp lett . 46 ( 1987 ) 549 ] .

fluxon transmission through impurities of different shape in a quasi - one - dimensional long josephson junction is investigated . the junction width is significantly less than its length but , at the same time , is of the order of the josephson penetration length @xmath0 or exceeds it . the retrapping current on the impurities of the point , line and rectangular shape is computed as a function of the junction width both numerically and analytically . good agreement between the analytic formulae and the numerical simulation results for the intermediate ( several @xmath0 ) junction width is observed . solitons , josephson junctions , fluxons , impurities

Thank you for your interest in spreading the word about Science. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. ||||| Chris Tzaros Are they singing The Heat is On? When it’s hot outside, zebra finches sing a special song to their eggs. That song appears to keep the chicks from growing too large after they hatch if the weather is toasty – and it even affects the number of baby birds in the next generation, though researchers aren’t sure exactly why. Several species of birds and their unborn offspring call to one another, says Mylene Mariette at Deakin University in Victoria, Australia. When they hatch, birds that are born well developed, such as ducks and chickens, recognise their parents by their voices. Advertisement Birds that hatch at an early stage, such as zebra finches, were not thought to do this. “We didn’t realise that they were able to hear before hatching,” Mariette says. But they do – and they seem to take this to a whole new level. Mariette and her colleague Katherine Buchanan placed microphones in 125 nests of captive zebra finches living in an outdoor aviary. The researchers realised that chicks might be listening from inside their eggs when they noticed that their parents, which normally call to one another, sometimes sang a specific song when they were alone with the eggs. The finches only sang this song when the weather was warm, and when their chicks were close to hatching. “Because they only do it toward the end of the incubation, it really looked like they do it to communicate with the egg,” Mariette says, rather than just calling out because they are hot. What else can we learn from birds? Birds do impressions – it’s time to take them seriously To see if the eggs were listening, the scientists incubated a group in the lab. During the five days before the chicks hatched, the researchers played recordings that included the hot-weather song to about half of them, and the same recordings, minus the hot-weather calls, to the rest. Mariette and Buchanan returned about 170 hatchlings to nests scattered around the aviary, some of which were sunnier and so warmer than others. Of the chicks played the warm-weather song, those that grew up in hotter nests tended to weigh less than those raised in cooler nests. The chicks that hadn’t heard the song were the opposite: those in the hotter nests grew to be heavier. As adults, the female finches that had heard the warm weather song and grew accordingly produced up to six fledglings during their first breeding season. The chicks from that group that didn’t follow their parents’ advice typically only had one or two fledglings. The parental calls, and their chicks’ reaction to them, can make the finches more productive as adults, says Mariette. “That’s a strategy we really didn’t know birds could do, and that could potentially help them deal with global warming,” she adds. “That’s good news.” The next step is to figure out what physiological changes are driving the chicks’ growth. Smaller birds may have an easier time shedding excess body heat, or perhaps the act of growing bigger is simply more stressful on birds’ bodies during hot weather, Mariette says. Figuring that out will be interesting, says Renée Duckworth at the University of Arizona in Tucson. Bird parents can influence their offspring in other ways, for example by changing the mix of hormones and nutrients that goes into the egg. Mylene Marietta But using sound to teach their babies how to grow is something we didn’t know about before, she adds. “It is surprising that vocal communication at such an early stage of development can have such persistent effects,” Duckworth says. “This is a remarkable study,” says Sonia Kleindorfer at Flinders University in Adelaide, Australia, because it shows how the sounds a bird hears in its egg can shape its development, even into adulthood. What seems like a useful warning in captivity, however, might prove deadly in the wild. Noisy adult finches might attract predators, so the parental calls might endanger baby birds, she says. Still, the existence of a previously overlooked finch call is a fascinating find, Kleindorfer adds. “Zebra finches are literally right in front of us in cages around the world,” she says. “What are we ignoring that is right before us?” Update, 18 August: An earlier version of this story contained an error about which group of birds produced fewer fledglings as adults. Journal reference: Science, DOI: 10.1126/science.aaf7049 ||||| Birds feeling the heat from warming weather may be able give their offspring an early weather advisory right through the eggshell—which could in turn help baby birds prepare for the forecast. A new study shows that the songs zebra finches sing to their eggs late in development may give the young a head start in dealing with warm weather once they hatch. Researchers have long known that birds like chickens or quails, which hatch fully capable of fending for themselves, can hear through their eggs—allowing them to imprint things like who their mother is. But or around 50 years, nobody believed anything happened inside the egg with birds that hatch dependent on their parents. A new study published today in Science upends that wisdom, showing that certain zebra finch calls can change their young's growth and behavior in adulthood. “This acoustic signal is potentially being used to program the development of offspring," says Kate Buchanan, an associate professor of animal ecology at Deakin University in Australia and the senior author of the new paper. “Hearing the call affects your rate of growth relative to the temperature that you experience. “Animals have very subtle ways of inferring how the environment is likely to change, and (being able) to develop and adapt accordingly," she added. "We’re only looking at the tip of the iceberg in terms of what we recognize so far… It is quite paradigm-shifting.” While researchers are just starting to understand this behavior, the implications may provide a rare instance of good news in terms of the ways animals can subtly adapt to a changing climate, she says. Zebra finches live in the harsh, dry scrub environment of the Australian Outback. The females do most of the incubation, and the birds often mate for life, Buchanan says. The males are brightly colored, and the zebra finches are notorious songsters, a trait that makes them popular with pet owners and researchers, who have studied the pear-sized birds' speech patterns ad nauseam. But despite so much attention, post-doctoral researcher at Deakin and lead author Mylene Mariette managed to find a new sound that nobody else had noticed before—probably due to the fact that it only pops up during the last few days of egg incubation when the conditions are right. Mariette had heard of incubation calling from previous research and believed what she was hearing might be related. Under Buchanan's supervision, she set about creating an experiment to test her theory. Since researchers still aren't sure whether the male or female does the incubation call, they recorded the sounds of 61 male and 61 female zebra finches nesting in outdoor bird cages under natural temperatures. Strangely, the birds only seemed to make this special noise when the temperature climbed above 78 F. Researchers then took finch eggs into an incubation chamber at a constant temperature (they replaced the ones in the nest with false eggs) and played back different sounds to two different groups of eggs during the last three to five days of incubation. Once the birds hatched, they placed them back in the outdoor finch nests, and found that their growth and development differed based on whether or not they had heard the sounds while still in the egg. When the temperature in the nest after hatching was higher, nestlings exposed to the incubation calls while in the egg tended to be smaller on average than hatchlings exposed to normal socialization sounds. Warmer temperatures have been correlated with smaller birds in many other species; being smaller may give them an advantage, because body size impacts thermoregulation and can reduce damage to the bird's molecules. That isn't all. Buchanan says that the birds who heard the incubation call continued to show effects even into adulthood, choosing nests that were hotter on average than the zebra finches that didn't hear the special call. “Hearing that call before you even hatch affects your development, affects your growth rate, probably affects your vocalization and it affects your behavior and choice 100 or 200 days later when you go to nest yourself," she says. Mark Hauber, a professor of animal behavior at the City University of New York, says that the paper is shocking, with major implications on how we understand early embryonic development and auditory learning in birds. “It’s so novel. It’s going to open up a brand new field of research,” he says. Hauber contributed to some of the only other research on incubation calling, in which the authors found that fairy wrens train their chicks to make certain sounds when born so the parents can distinguish them from cuckoos, a parasitic bird that lays eggs in other birds' nests before skipping out on the childcare struggle. Cuckoos don't have the brain mechanism to learn to identify a song, so fairy wrens use incubation calling as a strategy to avoid raising the parasitic cuckoos. “What was important about some of the more recent work is it showed that much of this learning already takes place inside the egg,” Hauber says. Buchanan says that there are wide implications for the new research that go beyond zebra finches in terms of what kinds of information parents can pass onto their offspring in the embryonic stage. “It makes me wonder what signal babies are picking up before they are born, whether they are hearing their parents arguing or loud noises,” she says. In terms of zebra finches, she notes that the birds breed opportunistically with regards to their unpredictable environment, laying eggs when conditions are right and possibly using this incubation call as a way to acclimatize to the shifting weather. She says that while the recent study shows how zebra finches may be able to cope with the changing climate, the birds wouldn't be able to cope with more extreme and sustained temperature increases. Hauber says that more investigation is needed to understand how they might be able to adapt to climate change, but he finds the research that Buchanan and Mariette made is intriguing. “What it tells us is that a species that we’ve used as a model is still full of surprises," he says.

– Several types of birds sing to unhatched eggs so their young will recognize their voices once they've hatched—but what the zebra finch does is something else entirely. In a study called "paradigm-shifting" by one of its authors, researchers at Australia's Deakin University say the birds sing a song to their eggs that keeps chicks from growing too big—but only when the weather is warm, with scientists suspecting that smaller birds are able to get rid of excess body heat more easily. Think of it as "an early weather advisory," per Smithsonian. After placing microphones in 125 zebra finch nests in an outdoor aviary, researchers heard finches singing a specific song in a certain scenario: when they were alone with eggs, the eggs were days away from hatching, and the temperature was above 78 degrees, reports New Scientist. The researchers then incubated 170 finch eggs in a lab, playing a recording of the song to only half before putting them back in nests. The chicks that heard the song and grew up in warmer nests weighed less than chicks in cooler nests, produced up to six fledglings in their first breeding season (compared to one or two), and chose warmer nests in later life. "Hearing that call before you even hatch affects your development, affects your growth rate," says the university's Kate Buchanan. Adds author Mylene Mariette, the "strategy ... could potentially help them deal with global warming." (Here's what happened when scientists got the birds drunk.)

the absence of a signal of supersymmetric partners at the lhc up to the mass range of 12 tev @xcite increased an interest in the heavy supersymmetry scenarios @xcite of the minimal supersymmetric standard model ( mssm ) , where the condition @xmath2125 gev for the lightest @xmath3-even scalar state , perhaps , observed by the atlas and cms collaborations @xcite is respected explicitly in the mssm parameter space . large radiative corrections to the mssm two - higgs doublet sector which raise up @xmath6 from the maximal tree - level value of @xmath7 to the observable value of 125 gev appear due to large values of soft supersymmetry breaking parameters , which are associated with large masses of third generation quark supersymmetric partners , large mixing of supersymmetric partners , and restricted from above by the availability of perturbative regime . for this reason acceptable domains of the mssm parameter space are rather limited @xcite although there are several variants of such fine tuning. in order to ease tensions of parametric scenarios of the mssm , two ways of action are appropriate , first , more precise calculations of radiative corrections at higher loops / decomposition of the effective potential in the higher inverse powers of @xmath8 ( i.e. including effective operators @xmath9 in the decomposition of coleman - weinberg type potential ) ; second , the transition to extensions of the mssm . for example , extensions of the mssm where the superpotential includes an additional chiral singlet field ( next to minimal supersymmetric standard model ( nmssm ) @xcite ) , or more chiral fields , are known . it is assumed that some new physics beyond the mssm exists at an energy scale which is not too far away . probably , such scale of the order of 10@xmath10 tev is somewhat higher than the mass scale of superpartners @xmath8 . in the framework of a picture where mssm is a low - energy limit of an extended theory ( not only nmssm , for example , supersymmetric grand unification models @xcite or supersymmetric left - right models @xcite ) all possible effective operators of higher dimension should be introduced with the following separation of the observables which are sensitive to effects of the extended theory for phenomenological analysis . the effective lagrangian of the mssm extension can be written as a sum of operators suppressed by inverse powers of the new physics scale @xmath11 and @xmath12 , each of which is @xmath13 invariant and respects @xmath14-parity . in the extended theory such operators are generated either at the tree - level or at the loop - level . it was expected that contributions of the tree - level operators to the specific observables were more important because the loop - level operators have an additional suppression factors proportional to @xmath15 . however , additional enhancements by large mssm parameters ( like @xmath16 which can compensate also an extra power of the mass scale @xmath17 ) make the situation with various contributions rather nontrivial . a number of studies prior to higgs boson discovery can be found in the literature . a complete list of the tree - level dimension - five and dimension - six effective operators can be found in @xcite . note that supersymmetry restricts possible effective operator categories , for example , no operators of dimension - five involving higgs - higgsino supermultiplet and gauge - gaugino supermultiplet exist since no gauge invariant form can be constructed using three mssm chiral superfields . analogously , no operators of dimension - six involving higgs - higgsino supermultiplet exist because operators of this type must contain five chiral superfields , apparently , such forms violate gauge invariance . various aspects related to an extensions by the dimension - five / dimension - six operators were systematically analyzed in @xcite . as mentioned above , radiative corrections coming from the loop diagrams with top quark and top superpartner are very important @xcite both for large @xmath18 and small @xmath18 parameter . the tree - level mass of the lightest @xmath3-even state @xmath19 is maximized at large @xmath18 . for small trilinear parameters @xmath20 and large stop mass scale @xmath8 when @xmath21 and @xmath22 are less than one ( in other words , in the case of moderate stop mixing parameter @xmath23 ) , the correction to @xmath6 at the one - loop is controlled by the logarithm @xmath24 which is large enough for @xmath8 of the order of 10100 tev . for large trilinear parameters @xmath20 ( or in the case of large stop mixing parameter ) the correction is maximized at @xmath25 ( so - called maximal mixing scenario at the one - loop ) , and much smaller @xmath8 values of the order of 1 tev are appropriate . at @xmath26 or even smaller , large mixing may appear due to large higgs superfield mass parameter @xmath27 of about 10 tev . nontrivial interplay of @xmath28 and @xmath18 parameters at the level of one - loop resummed higgs potential was analyzed in detail for the potential decomposition in the inverse powers of @xmath8 up to operators of the dimension - four . the case of small mass splittings for quark superpartners @xcite was generalized for the situation when each stop and sbottom is independently decoupled at its specific mass scale @xcite for some special mssm effective potentials . note that the two - loop effects may be included by using a renormalization group improvement of the effective potential @xcite . the scale dependence of the one - loop result is reduced if the two - loop renormalization group improvement of the one - loop effective potential is accounted for @xcite . in this paper the effective mssm higgs potential decomposition up to operators of the dimension - six involving scalars only is considered . contribution of the dimension - six operators to observables can be separated insofar , as already mentioned above , the dimension - six operators involving only scalar isodoublets appear at the loop - level only . in section 2 the mass basis for extended higgs sector is constructed . in section 3 analytical expressions for the threshold corrections are derived and some numerical evaluations for the mass spectra are performed . in this section we construct the basis for the mass states of physical scalars following @xcite , where the case of dimension - four operators has been considered . two higgs doublets of the form @xmath29 are used to define the general two - higgs doublet potential which includes the dimension - six terms . the potential can be written as @xmath30 where the upper index shows the operator dimension in fields , @xmath31 , \\ \label{u4 } u^{(4 ) } & = & \lambda_1 ( \phi_1^\dagger \phi_1)^2 + \lambda_2 ( \phi_2^\dagger \phi_2)^2 + \lambda_3 ( \phi_1^\dagger \phi_1)(\phi_2^\dagger \phi_2 ) + \lambda_4 ( \phi_1^\dagger \phi_2)(\phi_2^\dagger \phi_1)+\\ & + & [ \lambda_5/2 ( \phi_1^\dagger \phi_2)(\phi_1^\dagger\phi_2)+ \lambda_6 ( \phi^\dagger_1 \phi_1)(\phi^\dagger_1 \phi_2)+\lambda_7 ( \phi^\dagger_2 \phi_2)(\phi^\dagger_1 \phi_2)+h.c . ] , \nonumber \\ \label{u6 } u^{(6 ) } & = & \kappa_1 ( \phi^\dagger_1 \phi_1)^3 + \kappa_2 ( \phi^\dagger_2 \phi_2)^3 + \kappa_3 ( \phi^\dagger_1 \phi_1)^2 ( \phi^\dagger_2 \phi_2)+\kappa_4 ( \phi^\dagger_1 \phi_1 ) ( \phi^\dagger_2 \phi_2)^2+\\ & + & \kappa_5 ( \phi^\dagger_1 \phi_1 ) ( \phi^\dagger_1 \phi_2 ) ( \phi^\dagger_2 \phi_1)+ \kappa_6 ( \phi^\dagger_1 \phi_2 ) ( \phi^\dagger_2 \phi_1 ) ( \phi^\dagger_2 \phi_2)+ \nonumber \\ & + & [ \kappa_7 ( \phi^\dagger_1 \phi_2)^3+\kappa_8 ( \phi^\dagger_1 \phi_1)^2 ( \phi^\dagger_1 \phi_2)+\kappa_9 ( \phi^\dagger_1 \phi_1 ) ( \phi^\dagger_1 \phi_2)^2 + \nonumber \\ & + & \kappa_{10 } ( \phi^\dagger_1 \phi_2)^2 ( \phi^\dagger_2 \phi_2)+ \kappa_{11 } ( \phi^\dagger_1 \phi_2)^2 ( \phi^\dagger_2 \phi_1)+ \kappa_{12 } ( \phi^\dagger_1 \phi_2 ) ( \phi^\dagger_2 \phi_2)^2+\nonumber \\ & + & \kappa_{13 } ( \phi^\dagger_1 \phi_1 ) ( \phi^\dagger_1 \phi_2 ) ( \phi^\dagger_2 \phi_2)+h.c . ] , \nonumber\end{aligned}\ ] ] so the parameters @xmath32 and @xmath33 are of dimension one , @xmath34 are dimensionless and the dimension of @xmath35 is of inverse mass squared . in the general case @xmath36 , @xmath37 and @xmath38 are real , all other parameters can be complex . in this section the mass basis for the general case of explicitly @xmath3-violating potential @xcite with nonzero imaginary parts of @xmath27 , @xmath39 and @xmath40 parameters will be constructed . transformations of the @xmath41 states @xmath42 , eq . ( 1 ) , to the mass states @xmath19 , @xmath43 , @xmath44 , @xmath45 , @xmath46 , @xmath47 can be performed using two orthogonal rotations @xmath48 where @xmath49 ( in the following we denote @xmath50 , @xmath51 , etc . ) and the higgs potential ( [ u ] ) takes the form @xmath52 here @xmath53 denote the interaction terms of physical scalars and the coefficients @xmath54 , @xmath550,1,2 , which are dependent on the imaginary parts of @xmath56 and @xmath57 @xmath58 \ } \nonumber\end{aligned}\ ] ] are equal to zero in the mass basis . in a local minimum where derivatives of the potential in the fields are zero , @xmath59 and @xmath60 can be expressed as @xmath61 the real part of @xmath62 is fixed by zero eigenvalue of the mass matrix ( which ensures massless goldstone boson state and defines the @xmath3-odd scalar mass @xmath63 ) @xmath64 \right ) \nonumber\end{aligned}\ ] ] the requirement @xmath65 in eq . ( [ umass ] ) fixes the imaginary part of @xmath62 @xmath66 minimization conditions above must be performed for a generic two - doublet potential . in the following the case of mssm potential will be analyzed . the one - loop resummed mssm potential at the renormalization scale @xmath67 using dimensional reduction and the @xmath68-scheme can be written in the form @xmath69 where @xmath70 is a tree - level potential at the scale @xmath8 @xmath71\\ & + & \frac{g_1 ^ 2+g_2 ^ 2}{8}[(\phi_1^\dagger \phi_1)^2+(\phi_2^\dagger \phi_2)^2]+\frac{g_2 ^ 2-g_1 ^ 2}{4 } ( \phi_1^\dagger \phi_1)(\phi_2^\dagger \phi_2 ) -\frac{g_2 ^ 2}{4}(\phi_1^\dagger \phi_2)(\phi_2^\dagger \phi_1 ) , \nonumber\end{aligned}\ ] ] and @xmath72 is the squark mass matrix squared ( see the appendix ) . at the mass scale of quark superpartners the mass matrix elements are @xmath73 radiative corrections to these tree - level expressions are parametrized using @xmath74 @xmath75 @xmath76 , so corrections to the matrix elements of @xmath3-even states mass matrix are @xmath77 , \nonumber \\ \delta{\cal m}_{22}^2&=&-v^2 ( \delta \lambda_2 s_\beta^2+{\tt re } \delta \lambda_5 c_\beta^2+{\tt re } \delta \lambda_7 s_{2 \beta})+ \\ & + & v^4 [ { \rm re}\kappa_9 c_\beta^4+(3 { \rm re}\kappa_7+{\rm re}\kappa_{11}+{\rm re}\kappa_{13})c_\beta^3 s_\beta + \nonumber\\ & + & ( \kappa_4+\kappa_6 + 3 { \rm re}\kappa_{10})c_\beta^2 s_\beta^2 + 4 { \rm re}\kappa_{12}c_\beta s_\beta^3 + 3\kappa_2 s_\beta^4 ] , \nonumber \\ \delta{\cal m}_{12}^2&=&-v^2 ( \delta \lambda_{34 } s_\beta c_\beta + { \tt re } \delta \lambda_6 c_\beta^2+{\tt re } \delta \lambda_7 s_\beta^2 ) + \\ & + & v^4 [ { \rm re}\kappa_8 c_\beta^4+(\kappa_3+\kappa_5+{\rm re}\kappa_9)c_\beta^3 s_\beta+ \nonumber \\ & + & 2({\rm re } \kappa_{11}+{\rm re } \kappa_{13})c_\beta^2 s_\beta^2+(\kappa_4+\kappa_6+{\rm re}\kappa_{10})c_\beta s_\beta^3+{\rm re}\kappa_{12}s_\beta^4 ] . \nonumber \end{aligned}\ ] ] then the masses of @xmath3-even scalars can be expressed as @xmath78 where @xmath79 and the mixing angle @xmath80 is defined by @xmath81 the @xmath3-odd scalar mass @xmath82 can be expressed through @xmath6 . using eq . ( [ mhh ] ) one can define @xmath82 as an internal model parameter if the numerical value of the higgs mass @xmath2125 gev is fixed @xmath83 where @xmath84 the mass of charged higgs boson in the form @xmath85 \nonumber\end{aligned}\ ] ] can be obtained diagonalizing the corresponding mass matrix . two important conditions which restrict implicitly the mssm parameter space follow from eq . ( [ mhh ] ) : @xmath86 ( a ) ( b ) the one - loop expressions for parameters @xmath57 in front of the dimension - six terms can be obtained decomposing the effective potential ( [ eff ] ) in the inverse powers of @xmath8 in the approximation of degenerate squark masses @xcite . in the following we are using the notation @xmath87 ( see the appendix ) . effective potential terms of the dimension - six in the decomposition are @xmath88 \\ & + & \frac{1}{6 m_s^4 } { \rm tr}[({\cal m}_\gamma^2)^4 { \cal m}_\lambda^2 ] -\frac{1}{60 m_s^6 } { \rm tr}({\cal m}_\gamma^2)^6 ) . \nonumber\end{aligned}\ ] ] given the lagrangian of the higgs boson squarks interaction ( see the appendix ) , squark mass matrices @xmath89 can be calculated and @xmath57 factors in front of the dimension - six terms can be derived . for example , factors @xmath90 and @xmath91 written in the form which uses powers of ( @xmath92 ) and ( @xmath93 ) are @xmath94 @xmath95 in a more compact notation @xmath57 , @xmath551, ... 13 can be rewritten using gauge coupling dependent factors @xmath96 , @xmath551, ... 4 , and parameter dependent factors @xmath97 , @xmath98 and @xmath99 @xmath100 where ( @xmath101 ) @xmath102 @xmath103 @xmath104 @xmath105 @xmath106 @xmath107 @xmath108 @xmath109 @xmath110 @xmath111 @xmath112 meaningful numerical results following from the effective potential expansions in the inverse powers of @xmath113 are using the assumption of small mass splitting among the squark mass eigenstates ( or simultaneous decoupling of squark fields ) . in the literature it is usually considered that the expansion is valid if @xmath114 where @xmath115 are the stop masses . then @xmath116 can be defined as the average @xmath117 and @xmath118 obtained by means of the diagrammatic calculation and the covariant derivative expansion ( cde ) method @xcite for the case of either degenerate or non - degenerate stop mass spectrum , can be found in @xcite . for large @xmath18 the approximation of ( almost ) degenerate stop masses is not satisfactory at @xmath1190.5 tev and large @xmath120 mixing parameter values of a few tev , however , @xmath2125 gev is mostly available . ] . the contribution of dimension - six operators is small in the phase with softly broken symmetry if at least @xmath121 and @xmath122 @xcite . however , the dimension - six terms may play an important role in the @xmath123 parameter range of about / of the order of 10@xmath10 tev and moderate @xmath113 . for example , values of @xmath57 evaluated for @xmath124 tev , @xmath125 tev , @xmath126 are shown in fig . [ fig-1 ] , where the dimensionless couplings @xmath127 are depicted for @xmath113 values of 5 and 7 tev . the behavior of @xmath56 and @xmath127 as a function of @xmath113 at the multi - tev energy scale is shown in fig . [ fig-2 ] . one can see that significant values of @xmath127 are observed in @xmath113 range less than 8 tev . ( a ) ( b ) the higgs boson masses @xmath128 evaluated for two ( @xmath18 , @xmath44 , @xmath27 ) parameter sets at fixed value of the lightest @xmath3-even state mass @xmath129 gev and large @xmath120 mixing parameter of the order of 10 tev are shown in fig . [ fig-3 ] as a function of the squark mass scale @xmath113 . the @xmath3-odd scalar mass @xmath82 is calculated using eq.([m2a ] ) , where @xmath6 is an input parameter with fixed value . a pole of @xmath130 may take place when the denominator in eq.([m2a ] ) is zero . in the unphysical region of @xmath113 , for example , to the left from the pole in fig . [ fig-3](c ) , the restrictions imposed by eq.([2cond ] ) are not respected . contribution of the dimension - six terms @xmath131 to masses of scalars is very small in comparison with the dimension - four terms @xmath132 for moderate @xmath113 ( @xmath133 tev , fig . [ fig-3](a ) and @xmath134 tev , fig . [ fig-3](b ) ) but for smaller @xmath113 corrections are very important . in fig . [ fig-3](a ) the physical region of @xmath1350 indicated by vertical lines narrows to 2.3 tev ( lower bound ) . in the case ( b ) , see fig . [ fig-3 ] , the @xmath3-odd scalar mass squared is not positively defined for @xmath113 range from 6.3 to 8 tev . at moderate @xmath13610 positively defined masses squared of @xmath43 , @xmath44 and @xmath45 consistent with the input @xmath2125 gev are not possible for @xmath113 greater than 12 tev . note that nonstandard mass spectrum with extremely light pseudoscalar is available in this case . at fixed @xmath2125 gev the @xmath3-odd state @xmath44 can be as light as 2530 gev with @xmath43 and @xmath45 states in the decoupling regime or with masses of the order of electroweak scale . for example , higgs masses for ( b ) parameter set , see fig . [ fig-3 ] , and @xmath137 tev are @xmath129 gev , @xmath138 gev , @xmath139 gev , @xmath140 gev . the alignment limit when @xmath141 takes place for set ( b ) in the vicinity of @xmath1425.5 tev ; it is possible for @xmath143 in the decoupling regime only . the regime of alignment without decoupling without small @xmath82 is available if @xmath1445 , @xmath14510 tev and @xmath1465 tev . for this parameter set , see fig . [ fig-3](c ) , when curves are more stable with respect to corrections , there are two alignment limits . in fig . [ fig-3](d ) the first alignment limit takes place at @xmath1422.98 tev without decoupling and the second limit at 5.1 tev demonstrates decoupling of @xmath43,@xmath44 and @xmath45 states . figure [ fig-4 ] illustrates an increasing role of corrections from the @xmath131 terms to @xmath6 in the case of low @xmath18 scenarios @xcite which are found to be of about 1% at @xmath147 tev and @xmath148 more than 10 tev and of around 20% for the lower superpartner mass scale @xmath149 tev and @xmath148 less than 10 tev . in fig . [ fig-5 ] the condition @xmath2125@xmath1503 gev is translated to the mixing parameter quark superpartner plane @xmath151 , demonstrating sensitivity of the contours in the regime @xmath1460 ( see also @xcite , where similar contours are reconstructed using the diagrammatic calculation @xcite ) . increasing @xmath27 parameter of a few hundreds of gev changes strongly these exclusion contours , leaving only small acceptable domain in the left upper corner of the plot . ( a ) ( b ) ( c ) ( d ) ( a ) ( b ) ( c ) ( d ) ( a ) ( b ) in the absence of direct evidence motivating extensions of the standard model - like higgs sector , the effective field theory approach is a convenient framework to describe possible new physics either in a model - independent or in a model - dependent way . in both cases the mssm lagrangian is extended by higher - dimensional operators which are suppressed by the mass scale of new physics . in the model - dependent case of the mssm when the resummed effective potential is expanded up to dimension - six operators induced by the soft supersymmetry breaking terms , we calculated symbolically corrections to the effective sextic couplings and used them to determine the post - higgs discovery mass spectrum of the heavy mssm higgs bosons . an improved precision can be reached using such procedure especially at the low eft cut - off scale . corrections to the mass spectrum depend strongly on the domain in the mssm parameter space and are defined mainly by the quark superpartner mass scale and mixing in the sector of soft susy - breaking terms . even at the moderate mixing parameter values significant contributions to the heavy scalar mass spectrum of the order of 10 - 20% induced by the dimension - six operators are found at the squark mass scale @xmath152 23 tev . thus , for moderately heavy supersymmetry additional corrections induced by higher order terms in the expansion of the effective potential should be taken into account . one can observe that in a number of cases the restrictions on the mssm parameter space are not so much a consequence of the condition @xmath2125 gev as the presence of mass basis for the five higgs bosons , where mass hierarchy is acceptable from experimental point of view and there are no tachyonic states . m.d . is grateful to e. bagnashi and g. weiglein for useful discussions . this work was partially supported by grant no . most general scalar potential , including higgs boson and one generation of squarks , can be written as @xcite @xmath153 where @xmath154 contains mass squark terms , @xmath155 @xmath0-terms , @xmath156 @xmath1-terms of higgs - squark interactions and @xmath157 quartic squark interaction terms @xmath158 \tag{a4}\\ & + \overline{\lambda}_{ij}^q(\phi_i^\dagger \tilde{q})(\tilde{q}^\dagger \phi_j)+\frac{1}{2 } [ \lambda \epsilon_{ij}(i \phi_i^t \sigma_2 \phi_j)\tilde{d}^ * \tilde{u } \nonumber + h.c.]\end{aligned}\ ] ] and @xmath159 are determined by the tree - level susy relations @xmath160 , \tag{a5}\\ & \overline{\lambda}^q = { \rm diag } ( h_d^2-\frac{1}{2 } g_2 ^ 2 , \frac{1}{2 } g_2 ^ 2-h_u^2),\tag{a6}\\ & \lambda^u = { \rm diag}(-\frac{1}{4 } g_1 ^ 2 y_u , h_u^2+\frac{1}{4 } g_1 ^ 2 y_u),\tag{a7}\\ & \lambda^d = { \rm diag}(h_d^2-\frac{1}{4 } g_1 ^ 2 y_d , \frac{1}{4}g_1 ^ 2 y_d),\tag{a8}\\ & \lambda = -h_u h_d,\tag{a9}\\ & \gamma^{u}_{1,2}=h_u(-\mu , a_u ) , \qquad \gamma^d_{1,2}=h_d(a_d , -\mu ) , \tag{a10}\end{aligned}\ ] ] @xmath161 are couplings of @xmath162 , @xmath163 squark ( slepton ) hypercharges , @xmath164 yukawa couplings , @xmath165 trilinear couplings , @xmath27 higgs superfield mass parameter . g. lee and c. e. m. wagner , phys . d * 92 * , 075032 ( 2015 ) ( arxiv:1508.00576 [ hep - ph ] ) ; 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in the framework of the effective field theory approach to heavy supersymmetry radiative corrections in the higgs sector of the minimal supersymmetric standard model ( mssm ) for the effective potential decomposition up to the dimension - six operators are calculated . symbolic expressions for the threshold corrections induced by @xmath0- and @xmath1- soft supersymmetry breaking terms are derived and the higgs boson mass spectrum respecting the condition @xmath2125 gev for the lightest @xmath3-even scalar is evaluated . * radiative corrections to higgs masses for the mssm higgs potential with the dimension - six operators * m.n . dubinin@xmath4 , e.yu . petrova@xmath5 _ @xmath4skobeltsyn institute of nuclear physics , lomonosov moscow state university , 119991 leninskiye gory , moscow , russian federation _ + _ @xmath5physics department , lomonosov moscow state university , 119991 leninskiye gory , moscow , russian federation _ + pacs numbers : 14.80.da , 11.30.pb , 12.60.fr , 12.38.cy

the 1983 amendments to the social security act ( public law 98 - 21 ) enacted the medicare prospective payment system ( pps ) for the payment of hospital inpatient operating costs , but pending further study , continued cost - based payment of capital costs until october 1 , 1986 . department of health and human services ( dhhs ) issued proposed regulations for incorporating capital payments into pps . in july 1986 , legislation ( public law 99 - 349 ) was passed that extended the exclusion of capital from pps until october 1 , 1987 . in may and september 1987 , dhhs issued proposed and final regulations to fold capital payments into pps . however , in october 1987 , enactment of public law 100 - 119 prevented the final regulation from taking effect . the omnibus budget reconciliation act of 1987 ( public law 100 - 203 ) subsequently required dhhs to implement prospective payment for capital starting october 1 , 1992 . in february and august 1991 , dhhs once again issued proposed and final regulations for a third attempt to incorporate capital payments into pps . the august 1991 capital regulation took effect october 1 , 1991 , thus initiating a 10-year transition to full prospective payment of medicare 's share of inpatient capital - related costs . congressional persistence attests to the widespread belief that change was needed in medicare capital payment policy . in particular , there was recognition that to encourage efficient resource use , medicare payment policy should not influence hospitals ' choices of how to combine capital and operating inputs . there was also the understanding that with capital paid on a cost basis and operating costs on a prospective basis , medicare provided hospitals the incentive to substitute capital for operating cost . under these circumstances both the special nature of capital and the tradition of cost - based payment inhibited change . the durability and lumpiness of capital capital tends to be purchased in larger , less divisible quantities at less frequent intervals than operating inputs . the lumpiness of capital creates the need for long - term financing and the contractual commitments that accompany debt financing . debt obligations make it more difficult to change medicare capital - payment policy without imposing major adjustments on hospitals with very large debt service costs . another consequence of the lumpiness of capital is that , relative to its size , capital cost per discharge varies more among hospitals than does operating cost per discharge . as a result , a prospective payment based on the average capital cost will tend to have a greater relative impact in redistributing payments than was the case for operating cost . finally , the tradition of cost - based payment for hospitals has created a tendency to accentuate the uniqueness of capital in people 's thinking about medicare payment policy . only the tradition of cost - based payment is unique to hospitals . certainly , in the private sector , it is almost impossible to think of a good or service for which the unit of payment separately identifies capital from the other inputs used in producing the good or service . even in highly capital - intensive publicly regulated industries such as electric power , the return on capital is incorporated into a rate structure based on the unit of service ( e.g. , dollars per kilowatt hour ) . the experience of other industries clearly demonstrates that hospital capital can be paid on a per discharge basis and need not be paid separately from other input costs . however , a shift to prospective payment for hospital capital requires consideration of how to minimize the negative effects of transitional payment redistributions and how to structure the long run prospective payment for capital . the next section of this article addresses the issue of payment redistributions by presenting descriptive data on the variation of capital and operating costs . this information quantifies the extent to which capital costs are more variable than operating costs . the effect of capital - cost variability on total - cost variability is also assessed . the specifics of transitional payment mechanisms are beyond the scope of this article , but the details of the policy being implemented are described in the august capital regulation ( federal register , 1991 ) . the remainder of this article addresses the issue of the structure of the long - run prospective payment for capital by analyzing and comparing sources of variation in capital cost versus operating and total costs : the empirical models of capital- and total - cost variations that were estimated are described , and estimation results are presented . the regression results reported in this article differ from those found in the august capital regulation in two ways . first , given the focus of this article on comparative analyses , it was necessary to limit the data set to hospitals for which all variables were available . this meant that fewer hospitals were included in the regressions reported here than in the regression actually used to determine the capital payment adjustments in the august capital regulation . second , because the emphasis here is on understanding sources of cost variation rather than on determining specific payment adjustments , the variables included in the regressions are not identical to those reported in the august capital regression . the article identifies several problems in accounting for capital - cost variation and concludes that it is preferable to use the analysis of total cost ( the sum of capital and operating cost ) to develop a common set of adjustments for the capital and operating prospective payments rather than to use the analysis of capital cost to develop separate capital payment adjustments . it should be noted that this conclusion is not inconsistent with the august 1991 capital regulation , which establishes adjustment factors for the capital prospective payment based on analysis of total - cost variation . in the long run , it only makes sense to base the capital payment on total - cost variation if the operating payment is also based on total - cost variation . however , the health care financing administration ( hcfa ) currently lacks the statutory authority to modify the payment adjustments for the operating payment to conform with the capital adjustments . the logical conclusion is for legislative action to permit the use of the same payment adjustments for the operating and capital payments based on analysis of the combined capital and operating costs . data from medicare cost reports on the distributions of medicare inpatient capital and operating costs per discharge during the period 1985 - 89 are presented in table 1 . medicare capital costs consist of medicare 's share of a hospital 's depreciation and interest expenses , plus capital - related insurance costs , property taxes , leases , and rent . the main components of medicare operating costs are routine and ancillary costs . excluded are capital costs and the costs of approved graduate medical education programs . table 1 contains only the portions of capital and operating costs that have been allocated to medicare inpatient services . although capital and operating costs per discharge have risen during this period , there was little change in the shape of their distributions ( table 1 ) . for example , the ratio of the interquartile range ( the difference between the 75th and 25th percentile values ) to the median has remained relatively constant for both capital and operating costs . the relative interquartile range for operating cost only varied from .53 to .54 during the 1985 - 89 period . for capital cost , the same measure was higher and somewhat more variable , ranging from .88 to .94 . further , comparing the ratio of the mean to the median , it is clear that the capital - cost distribution is much more highly skewed to the right than the operating - cost distribution . for capital cost , for operating cost , the mean was only 6 - 8 percent higher than the median . this greater relative variation and skew ness illustrates that a capital payment system based on mean capital costs would tend to redistribute capital payments among hospitals to a greater extent than a comparable system for operating costs . however , because capital cost is on average much smaller than operating cost , the actual number of dollars redistributed would be expected to be smaller than in the case of operating cost . as shown in table 1 , the mean capital cost in 1989 was $ 476 , or about 11.7 percent of the mean operating cost ( $ 4,067 ) . the top 5 percent of hospitals had capital costs greater than $ 1,102 , which is 27 percent of the mean operating cost but only 16 percent of the 95th percentile operating cost ( $ 6,890 ) . although smaller in absolute dollars than in the case of operating cost , the redistribution of capital payments could be large , especially for hospitals in the tails of the distribution . another way to look at the impact of capital - cost variation is to consider its impact on total cost variation . on the one hand , the fact that capital cost represents only about 10.5 percent of total cost will limit its impact . capital and operating inputs may sometimes substitute for one another , which would tend to make them negatively correlated , and at other times may complement each other , which would tend to make them positively correlated . the pearson correlation coefficients shown in table 2 indicate that on balance capital and operating inputs are positively correlated . during 1985 - 89 , this fact will tend to increase the impact of capital cost on total cost variation . it also suggests that payment policy needs to treat both cost elements jointly , because hospitals ' decisions about capital and other inputs are related to one another . to estimate the effect on the variation in capital cost of capital 's relatively small share of total cost and the positive correlation between capital and operating cost , the increase in the standard deviation of total cost per discharge as a result of capital cost was calculated as follows : the variance ( var ) of a sum of two variables equals the sum of the two variances plus twice the covariance of the variables . noting that , by definition , the covariance is the product of the pearson correlation coefficient ( rho ) and the standard deviations ( sd ) of each variable yields : where tot , cap , and op represent total , capital , and operating costs per discharge . because the standard deviation ( the square root of the variance ) is measured in dollars per discharge , it provides a more interpretable measure of the increased variation than does the variance . if capital and operating costs were not correlated , the standard deviation of total cost would only be about 2 percent greater than the standard deviation of operating costs despite the much greater relative variation in capital cost . two percent of the 1989 standard deviation of total cost ( $ 1,928 ) is about $ 38 . however , taking into account the positive correlation between capital and operating costs makes the standard deviation of total cost about 11.5 percent ( or $ 200 ) greater than the standard deviation of operating cost . medicare cost report data confirm that capital cost exhibits much greater variability among hospitals than does operating cost or total cost . the positive correlation between capital and operating costs is responsible for greater variation in total cost than would be expected based on capital 's relatively small share of total cost . the positive correlation between capital and operating costs also supports the view that medicare hospital payment policy should not attempt to deal with capital cost independently . for example , the variables used to explain operating - cost differences and/or to adjust the pps operating payment ( case mix , wage index , teaching , disproportionate share , etc . ) explain more than 70 percent of the variation in medicare operating cost ( pettengill and vertrees , 1982 ; anderson and lave , 1986 ; sheingold , 1990 . ) however , the operating characteristics appeared to account for far less of the variation in medicare capital cost per discharge ( anderson and ginsburg , 1983 . ) often observers lacked relevant data and merely assumed that the greater unexplained capital - cost variation was largely the result of capital 's special age and financing characteristics , which was attributed earlier to its lumpiness . two analyses ( u.s . congressional budget office , 1988 ; prospective payment assessment commission , 1987 ) used examples for individual hypothetical hospitals to demonstrate the effect of age or position in the capital cycle on capital cost . direct empirical evidence on the impact of capital 's special characteristics has more recently begun to accumulate ( american hospital association , 1990 ; cleverly , 1986 ) . this article and the aha paper are among the first analyses to incorporate age and financing factors with the variables typically associated with operating - cost variation . this article differs from other work in its comparative analysis of the variation in capital and total costs . the approach taken in this article was to first apply a typical operating - cost model to capital cost . a log - linear cost function was estimated that included the following variables : the medicare case - mix index ( cmi ) . the level of teaching activity ( measured by the ratio of interns and residents to the average daily census : resday . ) the proportions of poor medicare and medicaid patients ( measured by the disproportionate - share percent with separate slopes for urban and rural hospitals with more and less than 100 beds : disproportionate share for urban hospitals with more than 100 beds ( dsul ) , with less than 100 beds ( dsus ) ; disproportionate share for rural hospitals with more than 100 beds ( dsrl ) , with less than 100 beds ( dsrs ) . in addition , dichotomous variables were included for hospitals with at least 100 beds ( bedsge100 ) , hospitals in metropolitan areas with populations of at least 1 million ( large ) , hospitals in other metropolitan areas ( other ) , and type of ownership ( proprietary : prop or government : govt . ) rural hospitals and voluntary hospitals constitute the omitted categories . second , a capital - cost model was specified that added variables to the operating cost model that attempt to capture the distinctive features of capital . there were two steps in this process : variables that reflect differences in the timing of capital spending were added first . the second set of capital variables reflects differences in financing , occupancy rates , and construction costs . third , the operating - cost model was applied to total cost , and finally , the full - capital model , consisting of all operating variables and both sets of capital variables , was estimated for total cost . before proceeding to the estimation results , because capital has a useful life measured in years , it tends to be purchased in relatively large amounts with less frequency than operating inputs . when new capital is put into service , capital costs rise sharply and then , in the absence of further major capital spending , gradually decline until the next major expenditure . when major projects come on line , a hospital can be expected to move up dramatically in the cross - sectional distribution of capital costs . thus , two otherwise identical hospitals would have different levels of capital cost if the timing of their capital spending is not coincident . the term capital cycle was not used because there need not be regularity or uniformity among hospitals in the pattern of capital spending to produce this type of cost variation ( federal register , 1991 ) . to control for this effect requires a measure of differences among hospitals in the length of time between major capital expenditures . hospitals with recent expenditures will have relatively high capital costs , and hospitals that have not made a major capital purchase for a long time will have relatively low capital costs . however , estimates of the age of a hospital 's capital can serve as proxies . three variables were used in this analysis : the ratio of accumulated depreciation to current depreciation ( age ) , remaining depreciable asset life ( the ratio of net asset value to current depreciation : rlif ) , and the ratio of total fixed assets to total assets ( tfata . ) if a hospital had a single asset with a fixed useful life , rlif would be highly negatively correlated with age because net asset value is the difference between gross asset value and accumulated depreciation . of course , hospitals have many assets of varying age and useful lives , and rlif and age are in fact positively correlated . an old , mostly depreciated plant would tend to increase age , whereas rlif might be more affected by recent equipment purchases . first , because a hospital balance sheet typically includes a variety of capital purchases made at different times , age and rlif at best represent average values . second , they are distorted by the fact that book value and depreciation reflect historical cost . inflation in capital - goods prices means that assets purchased more recently will be more heavily weighted than older assets . as a result however , because depreciation is the largest single component of our capital - cost variable , the use of historical cost also affects our dependent variable . although there may be some impact on the values of the coefficients for age and rlif , it is not clear what effect this measurement problem has on the explanatory power of the equation . third , the ability to separate current depreciation from interest and other capital expenses in medicare cost reports is subject to measurement error . finally , tfata also suffers from the use of historical cost accounting , but it is not affected by limitations in separating depreciation from the other components of capital cost . it should be noted that including these variables will tend to control for differences in the relative frequency of capital spending , but they will not explain why differences in the frequency of capital spending occur . it is beyond the scope of this article to attempt to explain interhospital differences in me frequency of capital spending . the age variables are important because of their impact on the overall explanatory power of the model and the effects they may have on the coefficients of the other variables . consider the following cases : two hospitals are identical except for the fact that one renovated its facility 2 years ago , and the other carried out a comparable renovation 10 years ago . in this case , controlling for age of capital would correctly treat the hospitals as having the same capital cost . a hospital that has been financially successful recently made a large capital expenditure last year because it needed to put its surplus to work . a financially strapped hospital has been unable to make badly needed capital repairs . in this case , controlling for age is also appropriate . the financially successful hospital 's capital cost is in effect lowered , and the financially strapped hospital 's capital cost is raised . the two hospitals are not treated as having different capital costs just because of differences in their financial circumstances . further , if successful and strapped hospitals tend to consistently have certain characteristics found in the operating model , failing to control for age would indirectly attribute differences in financial status to those operating characteristics . a hospital located in a rapidly growing area has made large capital expenditures every year for the last 5 years in order to meet the needs of its population . another hospital located in an area with three other hospitals has experienced declining occupancy for several years and has not made a major capital expenditure for many years . in this case , controlling for age differences will treat the hospitals as being alike , when it would be desirable to recognize the appropriateness of the higher cost of the first hospital . it will not be possible to do so unless other variables that distinguish these hospitals ' circumstances can be identified . in this particular example , several possibilities may be available ( occupancy rates , the rate of area population growth , degree of market competition , etc . ) . however , in general , it most likely will not be possible . the second factor specific to capital - cost variation pertains to debt financing . because medicare capital cost includes interest expense , hospitals that borrow relatively heavily will have higher medicare capital costs than hospitals that use more equity to finance their capital purchases . the ratio of total liabilities to total assets ( tlta ) was included in the cost equation to control for this source of variation . this variable was included instead of the ratio of long - term liabilities to total fixed assets because tlta was more highly correlated with capital cost . this result may occur because , on medicare cost report balance sheets , total categories appear to be more accurately reported than their components . it should be noted that tlta is included in the cost equation to account for variation in medicare capital cost ; no attempt is made to explain the variation in the relative use of debt financing . finally , two additional variables of special interest for capital were included : occupancy rate ( occup ) and a capital construction cost index ( cci ) . the occupancy rate could have been included in the set of operating characteristics but given the more fixed nature of capital cost , occup is expected to have a stronger effect on capital cost . the first three columns contain the capital models , and columns 4 and 5 show the total cost results . column 1 includes only the variables commonly found in operating - cost models . in column 2 the three age - related capital variables intended to account for differences in the timing of capital spending have been added . column 3 presents the full capital model including the effects of relative debt , occupancy , and construction costs . column 4 shows the result of applying the operating model to total cost , and column 5 adds the full set of capital variables to the total - cost model . the data set comprises 2,859 hospitals whose capital variables passed a series of consistency edits . although very similar in many ways , the greatest differences appear to be in urban - rural location and teaching status . only 23 percent of the 2,859 hospitals are in metropolitan areas with a population of more than 1 million , compared with about 26 percent of all hospitals . almost 50 percent of the sample hospitals are in rural areas , compared with less than 47 percent of all hospitals . there may be a systematic relationship between complexity or special features of corporate structure and the absence of usable balance sheets . the effects of this limitation on the cost models reported in this article could not be determined . two years of medicare cost report data ( pps-5 and pps-6 ) were pooled , and a dummy variable was included for the pps-6 year . all variables are derived from medicare cost reports with the exception of the cmi , which is based on fiscal year ( fy ) 1988 and fy 1989 medpar ; wi , which is constructed from the 1988 hcfa wage survey ( excluding the effects of the 1990 - 91 decisions of the medicare geographical classification review board ) ; and the cci , which was developed for hcfa by the center for health economics research ( pope , 1991 . ) the functional form of all models is a hybrid log - linear - exponential function . the dependent - cost variables and all independent variables are in logarithms with the exception of the teaching variable ( resday ) , the disproportionate share variables ( dsul , dsus , dsrl , and dsrs ) , and other dichotomous variables that are exponential in form . table 3 , column 1 shows that the operating - cost model explains 43 percent of the variation in capital cost . case mix shows the strongest effect , followed by the urban dummy variables and the beds variable . for example , the cmi coefficient is much greater than 1 , which implies that capital cost increases disproportionately with case mix . pps operating payments are designed to increase proportionately with case mix , and operating - cost models have supported that relationship . in addition , the urban variables typically are thought of as picking up residual unexplained locational effects not captured by the other key variables . therefore , the large magnitude of the urban variables , combined with the statistically insignificant or marginally significant performance of the wage index , teaching , and disproportionate - share variables , is particularly troublesome . the coefficient of prop indicates that proprietary hospitals ' capital costs are 38 percent higher and ( govt ) hospitals ' costs are 9 percent lower than those of voluntary hospitals . table 3 , column 2 indicates that adding the age of capital variables to the model improves the explanatory power noticeably ( the r increases to .55 ) . also , the behavior of the operating variables resembles somewhat more closely their behavior in operating - cost regressions ( sheingold , 1990 . ) the wage index is now positive and significant , and , as might be expected , its coefficient is much smaller than in operating - cost regressions . the disproportionate - share variables are qualitatively similar to the typical operating - cost model . though not significant , the large urban disproportionate - share variable is now positive , and the small urban and rural variables are negative and generally significant . however , the cmi coefficient still greatly exceeds 1 , and the teaching variable is very close to zero . interestingly , the urban and proprietary hospital dummy variables are reduced dramatically , and only the large urban variable remains statistically significant at the .05 level . this result implies that to a large extent , urban and proprietary hospitals ' higher capital costs result from their greater recent spending . in contrast , the coefficient of the bed - size variable is hardly affected by the addition of the age variables . the results for the full - capital model appear in column 3 of table 3 . there is a small improvement in explanatory power compared with the age - only capital model ( the r is .59 ) . with the exception of the construction - cost index , all the capital variables are strongly statistically significant . the only operating variable that changes much is the wage index , which becomes statistically insignificant . the small , statistically insignificant coefficients of the wage- and construction - cost indexes suggest effects of multicollinearity . indeed , the two indexes are highly positively correlated ( .80 ) . however , regressions not reported in table 3 indicate that merely dropping one of the indexes does not strengthen the remaining index . the interrelationships appear to be more complicated and involve the combination of age and financing variables . to further explore the issue of multicollinearity , the klein test was performed for the full - capital model ( maddala , 1977 . ) the r of each independent variable regressions was then compared with the r of the full - capital model . under the klein test , multicollinearity is likely to create problems when the r of an independent variable regression exceeds that of the main regression . only the wage- and construction - cost indexes fail the strict application of the klein test for all three capital models estimated . however , the cmi also fails the test for the model with only operating variables , and the occupancy rate would fail for similar models . unfortunately , the klein test does not provide a prescription for curing the ills of multicollinearity . a major econometric advantage of the total - cost models is that their higher overall explanatory power reduces the impact of the collinearities . table 3 , column 4 shows the results of applying the operating - cost model to total cost . the r is .72 , and all but two variables are statistically significant at the .05 level . the wage index behaves as expected ; there is a positive , highly significant teaching effect . the disproportionate - share variables for small urban and rural hospitals are negative and statistically significant . . the higher costs of proprietary hospitals compared with voluntary hospitals are statistically significant , but government hospitals ' costs do not differ significantly from those of voluntary hospitals . column 5 of table 3 presents the total - cost results using the full - capital model . although the addition of the capital variables increases the overall explanatory power only slightly ( the r is .73 ) , all of the capital variables are statistically significant with the exception of the variable rlif . however , the elasticities of the capital variables are no larger than .05 , except for the construction - cost index , whose elasticity is .16 . few of the operating - cost variables are affected by the addition of the capital variables , and their coefficients are very similar to those in column 4 . the largest change is the wage index , whose coefficient declines from .71 in column 4 to .60 in column 5 . the addition of the capital variables reduces the coefficient of prop , which is no longer significantly different from 0 at the .05 level . the results previously described demonstrate that the special characteristics of capital have an important effect on the cross - section variation in hospitals ' capital costs . the capital variables perform as expected and add substantial explanatory power to the capital - cost models . the chief implication of this finding is that hospitals ' past capital spending and financing decisions deserve serious attention in working out the transition from cost - based payment to prospective payment . in the long run , a hospital 's medicare prospective payment should , like market prices in general , be independent of the hospital 's capital timing and financing decisions . in this context , the age and financing variables are appropriately used as control variables , serving to prevent their effects from being attributed to other factors that may be used to adjust the long - run payment . however , other problems encountered in estimating the capital - cost models limit their usefulness for prospective payment . first , the medicare balance sheet data required for the construction of the key age and financing variables are unusable for a large number of hospitals . of special concern is the apparent systematic under - representation of certain types of hospitals , such as hospitals from large urban areas , major teaching hospitals , and proprietary hospitals . these types of hospitals may be more likely to have unusual capital items that complicate their balance sheets and result in their failing simple reasonableness screens . second , although the capital variables performed well in the capital - cost models , the key payment variables performed poorly compared with the total - cost model . the coefficient of the case - mix index was greater than 1 , which implies that payments and costs would not be consistent with one another across the range of case - mix values ( as previously discussed ) . also , multicollinearity made it impossible to obtain reasonable estimates of the effects of the wage- and construction - cost indexes . in addition to these limitations of the capital - cost models , there is another reason for preferring to base the long - run capital prospective payment on the total - cost model . in the total - cost model , the capital variables have little impact on the coefficients of the key operating variables . as a result , the capital variables could be ignored in designing payment adjustments based on total cost . assuming that this result holds more generally , the ability to estimate the total - cost model using all hospitals also offers a solution to the problem of sample unrepresentativeness encountered with the capital - cost model . as noted at the beginning of this article , capital 's special characteristics are not unique to hospitals . a single price covering both capital and operating inputs is the norm for most enterprises . a single price or , equivalently , a common set of adjustments for capital and operating payments is also the simplest way to make hospitals indifferent to medicare payment policy in choosing how to combine capital and operating inputs . the empirical findings of this article support using the total - cost models to develop a common set of adjustment factors for capital and operating prospective payment amounts .

the special characteristics of capital have an important effect on the cross - section variation in hospitals ' capital costs . variables reflecting capital age and financing differences perform as expected and add substantial explanatory power to capital cost models . however , even with the inclusion of these variables , the capital - cost models perform poorly compared with total - cost models . the empirical findings of this article support using the total - cost models to develop a common set of adjustment factors for capital and operating payment amounts in the medicare prospective payment system .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Freedom for Workers to Seek Opportunity Act''. SEC. 2. DEFINITIONS. In this Act: (1) Commerce.--The term ``commerce'' has the meaning given such term in section 3 of the Fair Labor Standards Act of 1938 (29 U.S.C. 203). (2) Covenant not to compete.--The term ``covenant not to compete'' means an agreement-- (A) between an employee and employer that restricts such employee from performing-- (i) any work for another employer for a specified period of time; (ii) any work in a specified geographical area; or (iii) work for another employer that is similar to such employee's work for the employer included as a party to the agreement; and (B) that is entered into after the date of enactment of this Act. (3) Employee; employer; enterprise; enterprise engaged in commerce or in the production of goods for commerce; goods.-- The terms ``employee'', ``employer'', ``enterprise'', ``enterprise engaged in commerce or in the production of goods for commerce'', and ``goods'' have the meanings given such terms in section 3 of the Fair Labor Standards Act of 1938 (29 U.S.C. 203). (4) Grocery store.--The term ``grocery store'' means an establishment that sells food for home preparation and consumption and offers for sale, on a continuous basis, a variety of foods in each of the following categories of staple foods, including perishable foods in at least two of the categories: (A) Meat, poultry, or fish. (B) Breads and cereals. (C) Vegetables and fruits. (D) Dairy products. (5) Grocery store employee.--The term ``grocery store employee'' means an employee who is employed by a grocery store. (6) Secretary.--The term ``Secretary'' means the Secretary of Labor. (7) State.--The term ``State'' has the meaning given such term in section 3 of the Fair Labor Standards Act of 1938 (29 U.S.C. 203). SEC. 3. PROHIBITION ON COVENANTS NOT TO COMPETE AND OTHER AGREEMENTS RESTRICTING THE MOBILITY OF GROCERY STORE EMPLOYEES. (a) Covenant Not To Compete.-- (1) In general.--No employer shall enter into a covenant not to compete with any grocery store employee of such employer, who in any workweek is engaged in commerce or in the production of goods for commerce (or is employed in an enterprise engaged in commerce or in the production of goods for commerce). (2) Notice.--An employer subject to subsection (a) shall post, in a conspicuous place on the premises of such employer, a notice of the prohibition set forth in such subsection. (b) Purchase Agreements.--No employer who owns or operates at least one grocery store may, in conjunction with the purchase of one or more grocery stores owned or operated by another employer, include in any agreement between such employers any provision that restricts either employer from hiring a grocery store employee of the other employer. SEC. 4. GROCERY STORE EMPLOYEE RETENTION OF SENIORITY AND BENEFITS AFTER ACQUISITION OR MERGER. An employer who acquires the operations of another employer (hereafter referred to as the former employer) and retains in employment a grocery store employee of the former employer at the same grocery store of the former employer shall continue to recognize, for all employment purposes, the seniority of such grocery store employee, and, to the extent practicable, make available to such employees any benefits made available by the former employer. SEC. 5. ENFORCEMENT. (a) In General.--The Secretary shall receive, investigate, attempt to resolve, and enforce a complaint of a violation of section 3 or 4 in the same manner that the Secretary receives, investigates, and attempts to resolve a complaint of a violation of section 6 or 7 of the Fair Labor Standards Act of 1938 (29 U.S.C. 206 and 207), subject to subsection (b). (b) Civil Fine.-- (1) Maximum fine.--The Secretary shall impose a civil fine-- (A) with respect to any employer who violates section 3(a) or 4, an amount not to exceed $5,000 for each employee who was the subject of such violation; and (B) with respect to any employer who violates section 3(b), an amount not to exceed $5,000. (2) Consideration.--In determining the amount of any civil fine under this subsection, the Secretary shall consider the appropriateness of the fine to the size of the employer subject to such fine and the gravity of the applicable violation.

Freedom for Workers to Seek Opportunity Act This bill: (1) prohibits employers from entering into not-to-compete covenants with any grocery store employees engaged in commerce or in the production of goods for commerce, and (2) requires an employer of such employees to post a notice of this prohibition in a conspicuous place on the employer's premises. No employers who own or operate at least one grocery store may, in conjunction with the purchase of one or more grocery stores owned or operated by another employer, include in any agreement between such employers any provision that restricts either employer from hiring a grocery store employee of the other employer. An employer who acquires the operation of another employer and retains in employment a grocery store employee of the former employee at the same grocery store of the former employer shall continue to recognize, for all employment purposes, the seniority of that grocery store employee, and, to the extent practicable, make available to such employees any benefits made available by the former employer. The Secretary of Labor shall: (1) enforce a complaint of a violation of this Act in the same manner as a complaint of a violation of the Fair Labor Standards Act of 1938, and (2) impose a specified civil fine on any employer who violates this Act.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Hadiya Pendleton and Nyasia Pryear- Yard Gun Trafficking and Crime Prevention Act of 2015''. SEC. 2. FIREARMS TRAFFICKING. (a) In General.--Chapter 44 of title 18, United States Code, is amended by adding at the end the following: ``Sec. 932. Trafficking in firearms ``(a) Offenses.--It shall be unlawful for any person, regardless of whether anything of value is exchanged-- ``(1) to ship, transport, transfer, or otherwise dispose to a person, 2 or more firearms in or affecting interstate or foreign commerce, if the transferor knows or has reasonable cause to believe that such use, carry, possession, or disposition of the firearm would be in violation of, or would result in a violation of any Federal, State, or local law punishable by a term of imprisonment exceeding 1 year; ``(2) to receive from a person, 2 or more firearms in or affecting interstate or foreign commerce, if the recipient knows or has reasonable cause to believe that such receipt would be in violation of, or would result in a violation of any Federal, State, or local law punishable by a term of imprisonment exceeding 1 year; ``(3) to make a statement to a licensed importer, licensed manufacturer, or licensed dealer relating to the purchase, receipt, or acquisition from a licensed importer, licensed manufacturer, or licensed dealer of 2 or more firearms that have moved in or affected interstate or foreign commerce that-- ``(A) is material to-- ``(i) the identity of the actual buyer of the firearms; or ``(ii) the intended trafficking of the firearms; and ``(B) the person knows or has reasonable cause to believe is false; or ``(4) to direct, promote, or facilitate conduct specified in paragraph (1), (2), or (3). ``(b) Penalties.-- ``(1) In general.--Any person who violates, or conspires to violate, subsection (a) shall be fined under this title, imprisoned for not more than 20 years, or both. ``(2) Organizer enhancement.--If a violation of subsection (a) is committed by a person in concert with 5 or more other persons with respect to whom such person occupies a position of organizer, a supervisory position, or any other position of management, such person may be sentenced to an additional term of imprisonment of not more than 5 consecutive years. ``(c) Definitions.--In this section-- ``(1) the term `actual buyer' means the individual for whom a firearm is being purchased, received, or acquired; and ``(2) the term `term of imprisonment exceeding 1 year' does not include any offense classified by the applicable jurisdiction as a misdemeanor and punishable by a term of imprisonment of 2 years or less.''. (b) Technical and Conforming Amendment.--The table of sections for chapter 44 of title 18, United States Code, is amended by adding at the end the following: ``932. Trafficking in firearms.''. (c) Directive to the Sentencing Commission.-- (1) In general.--Pursuant to its authority under section 994(p) of title 28, United States Code, the United States Sentencing Commission shall review and, if appropriate, amend the Federal sentencing guidelines and policy statements applicable to persons convicted of offenses under section 932 of title 18, United States Code (as added by subsection (a)). (2) Requirements.--In carrying out this section, the Commission shall-- (A) review the penalty structure that the guidelines currently provide based on the number of firearms involved in the offense and determine whether any changes to that penalty structure are appropriate in order to reflect the intent of Congress that such penalties reflect the gravity of the offense; and (B) review and amend, if appropriate, the guidelines and policy statements to reflect the intent of Congress that guideline penalties for violations of section 932 of title 18, United States Code, and similar offenses be increased substantially when committed by a person who is a member of a gang, cartel, organized crime ring, or other such enterprise or in concert with another person who is a member of a gang, cartel, organized crime ring or other such enterprise.

Hadiya Pendleton and Nyasia Pryear-Yard Gun Trafficking and Crime Prevention Act of 2015 This bill amends the federal criminal code to make trafficking in firearms a crime. Specifically, it prohibits, with respect to two or more firearms, the following: transfer to or receipt by a prohibited person or a person who plans a subsequent transfer that results in unlawful use, possession, or disposition of such firearms; providing false statements in connection with the purchase, receipt, or acquisition of such firearms; and directing, promoting, or facilitating such prohibited conduct. A person who commits or conspires to commit a gun trafficking offense is subject to a prison term of up to 20 years (or 25 years if such person also acted as an organizer).&nbsp; The U.S. Sentencing Commission must review and, if appropriate, amend the sentencing guidelines and policy statements that apply to persons convicted of trafficking in firearms.

vitamin b12 had been usually treated as sport nutrition , and used to keep old people from getting anemic in past years . recently studies have shown that vitamin b12 played a key role in the normal functioning of the brain and nervous system and the formation of blood . vitamin b12 is normally involved in several metabolisms such as dna synthesis and regulation , fatty acid synthesis , and energy production . vitamin b12 has some analogs including cyanocobalamin ( cncbl ) , methylcobalamin ( mecbl ) , hydroxocobalamin ( ohcbl ) , and adenosylcobalamin ( adocbl ) . in mammalian cells , cncbl and ohcbl are inactive forms and adocbl acts as a coenzyme of methylmalonyl co - a mutase in mitochondria . however , vitamin b12 was not used directly in human body , and it should be translated into activating forms such as mecbl or adocbl . mecbl differs from vitamin b12 in that the cyanide is replaced by a methyl group ( figure 1 ) . it is a coenzyme of methionine synthase , which is required for the formation of methionine from homocysteine in the methylation cycle which involves methylation of dna or proteins [ 25 ] . compared with other analogs , mecbl is the most effective one in being uptaken by subcellular organelles of neurons . therefore , mecbl may provide better treatments for nervous disorders through effective systemic or local delivery . as an auxiliary agent , mecbl has been always used to treat many diseases , such as b12 deficiency and alzheimer 's disease syndromes [ 6 , 7 ] . l - methylfolate , mecbl , and n - acetylcysteine improved memory , emotional functions , and communication with other people among alzheimer 's patients [ 7 , 8 ] . mecbl also has neuronal protection including promoting injured nerve and axonal regeneration [ 9 , 10 ] and confronting against glutamate - induced neurotoxicity [ 9 , 11 ] . in addition , mecbl improved nerve conduction in either patients of diabetic neuropathy [ 1214 ] or streptozotocin - diabetic rats and experimental acrylamide neuropathy . mecbl also improved visual function , rheumatoid arthritis , bell 's palsy , and sleep - wake rhythm disorder [ 19 , 20 ] . recently , mecbl has been demonstrated to have potential analgesic effects on neuropathic pain in experimental and clinical studies . mecbl is one active form of vitamin b12 which can directly participate in homocysteine metabolism . more and more researches showed that mecbl has beneficial effects on clinical and experimental peripheral neuropathy . clinical symptoms in legs , such as paresthesia , burning pains , and spontaneous pain , were ameliorated by mecbl [ 21 , 22 ] ( table 1 ) . the effects of single use of mecbl or combined use with other drugs were reviewed in diabetic neuropathy pain [ 12 , 23 ] ( table 1 ) . clinical evidence proved that mecbl had the capacity to inhibit the neuropathic pain associated with diabetic neuropathy . the intensity of the pain is variable and may be described as a hot , burning , cold , aching , or itching sensation with , at times , increased skin sensitivity . in clinics , it is still a challenge to treat diabetic neuropathic pain . carbamazepine and dolantin were not able to relieve these symptoms . similarly , therapeutic effects of aldose reductase inhibitors and nimodipine were not encouraging in clinic as much as basic studies showed . fortunately , mecbl may bring a glimmer of hope to treat diabetic neuropathic pain . between 70 and 80% but the causes are extensive , cancer , infection , inflammatory disorders , structural disorders of the spine itself , and disk herniation , are somewhat more common , and together account for back pain . it is supposed that the mecbl is becoming a decent choice for the therapy to the chronic low back pain . neurogenic claudication distance was improved significantly after the application of mecbl ( table 2 ) . however waikakul 's research demonstrated that mecbl was not good for pain on lumbar spinal stenosis . in a trial , the analgesic effect of mecbl has been investigated in nonspecific low back pain patients with intramuscular injection ( table 2 ) . the inconsistent effect of mecbl might be due to different causes of lumbar spinal stenosis and nonspecific low back pain . chronic neck pain is becoming a common problem in the adult population , for the prevalence of 30%50% in 12 months [ 27 , 28 ] . it was shown that spontaneous pain , allodynia , and paresthesia of patients with neck pain were improved significantly in the mecbl group , and with the increase of treatment time of mecbl , the analgesic effect was more obvious ( table 2 ) . the treatment of mecbl significantly reduced continuous pain , paroxysmal pain , and allodynia in the subacute herpetic neuralgia ( shn ) patients ( table 3 ) . it was reported that the numerical pain scales were decreased substantially with the treatment of mecbl combined with gabapentin and tramadol in gpn patients ( table 3 ) . and degree of interference in quality of life including mood , interpersonal relationship , and emotion the pain of trigeminal neuralgia ( tn ) can be described as agonizing , paroxysmal and lancinating which may be activated by small activities such as chewing , speaking , and swallowing . a clinical trial proved that the pain of tn patients was alleviated greatly in the mecbl group , and no recurrence of tn in pain symptoms was closed to 64% ( table 3 ) . the coapplication of mecbl and pioglitazone dramatically decreased allodynia and hyperalgesia in diabetic rats . and the combined application of mecbl and vitamin e alleviated thermal hyperalgesia in sciatic nerve crush injured rats . our recent work observed that tactile allodynia was markedly alleviated following a chronic treatment of mecbl injection in chronic compression of dorsal root ganglion ( ccd ) rats ( figure 2 ) . for many years , the b12 group of vitamins had been used to treat pain . in some countries , it was suggested that vitamin b12 may increase availability and effectiveness of noradrenaline and 5-hydroxytryptamine in the descending inhibitory nociceptive system . mecbl exerted therapeutic effects on neuropathic pain in diabetics , possibly through its neurosynthesis and neuroprotective actions [ 13 , 36 ] . previous studies showed that high doses of mecbl improved nerve conduction in either patients with diabetic neuropathy [ 1214 ] , streptozotocin - diabetic rats , or experimental acrylamide neuropathy . morphological and histological evidence confirmed that a long - term administration of mecbl promoted the synthesis and regeneration of myelin . these morphological and histological recoveries of myelin may result in improving nerve conduction velocity and neuronal function in peripheral neuropathy . mecbl advanced the incorporation of radioactive leucine into the protein fraction of the crushed sciatic nerve in vivo . as a result , the most terminals were degenerated in the mutant mouse , but the sprouts were more frequently observed in the mecbl treatment group . mecbl had the ability to promote the injured nerves regeneration . in the experimental acrylamide neuropathy and sciatic nerve injury models , the number of regenerations of motor fibers showed significant increase with high - dose methylcobalamin . and the combined use of l - methylfolate , mecbl , and pyridoxal 5-phosphate improved the calf muscle surface neural density . ectopic spontaneous discharges are likely to initiate spontaneous pain , hyperalgesia , and allodynia [ 4145 ] . it was reported that mecbl suppressed the ectopic firing induced by chemical materials in the dog dorsal root . our recent work demonstrated that mecbl markedly inhibited the ectopic spontaneous discharges of dorsal root ganglion neurons in ccd rats ( figure 3 ) . our results suggested that mecbl exhibited its anti - allodynic effect by inhibiting peripheral pain signals . mecbl or its combined use with other agents has the potential analgesic effect in specific patients and animal models , for example , nonspecific low back pain ; neck pain ; diabetic neuropathic pain , subacute herpetic neuralgia , glossopharyngeal neuralgia , and trigeminal neuralgia . however , its mechanisms underlying the analgesic effect were poorly understood . on the basis of recent work , ( 1 ) mecbl improved nerve conduction velocity ; ( 2 ) mecbl promoted injured nerve regeneration , recovering the neuromuscular functions in peripheral hyperalgesia and allodynia ; and ( 3 ) mecbl inhibited the ectopic spontaneous discharges from peripheral primary sensory neurons in neuropathic pain states . as a vitamin , mecbl may be a potential candidate for treating peripheral neuropathy with good safety .

methylcobalamin ( mecbl ) , the activated form of vitamin b12 , has been used to treat some nutritional diseases and other diseases in clinic , such as alzheimer 's disease and rheumatoid arthritis . as an auxiliary agent , it exerts neuronal protection by promoting regeneration of injured nerves and antagonizing glutamate - induced neurotoxicity . recently several lines of evidence demonstrated that mecbl may have potential analgesic effects in experimental and clinical studies . for example , mecbl alleviated pain behaviors in diabetic neuropathy , low back pain and neuralgia . mecbl improved nerve conduction , promoted the regeneration of injured nerves , and inhibited ectopic spontaneous discharges of injured primary sensory neurons . this review aims to summarize the analgesic effect and mechanisms of mecbl at the present .

usarsim is a high fidelity simulation of urban search and rescue ( usar ) robots and environments intended as a research tool for the study of human - robot interaction ( hri ) and multirobot coordination . usarsim is designed as a simulation companion to the national institute of standards and technology ( nist ) reference test facility for autonomous mobile robots for urban search and rescue@xcite . + as the time passed , the usarsim has been used for broader range of robot simulations . the acronym was converted to unified system for automation and robot simulation . but it is still usarsim . + aerial vehicles in this environment play a very important role@xcite . they act as the eyes of a bird , flying in the sky and informing the other robots about the environment . the better they take pictures , the better other robots will cooperate . in the other hand two main questions arise . the first one is how to merge these pictures to have a general map . the second question is what to do with this map . in the following parts we will talk about these issues . + there are two aerial vehicles implemented in the usarsim , a blimp named as passarola and a quadcopter named as airobot as shown in figure 1 . both of these vehicles have the ability to carry a camera to take some pictures . + the best and easiest way of using sequence of pictures is to create a photomap from them . this photomap would be very useful for localization purposes . creating such a map is not easy and takes a long time to develop an algorithm to handle it . there are several image processing algorithms used for registering sequence of images in order to create a photo map . one of these algorithms that uses fourier melin transform has been developed by dr bulow is used in our system . even if there is such an algorithm , we still have some problems . + one of the challenging problems in having a photomap is having a decent sequence of images that an image processing algorithm can handle@xcite . one of these problems is movements of the camera . according to the movements of camera the image processing algorithm has to do some scaling , rotation or translation processes . the less the changes , the better the final map will be . intrinsically , passarola has a huge amount of inertia that makes its movements smoother . that makes it move without abrupt changes in altitude or position . in the better word , its movements along x , y , and z axises will be smoother . thus we chose passarola for carrying the camera . + in the following parts of this report we will explain what we have done in detail . there is an implementation of fmi in matlab and another in c++ @xcite . the c++ one was in the experements folder of jacobotics source code and was basically developed to work with the philips webcam in order to test some parts of fmi algorithm . since that camera was a real camera and there are some issues regarding calibration , they had to be considered during photomaping . when we are working in a simulated area , no calibration is required@xcite . the first task we did was to change the fmi source code in c++ language . so we added a new parameter to its constructor under the name of calibration . if it is set in the constructor , calibration will be done . otherwise it wo nt do calibration . + the second task that we did was to move the fmi source code from experimnets to the library folder , and set the pathes and links . then everybody can use it easily . at the moment it is in the lib / mapping / fmi folder . + then we configured a blimp to have a downlooking camera and some other things like propellers etc . we added two important sections in jacobotics source code . one of them is an actuator to drive our blimp , and the other is an image grabber to take pictures and create a photomap of them . the actuator is inside /lib / virtual / actuators / passaroladrive . for using this package it is required to create an object from this type and use setmotorspeeds method . it receives three parameters and returns nothing . this method generally sets the motor speed of one of the propellers . the parameters are xzangle , thrustpropeller and tailpropeller + where + xzangle , float , is the rotation angle of the support thrust motors bars , that make possible change the altitude of the robot ( i.e up / down ) . the value is the absolute rotation angle , in radians per second . + thrustpropeller , float , is the module of the velocity vector to be applied by the front thrusters , to move the robot in the x0z plane ( i.e forward / backward and up / down as the value of xzangle ) . the value is the absolute linear velocity , in meters per second . + tailpropeller , float , is the rotational velocity ( i.e left / right ) . the value is the absolute rotational velocity , in meters per second . + the other section that i added was passarolaimagegrabber . it is placed in lib / virtual / autonomy / passarolaimagegrabber . this part is responsible for getting pictures from the image server and store them in files . these files could be used for testing fmi algorithm in offline mode , but it could be easily disabled . since we are in the phase of testing this algorithm , we prefered to enable this feautre . + the next importnat part done in this file is to apply fmi on the sequence of images captured from the camera . our fmi algorithm works only on special format pictures . since the image server can take picures only in colored format and rectangular format , we have to convert them to grayscale and square shape . for doing this task we used graphicmagick library . so for using this part the user has to install this package first . after cropping and converting the picture sequence , we applied fmi algorithm to it . the output of the fmi algorithm is x , y , rotation and scale . these variables associated with the new image can create the whole photomap . in order to create the photomap , we put the new picture in the appropriate place in our gui . we developed our own gui using opencv to present the output of the algorithm in online mode . one of the outputs is shown in figure 2 . the real environment that we applied our algorithm is shown in figure 3 . one of the problems of using opencv is that it needs a fixed size for the photomap . since we are creating the map in time , it is a growing map and we ca nt have a fixed size for it . there are several solutions for handling it , but everything should be done from scratch . so it would be easier to use their gui . + the idea was to send these variables and images to the original gui . then we had to send it on wireless simulation server to be captured by that gui . we talked with them and ravi said they are to change the image message and it is not possible to send it to their gui . the other option is not to use wss server and use some parts of their source code and develop our own qtobject in order to integrate it with their gui . but lots of things have to be changed , because their gui slows down when the number of images is increasing . so it is not again usable and we have to fix this problem of the gui first . by default qt is repainting everything on its canvas . it does nt care which part has recetly been changed . this will force high workload on cpu and memory of the computer , and slows down the overal progress . the idea is to render and repaint only the newer part in photomap . since it was suggested very late , a few days ago , we havent had enough time to do it yet . but we are trying to do it as soon as possible . having a general map of a disaster situation is very useful in a cooperative multirobot system . in this report we explained our approach for integrating fmi algorithm into jacobotics source code , in order to have a growing map of the environmet in a disaster situation . we showed that the job was done pretty well , but there are still some tasks to be done in near future . the most important task is to take it to a qt gui from an opencv one . + 1 usarsim : unified system for automation and robotics simulator ( usarsim ) ( 2006 ) b. zitova , j. flusser , image registration mehotds : a survey , elsevier , ( 2003 ) a. jacoff , e. messina , j. evans . experiences in deploying test arenas for autonomous mobile robots , in proceedings of performance metrics for intelligent systens , 2001 . nuchter , andreas , seyedshams feyzabadi , deyuan qiu , and stefan may . `` slam la carte - gpgpu for globally consistent scan matching . '' in ecmr , pp . 271 - 276 . 2011 . lucas , bruce d. , and takeo kanade . `` an iterative image registration technique with an application to stereo vision . baumann , peter , shams feyzabadi , and constantin jucovschi . `` putting pixels in place : a storage layout language for scientific data . '' data mining workshops ( icdmw ) , 2010 ieee international conference on . ieee , 2010 . maes , frederik , et al . `` multimodality image registration by maximization of mutual information . '' medical imaging , ieee transactions on 16.2 ( 1997 ) : 187 - 198 . feyzabadi , s. , and j. schonwalder . `` identifying tcp congestion control algorithms using active probing . '' passive and active measurement conference ( pam ) , poster .

creating a photomap plays a critical role in navigation . therefore , flying vehicles are usually used to create topdown maps of the environment . in this report we used two different aerial vehicles to create a map in a simulated environment * photomapping using + aerial vehicle in usarsim * + su kim

SECTION 1. SHORT TITLE. This Act may be cited as the ``Biofuel Engineering Training Act''. SEC. 2. DEFINITION. In this Act-- (1) the term ``biofuel engineering'' means the discipline concerned with utilization of harvested living plant material to produce fuels; and (2) the term ``Secretary'' means the Secretary of Energy. SEC. 3. STUDY AND DEVELOPMENT OF STANDARDS. The Secretary shall make a grant to an appropriate standard-setting or other entity to conduct a study of, and develop appropriate standards for, accreditation of undergraduate and graduate biofuel engineering programs at institutions of higher education, and to study and the needs of the biofuel industry for engineering support. Such study shall include-- (1) a determination of subspecialty requirements for engineers who will concentrate on creating other products in addition to fuel, including animal feed and other consumer products; (2) consideration of the interaction of biological feedstock with the structural material in the production and distribution systems, the carbon footprint of the production and distribution of biofuels, and related genetic challenges; and (3) supplemental courses of study that could be used by experienced engineers for transition into the new biofuel engineering discipline. SEC. 4. CENTERS OF EXCELLENCE FOR BIOFUELS RESEARCH AND TRAINING. (a) Establishment.--The Secretary shall establish, through the Office of Science, Centers of Excellence for Biofuels Research and Training at institutions of higher education or consortia of such institutions across the country. (b) Selection.-- (1) In general.--The Secretary shall award grants for the establishment of Centers of Excellence to eligible institutions through a competitive application process. (2) Criteria.--The Secretary shall establish selection criteria for awarding grants under paragraph (1). These criteria shall require participating institutions to-- (A) effectively integrate biofuels research, training, and instruction; (B) bring together the study and practice of a broad range of disciplines with relevance to biofuel engineering; (C) work with companies that are in the process of commercializing biofuels technology; and (D) work with local communities to assist with economic development and job creation in the biofuels sector. (c) Authorization of Appropriations.--There are authorized to be appropriated to the Secretary for carrying out this section $10,000,000 for each of fiscal years 2010 through 2014. SEC. 5. BIOFUEL ENGINEERING GRADUATE FELLOWSHIP PROGRAM. (a) Definition of Eligible Student.--In this section, the term ``eligible student'' means a student who attends an institution of higher education that offers a doctoral or masters degree in the biofuel engineering field. (b) Establishment.--The Secretary shall establish a graduate fellowship program for eligible students pursuing a doctoral degree in the biofuel engineering field. (c) Selection.-- (1) In general.--The Secretary shall award fellowships to eligible students under this section through a competitive merit review process, involving written and oral interviews. (2) Criteria.--The Secretary shall establish selection criteria for awarding fellowships under this section that require an eligible student-- (A) to pursue a field of science or engineering of importance to a mission area of the Department; (B) to demonstrate to the Secretary-- (i) the capacity of the eligible student to understand technical topics relating to the fellowship that can be derived from the first principles of the technical topics; (ii) imagination and creativity; (iii) leadership skills in organizations or intellectual endeavors, demonstrated through awards and past experience; (iv) excellent verbal and communication skills to explain, defend, and demonstrate an understanding of technical subjects relating to the fellowship; and (v) an understanding of how the many disciplines relevant to biofuel engineering interact in the biofuel engineering field; and (C) to be a citizen or legal permanent resident of the United States. (d) Awards.-- (1) Amount.--A fellowship awarded under this section shall-- (A) provide an annual living stipend; and (B) cover-- (i) graduate tuition at an institution of higher education described in subsection (a); and (ii) incidental expenses associated with curricula and research at the institution of higher education (including books, computers, and software). (2) Duration.--A fellowship awarded under this section shall be for up to 3 years of study within a 5-year period. (3) Portability.--A fellowship awarded under this section shall be portable with the eligible student. (e) Administration.--The Secretary-- (1) shall administer the program established under this section through the Office of Science; and (2) may enter into a contract with a nonprofit entity to administer the program, including the selection and award of fellowships. (f) Authorization of Appropriations.--There are authorized to be appropriated to the Secretary to carry out this section $3,500,000 for each fiscal year. SEC. 6. AVAILABILITY OF FEDERAL FACILITIES. Agencies of the Federal Government, including national laboratories, shall make research facilities available to accredited biofuel engineering programs for faculty and students to enhance education and training opportunities.

Biofuel Engineering Training Act - Directs the Secretary of Energy to award a grant to an appropriate standard-setting or other entity to: (1) develop appropriate standards for the accreditation of undergraduate and graduate biofuel engineering programs at institutions of higher education (IHEs); and (2) study the needs of the biofuel industry for engineering support. Requires the Secretary to award competitive grants to IHEs to establish Centers of Excellence for Biofuels Research and Training that: (1) integrate biofuels research, training, and instruction; (2) coordinate the broad range of disciplines relevant to biofuels engineering; and (3) work with companies that are commercializing biofuels technology, and local communities spurring economic development and job creation in the biofuels sector. Directs the Secretary to award portable graduate fellowships to students pursuing doctorates in biofuels engineering. Requires the fellowships, which are for up to three years of study, to provide recipients with an annual living stipend, and cover graduate tuition and incidental expenses. Requires federal agencies, including national laboratories, to make research facilities available to accredited biofuel engineering programs.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Health Care Access for Small Businesses Act of 2006''. SEC. 2. THREE-SHARE PROGRAMS. The Social Security Act (42 U.S.C. 301 et seq.) is amended by adding at the end the following: ``TITLE XXII--PROVIDING FOR THE UNINSURED ``SEC. 2201. THREE-SHARE PROGRAMS. ``(a) Pilot Programs.--The Secretary, acting through the Administrator, shall award grants under this section for the startup and operation of 50 eligible three-share pilot programs for a 5-year period. ``(b) Grants for Three-Share Programs.-- ``(1) Establishment.--The Administrator may award grants to eligible entities-- ``(A) to establish three-share programs; ``(B) to provide for contributions to the premiums assessed for coverage under a three-share program as provided for in subsection (c)(2)(B)(iii); and ``(C) to establish risk pools. ``(2) Three-share program plan.--Each entity desiring a grant under this subsection shall develop a plan for the establishment and operation of a three-share program that meets the requirements of paragraphs (2) and (3) of subsection (c). ``(3) Application.--Each entity desiring a grant under this subsection shall submit an application to the Administrator at such time, in such manner and containing such information as the Administrator may require, including-- ``(A) the three-share program plan described in paragraph (2); and ``(B) an assurance that the eligible entity will-- ``(i) determine a benefit package; ``(ii) recruit businesses and employees for the three-share program; ``(iii) build and manage a network of health providers or contract with an existing network or licensed insurance provider; ``(iv) manage all administrative needs; and ``(v) establish relationships among community, business, and provider interests. ``(4) Priority.--In awarding grants under this section the Secretary shall give priority to an applicant-- ``(A) that is an existing three-share program; ``(B) that is an eligible three-share program that has demonstrated community support; or ``(C) that is located in a State with insurance laws and regulations that permit three-share program expansion. ``(c) Grant Eligibility.-- ``(1) In general.--The Secretary, acting through the Administrator, shall promulgate regulations providing for the eligibility of three-share programs for participation in the pilot program under this section. ``(2) Three-share program requirements.-- ``(A) In general.--To be determined to be an eligible three-share program for purposes of participation in the pilot program under this section a three-share program shall-- ``(i) be either a non-profit or local governmental entity; ``(ii) define the region in which such program will provide services; ``(iii) have the capacity to carry out administrative functions of managing health plans, including monthly billings, verification/enrollment of eligible employers and employees, maintenance of membership rosters, development of member materials (such as handbooks and identification cards), customer service, and claims processing; and ``(iv) have demonstrated community involvement. ``(B) Payment.--To be eligible under paragraph (1), a three-share program shall pay the costs of services provided under subparagraph (A)(ii) by charging a monthly premium for each covered individual to be divided as follows: ``(i) Not more than 30 percent of such premium shall be paid by a qualified employee desiring coverage under the three-share program. ``(ii) Not more than 30 percent of such premium shall be paid by the qualified employer of such a qualified employee. ``(iii) At least 40 percent of such premium shall be paid from amounts provided under a grant under this section. ``(iv) Any remaining amount shall be paid by the three-share program from other public, private, or charitable sources. ``(C) Program flexibility.--To provide program design flexibility to accommodate the needs of different States, regions, and communities, both urban and rural, a three-share program may include the following: ``(i) Income eligibility guidelines for enrollment purposes. ``(ii) Procedures to permit the enrollment of individuals, as well as small businesses, in which case the enrollee would be responsible for payment of the employer's share of the premium. ``(iii) For individual enrollees, and employer groups of less than 4 individuals, the program may impose limitations on the payment of services for pre-existing health conditions during the first year of enrollment. ``(3) Coverage.-- ``(A) In general.--To be an eligible three-share program under this section, the three-share program shall provide at least the following benefits: ``(i) Physicians services. ``(ii) In-patient hospital services. ``(iii) Out-patient services. ``(iv) Emergency room visits. ``(v) Emergency ambulance services. ``(vi) Diagnostic lab fees and x-rays. ``(vii) Prescription drug benefits. ``(B) Limitation.--Nothing in subparagraph (A) shall be construed to require that a three-share program provide coverage for services performed outside the region described in paragraph (2)(A)(i). ``(C) Preexisting conditions.--A program described in subparagraph (A) shall not be an eligible three- share program under paragraph (1) if any individual can be excluded from coverage under such program because of a preexisting health condition. ``(d) Grants for Existing Three-Share Programs To Meet Certification Requirements.-- ``(1) In general.--The Administrator may award grants to three-share programs that are operating on the date of enactment of this section. ``(2) Application.--Each eligible entity desiring a grant under this subsection shall submit an application to the Administrator at such time, in such manner, and containing such information as the Administrator may require. ``(e) Application of State Laws.--Nothing in this section shall be construed to preempt State law. ``(f) Distressed Business Formula.-- ``(1) In general.--Not later than 60 days after the date of enactment of this section, the Administrator of the Health Resources and Services Administration shall develop a formula to determine which businesses qualify as distressed businesses for purposes of this section. ``(2) Effect on insurance market.--Granting eligibility to a distressed business using the formula under paragraph (1) shall not interfere with the insurance market. Any business found to have reduced benefits to qualify as a distressed business under the formula under paragraph (1) shall not be eligible to be a three-share program for purposes of this section. ``(g) Definitions.--In this section: ``(1) Administrator.--The term `Administrator' means the Administrator of the Health Resources and Services Administration. ``(2) Covered individual.--The term `covered individual' means-- ``(A) a qualified employee; or ``(B) a child under the age of 23 or a spouse of such qualified employee who-- ``(i) lacks access to health care coverage through their employment or employer; ``(ii) lacks access to health coverage through a family member; ``(iii) is not eligible for coverage under the medicare program under title XVIII or the medicaid program under title XIX; and ``(iv) does not qualify for benefits under the State Children's Health Insurance Program under title XXI. ``(3) Distressed business.--The term `distressed business' means a business that-- ``(A) in light of economic hardship and rising health care premiums may be forced to discontinue or scale back its health care coverage; and ``(B) qualifies as a distressed business according to the formula under subsection (g). ``(4) Eligible entity.--The term `eligible entity' means an entity that meets the requirements of subsection (a)(2)(A). ``(5) Qualified employee.--The term `qualified employee' means any individual employed by a qualified employer who meets certain criteria including-- ``(A) lacking access to health coverage through a family member or common law partner; ``(B) not being eligible for coverage under the medicare program under title XVIII or the medicaid program under title XIX; and ``(C) agreeing that the share of fees described in subsection (a)(2)(B)(i) shall be paid in the form of payroll deductions from the wages of such individual. ``(6) Qualified employer.--The term `qualified employer' means an employer as defined in section 3(d) of the Fair Labor Standards Act of 1938 (29 U.S.C. 203(d)) who-- ``(A) is a small business concern as defined in section 3(a) of the Small Business Act (15 U.S.C. 632); ``(B) is located in the region described in subsection (a)(2)(A)(i); and ``(C) has not contributed to the health care benefits of its employees for at least 12 months consecutively or currently provides insurance but is classified as a distressed business. ``(h) Evaluation.--Not later than 90 days after the end of the 5- year period during which grants are available under this section, the General Accounting Office shall begin preparing a report for the Secretary and the appropriate committees of Congress concerning-- ``(1) the effectiveness of the programs established under this section; ``(2) the number of individuals covered under such programs; ``(3) any resulting best practices; and ``(4) the level of community involvement. ``(i) Authorization of Appropriations.--There is authorized to be appropriated and there is appropriated to carry out this section $100,000,000 for each of fiscal years 2007 through 2012.''.

Health Care Access for Small Businesses Act of 2006 - Amends the Social Security Act to create a new title XXII to require the Secretary of Health and Human Services, acting through the Administrator of the Health Resources and Services Administration, to award grants for the startup and operation of 50 eligible three-share pilot programs for a five-year period. Characterizes a three-share program as three-way health insurance premium sharing among employer, employee, and the grant funds. Authorizes the use of grants to establish three-share programs, provide for contributions to premiums, and establish risk pools. Requires grant applicants to: (1) be either nonprofits or local governmental entities; (2) define the program's service region; (3) have the capacity to carry out administrative functions associated with managing health plans; and (4) have demonstrated community involvement. Requires programs to pay for the costs of services through monthly premiums, divided among employee, employer, and grant funds according to specified percentages. Sets forth minimal coverage requirements for three-share program eligibility. Requires the Administrator to develop a formula to determine which businesses qualify as distressed businesses for purposes of this Act.

do events have already been simulated by a variety of models , ranging from simple conceptual ones to earth system models of intermediate complexity ( emics ) . conceptual models are most suitable to perform large numbers of long - term investigations because they require very little computational cost . however , they are often based on ad - hoc assumptions and only consider processes in a highly simplified way . in addition to that , the number of adjustable parameters is typically large compared to the degrees of freedom in those models . this implies that seemingly good results can often be obtained merely by excessive tuning . nevertheless , conceptual models can provide important help for the interpretation of complex climatic processes . the gap between conceptual models and the most comprehensive general circulation models ( gcms ) , which are not yet applicable for millennial - scale simulations because of their large computational cost , is bridged by emics @xcite . emics include most of the processes described in comprehensive models ( in a more reduced form ) , and interactions between different components of the earth system ( atmosphere , hydrosphere , cryosphere , biosphere , etc . ) are simulated . the number of degrees of freedom typically exceeds the number of adjustable parameters by orders of magnitude . since many emics are fast enough for studies on the multi - millennial time scale , they are the most adequate tools for the simulation of do events . the simple conceptual model which we use here is an extended version of the model described by @xcite ( in the supplementary material of that publication ) . here we use the model to demonstrate and analyse two apparently counterintuitive resonance phenomena ( _ stochastic resonance _ and _ ghost resonance _ ) that can exist in a large class of highly nonlinear systems . due to the complexity of many of those systems it is often impossible to precisely identify the reasons for the occurrence of these resonance phenomena . our conceptual model , in contrast , has a very clear forcing - response relation as well as a very low computational cost and thus provides a powerful tool to explore these phenomena and to test their robustness . furthermore , we describe and discuss the applicability of the model for improved statistical analyses ( i.e. monte - carlo simulations ) on the regularity of do events . in the following the key assumptions of the conceptual model are first discussed . in the supplementary material we then compare the model performance under a number of systematic forcing scenarios with the performance of a more comprehensive model ( the emic climber-2 ) , compare supplementary information file and supplementary figs . 1 - 6 . in the framework of the conceptual model we finally demonstrate and interpret two hypotheses that were previously suggested in order to explain the recurrence time of do events , and we discuss how these hypotheses could be tested our conceptual model is based on three key assumptions : 1 . do events represent repeated transitions between two different climate states , corresponding to warm and cold conditions in the north atlantic region . these transitions are rapid compared to the characteristic life - time of the two climate states ( i.e. in first order approximation they occur instantaneously ) and take place each time a certain threshold is crossed . 3 . with every transition between the two states the threshold overshoots and afterwards approaches equilibrium following a millennial - scale relaxation process . this implies that the conditions for a switch between both states ameliorate with increasing duration of the cold and warm intervals . our three assumptions are supported by paleoclimatic evidence and/or by simulations with a climate model : 1 . since long , do events have been regarded as repeated oscillations between two different climate states @xcite . it has been suggested that these states are linked with different modes of operation of the thc @xcite . this seminal interpretation has since then influenced numerous studies and is now generally accepted @xcite . indirect data indicate that the glacial thc indeed switched between different modes of operation @xcite which , according to their occurrence during cold and warm intervals in the north atlantic , were labelled stadial and interstadial modes . a third mode named heinrich mode ( because of its presence during the so - called heinrich events ) is not relevant here . high - resolution paleoclimatic data show that transitions from cold conditions in the north atlantic region to warm ones often happened very quickly , i.e. on the decadal - scale or even faster @xcite . the opposite transitions were slower , i.e. on the century - scale @xcite , but nevertheless still faster that the characteristic life - time of the cold and warm intervals ( which is on the centennial to multi - millennial time scale , compare fig . the abruptness of the shifts from cold conditions to warm ones has commonly been interpreted as evidence for the existence of a critical threshold in the climate system that needs to be crossed in order to trigger a shift between stadial and interstadial conditions @xcite . such a threshold could be provided by the thc ( more precisely , by the process of deep - water formation ) : when warm and salty surface water from lower latitudes cools on its way to the north atlantic , its density increases . if the density increase is large enough ( i.e. if the surface gets denser than the deeper ocean water ) , surface water starts to sink . otherwise , surface water can freeze instead of sinking . the onset of deep - water formation can thus hinder sea - ice formation and facilitate sea - ice melting ( due to the vertical heat transfer between the surface and the deeper ocean ) . a switch between two fundamentally different modes of deep - water formation can thus dramatically change sea ice cover and can cause large - scale climate shifts . such nonlinear , threshold - like transitions between different modes of deep - water formation are at present considered as the most likely explanation for do events @xcite . 3 . the time - evolution of greenland temperature during the warm phase of do events has a characteristic saw - tooth shape ( fig . [ fig : figure1 ] ) . highest temperatures typically occur during the first decades of the events . these temperature maxima are followed by a gradual cooling trend over centuries / millennia , before the system returns to cold conditions at the end of the events . this asymmetry supports the idea that the system overshoots in some way during the abrupt warming at the beginning of the events and that the subsequent cooling trend represents a millennial - scale relaxation towards a new equilibrium @xcite . we note that the time - evolution of greenland temperature provides no clear evidence for an overshooting during the opposite transitions ( i.e. from the warm state back to the cold one ) . this , however , is not necessarily in contradiction to our assumption : this lack of an overshooting in the temperature fields does not necessarily mean that the ocean - atmosphere system did not overshoot , since greenland temperature evolution in the stadial state might have been dominated by factors other than the thc ( respectively its stability ) , e.g. by greenland ice accumulation , which would mask the signature of the thc in the ice core data . + we will show later ( in sect . 3.3 . ) that the assumption of an overshooting in the stability of the system is in fact strengthened by the analysis of model results obtained with the coupled model climber-2 . in that model the overshooting results from the dynamics of the transitions between the two climate states : in the stadial state deep convection occurs south of the greenland - scotland ridge ( i.e. at about 50 @xmath0n ) . in the interstadial state , however , deep convection takes place north of the ridge ( i.e. at about 65 @xmath0n ) . the onset of deep convection north of the greenland - scotland ridge , which releases accumulated energy to the atmosphere ( i.e. heat that is stored mainly in the deep ocean ) , in first place starts do events in the model . this heat release leads to a reduction of sea ice , which in turn further enhances sea surface densities between 50 @xmath0n and 65 @xmath0n ( e.g. by increased local evaporation and reduced sea ice transport into that area ) . as a result deep convection also starts between 50 @xmath0n and 65 @xmath0n , and much more heat can be released to the atmosphere . without a further response of the thc the system would return quickly ( within years or decades , i.e. with the convective time scale ) to its original state . in climber-2 , however , the changes in deep convection trigger a northward extension and also an intensification of the ocean circulation ( i.e. an overshooting of the atlantic meridional overturning circulation ; compare @xcite ) , which maintains the interstadial climate state since it is accompanied by an increase in the salinity and heat flux to the new deep convection area ( at about 65 @xmath0n ) . in response to the overshooting of the overturning circulation , the system relaxes slowly ( within about 1000 years , i.e. with the advective time scale ) towards the stadial state . we note that the advective time scale corresponds to the millennial relaxation time in our conceptual model . the model climber-2 also supports the validity of our overshooting assumption during the opposite transition ( from the warm state back to the cold one ) , as we will show in sect . we would like to stress that our interpretation of the processes during do events is , of course , not necessarily true since we can only speculate that the underlying mechanism of the events is correctly captured by climber-2 . we implement the above assumptions in the following way ( compare fig . [ fig : figure2 ] ) : first we define a discrete index s(t ) that indicates the state of the system at time t ( in years ) . since we postulate the existence of two states , s can only take two values ( s=1 : warm state , s=0 : cold state ) . we further define a threshold function t(t ) that describes the stability of the system at time t ( i.e. the stability of the current model state ) . dynamics of our conceptual model . shown is the time evolution of the model , in response to a forcing that is large enough to trigger switches between both model states . top : forcing f ( black ) and threshold function t ( red ) . bottom : model state s ( grey ; s=0 corresponds to the cold state , s=1 to the warm one ) and state variable s ( green ) . at time @xmath1 the forcing falls below the threshold function and a shift from the cold state into the warm one is triggered . with this transition , the threshold function switches to a non - equilibrium value ( representing an overshooting of the system ) and afterwards approaches equilibrium following a millennial - scale relaxation . at time @xmath2 the forcing exceeds the threshold function , and a transition from the warm state back into the cold one is triggered . with this transition , the threshold function switches to another non - equilibrium value and approaches equilibrium following another millennial - scale relaxation , until the forcing again falls below the threshold function and the next switch into the warm state is triggered . note that the state variable s is chosen to be identical to the threshold function t. for convenience , discontinuities in t and s are eliminated by linear interpolation . t , s and f are normalised in the figure . , width=302 ] second we define rules for the time evolution of the threshold function t. when the system shifts its state , we assume a discontinuity in the threshold function : with the switch from the warm state to the cold one ( at time t in fig . [ fig : figure2 ] ) t takes the value a@xmath3 . likewise , with the switch from the cold state into the warm one ( at time t in fig . [ fig : figure2 ] ) t takes the value a@xmath4 . as long as the system does not change its state the evolution of t is assumed to be given by a relaxation process : @xmath5 ( s labels the current model state , @xmath6 denotes the relaxation time in that state , b@xmath7 is a state - dependent constant that labels the equilibrium value of t in each model state ) . these assumptions result in the following expression for the threshold function t : @xmath8 note that in the above expression the index s again denotes the current state of the model ( i.e. s=0 stands for the cold state and s=1 for the warm one ) , @xmath9 labels the time of the last switch from the warm state into the cold one , and @xmath10 indicates the time of the last switch from the cold state into the warm one . third we assume that transitions from one state to the other are triggered each time a given forcing function f(t ) crosses the threshold function t. more precisely , we assume that when the system is in the cold state ( @xmath11 = 0 $ ] ) and the forcing is smaller than the threshold value ( @xmath12 < t[t''+1]$ ] ) the system switches into the warm state ( @xmath13 = 1 $ ] ) . this shift marks the start of a do event . likewise , when the system is in the warm state ( @xmath14 = 1 $ ] ) and the forcing is larger than the threshold value ( @xmath15 > t[t'+1]$ ] ) the system switches into the cold state ( @xmath16 = 0 $ ] ) . that shift represents the termination of a do event . if none of these conditions is fulfilled , the system remains in its present state ( i.e. @xmath17 = s[t]$ ] ) . to simplify the comparison of the model output with paleoclimatic records we further define a state variable s , which represents anomalies in greenland temperature during do events . for simplicity we assume that the state variable is equal to the threshold function : @xmath18 ( i.e. we assume that greenland temperature evolution during do events is closely related to the current state of the thc , respectively to its stability ) . we stress that this assumption is of course highly simplified , because greenland temperature is certainly not only influenced by the thc but also by other processes such as changes in ice accumulation during do oscillation . however , this assumption is not crucial for the dynamics of our model , since the timing of the switches between both model states is solely determined by the relation between the forcing function f and the threshold function t. this means that even if we included a more realistic relation between t and s , the timing of the simulated climate shifts would be unchanged and the model dynamics would thus essentially be invariant . note that @xmath9 and @xmath10 are not adjustable ; they rather represent internal time markers . thus , six adjustable parameters exist in our model as described here , namely @xmath19 , @xmath20 , @xmath21 , @xmath22 , @xmath23 and @xmath24 . our choice for these parameters is shown in table [ tab : table1 ] . with these parameter values the system is bistable ( i.e. no transition is ever triggered in the absence of any forcing , since @xmath25 and @xmath26 ) and almost symmetric . that means that the average duration of the simulated warm and cold intervals is almost equal . when compared with greenland paleotemperature records this situation most likely corresponds to the time interval between about 27000 and 45000 years before present , during which the duration of the cold and warm intervals in do oscillations was also comparable ( fig . 1 ) . the model can , however , also represent an unstable ( for @xmath27 and @xmath28 ) or a mono - stable system , in which the stable state is either the warm one ( for @xmath27 and @xmath26 ) or the cold one ( for @xmath25 and @xmath28 ) ; when compared to the ice core data this situation is closer to the time interval between 15000 and 27000 years before present , since during that time the system was preferably in its cold state and the forcing apparently crossed the threshold only infrequently and during short periods of time . [ tab : table1 ] cll parameter & chosen value + a@xmath3 & -27 + a@xmath4 & 27 + b@xmath3 & -9.7 + b@xmath4 & 11.2 + @xmath23 & 1200 + @xmath24 & 800 + in order to test our conceptual model we compare its performance under a number of systematic forcing scenarios with the performance of the far more comprehensive model climber-2 ( a short description of that model is given in the appendix ; a detailed description exists in the publication of @xcite ) . analogous to @xcite , we investigate the response of both models to a forcing that consists of two century - scale sinusoidal cycles . in the conceptual model , the forcing is implemented as the forcing function f. in the emic , the forcing is added to the surface freshwater flux in the latitudinal belt 50 - 70 @xmath29n , following @xcite and @xcite . this anomaly changes the vertical density gradient in the ocean and can thus trigger do events . switches from the cold state into the warm one are excited by sufficiently large ( order of magnitude : a few centimetre per year in the surface freshwater flux into the relevant area of the north atlantic ) negative freshwater anomalies ( i.e. by positive surface density anomalies that are strong enough to trigger buoyancy [ deep ] convection ) , and the opposite switches are triggered by sufficiently large positive freshwater anomalies ( i.e. by negative surface density anomalies that are strong enough to stop buoyancy [ deep ] convection ) . this justifies our choice for the logical relations that govern the dynamics of the transitions in the conceptual model ( i.e. @xmath30 as the condition for the switch from the cold state to the warm one , @xmath31 for the opposite switch ) . a detailed comparison between both model outputs is presented in the supplementary material . we here only summarise the main results : we find a general agreement between both models , which is robust when the forcing parameters are varied over some range ( supplementary figs . 1 - 6 ) . the conceptual model reproduces the existence of three different regimes ( _ cold _ , _ warm _ , _ oscillatory _ ) in the output of the emic and also their approximate position in the forcing parameter - space . by construction only the nonlinear component in the response of the emic to the forcing is reproduced by the conceptual model ( this component represents the saw - tooth shape of do events ) . a second , more linear component is not included in the conceptual model ( this component represents small - amplitude temperature anomalies which are superimposed on the saw - tooth shaped events in the emic ) . in particular , the conceptual model very well reproduces the timing of the onset of do events in the emic . the fact that our conceptual model , despite its simplicity , agrees in so many aspects with the much more detailed model climber-2 suggests that it indeed captures the key features in the dynamics of do events in that model . we would like to stress that the output of the emic indeed supports our assumption of an overshooting in the stability of the system during the transitions between both climate states : when driven by a periodic forcing ( with a period of 1470 years ) , the emic can show periodic oscillations during which it remains in either of its states for more than one forcing period ( i.e. for considerably more than 1470 years , compare supplementary fig . this implies that ( at least in the emic ) the conditions for a return to the opposite state indeed ameliorate with increased duration of the cold or warm intervals . if the thresholds in the model were constant ( or gradually increasing with increasing duration of the simulated cold / warm intervals ) , in contrast , the duration of the cold and warm intervals during the simulated oscillation could never be longer than 1470 years : if a periodic forcing does not cross a constant ( or gradually increasing ) threshold within its first period , it never crosses the threshold , due to the periodicity of the forcing . strongly nonlinear systems can show complex and apparently counterintuitive resonance phenomena that can not occur in simple linear systems . in this section we use our conceptual model to demonstrate and to discuss two of these phenomena , i.e. stochastic resonance ( sr ) and ghost resonance ( gr ) . since the explanation of the 1470-year cycle ( and in fact even its significance ) is still an open question , we further discuss how future tests could distinguish between the proposed mechanisms . stochastic resonance . the input consists of : 1 . a sub - threshold sinusoidal signal with a period of 1470 years and an amplitude of 4.5 msv ( about 40 percent of the threshold value b@xmath4 above which do events occur in the model ) , 2 . a random gaussian - distributed signal with white noise power signature ( standard deviation @xmath32 = 8 msv ) and a cutoff frequency of 1/(50 years ) . the cutoff is used since no damping exists in the model and it thus shows an unrealistically large sensitivity to high - frequency ( i.e. decadal - scale or faster ) forcing . a : total input ( black ) , periodic input component ( grey ) , model output ( green ) . dashed lines are spaced by 1470 years . b : relative frequency to obtain a spacing of 1470 years @xmath3310% ( triangles ) respectively @xmath3320% ( squares ) between successive events , as a function of the noise level @xmath32 . , width=321 ] in linear systems that are driven by a periodic input , the existence of noise generally reduces the regularity of the output ( e.g. the coherence between the input and the output ) . this is not necessarily the case in nonlinear systems : excitable or bistable nonlinear systems with a threshold and with noise , which are driven by a sinusoidal sub - threshold input , can show maximum coherence between the input and the output for an intermediate noise level , for which the leading output frequency of the system is close to the input frequency . this phenomenon is called stochastic resonance ( sr ) @xcite . sr has been suggested to explain the characteristic timing of do events @xcite , i.e. the apparent tendency of the events to occur with a spacing of about 1470 years or integer multiples thereof . it has further been demonstrated that do events in the model climber-2 can be subject to sr @xcite . here we apply our conceptual model to reproduce these results and to reanalyse the underlying mechanism . we use an input that is composed of : ( i ) a sinusoidal signal with a period of 1470 years , ( ii ) additional white noise . figures [ fig : figure3 ] and [ fig : figure4 ] show that for a suitable noise level the model can indeed show do events with a preferred spacing of about 1470 years or integer multiples thereof . the reason for this pattern in the output is easily understandable in the context of the model dynamics : do events in the model are triggered by pronounced minima of the total input ( total input = periodic signal plus noise ) . these minima generally cluster around the minima of the sinusoidal signal , and the start of the simulated events thus has a tendency to coincide with minima of the sinusoidal signal ( fig . [ fig : figure3]a ) . some minima of the sinusoidal signal , however , are not able to trigger an event , because the magnitude of the noise around these minima is too small so that the threshold function is not reached by the total input . consequently , a cycle is sometimes missed , and the spacing of successive events can change from about 1470 years to multiples thereof . unlike the model climber-2 ( which has a complex relationship between the input and the output and also a large computational cost ) our conceptual model can be used for a detailed investigation of the sr , e.g. because the dynamics of the model is simple and precisely known and because probability measures ( such as waiting time distributions ) can be explicitly computed . in fact , the resonant pattern in the conceptual model ( fig . [ fig : figure3 ] ) is due to two time - scale matching conditions : the noise level is such that the average waiting time between successive noise - induced transitions is comparable to _ half _ of the period of the periodic forcing , and also comparable to the relaxation times @xmath23 and @xmath24 of the threshold function ( compare fig . [ fig : figure4]b ) . this situation is different from the usual sr , in which thresholds ( or potentials ) are constant in time ( apart from the influence of the periodic input ) . in the usual sr , only one time - scale matching condition exists @xcite , namely the one that the average waiting time between successive noise - induced transitions ( i.e. the inverse of the so - called kramers rate ) is comparable to _ half _ of the period of the periodic forcing . in order to investigate the implications of the second condition we simulate histograms for four different scenarios in the conceptual model ( fig . [ fig : figure4 ] ) : 1 . noise - only input , constant threshold ( fig . [ fig : figure4]a ) ; 2 . noise - only input , overshooting threshold ( fig . [ fig : figure4]b ) ; 3 . noise plus periodic input , constant threshold ( fig . [ fig : figure4]c ) ; 4 . noise plus periodic input , overshooting threshold ( fig . [ fig : figure4]d ) . we note that 3 . corresponds to the usual sr , while 4 . describes our _ overshooting stochastic resonance_. as can be seen from the histograms , the existence of the millennial - scale relaxation process leads to a synchronisation in the sense that the waiting times between successive events are confined within a much smaller time interval ( about 1000 - 4500 years with the overshooting , compared to about 0 - 10000 years without overshooting ) . this confinement is plausible since the transition probability between both model states strongly depends on the magnitude of the threshold , which declines with increasing duration of the cold or warm intervals : when the standard deviation of the noise level is chosen such that the average waiting time between successive noise - induced transitions is comparable to the relaxation times @xmath23 and @xmath24 , as in fig . [ fig : figure4 ] , the overshooting relaxation strongly reduces the transition probability for waiting times much smaller than the relaxation time ( since the corresponding values of the threshold function are large ) and increases the transition probability for waiting times of the order of the relaxation time or larger ( since the corresponding values of the threshold function are considerably smaller ) . the probability to find an only century - scale spacing between successive events is thus small , because the corresponding transition probabilities are small . on the other hand , the probability to find a multi - millennial spacing is also small , because the states are already depopulated before ( i.e. the probability to obtain lifetimes considerably larger than the relaxation time is almost zero ) . this explains why the possible values for the spacing between successive do events are restricted to a much smaller range than in the usual sr ( i.e. in the case with constant thresholds ) . this synchronisation effect is indeed not unique to the conceptual model : the output of the coupled model climber-2 shows a similar pattern ( with possible waiting times between successive do events of e.g. about 1500 - 5000 years or about 1000 - 3000 years , depending on the noise level ; compare fig . 4a - d in the publication of @xcite ) . this similarity is of course not surprising , since the conceptual model is apparently able to mimic the events in the emic and since an overshooting in the stability of both states clearly also exists in climber-2 ( compare sect . we note that in the gisp2 ice core data , do events in the time interval 27000 - 45000 years before present ( which , as discussed in sect . 3.2 , is the best analogue to the `` background climate state '' in our conceptional model , since the duration of the cold and warm intervals in the data is comparable in that interval ) have spacings of about 1000 - 3000 years ( compare fig . 1 ) and were reported to cluster around values of either about 1470 years or about 2940 years @xcite . because the sr mechanism could explain such a pattern ( compare fig . [ fig : figure4]d ) it has originally been proposed . however , this mechanism requires a sinusoidal input with a period of about 1470 years , which has so far not been detected . in linear systems which are driven by a periodic input , the frequencies of the output are always identical to the input frequencies . this is not necessarily the case in nonlinear systems . for example , nonlinear excitable ( or bistable ) systems that are driven by an input with frequencies corresponding to harmonics of a fundamental frequency ( which itself is not present in the input ) can show a resonance at the fundamental frequency , i.e. at a frequency with zero input power . this phenomenon , which was first described in order to explain the pitch of complex sounds @xcite and later observed experimentally e.g. in laser systems @xcite , is called ghost resonance ( gr ) . gr and sr can indeed occur in the same class of systems , e.g. in bistable or excitable systems with thresholds . however , unlike sr , gr requires a periodic driver with more than one frequency . although many geophysical systems might be subject to gr ( since the relevant processes often have thresholds ) , the occurrence of this mechanism has so far not expressly been demonstrated in geoscience . ghost resonance . top : forcing ( black ) and model response ( green ) . middle : amplitude spectrum of the forcing . bottom : amplitude spectrum of the model response . we use two sinusoidal forcing cycles , with frequencies of 7/(1470 years ) and 17/(1470 years ) , respectively , and with equal amplitudes . these two cycles coincide every 1470 years and create peaks of particularly pronounced magnitude , spaced by exactly that period . thus , despite the fact that there is no spectral power at the corresponding frequency ( see middle panel ) , the forcing repeatedly crosses the threshold at those intervals . consequently , the response of the conceptual model ( i.e. the time evolution of the state variable s ) shows strictly repetitive do events with a period of 1470 years ( as indicated by the dashed lines , which are spaced by 1470 years ) . despite the lack of a 1470-year spectral component in the forcing , the output shows a very prominent peak at the corresponding frequency . , width=321 ] here we discuss a hypothesis that was recently proposed to explain the 1/(1470 years ) leading frequency of do events @xcite . the underlying mechanism of the hypothesis is in fact the first reported manifestation of gr in a geophysical model system . according to that hypothesis the 1/(1470 years ) frequency of do events could represent the nonlinear climate response to forcing cycles with frequencies close to harmonics of 1/(1470 years ) . our conceptual model illustrates the plausibility of this mechanism : we use a bi - sinusoidal input with frequencies of 7/(1470 years ) and 17/(1470 years ) , i.e. with frequencies corresponding to the 7th and the 17th harmonic of a 1/(1470 years ) fundamental frequency , and with equal amplitudes . a spectral component corresponding to the fundamental frequency is not explicitly present in the input . since the two sinusoidal cycles correspond to harmonics of the missing fundamental , the input signal repeats with a period of 1470 years . for an appropriate range of input amplitudes , the output of the conceptual models shows periodic do events with a period of 1470 years ( fig . [ fig : figure5 ] ) . unlike the input , the model output exhibits a pronounced frequency of 1/(1470 years ) , corresponding to the leading frequency of do events and to the fundamental frequency that is absent in the input . this apparent paradox is explained by the fact that the two driving cycles enter in phase every 1470 years , thus creating pronounced peaks spaced by that period . because the magnitude of these peaks results from constructive interference of the two driving cycles , it is indeed robust that a threshold process can be much more sensitive to these peaks than to the two original driving cycles @xcite . the main strength of the gr mechanism is that unlike the sr mechanism it can relate the leading frequency of do events to a main driver of natural ( non - anthropogenic ) climate variability , since proxies of solar activity suggest the existence of solar cycles with periods close to 1470/7 ( = 210 ) years ( de vries or suess cycle ) and 1470/17 ( @xmath3486.5 ) years ( gleissberg cycle ) @xcite . so far , however , no empirical evidence for this mechanism has been found @xcite , nor has it been shown yet that changes in solar activity over the solar cycles are sufficiently strong to actually trigger do events . in order to investigate the stability of this mechanism we further add a stochastic component ( i.e. white noise ) to the forcing . in this case the events are of course not strictly periodic anymore . similar to the sr case , an optimal ( i.e. intermediate ) noise level exists for which the waiting time distribution of the simulated events exhibits a maximum at a value of 1470 years , corresponding to the period of the fundamental frequency of the two input cycles ( fig . [ fig : figure6 ] ) . in contrast to the sr case , in which a fairly simple waiting time distribution with a few broad maxima of century scale width is obtained ( compare fig . [ fig : figure4]d ) , we now find a much more complex pattern with a large number of very sharp lines of only decadal scale width . since the waiting time distributions of both mechanisms are considerably different , it could at least in principle be possible to distinguish between both mechanisms by analysing the distribution of the observed do events . in practise , however , this approach is complicated by the fact that only about ten events appear to be sufficiently well dated for this kind of analysis , and even their spacing has an uncertainty of about 50 years @xcite , which is already of the same order as the width of the peaks in fig . [ fig : figure6]b . we note that the mechanism that is described in fig . [ fig : figure6 ] is known as ghost stochastic resonance ( gsr ) , and its occurrence and robustness has already been reported before in other systems with thresholds and multiple states of operation @xcite . at least in our system , however , this mechanism is even more complex than the other two types of resonance ( sr , gr ) . it is beyond the scope of this paper to describe the gsr mechanism in more detail . ghost stochastic resonance . the input consists of : 1 . two sinusoidal forcing cycles with frequencies of 7/(1470 years ) and 17/(1470 years ) , respectively , and with an amplitude of 8 msv , 2 . a random gaussian - distributed signal with white noise power signature and a cutoff frequency of 1/(50 years ) , as in fig . [ fig : figure3 ] . in a , the relative frequency to obtain a spacing of 1470 years @xmath331% ( triangles ) respectively @xmath332% ( squares ) between successive events is shown as a function of the noise level @xmath32 . b shows the distribution of the spacing @xmath35 t between successive events ( standard deviation of the noise : 5.5 msv ) . , width=302 ] the most direct way to test which of the proposed mechanisms if any provides the correct explanation for the timing of do events would be to reconstruct decadal - scale density anomalies in the north atlantic in connection with the events this is not possible since even the most highly resolved oceanic records do not allow to reconstruct the variability of the glacial ocean on that time scale . thus , only indirect tests can be performed . the identification of the postulated 1/(1470 years ) forcing frequency , which has so far not been detected , would certainly give further support for the sr mechanism . and in order to support the gr mechanism , it remains crucial to demonstrate that century - scale solar irradiance variations are indeed of sufficiently large amplitude to trigger repeated transitions ( with a preferred time scale of about 1470 years ) between the two glacial climate states . this could be tested with climate models . an elegant and simple test is to make use of the observation that do events in the earth system model climber-2 represent the nonlinear response to the forcing , and that an additional ( and much smaller ) linear response is superimposed on the events . in the absence of any threshold crossing ( e.g. in the holocene , during which do events did not occur ) the response to the forcing , in contrast , does not show a strong nonlinear component . this suggests that holocene climate archives from the north atlantic region might be able to reveal what triggered glacial do events . this approach has two major advantages : first , more reliable ( e.g. better resolved and dated ) records are available to solve this issue . second , linear analysis methods can be used for that purpose , e.g. linear correlations . in the context of the gr mechanism , for example , the existence of a pronounced correlation between holocene climate indices from the north atlantic and solar activity proxies ( reconstructed e.g. from @xmath36c variations in precisely dated tree rings ) would be expected . up to now at least one study exists that supports this prediction of a linear relationship between century - scale solar forcing and north atlantic climate variability throughout the holocene : proxies of drift ice anomalies in the north atlantic show a persistent correlation and a statistically significant coherency with `` rapid ( 100- to 200-year ) , conspicuously large - amplitude variations '' in solar activity proxies @xcite , in accordance with the proposed gr mechanism . the most challenging test , however , is the direct analysis of the glacial climate records . we are convinced that one of the main difficulties in this approach is the high degree of nonlinearity of the events , which according to our interpretation has so far not been adequately addressed in many previous studies . for example , several attempts have already been made in order to investigate the 1470-year cycle by means of linear spectral analysis methods , and significance levels have commonly been calculated by assuming a red noise background . to us this assumption seems to be oversimplified , since the system responds at a preferred time scale even when driven by white noise ( compare fig . [ fig : figure4]b ) . we thus suspect that the significance levels obtained by this method are unrealistically high . we further think that the reported lack of a clear phase relation between solar activity proxies and do events @xcite can not rule out the idea that solar forcing synchronised do events , since in the case of an additional stochastic forcing component ( i.e. in the gsr case ) the events are triggered by the _ combined _ effect of solar forcing and noise . thus , the observed lack could also imply that only some of the events were in first place triggered by the sun , whereas others were caused mainly by random variability ( e.g. by noise ) . a new and promising approach , which is based on a monte - carlo method , has recently been proposed in order to test the significance of the glacial 1470-year climate cycle : @xcite define a certain measure in order to distinguish between different hypotheses for the timing of do events , and they explicitly calculate the value of this measure for the series of events observed in the ice core . they then compare the calculated value with the values obtained by several hypothetic processes , e.g. by a random process ( for which assumptions concerning the probability distribution of the recurrence times of the events have to be made ) . significance levels are obtained from the ( numerically estimated ) probability distributions of the measure as generated by the considered process . although we do not share their conclusions ( because we think that more adequate measures can be chosen , which give considerably different results ) we think that this approach is elegant because significance levels are not calculated based on linear theories . the method is thus also applicable to highly nonlinear time series . a major hurdle in this method is that for each considered process the probability distribution of the waiting times which is unknown for almost all processes somehow has to be specified . for example , ditlevsen et al . use a simple mathematical ( i.e. an exponential ) distribution in order to mimic random do events . in order to improve their novel approach , some method is thus needed to calculate waiting time distributions in response to any possible input . comprehensive models are not applicable , due to their large computational cost . our conceptual model , in contrast , is well designed for that purpose because it is combines the ability to mimic the complex nonlinearity of do events as described by an accepted earth system model with the extremely low computational cost of a very simple ( zeroth order ) model . we thus think that our work is an important step in order to develop improved statistical analysis methods which are able to cope with the extreme nonlinearity of do events . [ sec : end ] we here discussed do events in the framework of a very simple conceptual model that is based on three key assumptions , namely ( i ) the existence of two different climate states , ( ii ) a threshold process and ( iii ) an overshooting in the stability of the system at the start and the end of the events , which is followed by a millennial - scale relaxation . these assumptions are in accordance with paleoclimatic records and/or with simulations performed with climber-2 , a more complex earth system model . in a couple of systematic tests we showed ( in the supplementary material ) that despite its simplicity , our model very well reproduces do events as simulated with climber-2 , whose dynamics is based on a ( albeit reduced ) description of the underlying hydro-/thermodynamic processes . the correspondence between both models thus strengthens our interpretation that the conceptual model can successfully mimic key features of do events , and that these can be regarded as a new type of non - equilibrium oscillation ( i.e. as an _ overshooting relaxation oscillation _ ) between two states of a nonlinear system with a threshold . although we discussed our model dynamics in the context of the ( thermohaline ) ocean circulation , our model does not explicitly assume that do events are linked with changes in the ocean circulation : threshold behaviour and multiple states exist in many compartments of the climate system ( not only in the ocean , but e.g. also in the atmosphere and in the cryosphere ) . our model thus can not rule out a leading role of non - oceanic processes in do oscillations . the millennial time scale of the events ( which is represented in our model by the assumption of a millennial - scale relaxation ) , however , corresponds to the characteristic time scale of the thermohaline circulation and thus points to a key role of the ocean in do oscillations . the main strength of our model is its simplicity : due to the obvious relationship between forcing and response , the model can demonstrate why even a simple bistable ( or excitable ) system with a threshold can respond in a complex way to a simple forcing , which consists of only one or two sinusoidal inputs and noise . we applied our model to discuss two highly nonlinear and apparently counterintuitive resonance mechanisms , namely stochastic resonance and ghost resonance . in doing so we reported a new form of stochastic resonance ( i.e. an _ overshooting stochastic resonance _ ) , in which the overshooting of the system leads to a further synchronisation effect compared to the usual stochastic resonance . our study provides the first explicitly reported manifestation of ghost resonance in a geophysical ( model ) system . since threshold behaviour and multiple equilibria are not unique to do events but exist in many geophysical systems , we would indeed expect that ghost resonances could be inherent in many geosystems and not just in our model . in addition to its applicability to demonstrate and interpret nonlinear resonance mechanisms , and to test their stability , we further illustrated the ability of our conceptual model to simulate probability measures ( e.g. waiting time distributions , which are required in order to test the significance and the cause of the proposed glacial 1470-year climate cycle by means of monte - carlo simulations ) . because it combines the ability to reproduce essential aspects of do events with the extremely low computational cost of a conceptual model ( which is up to 10@xmath37 times lower than in the earth system model climber-2 ) , we think that our model represents an important advance in order to develop adequate nonlinear methods for improved statistical analyses on do events . the earth system model climber-2 , which we used for our analysis , has dynamic components of the atmosphere , of the oceans ( including sea ice ) and the vegetation . dynamic ice sheets were not included in our study . climber-2 is a global model with coarse resolution : for the atmosphere and the continents the spatial resolution is 10@xmath29 in latitude , and 7 sectors are considered in longitude . the ocean is zonally averaged with a latitudinal resolution of 2.5@xmath29 for the three large ocean basins . a detailed description of the model is given in the publication of @xcite . do events in the model represent abrupt switches between two different climate states ( _ stadial _ [ i.e. cold ] and _ interstadial _ [ i.e. warm ] ) , corresponding to two different modes of the thc : in the interstadial mode , north atlantic deep water ( nadw ) forms at about 65 @xmath0n and much of the north atlantic is ice - free . in the stadial mode , nadw forms at about 50 @xmath0n and a considerably larger area of the north atlantic is ice - covered . we note that for the climatic background conditions of the last glacial maximum ( lgm ) only the stadial mode is stable in the model whereas the interstadial mode is excitable but unstable @xcite . moreover , the stability of both modes depends on the actual climate state ( e.g. on the configuration of the laurentide ice sheet and on the freshwater input into the north atlantic ) , and the stability properties of the system change when the background conditions are modified ( more precisely , the system can be bistable or mono - stable ) . transitions between both modes can be triggered by anomalies in the density field of the north atlantic , for example by variations in the surface freshwater flux ( since the density of ocean water increases with increasing salinity ) . in our study we thus implement the forcing as a perturbation in the freshwater flux ( in the latitudinal belt 50 - 70 @xmath29n ) : we start the model with the climatic background conditions of the last glacial maximum ( lgm ) . following earlier simulations @xcite we then add a small constant offset of 17 ( @xmath38 ) to the freshwater flux . for this climate state ( which we label perturbed lgm ) the thc is in fact bistable and do events can be triggered more easily than for lgm conditions . this perturbed lgm state gives us the background conditions for the model simulations as presented in this paper . the authors thank r. calov , a. mangini , s. rahmstorf , k. roth and a. witt for discussion , and p. ditlevsen ( in particular for observing the difference between the usual stochastic resonance and our overshooting stochastic resonance ) and two anonymous reviewers for helpful comments . h. braun was funded by deutsche forschungsgemeinschaft , dfg project number ma 821/33 . alley , r. b. and clark , p. u. , the deglaciation of the northern hemisphere : a global perspective , ann . earth planet . , 27 , 149182 , 1999 . alley , r. b. , clark , p. u. , keigwin , l. d. , and webb , r. s. , making sense of millennial - 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here we use a very simple conceptual model in an attempt to reduce essential parts of the complex nonlinearity of abrupt glacial climate changes ( the so - called dansgaard - oeschger events ) to a few simple principles , namely ( i ) the existence of two different climate states , ( ii ) a threshold process and ( iii ) an overshooting in the stability of the system at the start and the end of the events , which is followed by a millennial - scale relaxation . by comparison with a so - called earth system model of intermediate complexity ( climber-2 ) , in which the events represent oscillations between two climate states corresponding to two fundamentally different modes of deep - water formation in the north atlantic , we demonstrate that the conceptual model captures fundamental aspects of the nonlinearity of the events in that model . we use the conceptual model in order to reproduce and reanalyse nonlinear resonance mechanisms that were already suggested in order to explain the characteristic time scale of dansgaard - oeschger events . in doing so we identify a new form of stochastic resonance ( i.e. an _ overshooting stochastic resonance _ ) and provide the first explicitly reported manifestation of _ ghost resonance _ in a geosystem , i.e. of a mechanism which could be relevant for other systems with thresholds and with multiple states of operation . our work enables us to explicitly simulate realistic probability measures of dansgaard - oeschger events ( e.g. waiting time distributions , which are a prerequisite for statistical analyses on the regularity of the events by means of monte - carlo simulations ) . we thus think that our study is an important advance in order to develop more adequate methods to test the statistical significance and the origin of the proposed glacial 1470-year climate cycle . [ sec : intro ] do events as seen in the gisp2 ice - core from greenland @xcite . the figure shows greenland temperature changes over the interval between 10000 and about 40000 years before present . do events ( 0 - 10 ) manifest themselves as saw - tooth shaped warm intervals . dashed lines are spaced by 1470 years . , width=302 ] time series of north atlantic atmospheric / sea surface temperatures during the last ice age reveal the existence of repeated large - scale warming events , the so - called dansgaard - oeschger ( do ) events @xcite . in climate records from the north atlantic region the events have a characteristic saw - tooth shape ( fig . [ fig : figure1 ] ) : they typically start with a warming by up to 10 - 15 k @xcite over only a few years / decades . temperatures remain high for centuries / millennia until they drop back to pre - events values over a century or so . a prominent feature of do events is their millennial time scale : during marine isotope stages ( mis ) 2 and 3 , successive events in the gisp2 ice core were reported to be often spaced by about 1470 years or multiples thereof @xcite , compare fig . [ fig : figure1 ] . a leading spectral peak corresponding to the 1470-year period was found @xcite , and this spectral component was reported to be significant at least over a certain time interval @xcite . we note , however , that the statistical significance of this pattern is still under debate @xcite , in particular because of the lack of adequate nonlinear analysis methods . it was proposed that do events represent rapid transitions between two fundamentally different modes of the thermohaline ocean circulation ( thc ) @xcite , most likely corresponding to different modes of deep - water formation @xcite . the origin of these transitions is also under debate : in principle they could have been caused by factors from outside of the earth system @xcite , but they could also represent internal oscillations of the climate system @xcite . several nonlinear resonance mechanisms have been suggested in order to explain the characteristic timing of do events , including coherence resonance @xcite and stochastic resonance @xcite .

This election season has been surprising for any number of reasons, from Russia’s alleged cyber-intervention that tipped the scales toward its favorite useful idiot to the shock victory of a former reality-TV show host who was caught on tape bragging about sexually assaulting women with impunity. It’s also resulted in some far-fetched alliances: Hillary Clinton and Mary J. Blige (cringe), Mitt Romney and Donald Trump (sad!), and Kanye and Donald (ugh). Enter: Samantha Bee and Glenn Beck. Five years ago, around the time Beck’s views were considered too far-right for even Fox News, this union would seem—in the immortal words of Vizzini—inconceivable, yet in recent months, Beck has experienced a Scrooge-like transformation. He’s penned a New York Times op-ed in support of Black Lives Matter; branded Trump “under-educated” and a “danger to the republic”; and came out against Steve Bannon and the “alt-right,” calling the ex-Breitbart puppeteer-turned-Trump chief strategist a “terrifying man” with a “clear tie to white nationalists.” Whether or not this is a calculated move on Beck’s part given his cratering media empire is anyone’s guess. On Monday night, Bee welcomed Beck on her late-night program Full Frontal for a Christmastime chat. Dressed in matching ugly Christmas sweaters, the disparate duo first exchanged a few pleasantries. “My audience would like to stab you relentlessly in the eye,” said Beck. “My audience wants to kill me for normalizing a lunatic like yourself,” Bee replied. The comedienne then explained why she decided to reach out to Beck and have him on her program. “I think that our future is going to require a broad coalition of nonpartisan decency. It’s not just individual people against Donald Trump; it’s all of us against Trumpism,” she offered.“I agree,” said Beck. “As a guy who has done damage, I don’t want to do any more damage. I know what I did. I helped divide—I’m willing to take that. My message to you is: Please don’t make the mistakes I made. And I think all of us are doing it. We’re doing it on Facebook, we’re doing it on Twitter. We tear each other apart and we don’t see the human on the other side.” Beck then took Bee to task for adopting “a lot of my catastrophe traits,” insinuating that she, like many of her fellow left-leaning political satirists, has a tendency to overstate the direness of things, turning the volume up to 11 on even the most minor transgressions. “Do you believe there’s a chance we fall into a dictatorship under Donald Trump?” asked Beck. “Do you believe there’s a chance we lose our freedom of speech and press under this president?” At the conclusion of their surreal tête-à-tête, they held hands (“It feels so creepy,” joked Beck), before Bee gifted Beck with a ‘Strange Bedfellows’ cake of them lying together in bed. Then, they ate each other’s cake heads, because that’s what odd friendship tastes like. ||||| The interactive transcript could not be loaded. Rating is available when the video has been rented. This feature is not available right now. Please try again later.

– Some "far-fetched alliances" emerged from Election 2016 (Kanye West and Donald Trump—really?), notes the Daily Beast, but on Monday night, another unlikely celebrity pair put on their best ugly Christmas sweaters and dished about Trump on late-night TV. On Full Frontal, conservative pundit Glenn Beck joined host Samantha Bee, whom he greeted with, "My audience would like to stab you relentlessly in the eye," which Bee countered with: "My audience wants to kill me for normalizing a lunatic like yourself." But the meeting then took a more conciliatory turn, with Bee noting, "Our future is going to require a broad coalition of non-partisan decency. It's not just individual people against Donald Trump, it's all of us against Trumpism." Beck agreed, admitting culpability "as a guy who has done damage" in the past and sending a message out to the audience: "Please don't make the mistakes that I made." Watch the clip above to see their conversation, as well as some "creepy" skin-touching. (Beck also has things to say about Trump's chief strategist, Steve Bannon.)

SYSTEM. (a) In General.--Not later than one year after the date of the enactment of this Act, the Secretary of the Treasury shall modify the Employee Plans Compliance Resolution System (as described in Revenue Procedure 2013-12) to achieve the results specified in the succeeding subsections of this section and to further facilitate corrections and compliance in such other means as the Secretary deems appropriate. (b) Loan Error.-- (1) In the case of plan loan errors for which corrections are specified under the voluntary compliance program, self- correction shall be made available by methods applicable to such loans through the voluntary compliance program. (2) The Secretary of Labor shall treat any loan error corrected pursuant to paragraph (1) as meeting the requirements of the Voluntary Fiduciary Correction Program of the Department of Labor. (c) 457(b) Plan Correction.--The Secretary of the Treasury shall update the Employee Plans Compliance Resolution System to provide the same type of comprehensive correction program that is available under such system to retirement plans qualified under section 401(a) of the Internal Revenue Code of 1986 to plans maintained pursuant to section 457(b) of such Code by an employer described in section 457(e)(1)(A) of such Code. (d) EPCRS for IRAs.--The Secretary of the Treasury shall expand the Employee Plans Compliance Resolution System to allow custodians of individual retirement plans to address inadvertent errors for which the owner of an individual retirement plan was not at fault, including (but not limited to)-- (1) waivers of the excise tax that would otherwise apply under section 4974 of the Internal Revenue Code of 1986, (2) under the self-correction component of the Employee Plans Compliance Resolution System, waivers of the 60-day deadline for a rollover where the deadline is missed for reasons beyond the reasonable control of the account owner, and (3) rules permitting a nonspouse beneficiary to return distributions to an inherited individual retirement plan described in section 408(d)(3)(C) of the Internal Revenue Code of 1986 in a case where, due to an inadvertent error by a service provider, the beneficiary had reason to believe that the distribution could be rolled over without inclusion in income of any part of the distributed amount. (e) Required Minimum Distribution Corrections.--The Secretary of the Treasury shall expand the Employee Plans Compliance Resolution System to allow plans to which such system applies and custodians of individual retirement plans to self-correct, without an excise tax, any inadvertent errors pursuant to which a distribution is made no more than 180 days after it was required to be made. (f) Automatic Feature Error Correction.--In order to promote the adoption of automatic enrollment and automatic escalation, the Secretary of the Treasury shall modify the Employee Plans Compliance Resolution System to establish specific correction methods for errors in implementing automatic enrollment and automatic escalation features. Subtitle D--Modifications to the Employee Retirement Income Security Act of 1974 SEC. 241. ELECTRONIC COMMUNICATION OF PENSION PLAN INFORMATION. (a) Amendment to Employee Retirement Income Security Act of 1974.-- Part 1 of subtitle B of title 1 of the Employee Retirement Income Security Act of 1974 (29 U.S.C. 1021 et seq.) is amended by adding at the end the following new section: ``SEC. 112. ELECTRONIC COMMUNICATION OF PENSION PLAN INFORMATION. ``Any document that is required or permitted under this title to be furnished to a plan participant, beneficiary, or other individual with respect to a pension plan may be furnished in electronic form if-- ``(1) the system for furnishing such a document-- ``(A) is designed to result in access to the document by the participant, beneficiary, or other specified individual through electronic means, including-- ``(i) the direct delivery of material to an electronic address of such participant, beneficiary, or individual, ``(ii) the posting of material to a website or other internet or electronic-based information repository to which access has been granted to such participant, beneficiary, or individual, but only if proper notice of the posting has been provided (which may include notice furnished by other electronic means if the content of the notice conveys the need to take action to access the posted material), and ``(iii) other electronic means reasonably calculated to ensure actual receipt of the material by such participant, beneficiary, or individual, and ``(B) protects the confidentiality of personal information relating to such participant's, beneficiary's, or individual's accounts and benefits; ``(2) the participant or beneficiary has not elected to receive a paper version of such document; ``(3) notice is provided to each participant or beneficiary, in electronic or non-electronic form, before a document is furnished electronically, that apprises the individual of the right to elect to receive a paper version of such document; and ``(4) the electronically furnished document-- ``(A) is prepared and furnished in a manner that is consistent with the style, format, and content requirements applicable to the particular document; and ``(B) includes a notice that apprises the individual of the significance of the document when it is not otherwise reasonably evident as transmitted. For purposes of this section, the term `document' includes reports, statements, notices, notifications, and other information.''. (b) Amendment to Internal Revenue Code of 1986.--Section 414 of the Internal Revenue Code of 1986 is amended by adding at the end the following new subsection: ``(y) Electronic Communication of Pension Plan Information.--Any document that is required or permitted under this title to be furnished to a plan participant, beneficiary, or other individual with respect to a pension plan may be furnished in electronic form if-- ``(1) the system for furnishing such a document-- ``(A) is designed to result in access to the document by the participant, beneficiary, or other specified individual through electronic means, including-- ``(i) the direct delivery of material to an electronic address of such participant, beneficiary, or individual, ``(ii) the posting of material to a website or other internet or electronic-based information repository to which access has been granted to such participant, beneficiary, or individual, but only if proper notice of the posting has been provided (which may include notice furnished by other electronic means if the content of the notice conveys the need to take action to access the posted material), and ``(iii) other electronic means reasonably calculated to ensure actual receipt of the material by such participant, beneficiary, or individual, and ``(B) protects the confidentiality of personal information relating to such participant's, beneficiary's, or individual's accounts and benefits; ``(2) the participant or beneficiary has not elected to receive a paper version of such document; ``(3) notice is provided to each participant or beneficiary, in electronic or non-electronic form, before a document is furnished electronically, that apprises the individual of the right to elect to receive a paper version of such document; and ``(4) the electronically furnished document-- ``(A) is prepared and furnished in a manner that is consistent with the style, format, and content requirements applicable to the particular document; and ``(B) includes a notice that apprises the individual of the significance of the document when it is not otherwise reasonably evident as transmitted. For purposes of this subsection, the term `document' includes reports, statements, notices, notifications, and other information.''. (c) Effective Date.--The amendments made by this section shall apply with respect to documents furnished with respect to plan years beginning after December 31, 2013. SEC. 242. MODIFICATION OF DEADLINES FOR SUMMARY PLAN DESCRIPTION UPDATES. (a) In General.--Paragraph (1) of section 104(b) of the Employee Retirement Income Security Act of 1974 (29 U.S.C. 1024(b)(1)) is amended to read as follows: ``(1)(A) The administrator shall furnish to each participant, and each beneficiary receiving benefits under the plan, a copy of the summary plan description, and all modifications and changes referred to in section 102(a)-- ``(i) within 90 days after becoming a participant, or in the case of a beneficiary, within 90 days after first receiving benefits, or ``(ii) if later, within 120 days after the plan becomes subject to this part. ``(B)(i) Except as provided in clause (ii), the administrator shall furnish to each participant, and each beneficiary receiving benefits under the plan, every fifth year after the plan becomes subject to this part an updated summary plan description described in section 102 which integrates all plan amendments made within such five-year period, except that in a case where no amendments have been made to a plan during such five-year period, this sentence shall not apply. Notwithstanding the foregoing, the administrator shall furnish to each participant, and to each beneficiary receiving benefits under the plan, the summary plan description described in section 102 every tenth year after the plan becomes subject to this part. ``(ii) In the case of a pension plan, the administrator shall furnish to each participant, and each beneficiary receiving benefits under the plan, 210 days after the end of each remedial plan review period, an updated summary plan description described in section 102 which integrates all plan amendments made during such period, except that if no amendments have been made to a plan during such period, an updated summary plan description shall be furnished not later than 210 days after the end of the subsequent remedial plan review period (without regard to whether plan amendments were made during such subsequent period). ``(C)(i) If there is a modification or change described in section 102(a) (other than a material reduction in covered services or benefits provided in the case of a group health plan (as defined in section 733(a)(1))), a summary description of such modification or change shall be furnished not later than 210 days after the end of the plan year in which the change is adopted to each participant, and to each beneficiary who is receiving benefits under the plan. ``(ii) For purposes of clause (i), any amendment to a pension plan adopted during a remedial plan review period shall be treated as adopted in the plan year in which the amendment took effect. ``(D) If there is a modification or change described in section 102(a) that is a material reduction in covered services or benefits provided under a group health plan (as defined in section 733(a)(1)), a summary description of such modification or change shall be furnished to participants and beneficiaries not later than 60 days after the date of the adoption of the modification or change. In the alternative, the plan sponsors may provide such description at regular intervals of not more than 90 days. ``(E) In this paragraph, the term `remedial plan review period' means, with respect to any pension plan, the period established by the Secretary of the Treasury under the authority of subsection (b) of section 401 of the Internal Revenue Code of 1986 as the regular cycle of review by the Secretary of the Treasury for determining whether the pension plan continues to meet the requirements of such Code for treatment as a qualified plan under subsection (a) of such section 401.''. (b) Effective Date.--The amendments made by this section shall apply with respect to summary plan descriptions furnished under section 104(b) of the Employee Retirement Income Security Act of 1974 (29 U.S.C. 1024(b)), and modifications or changes described in section 102(a) of such Act (29 U.S.C. 1022(a)), with respect to plan years beginning after December 31, 2013. SEC. 243. MODIFICATION OF SMALL PLAN SIMPLIFIED REPORTING REQUIREMENTS. (a) In General.--Section 104(a)(2) of the Employee Retirement Income Security Act of 1974, as amended by section 201(c) of this Act, is amended by striking ``100 participants'' and inserting ``100 participants who have an accrued benefit under the plan''. (b) Effective Date.--The amendments made by this section shall apply to plan years beginning after December 31, 2013. SEC. 244. FIDUCIARY REQUIREMENT REGARDING SELECTION OF ANNUITY PROVIDER AND ANNUITY CONTRACT. (a) In General.--Section 404 of the Employee Retirement Income Security Act of 1974 (29 U.S.C. 1104) is amended by adding at the end the following: ``(e) Ability of Annuity Providers To Make Payments.--In the case of the selection of an annuity provider and annuity contract in connection with the payment of benefits under a defined contribution plan, the fiduciary requirement under subsection (a)(1)(B) is deemed satisfied with respect to determining the ability of the annuity provider to make all payments due under the contract to the extent that such payments are guaranteed by a State guaranty association under applicable State law in effect as of the date of issuance of the contract.''. (b) Effective Date.--The amendment made by subsection (a) shall apply to annuity contracts purchased after the date of enactment of this Act. TITLE III--INDIVIDUAL RETIREMENT INVESTMENT ADVICE REFORM SEC. 301. TRANSFER TO SECRETARY OF THE TREASURY OF AUTHORITIES REGARDING INDIVIDUAL RETIREMENT PLANS. (a) In General.--Section 102 of Reorganization Plan No. 4 of 1978 (ratified and affirmed as law by Public Law 98-532 (98 Stat. 2705)) is amended-- (1) in subsection (a)-- (A) by striking ``and'' at the end of clause (ii), (B) by striking ``and'' at the end of clause (iii), and (C) by inserting ``(iv) regulations, rulings, opinions, and exemptions relating to individual retirement accounts described in section 408(a) of the Code and individual retirement annuities described in section 408(b) of the Code, including simplified employee pensions under section 408(k) of the Code and simple retirement accounts under section 408(p) of the Code; and (v) regulations described in section 103(b) of this Plan; and'' at the end of clause (iii) (as amended by subparagraph (B)), and (2) by adding at the end the following new flush sentence: ``The Secretary of the Treasury shall consult with the Securities and Exchange Commission in prescribing regulations, rulings, opinions, and exemptions under subsection (a)(iv) that provide guidance of general application as to the professional standards of care (whether involving fiduciary, suitability, or other standards) owed by brokers and investment advisors to owners and account holders of accounts and annuities described in such subsection.''. (b) Joint Authority.--Section 103 of such Plan is amended-- (1) by striking ``In the case of'' and inserting: ``(a) In the case of''; and (2) by adding at the end: ``(b)(1) The Secretary of the Treasury and the Secretary of Labor shall have joint authority to issue regulations described in this subsection, and any such regulations shall be issued jointly by such Secretaries. ``(2) A regulation is described in this subsection if (i) the regulation is not described in clause (i), (ii), (iii), or (iv) of section 102(a) of this Plan and (ii) defines or interprets a term or requirement that is included in section 4975 of the Code or section 406 of ERISA. The determination of whether any regulation is described in this subsection shall be made without regard to whether any such term or requirement is also used or defined in any other provision of the Code or ERISA.''. (c) Effective Date.-- (1) In general.--The amendments made by this section shall apply to regulations, rulings, opinions, and exemptions which have not been finalized as of July 8, 2013. (2) Transition.--Any final regulation, ruling, opinion, or exemption described in section 102(a)(iv) or 103(b) of Reorganization Plan No. 4 of 1978 (as added by the amendments made by this section) which was issued by the Secretary of Labor before July 9, 2013, shall apply until such time as such regulation, ruling, opinion, or exemption is revoked or modified pursuant to such amendments.

Secure Annuities for Employee Retirement Act of 2013 or the SAFE Retirement Act of 2013 - Title I: Public Pension Reform - Amends the Internal Revenue Code to provide for annuity accumulation retirement plans for state and local government employees beginning after 2014. Directs the Comptroller General (GOA) to conduct a study of federal employee pension plans. Title II: Private Pension Reform - Subtitle A: Enhanced Pension Plan Coverage - Amends the Internal Revenue Code, with respect to 401(k) plans, to allow employers who do not maintain a qualified retirement plan to establish a starter 401(k) deferral-only arrangement. Allows contributions to such arrangements of up to $8,000 per year and catch-up contributions for individuals age 50 and older. Increases from $500 to $5,000 the cap on the tax credit for the pension start-up costs of small employers. Allows employers to replace certain pension plans with safe harbor 401(k) plans. Eliminates the 10% cap on contributions to automatic 401(k) plans. Revises rules relating to the election of safe harbor 401(k) status and multiple employer defined contributions. Subtitle B: Pension Plan and Retirement Savings Simplification - Revises rules relating to pension plan amendments, discrimination testing, restrictions on hardship distributions, rollovers, forfeitures, notice requirements for new plan participants, and plan terminations. Terminates rules relating to top-heavy pension plans (plans that have a higher concentration of accrued benefits for key employees) for plan years beginning after December 31, 2013. Allows a new tax credit for contributions to a secure deferral arrangement. Subtitle C: Longevity Reforms - Modifies minimum distribution requirements to allow 25% of the account balance for the purchase of a deferred joint and survivor life annuity. Requires the annuity to be purchased on or before the date of the plan participant's initial required minimum distributions. Prohibits any deferral period from extending beyond the date the participant attains age 85. Requires the Secretary of the Treasury to update or provide new mortality tables for purposes of determining a plan participant's minimum required distribution. Requires a new update every five years. Allows plan participants to convert their required minimum distribution into a Roth individual retirement account (Roth IRA). Allows a plan sponsor to transfer responsibility for the administration of the joint and survivor annuity rules to the annuity provider. Requires the Secretary to modify the Employee Plans Compliance Resolution System to allow for the correction of loan errors and inadvertent errors in retirement plans, IRAs, and required minimum distribution requirements. Subtitle D: Modifications to the Employee Retirement Income Security Act of 1974 - Amends the Employee Retirement and Income Security Act of 1974 (ERISA) and the Internal Revenue Code to: (1) authorize all documents required or permitted to be furnished to a plan participant to be furnished in electronic form unless the plan participant has elected to receive paper documents; (2) modify the deadline for summary plan description updates; (3) make the annual audit requirement applicable to 100 participants who have an accrued benefit under the plan (currently, 100 participants); and (4) deem the fiduciary duty in selecting an annuity provider and annuity contract in connection with the payment of benefits under a defined contribution plan satisfied to the extent that the contracts are guaranteed by a state guaranty association. Title III: Individual Retirement Investment Advice Reform - Transfers authority to the Secretary of the Treasury for the enforcement of prohibited transaction rules for individual retirement accounts (IRAs). Requires the Secretary to consult with the Securities and Exchange Commission (SEC) in prescribing rules relating to the professional standards of care owed by brokers and investment advisors to holders of IRA accounts and annuities. Provides for the joint issuance of regulations for prohibited transaction rules applicable to employer-sponsored retirement plans by the Secretary of the Treasury and the Secretary of Labor.

(CNN) Kim Davis, the Kentucky clerk who's refused to issue same-sex marriage licenses, has appealed the contempt of court ruling that landed her in jail last week, according to court documents obtained by CNN. "While most Americans are enjoying the extended holiday weekend with family and friends, Kim Davis sits in isolation for the fourth day in jail," her attorney, Mat Staver, said in a statement Sunday. "We are working through the holiday to secure Kim's freedom." A federal judge ordered her to jail Thursday, ruling she was in contempt of court for refusing to issue the licenses and not allowing her deputies to distribute them for her. U.S. District Judge David Bunning said Davis would remain behind bars until she complies. Five of her deputies agreed Thursday to issue marriage licenses in her absence and the Rowan County Clerk's Office began doing so the following day. How long will Davis stay in jail? Staver said Davis has no plans to resign and would remain in jail until a compromise is reached. He said his client would be willing to issue licenses if her name and title were not on them. Davis' husband, Joe, told reporters Friday that his wife was willing to stay in jail until that proposed compromise happened. Kim Davis' husband protesting outside clerks office. Says she's willing to stay in jail "as long as it takes." pic.twitter.com/kGykcj8cH6 — Sonia Moghe (@soniamoghe) September 4, 2015 "As long as it takes," Joe Davis said. "Hopefully (Kentucky Gov. Steve) Beshear will have the guts to do his job." Staver also criticized Beshear on Friday, saying, "She is incarcerated not because of anything she's done but because of what the governor has failed to do." He said the governor could issue an executive order to solve the problem. JUST WATCHED Attorney: Kim Davis 'has no intention' of resigning Replay More Videos ... MUST WATCH Attorney: Kim Davis 'has no intention' of resigning 01:22 The legislature could pass a law removing clerks' names from the licenses, but it won't be in session until January. Beshear said last week he won't call lawmakers for a special session to deal with the issue, adding that to do so would cost "hundreds of thousands of dollars of taxpayers' money." Deputies take over Beshear on Thursday welcomed the news that Davis' deputies agreed to issue the licenses. "The future of the Rowan County Clerk continues to be a matter between her and the courts. Deputy clerks have said they will commence issuing marriage licenses beginning (Friday)," he said. "It appears that the citizens of Rowan County will now have access to all the services from the clerk's office to which they are entitled." Outside Rowan County Clerk's office right now: dueling protests, both going strong. Marriage licenses being issued pic.twitter.com/iK5ZM2svA0 — Sonia Moghe (@soniamoghe) September 4, 2015 In court papers, attorneys for Davis argued that she is unable to comply with the court orders because issuing same-sex marriage licenses "irreparably and irreversibly violates her conscience." But American Civil Liberties Union attorneys contended Davis has no legal basis to avoid performing her duties as a government clerk. JUST WATCHED Same-sex marriage showdown in Kentucky Replay More Videos ... MUST WATCH Same-sex marriage showdown in Kentucky 02:52 A federal prosecutor said it was time for Davis and her county to comply. "Government officials are free to disagree with the law, but not disobey it," U.S. Attorney Kerry B. Harvey said in a statement. "The county clerk has presented her position through the federal court system, all of the way to the U.S. Supreme Court. It is time for the clerk and the county to follow the law." Bunning said he, too, was religious, but he explained that when he took his oath to become a judge, that oath trumped his personal beliefs, CNN affiliate WKYT-TV reported "Her good faith belief is simply not a viable defense," Bunning said. Jailing was 'not what everyone was hoping for' Staver, founder of Liberty Counsel, which represented Davis, said he was stunned by Thursday's ruling ordering Davis to jail. JUST WATCHED Counsel: Ky. clerk wants her name off marriage license Replay More Videos ... MUST WATCH Counsel: Ky. clerk wants her name off marriage license 03:18 "Knowing Kim Davis and her strong Christian resolve and convictions, she may be jailed behind bars, but her conscience remains free," he told CNN's "The Lead with Jake Tapper" on Thursday. Daniel Canon, an attorney who was working with the ACLU on the case against Davis, said his clients had not asked for Davis to be jailed. But now that she is, he said, there should be "some assurance that Ms. Davis is not going to continue to impose her religious beliefs." Ryan Anderson, a senior research fellow at the Heritage Foundation, a Washington-based conservative think tank, said the legislature should remove clerks' names from the licenses as Davis has asked. "Hopefully she'll get out of jail because the state of Kentucky will realize that there are compromises we can reach that will protect both the rights of gays and lesbians to receive marriage licenses and the rights of someone like Kim Davis not to have her name on that marriage license," he said. Anderson acknowledged that Davis could resign, but he said she shouldn't have to. "We have a rich history in the United States of accommodating conscientious objectors," Anderson said. "Kentucky accommodates conscientious objectors for other types of licensings. ... The question should be: If we can accommodate someone, why shouldn't we?" JUST WATCHED Clerk chooses jail over issuing same sex licenses Replay More Videos ... MUST WATCH Clerk chooses jail over issuing same sex licenses 02:28 Beshear, the governor, says he has no power to remove Davis from office. A different person Some scoff at the clerk, suggesting she's a hypocrite because she has been divorced three times Davis said she's a different person since becoming a Christian four and a half years ago. "I am not perfect," she said in a statement. "No one is. But I am forgiven." Staver said Davis occupies a cell by herself. She slept well the first night and has been studying the Bible, he said. "She has a clean conscience even though she's incarcerated behind these bars," he said. ||||| LEXINGTON, Ky. (AP) — A defiant county clerk is willing to stay in jail for her beliefs, but she'd prefer to be a free woman. This Thursday, Aug. 3, 2015 photo made available by the Carter County Detention Center shows Kim Davis. The Rowan County, Ky. clerk went to jail Thursday for refusing to issue marriage licenses to gay... (Associated Press) Attorneys for Rowan County Clerk Kim Davis have officially appealed a judge's decision to put her in jail for refusing to issue marriage licenses to same-sex couples. The three-page motion does not include arguments as to why Davis should be released but amends Davis' earlier appeal of the judge's order. Davis, an apostolic Christian, says gay marriage is a sin. She also says it would be a sin for her to issue a marriage license to a same-sex couple because the licenses are issued under her authority. She tried in vain to have state lawmakers change the law as a legal challenge to Kentucky's same-sex marriage ban wound its way through the federal appeals court. Davis stopped issuing all marriage licenses in June the day after the U.S. Supreme Court legalized same-sex marriage nationwide. Two gay couples and two straight couples sued her. U.S. District Judge David Bunning ordered Davis to issue the licenses and the Supreme Court upheld his ruling. But Davis still refused to do it, saying she could not betray her conscience or her God. Thursday, Bunning ruled Davis was in contempt of court for disobeying his order and sent her to jail. Her deputy clerks then issued marriage licenses to gay couples Friday with Davis behind bars. "Civil rights are civil rights and they are not subject to belief," said James Yates, who got a marriage license Friday after having been denied five times previously. Mat Staver, one of Davis' attorneys, said the marriage licenses issued Friday are "not worth the paper they are written on" because Davis refused to authorize them. But Rowan County Attorney Cecil Watkins says the licenses are valid. Bunning said he did not know if the licenses were valid but ordered them issued anyway. Bunning indicated Davis will be in jail at least a week. She could stay longer if she continues to not obey the judge's order. Bunning had offered to release Davis from jail if she promised not to interfere with her deputy clerks as they issued the licenses. But Davis refused. Staver called the contempt hearing "a charade" saying Bunning had his mind made up before the hearing began. Kentucky law requires marriage licenses be issued under the authority of the elected county clerk. Davis views issuing marriage licenses to same-sex couples as a stamp of approval of something she believes is a sin. She has said she will not issue marriage licenses until the state legislature changes the law so the licenses can be issued under someone else's authority. The state legislature is not scheduled to meet again until January and Democratic Gov. Steve Beshear has refused to call a special session. Davis has refused to resign her $80,000-a-year job. As an elected official the only way she could lose her job is to lose an election or have the state legislature impeach her, which is unlikely given the conservative nature of the state General Assembly. "She's not going to resign, she's not going to sacrifice her conscience, so she's doing what Martin Luther King Jr. wrote about in his Letter from the Birmingham Jail, which is to pay the consequences for her decision," Staver said. Davis' plight has reignited the gay marriage debate and the limits of religious freedom. Her imprisonment has inspired spirited protests from both sides in this small eastern Kentucky community known mostly as the home to Morehead State University. On Saturday, about 300 people rallied in support of Davis at the Carter County Detention Center where she is being held. Another rally is scheduled for Tuesday with Republican presidential candidate Mike Huckabee. ||||| Rowan County Clerk Kim Davis, who spent her fourth day behind bars Sunday, has filed an appeal notice of the judge’s decision that put her in a Kentucky jail for failing to follow his order to issue marriage licenses to same-sex couples. Attorneys representing Davis announced Sunday that they had filed a notice of appeal of last week’s ruling by District Court Judge David L. Bunning that held the clerk in contempt for failing to issue the licenses. Davis argued that her religious beliefs prevented her from signing or even having her name on the licenses despite a June ruling by the U.S. Supreme Court that gay couples had a constitutional right to marry. “While most Americans are enjoying the extended holiday weekend with family and friends, Kim Davis sits in isolation for the fourth day in jail,” Mat Staver, founder and chairman of Liberty Counsel, said in a statement. “We are working through the holiday to secure Kim’s freedom.” Staver said Liberty Counsel on Sunday afternoon filed a notice with a full brief to come. “Liberty Counsel attorneys are continuing to work on the legal brief that will later be filed in which the Sixth Circuit Court of Appeals will be asked to expedite the appeal and set the contempt order aside,” Staver said. Staver said the lawyers will argue that Davis was “entitled to proper notice and due process when she is threatened with the loss of her freedom. There was no indication that she would be incarcerated. We will be presenting our arguments on appeal and asking for an expedited ruling,” Staver said. Davis stopped issuing licenses to all couples, gay and straight, after the Supreme Court ruled. Despite repeated decisions against her, she has continued to cite “God's authority” for defying the courts. Throughout, Davis has maintained that her Christian beliefs gave her no choice but to oppose the licenses. After a life that included personal problems and four marriages, Davis said she became a devout Christian four years ago after the death of her mother-in-law. “To issue a marriage license which conflicts with God’s definition of marriage, with my name affixed to the certificate, would violate my conscience,” Davis said last week in a statement. “It is not a light issue for me. It is a heaven or hell decision.” Davis was ordered by Bunning to issue the licenses and she refused. She then appealed, losing at the U.S. 6th Circuit and finally last week at the Supreme Court. The case went back to Bunning on Thursday and he had to decide what steps to take to force Davis to comply with his order. NEWSLETTER: Get the day's top headlines from Times Editor Davan Maharaj >> Lawyers for the couples who brought the original suit asked for a fine rather than imprisonment, but Bunning acted forcefully in protecting judicial power. “The court cannot condone the willful disobedience of its lawfully issued order,” said Bunning, according to news reports from the courtroom. “If you give people the opportunity to choose which orders they follow, that’s what potentially causes problems.” Bunning sent Davis to jail for disobeying his order. Her deputy clerks then issued marriage licenses to gay couples Friday. Through her lawyers, Davis has maintained that the marriage license are not valid because she did not authorize them. Follow @latimesmuskal for national news. ALSO Colin Powell backs Iran deal as Congress prepares for a vote 'In God We Trust' decals on police cars draw complaints Doyle McManus: Trump can't actually win, can he?

– Kim Davis is prepared to stay in jail indefinitely rather than issue marriage licenses to same-sex couples or quit her job, but her lawyers are trying to get the Kentucky county clerk out immediately. "While most Americans are enjoying the extended holiday weekend with family and friends, Kim Davis sits in isolation for the fourth day in jail," attorney Mat Staver said in a statement yesterday, per CNN. "We are working through the holiday to secure Kim's freedom." An appeal of the contempt of court ruling that sent Davis to jail has been filed and Staver says lawyers will argue that Davis did not receive "proper notice and due process" before she was incarcerated, the LA Times reports. Davis—whose deputy clerks in Rowan County, apart from her son, are now issuing marriage licenses to all couples legally entitled to them—has signaled that she is willing to accept a compromise that would see her name removed from the licenses, but that may not happen until January. Staver, comparing his client to Martin Luther King Jr., says she is not going to resign or "sacrifice her conscience" but is willing to suffer the consequences of her decision. Around 300 protesters supporting Davis gathered outside the county detention center on Saturday and Mike Huckabee plans to join another rally tomorrow, the AP reports.

of page NEWS The Journal of Investigative Dermatology’s 2014 Impact Factor is now 7.216*, retaining its position as the #1 journal in Dermatology. Thank you to our authors, reviewers, readers, and editorial board members for your contributions in making us the premier Dermatology journal. (*Thomson Reuters 2014 Journal Citation Reports®) In a new episode of Skinpod, Dr. Sarah Aaron, Assistant Professor of Dermatology at the UCSF Medical Center, discusses her research on viral oncogenesis and cutaneous squamous cell carcinoma (cSCC). Listen to the episode now. Milestones in Cutaneous Biology Much of the current cancer lexicon is derived from studies of human or rodent skin. Furthermore, the three major cancer-causing environmental agents, UV light, fossil fuel combustion products, and papilloma viruses, were recognized by astute clinicians and experimental biologists because they produced skin tumors. In fact, clinical observations and experimental studies of skin significantly advanced our understanding of cancer development and progression. Read more in the Milestones in Cutaneous Malignancy. Intersociety Collegiality Awards: Readers of the JID are reminded of a series of awards available for SID, ESDR and JSID members to encourage participation of members of one society at one of the other society meetings. This initiative is supported by the Boards of all 3 societies. The objective is to promote the academic and international profile of "young investigators" involved in skin research. To date, more than 20 awards have been made and the personal and career benefits are both rewarding and satisfying. For further details, please refer to information posted on SID, ESDR and JSID webpages. ||||| A man with almost no hair on his body has grown a full head of it after a novel treatment by doctors at Yale University. There is currently no cure or long-term treatment for alopecia universalis, the disease that left the 25-year-old patient bare of hair. This is the first reported case of a successful targeted treatment for the rare, highly visible disease. The patient has also grown eyebrows and eyelashes, as well as facial, armpit, and other hair, which he lacked at the time he sought help. "The results are exactly what we hoped for," said Brett A. King, M.D., assistant professor of dermatology at Yale University School of Medicine and senior author of a paper reporting the results online June 18 in the Journal of Investigative Dermatology. "This is a huge step forward in the treatment of patients with this condition. While it's one case, we anticipated the successful treatment of this man based on our current understanding of the disease and the drug. We believe the same results will be duplicated in other patients, and we plan to try." The patient had previously been diagnosed with both alopecia universalis, a disease that results in loss of all body hair, and plaque psoriasis, a condition characterized by scaly red areas of skin. The only hair on his body was within the psoriasis plaques on his head. He was referred to Yale Dermatology for treatment of the psoriasis. The alopecia universalis had never been treated. King believed it might be possible to address both diseases simultaneously using an existing FDA-approved drug for rheumatoid arthritis called tofacitinib citrate. The drug had been used successfully for treating psoriasis in humans. It had also reversed alopecia areata, a less extreme form of alopecia, in mice. "There are no good options for long-term treatment of alopecia universalis," said King, a clinician interested in the treatment of rare but devastating skin diseases. "The best available science suggested this might work, and it has." After two months on tofacitinib at 10 mg daily, the patient's psoriasis showed some improvement, and the man had grown scalp and facial hair -- the first hair he'd grown there in seven years. After three more months of therapy at 15 mg daily, the patient had completely regrown scalp hair and also had clearly visible eyebrows, eyelashes, and facial hair, as well as armpit and other hair, the doctors said. "By eight months there was full regrowth of hair," said co-author Brittany G. Craiglow, M.D. "The patient has reported feeling no side effects, and we've seen no lab test abnormalities, either." Tofacitinib appears to spur hair regrowth in a patient with alopecia universalis by turning off the immune system attack on hair follicles that is prompted by the disease, King said. The drug helps in some, but not all, cases of psoriasis, and was mildly effective in this patient's case, the authors said. King has submitted a proposal for a clinical trial involving a cream form of tofacitinib as a treatment for alopecia areata. He cited work by Columbia University scientist Angela Christiano as the reason he decided to try tofacitinib as a therapy in this patient with both alopecia universalis and psoriasis. She has shown that tofacitinib and a related medicine reverse alopecia areata in mice. King called her work exemplary and a clear example of how society's investment in science research leads to improvement in human life. "This case highlights the interplay between advances in science and the treatment of disease," he said, "and it provides a compelling example of the ways in which an increasingly complex understanding of medicine, combined with ingenuity in treatment, benefits patients." ### The paper is titled "Killing Two Birds with One Stone: Oral Tofacitinib Reverses Alopecia Universalis in a Patient with Plaque Psoriasis." ||||| There is currently no cure or long-term treatment for alopecia universalis--a disease that left a 25-year-old subject without hair on his head, including eyebrows and eyelashes. Yet a novel treatment by doctors at Yale University in New Haven, Conn., that involved an arthritis drug helped the young patient grow back the hair he never had. Advertisement "The results are exactly what we hoped for," said Brett A. King, M.D., assistant professor of dermatology at Yale University School of Medicine and senior author of a paper, published in the Journal of Investigative Dermatology. "This is a huge step forward in the treatment of patients with this condition. While it's one case, we anticipated the successful treatment of this man based on our current understanding of the disease and the drug. We believe the same results will be duplicated in other patients, and we plan to try." Before treatment, the patient had been diagnosed with both alopecia universalis and plaque psoriasis, a condition characterized by scaly red patches of skin. Researchers referred him to Yale Dermatology for treatment of the psoriasis in order to deal with symptoms of the disease, according to a news release. Researchers said they believed that both could potentially be addressed simultaneously using an existing FDA-approved drug for rheumatoid arthritis known as tofacitinib citrate. The drug had previously been used to successfully treat psoriasis in humans and was found to reverse a less extreme form of alopecia in mice. Advertisement The patient was put on the drug for two months at 10 mg per day. His psoriasis showed some improvement and he was able to grow the first scalp and facial hair that he'd seen in seven years. Following three months of the therapy at 15 mg per day, he had completely regrown scalp hair and clearly had visible eyebrows, eyelashes and facial hair, armpit hair and hair in other areas, as well. Researchers note that as tofacitinib was mildly effective in this patient's case by turning off the immune system's attack on hair follicles that's prompted by alopecia universalis, the drug may not be so successful for other cases. ©2016 ScienceWorldReport.com All rights reserved. Do not reproduce without permission. The window to the world of science news Advertisement Advertisement

– It turns out an FDA-approved rheumatoid arthritis drug might just cure baldness—at least the form caused by a rare immune disease. During an eight-month trial of the drug, a 25-year-old man whose body was nearly hairless grew, well, a lot of it, including plenty atop his head, armpit hair, eyebrows, and eyelashes, Yale researchers say. The scalp and facial hair he grew was the first he'd grown there in seven years. The man, who suffers from a rare disease known as alopecia universalis, reported no side effects after taking tofacitinib citrate, which had reversed a less severe form of alopecia in mice and been used to treat plaque psoriasis, a skin condition the man also suffered from, according to Science World Report. A co-author of the paper reporting the results noted, "We've seen no lab test abnormalities, either." Alopecia universalis, which causes the immune system to attack hair follicles, has no cure or approved long-term treatment, making this "a huge step forward in the treatment of patients with this condition," a researcher explained in a study of the case. "While it's one case ... we believe the same results will be duplicated in other patients, and we plan to try." The drug was only somewhat effective in treating the man's psoriasis. (Another big breakthrough could lead to treatments for baldness.)

chemokines are small cytokines known for their ability to induce migration of cells such as lymphocytes , dendritic cells ( dc ) , macrophages , and stem cells . based on the cellular context and the site of expression , chemokines can be divided into inflammatory chemokines , that are synthesized and promote recruitment of cells during inflammation and homeostatic chemokines , that are constitutively expressed in specific tissues where they regulate leukocyte homing [ 1 , 2 ] . some chemokines participate both in immune defense during inflammation and in physiological trafficking of resting leukocytes [ 1 , 2 ] . moreover , some inflammatory chemokines are crucial components of tumor microenvironment and have a pivotal role in tumor progression , enhancing cancer cell migration to distant organs . chemokine scaffold , that is , a conserved protein structure , dependent on two disulfide bonds linking cysteine residues . based on the relative position of their cysteine residues located in the n - terminal region , chemokines can be divided into four subfamilies , cxc , cc , c , and cx3c [ 1 , 2 ] . cxc chemokines can be further subdivided depending on the presence or absence of an elr ( glu , leu , and arg ) amino acid motif . elr cxc chemokines attract neutrophils and possess angiogenic properties , whereas elr cxc chemokines are angiostatic and attract t and b lymphocytes as well as natural killer ( nk ) cells . cc chemokines promote the migration of monocytes , dc , lymphocytes , eosinophils , and basophils . lymphotactin / xcl1 and fractalkine / cx3cl1 are the only members of the c and cx3c chemokine families , respectively . lymphotactin attracts t and b lymphocytes and nk cells , whereas fractalkine attracts predominantly t and b lymphocytes , nk cells , and monocytes [ 1 , 2 ] . chemokines mediate their functions through binding to seven transmembrane g - protein - coupled receptors defined as cxcr , ccr , cr , or cx3cr [ 1 , 2 ] . furthermore , some chemokines bind to multiple receptors and some receptors recognize more than one chemokine . cx3cl1 consists of a chemokine domain linked to a transmembrane domain via an extended mucin - rich stalk of an extracellular domain . the chemokine is synthesized as membrane - anchored form and may be cleaved in the soluble form by different metalloprotease . [ 5 , 6 ] . the membrane - anchored cx3cl1 form functions as an adhesion molecule promoting retention of leucocytes to endothelial cells under physiological flow conditions . the soluble cx3cl1 form is released following constitutive shedding operated by a disintegrin and metalloprotease ( adam)10 , whereas shedding under inflammatory conditions is mediated primarily by adam17 [ 8 , 9 ] . soluble cx3cl1 resembles a conventional chemokine exhibiting efficient chemotactic activity for human monocytes , nk cells , t cells , dendritic cells and , as demonstrated by our group , for a subset of germinal center b cells [ 5 , 11 ] . cx3cl1 expression has been reported in many cell types of hematopoietic or nonhematopoietic origin , such as endothelial and epithelial cells , lymphocytes , neurons , microglial cells , and osteoblasts . cx3cl1-driven chemotaxis and adhesion are mediated by cx3cr1 that is expressed on different cell types such as nk cells , cd14 monocytes , cytotoxic effector t cells , b cells , neurons , microglia , smooth muscle cells , and tumor cells [ 11 , 1315 ] . cx3cl1 is involved in leukocyte recruitment associated with numerous inflammatory disorders and in tumorigenesis process in which the chemokine show pro- and antitumoral properties . the different roles of cx3cl1 make it an attractive candidate for the development of therapeutic strategies . this review will summarize the multiple roles of the cx3cl1/cx3cr1 axis in the pathogenesis of inflammation and cancer . chemokines and adhesion molecules provide signals for trafficking , adhesion , and migration of leukocytes at sites of injury and inflammation . in this context , cx3cl1 promotes the accumulation of immune cells that express cx3cr1 , generating a vascular gateway for cytotoxic effector cells and being detrimental in several inflammatory diseases [ 6 , 17 , 18 ] . increased levels of soluble cx3cl1 have been detected in serum , bronchoalveolar lavage fluids , and supernatants from airway smooth muscle cells , lung endothelium , and airway epithelium of allergic asthma and rhinitis patients . both high secretion of cx3cl1 and upregulation of cx3cr1 function by nave and memory cd4 t cells play a critical role in the recruitment of inflammatory cells after allergen stimulation [ 19 , 20 ] . it has been demonstrated that transfer of cd4 t cells from wild type mice into cx3cr1 deficient mice restores the clinical features of asthma , highlighting the therapeutic potential of the cx3cl1/cx3cr1 axis . rheumatoid arthritis ( ra ) is a chronic joint disease characterized by massive infiltration of inflammatory cells into multiple joints , leading to hyperplasia of synovium and destruction of cartilage and bone . previous studies have defined the role of cx3cl1 in pathogenesis of ra and other chronic diseases such as polymyositis and dermatomyositis [ 2326 ] . cx3cl1 has been detected on fibroblast - like synoviocytes and endothelial cells in ra synovium where it contributes to the accumulation of cx3cr1 t cells , macrophages , and dendritic cells . following interaction of cx3cl1 with its receptor , these latter inflammatory cells adhere to endothelial cells , migrate into the synovium , and secrete cytokines [ 2326 ] . in a murine model of collagen - induced arthritis ( cia ) , inhibition of cx3cl1 attenuated clinical symptoms , ameliorated histopathological features , and reduced joint infiltration of inflammatory cells . similarly to human ra , polymyositis and dermatomyositis are characterized by chronic muscle inflammation with infiltration of cx3cr1 cytotoxic t cells and macrophages , recruited by cx3cl1 expressing vascular endothelial cells and other inflammatory cells . in experimental autoimmune myositis , the treatment with anti - cx3cl1 antibody reduced the numbers of muscle infiltrating cells and ameliorated histological inflammatory lesions pointing to the potential therapeutic role of cx3cl1 inhibition and/or cx3cl1/cx3cr1 block in the treatment of ra and inflammatory myopathies . atherosclerosis is a disease affecting arterial blood vessels as the result of fatty materials accumulation such as cholesterol . monocytes - derived foam cells are the hallmark in both early and advanced atherosclerotic lesions and evidence indicates that chemokines play important roles in directing migration of these cells from the blood to the vessel wall [ 29 , 30 ] . in this respect , high levels of cx3cl1 have been found in vascular smooth muscle cells ( vsmcs ) of coronary atherosclerotic plaques , whereas mononuclear cells and vascular endothelium express cx3cr1 [ 31 , 32 ] . the cx3cl1 membrane - bound form promotes cell - cell interactions , whereas the soluble form , cleaved by the cysteine protease cathepsin s and expressed by vsmcs , regulates the adhesion and capture of circulating monocytes to the sites of atherogenesis . genetic deletion of cx3cl1 or its cognate receptor dramatically reduces monocyte recruitment in the artery wall and the subsequent development of lesions in murine models of atherosclerosis , suggesting that the chemokine / receptor axis represents an attractive therapeutic target for clinical trials in cardiovascular disease . recent studies in mice show that treatment with a cx3cr1 antagonist induces potent inhibition of atherosclerotic lesions . an important role for the cx3cl1/cx3cr1 axis has also been demonstrated in renal diseases such as glomerulonephritis , tubulointerstitial nephritis , pyelonephritis , and renal allograft rejection . upregulation of cx3cl1 , expressed preferentially on the apical membrane of renal tubular epithelial cells , has been reported in glomerulonephritis where cx3cl1 acts as a chemoattractant and adhesion molecule [ 35 , 36 ] . indeed the apical cx3cl1 , firmly anchored to the membrane , facilitates recruitment and retention of the majority of cx3cr1 leukocytes that infiltrate the kidney during glomerulonephritis or other nephropathies [ 35 , 36 ] . both cx3cl1 and cx3cr1 are upregulated in patients with chronic liver disease and associated with the severity of liver fibrosis . an increased expression of adam10 and adam17 by hepatic stellate cells ( hsc ) has been demonstrated in these patients . shedding of cx3cl1 by the two metalloproteases facilitates the recruitment and adhesion of cx3cr1 inflammatory cells and the paracrine stimulation of hsc in liver disease [ 37 , 38 ] . the cx3cl1/cx3cr1 axis plays also important roles in inflammatory bowel diseases . in patients with crohn 's disease , there is a significant increase of cx3cl1 mrna expression in inflamed lesions compared to noninflamed colonic mucosa suggesting a relevant impact of this chemokine in intestinal inflammation . experiments in mice demonstrate that intestinal lamina propria ( lp ) macrophages express high levels of cx3cr1 . thus , deletion of cx3cr1 resulted in a significant reduction of macrophage recruitment to lp with a decreased translocation of bacteria to mesenteric lymph nodes and their ability to take up pathogens . these findings point to cx3cr1 as a specific marker for lp macrophages and a critical component in maintaining lp macrophage homeostasis . in recent years , increasing evidence for an inflammatory component in age - related macular degeneration has been demonstrated . under physiological conditions , cx3cl1 is constitutively expressed in retina and retinal pigment epithelium , whereas microglia cells express cx3cr1 . dysfunction in cx3cl1/cx3cr1 signaling leads to accumulation in the subretinal space of both inflammatory macrophages and microglia cells that participate to the development of retinal degeneration . recently , two common single - nucleotide polymorphisms ( snps ) located in the open reading frame of the human cx3cr1 gene have been described , namely t280 m and v249i . a methionine replaces a threonine residue whereas a valine is replaced by an isoleucine in the v249i variant . the frequencies of these two variants are significantly associated to a lower risk of inflammatory diseases such as atherosclerosis , coronary artery disease , susceptibility to human immunodeficiency virus infection , age - related macular degeneration , and crohn 's disease [ 4449 ] . cx3cl1 is abundantly expressed by neurons in the central nervous system ( cns ) , where it regulates the communication between neurons , glia , and microglia cells , sustaining the normal microglial activity through interaction with its receptor . cx3cr1 is also highly expressed by microglia , astrocytes , and hippocampal neurons in the cns [ 50 , 51 ] . thus , cx3cl1 serves as a neuronal regulatory protein controlling microglia activation under physiological conditions . depending on type of cns injury , the cx3cl1/cx3cr1 alzheimer 's disease ( ad ) is a progressive neurodegenerative disorder characterized by alteration of neurons and loss of memory and cognitive function . the pathological hallmarks of ad are massive deposits of amyloid beta ( a ) in the brain leading to microglia activation and neuroinflammation . proinflammatory chemokines , cytokines , and neurotoxins contribute to neuronal degeneration observed in ad . in mice overexpressing amyloid precursor protein , cx3cr1 depletion results in a reduction of a deposition and amelioration of the disease [ 52 , 53 ] . in contrast , other experimental ad models show that cx3cr1 deficiency enhances microglia activation and worsens memory and cognitive functions [ 54 , 55 ] suggesting that this discrepancy may be related to the different mouse models used in these studies . depletion of dopaminergic neurons in the substantia nigra characterizes parkinson 's disease ( pd ) . recent evidence suggests that microglia activation is a key component contributing to this dopaminergic degeneration [ 56 , 57 ] . high cx3cl1 levels correlate with the progression and severity of the disease as demonstrated in cx3cl1 or cx3cr1 deficient mice which show an increased brain neurodegeneration [ 58 , 59 ] . in a mouse model of pd , the two forms of endogenous cx3cl1 have been detected with different effects on disease progression . the soluble form exhibits neuroprotective capability since it decreases dopaminergic neuron loss , reduces impairment of motor coordination , and ameliorates microglial activation and proinflammatory cytokine release . in contrast , the membrane - bound form is not neuroprotective but mediates proinflammatory functions . further studies are necessary to expand the knowledge on the role of both forms in in vivo models of neuroinflammation and neurodegeneration . human immunodeficiency type i ( hiv ) infection causes hiv - associated neurocognitive disorders ( hand ) including hiv - dementia . the above - discussed balance between neuroprotective and neurotoxic roles of cx3cl1 is also observed in hiv dementia . on the one hand , cx3cl1 has a clear protective effect since its upregulation and secretion inhibit apoptosis of hippocampal neurons induced by neurotoxic viral proteins [ 61 , 62 ] . on the other hand , cx3cl1 is involved in neuronal damage through its activity on microglia cells that secrete proinflammatory cytokines . moreover , microglia and macrophages expressing cx3cr1 are in turn activated and recruited to the neuronal injury sites , thus amplifying the inflammatory response [ 51 , 63 ] . the role of cx3cl1/cx3cr1 axis in the different neurological disease is summarized in table 1 . the expression of cx3cr1 in nk cells and some t cells subsets has provided the rationale to exploit the role of the chemokine / receptor in cancer immunotherapy setting the stage for potential therapeutic approaches . the dual function of cx3cl1 as chemoattractant for leukocytes and adhesion molecule for tumor cells that express the receptor may explain the discrepancies reported in the literature regarding the tumorigenesis process . recently , expression and function of cx3cl1 and cx3cr1 have been demonstrated in glioma tumors irrespectively of their histotype and clinical severity . gliomas are the most common brain tumor in humans , characterized by high invasion rate and diffuse infiltration of the cns . gliomas include heterogeneous tumors classified according to the pathological characteristics as astrocytomas , oligodendrogliomas , and glioblastoma [ 64 , 65 ] . cx3cl1 negatively regulates glioma cell invasiveness by promoting tumor cell aggregation when expressed as transmembrane protein . the induction of cell to cell contact by cx3cl1 prevented detachment of tumor cells from the tumor aggregate that is required for the invasion process [ 64 , 65 ] . treatment of glioma cells with recombinant transforming growth factor ( tgf)-beta 1 reduced cx3cl1 expression at mrna level , facilitating glioma cell detachment and dispersion . moreover , erreni and colleagues demonstrated that glioblastoma cancer stem cells and progenitor cells express both cx3cl1 and cx3cr1 , indicating that this axis operates early in tumorigenesis process . neuroblastoma ( nb ) is the most common extracranial tumor of childhood that originates from the neural crest and presents with metastases at diagnosis in about half of patients . this tumor regresses spontaneously in infant , whereas children older than one year have poor prognosis . the bone marrow is the preferred site of nb metastases , but also bone , liver , and skin are frequently involved [ 67 , 68 ] . previous studies have demonstrated that several human nb cell lines express functional cx3cr1 and cx3cl1 . soluble cx3cl1 stimulates nb cells that express cx3cr1 to transmigrate through cx3cr1/cx3cl1 human bone - marrow endothelium , suggesting a prometastatic effect of the chemokine / receptor axis . in other studies , delivery of the cx3cl1 gene into nb cell lines induces an effective antineuroblastoma immune response mediated by nk cells and t lymphocytes . this chemokine gene therapy is amplified by anti - gd2 antibody / il-2 fusion protein and may provide a promising approach for neuroblastoma . tumors of nonneuronal origin , for example , prostate , pancreas , and breast cancer , show overexpression of cx3cr1 that regulates adhesion and migration of tumor cells to metastatic sites . in prostate cancer , shulby and colleagues demonstrated in vitro that cx3cl1 and its receptor direct prostate cancer cells to the bone marrow and guide their preferential migration towards human osteoblasts . bone marrow endothelial cells express the membrane form of cx3cl1 , that is cleaved by osteoblasts and released as soluble molecule able to attract prostate cancer cells . not only osteoblasts but also mesenchymal stromal cells secrete soluble cx3cl1 in the acellular fraction of bone marrow . this generates a gradient that attracts cx3cr1-bearing cells from the blood to the bone marrow . these findings support the rationale for the use of cx3cr1 , cx3cl1 , and metalloproteases responsible for its cleavage as potential therapeutic targets for prostate cancer . pancreatic ductal adenocarcinoma ( pdac ) represents a highly aggressive tumor characterized by rapid progression and chemoresistance . the peculiarity of this tumor is tropism for local peripheral nerves that is a major cause of local tumor recurrence . tumor cells from pdac patients strongly expressed cx3cr1 that mediates migration to cx3cl1 constitutively expressed by neural cells . the high frequency of cx3cr1 and the marked perineural invasion in padc patients supported the concept that cx3cr1 may have an important role in the spreading of pancreatic cancer cells along peripheral nerves and in predicting early tumor relapse after surgery . to confirm this hypothesis , marchesi and colleagues demonstrated that a tumor infiltrated in peripheral nerves was present only in mice injected with cx3cr1-transfected padc cells . in conclusion , the cx3cr1/cx3cl1 axis could represent a potential therapeutic approach using antagonists to cx3cr1 capable to inhibit tumor neurotropism in padc . in epithelial ovarian carcinoma ( eoc ) cx3cl1 is produced by epithelial cells and promotes malignant cell proliferation . cx3cr1 is virtually absent in normal ovarian surface epithelium and accumulates during the course of tumorigenesis process [ 76 , 77 ] . the interaction between cx3cl1 and cx3cr1 facilitates cell migration and cell adhesion between eoc cells and peritoneal mesothelial cells , contributing to eoc cell proliferation . metastasis is the main cause of morbidity and mortality associated with this tumor [ 78 , 79 ] . several experimental models have analyzed the influence of the cx3cr1/cx3cl1 axis in the biology of breast cancer and the possible therapeutic targeting of cx3cl1 . normal and malignant breast tissues express cx3cr1 but its overexpression increases the ability of tumor cells to migrate to skeleton and brain where bone stromal cells and neurons release soluble cx3cl1 [ 79 , 80 ] . in this view , cx3cl1 transgenic mice inoculated with cancer cells show a strong reduction of skeletal dissemination compared to wild - type animals . in addition high levels of cx3cl1 correlate with good prognosis and are identified as prognostic factors for disease survival . these antitumoral effects are due to immunological mechanisms since the chemokine enhances the recruitment of cd8 t cells , cd1a , dcs , and nk cells , inducing both innate and adaptive immunity . therefore , cx3cl1 expression could be considered an essential biomarker for predicting prognosis and identify patients eligible for immunomodulating therapy in breast cancer . cx3cl1 is considered a prognostic biomarker also for patients with colorectal cancer and hepatocellular carcinoma . colorectal cancer ( crc ) is the second cause of cancer death since one half of all patients develop metastasis especially in the liver and lung . high cx3cl1 expression has been found to be a marker of better prognosis in crc . in murine models soluble cx3cl1 , produced by colon cancer cells , drastically reduced their metastatic potential and growth in the target organs through immune mechanisms . the antitumor effects of cx3cl1 are mostly related to attraction of cytotoxic effector t lymphocytes and nk cells . expression of both cx3cl1 and cx3cr1 influences the clinical features and prognosis in patients with hcc since high expression of the chemokine / receptor axis correlates with better prognosis and tumor differentiation . in a murine model , tang and colleagues showed that transfer of the cx3cl1 gene into tumor cells elicited tumor - specific cytotoxic t cells and increased production of il-2 and ifn- in tumor tissue leading to inhibition of hcc growth . in this respect , cx3cl1 may be considered a chemokine suitable for immunoprevention or gene therapy in colorectal cancer , hepatocellular carcinoma , and , more recently , in gastric adenocarcinoma where its expression correlates with induction of both innate and adaptive immunity . in conclusion , two different mechanisms operate in cancer , leading to protumoral or antitumoral effects of cx3cl1 . on the one hand , cx3cl1 stimulates a strong immune response with the recruitment of nk cells and tumor - specific t cells . on the other hand , cx3cl1 plays a pivotal role in tumor angiogenesis , as well as in adhesion and migration of cancer cells , reinforcing their ability to spread and metastasize . we have previously demonstrated that cx3cl1 is expressed on human nave , germinal center ( gc ) , and memory b cells , the major b cell subsets from secondary lymphoid tissues . in these sites , soluble cx3cl1 produced by t follicular helper and follicular dendritic cells was found to control both the trafficking of human cx3cr1 centrocytes present in the gc light zone and their in vivo survival and differentiation . recently , a novel role for cx3cr1/cx3cl1 axis has been also delineated for b cell malignancies . our group demonstrated the involvement of cx3cr1 in the crosstalk between neoplastic b cells and tumor microenvironment of patients with chronic lymphocytic leukemia ( b - cll ) . b - cll cells were found to coexpress cx3cr1 and membrane - anchored cx3cl1 on the cell surface and constitutively release the soluble form of the chemokine . only a fraction of b - cll samples was found to be attracted in vitro by cx3cl1 . leukemic b cells upregulated cxcr4 upon incubation with cx3cl1 and this was paralleled by increased chemotaxis to cxcl12 . nurse - like cells generated from cll patient blood coexpressed cx3cr1 and cx3cl1 , but only a small proportion of them migrated in vitro to cx3cl1 that is not secreted by nurse - like cells . based upon these findings , we have proposed a model whereby the cx3cr1/cx3cl1 axis may contribute to interactions between cll cells and tumor microenvironment by increasing cxcl12-mediated attraction of leukemic cells to nlc and promoting directly adhesion of cll cells to nlc . in studies by other groups , cx3cr1 expression was investigated in different types of b cell lymphomas by reverse transcriptase - polymerase chain reaction ( rt - pcr ) , immunohistochemistry , and flow cytometry . b cell lymphomas include about 80% of the malignant lymphomas and comprise different subtypes . in particular , diffuse large b cell lymphoma ( dlbcl ) is the most frequent subtype , representing 30%35% of all non - hodgkin lymphomas ( nhl ) . dlbcl has predominant centroblastic morphology , is highly proliferating and invades the gc subverting the physiological microenvironment . follicular lymphoma ( fl ) has centrocytic and centroblastic components in different ratios depending on tumor grade and , compared to dlbcl , shows lower proliferative activity and slower invasion of gc by tumor cells . mantle cell lymphoma ( mcl ) is a relatively rare type of nhl that displays an aggressive course with a continuous relapse pattern . marginal zone lymphomas ( mzls ) are indolent b cell lymphomas with variable symptoms related to lymphoma location . in particular , extranodal mzls of mucosa - associated lymphoid tissue ( malt ) arise in gastrointestinal tract but may affect every organ in the body . malt lymphoma infiltrates b cell follicles in the peyer 's patch marginal zone , spreading in the surrounding tissue , and show the same cytological features and immunophenotype as mzls . dlbcl , fl , mcl , and malt lymphoma were found to express cx3cr1 at mrna and protein levels suggesting a functional role for this receptor in the interaction between lymphoma cells and tumor microenvironment [ 94 , 95 ] . cx3cr1 expression in human fl , mcl , and mzl has been confirmed by our group ( table 2 ) ( unpublished data ) . in addition , we have demonstrated for the first time that freshly isolated malignant b cells express the membrane - bound form of cx3cl1 ( table 2 ) ( unpublished data ) . to investigate the functional activity of cx3cr1 in contrast , the chemokine did not induce locomotion of fl and mzl cells ( table 2 ) ( unpublished data ) . these preliminary results provide evidence that lymphoma b cells show a different migratory behavior in response to cx3cl1 compared to their normal counterparts . thus , fl cells , which are of gc origin , did not migrate in vitro to soluble cx3cl1 that , in contrast , was found by our group to be chemotactic for normal gc b cells . in contrast , a minority of mcl cell fractions migrated to soluble cx3cl1 whereas their normal counterparts , that is , nave b cells , did not . the cx3cl1/cx3cr1 axis plays an important function in the pathophysiology of several inflammatory , infectious , and neurological processes and in various forms of cancers . as apparent from this review , the cx3cl1/cx3cr1 axis promotes inflammation and tumor growth in the majority of disease models discussed . cx3cl1 shedding may be blocked using chemical antagonists of adam10/adam 17 or cathepsin s , although this approach is far from being selective .

fractalkine / cx3cl1 , the only member of the cx3c chemokine family , exists as a membrane - anchored molecule as well as in soluble form , each mediating different biological activities . it is constitutively expressed in many hematopoietic and nonhematopoietic tissues such as endothelial and epithelial cells , lymphocytes , neurons , microglial osteoblasts . the biological activities of cx3cl1 are mediated by cx3cr1 , that is expressed on different cell types such as nk cells , cd14 + monocytes , cytotoxic effector t cells , b cells , neurons , microglia , smooth muscle cells , and tumor cells . the cx3cl1/cx3cr1 axis is involved in the pathogenesis of several inflammatory cancer including various b cell malignancies . in tumors the interaction between cancer cells and cellular microenvironment creates a context that may promote tumor growth , increase tumor survival , and facilitate metastasis . therefore the role of the cx3cl1/cx3cr1 has attracted interest as to the development of potential therapeutic approaches . here we review the different effects of the cx3cl1/cx3cr1 axis in several inflammatory and neurodegenerative diseases and in cancer , with emphasis on human b cell lymphomas .

pterygium , a word derived from pterygion ( ancient greek for a wing ) is a wing - shaped , fibro - vascular overgrowth arising from subconjunctiva tissue extending across the limbus onto the cornea . it is a degenerative condition of the subconjunctival tissue , which proliferates as a vascularized granulation tissue to invade the cornea , destroying superficial layers of stroma and bowman s membrane.1 several theories have been proposed to explain the pathogenesis of the pterygium such as inflammatory theory ( kamel ) , neoplastic theory ( mcreynolds and schreiter ) , degenerative theory ( fuchs and schoinger ) , and immunologic theory . various methods of surgical management of pterygia are excision , avulsion , and excision with primary closure , transplantation of the head of the pterygium , conjunctival autograft , limbal conjunctival autograft , and amniotic membrane graft . the pterygium surgery with conjunctival autograft remains the gold standard with less incidence of recurrence after its initial description in 1985.1 recurrence rates consistently reported are in the range of 5%10%.2 the recent technique is to use tissue fibrin glue for anchoring the graft to the bed . the favored site to harvest the autograft is superotemporal2 because this location in an oblique quadrant will avoid inadvertent injury to extraocular muscle , while its position under the upper lid will aid with patient comfort and healing of the donor site . however , in this study , we report outcomes with a novel technique of the pterygium management using conjunctival autograft harvested from the body of the pterygium . we also discuss our experience regarding the patient acceptability , visual results , and potential complications in a 6-month follow - up period with this new technique . the study was approved by the institutional review board of nethradhama superspeciality eye hospital , bangalore and adhered to the tenets of the declaration of helsinki . informed consent was obtained from all the patients participating in the study . in the above review of literature , the sample size for similar studies was as low as 20 and as high as 88 eyes . in view of 6-month follow - up required in this study and an average pterygium surgeries of eleven per month in the hospital set up the sample size was selected as 25 eyes . a total of 25 eyes of 25 patients with the primary pterygium diagnosed on slit - lamp were selected for the study . however , recurrent pterygia , ocular surface disorders , severe dry eye , and the patients already on antimetabolites were excluded from the study . a detailed preoperative clinical examination was conducted on all patients which included recording of uncorrected visual acuity ( ucva ) and corrected distance visual acuity ( cdva ) using snellen s test charts and logmar , slit - lamp examination , keratometry readings using orbscan ii ( technolas , munich , germany ) , dry eye assessment using schirmer s 1 and 2 tests , dilated fundus examination with pupillary dilatation using 90d and indirect ophthalmoscopy was done . the pterygium was classified into three types depending on the extent of corneal involvement:3 type 1 : extends less than 2 mm on the corneatype 2 : involves up to 4 mm on the corneatype 3 : encroaches onto more than 4 mm of the cornea and involves the visual axis . type 1 : extends less than 2 mm on the cornea type 2 : involves up to 4 mm on the cornea type 3 : encroaches onto more than 4 mm of the cornea and involves the visual axis . all the patients were operated by a single , experienced corneal surgeon ( vb ) under topical anesthesia using an operating microscope . mumbai , india ) , eye drops were instilled in the eye twice at an interval of 10 minutes before surgery and intraoperatively as required . after instillation of topical anesthesia , the conjunctival tissue over the body of the pterygium was marked using a marker . it was then isolated from the underlying degenerative tissue using blunt dissection . using an atraumatic conjunctival forceps and vannas scissors , blunt and sharp dissection was performed to separate the pterygium from underlying sclera and surrounding conjunctiva . the body of the pterygium , along with underlying tenons was excised using westcott scissors . the wound bed was smoothened by scraping and bleeding vessels cauterized using wet field cautery . the harvested graft was then placed over the bare scleral bed , while maintaining the orientation that is epithelium side up and limbal edge toward limbus . fibrin glue ( tisseel fibrin sealant baxter ag , vienna , austria ) was used to attach the autograft in place . two to three drops of the thrombin solution were applied on the scleral bed followed by the fibrinogen component . the conjunctival autograft was then immediately flipped over the area of conjunctival defect and smoothened out with a non - toothed forceps , while maintaining proper alignment of the edges ( figure 2 ) . it was ensured that the bare sclera was completely covered . in certain situations where the graft was insufficient , an amniotic membrane was used to cover the remaining bare sclera using fibrin adhesive . the graft was dried and allowed to adhere to the bed for 3 minutes , following which the lid speculum was removed . postoperatively , patients were prescribed tapering doses of zylopred ( gatifloxacin 0.3% and loteprednol 0.5% , allergan , inc . , irvine , ca , usa ) and lubricants for a period of 6 weeks . all patients were followed - up for a minimum period of 6 months . on all postoperative visits , slit - lamp photography ( figure 3 ; ucva , best - corrected visual acuity [ bcva ] ) , astigmatism , and complications were recorded and subjective questionnaire regarding patient comfort was taken from all patients . the results of continuous measurements were presented on mean standard deviation ( sd ) and results of categorical measurements were presented in number ( % ) . student s t - test ( two - tailed , dependent ) was used to find the significance of study parameters on a continuous scale within each group . a total of 25 eyes of 25 patients underwent the pterygium excision with this new technique . the number of eyes classified preoperatively as grade 1 , 2 , or 3 were 10 , 11 , and 4 eyes . the procedure was well tolerated and the patients did not report any significant subjective complaints of excessive pain , irritation , or discomfort both intra as well as postoperatively . a significant flattening in mean simulated keratometry ( sim k ) was observed over time . a significant reduction in mean sim k was seen from a preoperative value of 2.3082.25 sd to 1.2480.99 sd at 1 month postoperatively , which was statistically significant ( p - value < 0.026 ) . keratometry remained stable and no significant changes in sim k observed between 1 month and subsequent follow - up visits ( table 1 ) . the ucva improved in all the three types of pterygium . in type 2 , the preoperative mean was 0.3500.20 sd , which significantly improved to 0.200.14 sd at 1-month postoperation ( p - value = 0.005 ) . similarly , in type 3 preoperative mean improved from 0.530.18 sd to 0.2750.05 sd on 1 month post - operatively . further on , in both type 2 and 3 pterygium groups , ucva remained stable at the end of the 3rd month and until the last follow - up ( p - value < 0.05 ) ( table 2 ) . out of the total 25 patients , one case had cataract due to which there was not much improvement in the ucva . preoperative bcva in type 1 remained same but in types 2 and 3 , there was a significant improvement . in type 2 , preoperative mean logmar of 0.1090.15 sd improved to 0.0180.075 sd at postoperative 1 month ( tables 3 and 4 ) , which was statistically significant ( p=0.03 ) . however , in type 3 , though there was improvement in bcva postoperative , it was not statistically significant attributing to significant corneal scarring . two patients required an amniotic membrane grafting ( amg ) to cover the bare sclera as the conjunctiva harvested was smaller but did not alter the visual outcome . minor complications like congestion of 21 eyes ( 84% ) on day 1 , chemosis in five eyes ( 20% ) on day 1 and subconjunctival hemorrhage in six eyes ( 24% ) . discomfort was experienced in 13 eyes ( 52% ) , foreign body sensation in eight eyes ( 32% ) and tearing in four eyes ( 16% ) on postoperative day 1 . all these subjective complaints that improved in due course of time and all patients were symptomatically comfortable by 2 weeks ( table 5 ) shows complications after surgery ( table 6 ) . there was no incidence of graft dislocation , infection , necrosis , or other graft - related complications during the follow - up period of 6 months ( table 5 ) . slit - lamp examinations showed clear cornea with well - apposed graft during the 6 months of follow - up in all the cases ( figure 2 and table 5 ) . none of the eyes showed any evidence of recurrence of the pterygium at the end of the follow - up period . a significant flattening in mean simulated keratometry ( sim k ) was observed over time . a significant reduction in mean sim k was seen from a preoperative value of 2.3082.25 sd to 1.2480.99 sd at 1 month postoperatively , which was statistically significant ( p - value < 0.026 ) . keratometry remained stable and no significant changes in sim k observed between 1 month and subsequent follow - up visits ( table 1 ) . the preoperative mean was 0.3500.20 sd , which significantly improved to 0.200.14 sd at 1-month postoperation ( p - value = 0.005 ) . similarly , in type 3 preoperative mean improved from 0.530.18 sd to 0.2750.05 sd on 1 month post - operatively . further on , in both type 2 and 3 pterygium groups , ucva remained stable at the end of the 3rd month and until the last follow - up ( p - value < 0.05 ) ( table 2 ) . out of the total 25 patients , one case had cataract due to which there was not much improvement in the ucva . preoperative bcva in type 1 remained same but in types 2 and 3 , there was a significant improvement . in type 2 , preoperative mean logmar of 0.1090.15 sd improved to 0.0180.075 sd at postoperative 1 month ( tables 3 and 4 ) , which was statistically significant ( p=0.03 ) . however , in type 3 , though there was improvement in bcva postoperative , it was not statistically significant attributing to significant corneal scarring . two patients required an amniotic membrane grafting ( amg ) to cover the bare sclera as the conjunctiva harvested was smaller but did not alter the visual outcome . minor complications like congestion of 21 eyes ( 84% ) on day 1 , chemosis in five eyes ( 20% ) on day 1 and subconjunctival hemorrhage in six eyes ( 24% ) . discomfort was experienced in 13 eyes ( 52% ) , foreign body sensation in eight eyes ( 32% ) and tearing in four eyes ( 16% ) on postoperative day 1 . all these subjective complaints that improved in due course of time and all patients were symptomatically comfortable by 2 weeks ( table 5 ) shows complications after surgery ( table 6 ) . there was no incidence of graft dislocation , infection , necrosis , or other graft - related complications during the follow - up period of 6 months ( table 5 ) . slit - lamp examinations showed clear cornea with well - apposed graft during the 6 months of follow - up in all the cases ( figure 2 and table 5 ) . none of the eyes showed any evidence of recurrence of the pterygium at the end of the follow - up period . although extensive studies on the pterygium have unraveled the etiopathogenesis of this benign looking entity , the attempts to get rid of it have proved futile . furthermore , the phenomenon of recurrence with its devastating effect on vision has seriously questioned the utility of simple excision as a mode of management of pterygium . various researchers have reported a recurrence rate anywhere ranging from 30% to 80%.46 the existence of multiple adjuvant therapies for the pterygium in the present era , substantiate the fact that there is no single satisfactory and universally acceptable treatment modality for treating it . this study was contemplated with the objective to study the results of the pterygium excision with self - conjunctival autograft of the pterygium using fibrin glue in the surgical management of pterygium . since the pathology in the pterygium is subconjunctival degeneration , while the overlying conjunctiva being healthy , it may be unnecessary to sacrifice the healthy conjunctiva which itself may be utilized to cover the bare sclera after the excision of pterygium , instead of harvesting conjunctival tissue from another site . it has been found the conjunctival deficiency or scarring in the superior or superotemporal part due to the earlier pterygium surgery poses a surgical challenge in subsequent glaucoma or other ocular procedures . hence , this technique would also preserve the conjunctiva for surgeries such as glaucoma procedures , if the need arises in the future . in this study , we observed a statistically significant reduction in overall mean astigmatism postoperatively by orbscan , which indicates that as the type of the pterygium increases , the amount of astigmatism also increases in the same proportion . a similar observation was found by earlier researchers.7,8 they also found that the size of the pterygium was directly proportional to the amount of the astigmatism induced by it . they also suggested early surgical intervention reduces the mean induced corneal astigmatism.8 we observed significant improvement in the ucva after successful pterygium surgery that was significant in type 2 and type 3 pterygium . though in type 1 , there was an improvement in the ucva , it was not statistically significant . type 1 pterygium patients showed improvement in the ucva postoperative 1 month and were constant till 6 months . these observations were similar to the study carried out by maheshwari.7 lindsay and sullivan also found a similar significant correlation between successful pterygium surgery and improvement in visual acuity.9 allan et al compared preoperative unaided visual acuity with 3-month postoperative unaided visual acuity on snellen s chart in 93 eyes . they found unaided visual acuity was either unchanged or improved in 86 out of 93 cases , while seven eyes showed the decline in visual acuity on snellen s chart . the decline in visual acuity was not related to surgery but was either due to astigmatism , cataract , or retinal pathology.10 this observation is also similar to our study . we compared preoperative unaided visual acuity with postoperative visual acuity and found that 16 cases ( 64% ) reported improved visual acuity , eight cases ( 32% ) showed unaltered visual acuity while one case ( 4% ) showed deterioration in visual acuity . this decline was unrelated to the surgery , but it was because of progression of senile cataract . we also studied the complication profile with this new technique , which was found to be favorable with only minor postoperative issues such as congestion , graft edema , subconjunctival hemorrhage etc . however , there were no graft - related or serious vision related complications , no graft inversion or dislocation was noticed . also , there was no incidence of recurrence found at the end of mean follow - up of 6 months . however , with the conventional technique of the pterygium excision with conjunctival autografting , some complications have been reported in literature . allan et al in their study , encountered three cases of wound dehiscence , one case of conjunctival cyst and one case of tenon s granuloma.10 similarly , ma et al in a series of 80 eyes treated with the pterygium excision with conjunctival autografting had two cases of pyogenic granuloma and four cases of conjunctival inclusion cysts . all these complications were amenable to correction with minor surgical revision and did not have any sequelae.11 hence , our technique appears to be equally safer compared to the conventional technique in terms of postoperative complications . the conjunctiva harvested from the body of the pterygium after dissecting it from underlying subconjunctival tissue may offer a simple and effective way to treat pterygium . this technique also has the added advantage as the superior conjunctiva is untouched and can be used for future surgeries if required . the recurrence rate is not expected to be any different from the conventional technique , since the only difference exists in the method and site of harvesting the conjunctiva while the rest of the procedure being essentially the same . however , longer follow - up is required to study the long - term safety , efficacy , complications , and the incidence of recurrence with this technique .

purposeto evaluate the efficacy of conjunctival autograft after the pterygium excision with fibrin adhesive using conjunctiva over the pterygium.patients and methodsthis prospective study included 25 eyes of 25 patients with a mean age of 4010 years , who underwent the pterygium excision with conjunctival autograft derived from the body of the pterygium and attached using fibrin glue . the mean follow - up period was 6 months . on all postoperative visits , changes in uncorrected visual acuity , corrected distance visual acuity , astigmatism , complications , and the evidence of recurrence were recorded.resultsat the end of mean follow - up , uncorrected visual acuity and corrected distance visual acuity improved by one or two lines in all eyes treated . mean astigmatism reduced significantly from a preoperative value from 2.308d to 1.248d postoperatively ( p<0.026 ) . minor postoperative complications such as congestion , chemosis , and subconjunctival hemorrhage were seen , which resolved with time . no major sight - threatening or graft - related complications were detected . there was no evidence of recurrence during a follow - up period of 6 months.conclusionself-conjunctival autograft following the pterygium excision appears to be a feasible , safe , and effective alternative method for management of pterygium . it also preserves the superior conjunctiva for future surgeries . however , longer follow - up is required to study the long - term outcomes , especially the incidence of recurrence .

Seattle Gum Wall (Photo: Pike Place Market) SEATTLE -- Big changes are coming for the famous Gum Wall in Seattle's Pike Place Market. For the first time in 20 years, the market plans to clean all the gum off the wall. Pike Place Market says a total scrub down is needed because of the sugar in the gum. Market Theater's walls in Post Alley will be steam cleaned starting Nov. 10. The cleaning is expected to take multiple days due to the volume of gum on the walls. Once the wall is clean, people will be allowed to put gum back up again. The Gum Wall has grown to eight feet high and over 54 feet wide, with approximately 150 piece of gum per brick. According to Pike Place, an estimated one million gum wads cover the wall. The Gum Wall is located in Post Alley, under the market. It was started 20 years ago by people waiting in line for a late night improv show. Before the clean-up begins, Pike Place is holding a contest for Gum Wall photos. You can find more information here. Read or Share this story: http://www.king5.com/story/news/2015/11/03/gumwallscrubdown/75080416/ ||||| The gum wall at Pike Place Market was started 20 years ago by audience members waiting in line for our late night improv show. For the first time in 20 years, the Pike Place Market gum wall will get a major scrub, market staff said. The steam cleaning of the wall and adjacent walls in Post Alley will begin at 8 a.m. Nov. 10 and is anticipated to last until Thursday, November 12 or November 13 due to its multi-ton volume, staff said. “The gum will be allowed back within the boundary of the original wall, which is left (north) of the Market Theater,” market spokeswoman Emily Crawford said. The gum wall was started 20 years ago by audience members waiting in line for our late night improv show. Did you know the Pike Place Market gum wall isn't the only one of its kind? Check out the others! >>kiro.tv/GumWallPICS “Since then, it has been cleaned and recreated three times,” said Kent Whipple, Marketing and Development Director for Unexpected Productions, the improv theater troupe that operates the Market Theater in Post Alley. “The Wall is like the art that takes place behind it, constantly changing from the sharing of its participants. And, like a good improv story, has a beginning, middle and end. The Wall is ready to start a new story. We are excited to see the new incarnation.” The Market also is hosting a photo contest celebrating the Gum Wall, which has more than 80,000 tagged posts on Instagram. “We recognize the Gum Wall is one of the most photographed locations at Pike Place Market,” said Crawford, who is Director of Communications and Marketing for Pike Place Market Preservation and Development Authority. “The photo contest provides an opportunity for fans around the world to share their Gum Wall memories.” For people who want to stick one last piece of gum on the wall before it is cleaned, the Gum Wall photo contest runs from Tuesday, November 3 to Monday November 9, 2015. Voting ends on Thursday, November 12, 2015 with the winner announced the next day. Photos can be posted to the Pike Place Market Facebook page or the contest web page. ||||| The popular, sticky Pike Place Market attraction will get a heavy-duty scrubdown next week. Officials know the gum is sure to come back, but they’re hoping it will be contained to a smaller area. Once named the world’s second-germiest tourist attraction, Pike Place Market’s gum wall will soon be scrubbed of 20 years’ buildup of sugary stickum. Emily Crawford, a spokeswoman for the Pike Place Market Preservation & Development Authority (PDA) said the gum wall is cleaned “every other month” by the PDA with a steamer, but this will be the first time all the gum is removed from the original wall. Related: Where will all of the gum go? The PDA has hired a contractor, Cascadian Building Maintenance, “because it’s going to be a very large job,” Crawford said. Kelly Foster, of Cascadian Building Maintenance, said the gum will be removed with an “industrial steam machine that works like a pressure washer.” The machine will melt the gum with 280-degree steam; it will fall to the ground, and a two- to three-man crew will collect the gum in five-gallon buckets. “This is probably the weirdest job we’ve done,” Foster said. Crawford said the PDA estimates 1 million pieces of gum are adhered to the walls of Post Alley, and the buildup is in some places 6 inches thick. The cleaning job is expected to cost $4,000. More accurate figures on the amount of gum could be forthcoming. “We want to weigh it,” she said. Crawford said the gum needs to be cleaned off the walls to preserve the historic buildings in the Market district. “It was never part of the charter or the history of the Market to have the walls covered with gum,” she said. “Gum is made of chemicals, sugar, additives. Things that aren’t good for us. I can’t imagine it’s good for brick.” Crawford said cleaning will begin Nov. 10. The job will likely take three or four days. Colorful globs of salivated chew will no doubt return shortly, the PDA expects. “We’re not saying it can’t come back,” Crawford said. “We need to wipe the canvas clean and keep (it) fresh.” The PDA hopes that fresh start hinders gum-wall sprawl. In recent years, Crawford said gum has advanced to new turf “far beyond the original wall.” Her theory: “It’s so gross,” she said. “People don’t actually want to touch or get near the gum wall. They’re looking for empty surfaces.” The PDA plans to place more public art in the alleyway and hopes having 20 years of gum removed will keep future visitors more targeted when in placing their gum. Meantime, the Market is holding a photo contest on its Facebook page, where people can vote on favorite gum-wall pictures.

– One of America's grossest tourist attractions is getting a scrub-down. Seattle's gum wall in Pike Place Market, which has been collecting wads of chewed gum for 20 years, will be reduced to plain old brick beginning Tuesday courtesy of a contractor with an industrial steam machine, reports the Seattle Times. The area's Preservation and Development Authority says the wall has attracted 1 million pieces of gum, spread eight feet high by 54 feet wide, and the gunk is six inches thick in spots, per KING 5. And though it's cleaned every other month with a light steaming, officials say it's time the gum is removed to preserve the Market district's historic buildings. Won't people just create a new gum wall? Probably, the PDA admits. But the hope is that it will be contained to the original wall, since the stuff has moved "far beyond," a rep says. "Gum is made of chemicals, sugar, additives. Things that aren't good for us. I can't imagine it's good for brick," she adds. "It was never part of the charter or the history of the Market to have the walls covered with gum." The attraction actually started accidentally, when audience members waiting in line for a late night improv show at the Market Theater found the wall was a great place to leave their gum. "The wall is like the art that takes place behind it, constantly changing from the sharing of its participants. And, like a good improv story, has a beginning, middle and end," a rep for the improv theater troupe tells KIRO. "The wall is ready to start a new story. We are excited to see the new incarnation." Workers will use 280-degree steam to melt the gum, which will then be collected and weighed. (Click for more icky tourist attractions.)

gastric specification in the mouse begins during gastrulation with derivation of the endodermal germ layer that eventually will seed the epithelial lining of the digestive , respiratory , and urogenital systems . the endoderm germ layer is formed by the ingression of epiblast cells through the primitive streak . as the cells exit the primitive streak , they arrange into a single - layered epithelial sheet on the outside of the embryo ( embryonic day [ e]6e7.5 ) . this sheet forms pockets at the anterior ( future foregut ) and posterior ( future hindgut ) end of the embryo and progressively zippers into a complete gut tube . zippering of the gut tube , mesodermal growth , and embryonic turning transform the endodermal sheet on the outside of the embryo into an internal tube consisting of 3 major regions : foregut , midgut , and hindgut ( e7.5e9 ) . regional and subsequent organ identity is assembled within the naive , as yet unspecified , gut tube through the integration of signaling inputs from mesodermal tissues located apposed to the endoderm and the endodermal progenitors themselves . one recognizable output of the stage when regional identity is acquired is a pattern of expression of overlapping transcription factor domains that facilitate subsequent organ - specific differentiation programs . stomach epithelial progenitors derive from the foregut region of the endoderm , which also gives rise to liver , pancreas , lungs , and the luminal gastrointestinal organs from the pharynx to the anterior duodenum . signaling pathways and transcription factors that drive specification of pregastric endodermal progenitors from other emerging organs within the foregut have not been well characterized . however , a number of signaling pathways that promote or restrict foregut identity by patterning the anterior / posterior axis of the endoderm are known . retinoic acid ( ra ) , for example , has a complex spatiotemporal role patterning the anterior posterior axis of the endoderm . during late gastrulation , ra signaling promotes the specification of posterior endodermal fates over anterior endodermal fates , particularly at the foregut midgut boundary.12 , 13 subsequently , ra signaling is required to promote the development of a number of foregut tissues . animals with defective ra signaling have abnormal stomach development , but a specific consequence to gastric specification is unclear . wnt and fibroblast growth factor ( fgf ) signals produced by the mesoderm promote expression of posterior endodermal markers such as cdx2 over anterior endodermal markers.15 , 16 , 17 studies in zebrafish also have shown that bone morphogenetic protein ( bmp ) signaling drives posterior over anterior endodermal fates . through the study of other endodermal organs , a number of tissues have been shown to produce important signaling molecules to promote foregut organ specification . for example , the dorsal aorta and notochord produce several key signaling molecules involved in dorsal pancreatic specification.19 , 20 these same tissues also could impact pregastric gene expression given the proximity of gastric and dorsal pancreatic progenitors . ventral tissues , including cardiac mesoderm , also could impact gastric specification from other ventral organs such as the liver and lung . other signaling pathways such as sonic hedgehog ( shh ) have been implicated in gastric growth through epithelial to mesenchyme signaling , although shh does not appear to be involved in gastric specification . during endodermal specification , a highly conserved core transcription network ( including foxa , gata , sox17 , and mixl1 transcription factors ) is activated and guides the growth and survival of endodermal cells before regionalization . expression of these transcription factors in early endoderm is necessary to generate foregut progenitors that give rise to the stomach . as the endoderm regionalizes , a number of transcription factors are expressed either throughout the foregut endoderm or regionally in the pregastric domain . broadly expressed transcription factors such as foxa1/2/3 , gata4/6 , hnf1 , and sox2 all could play an important role in gastric specification ( figure 2 ) . for example , the foxa family is expressed throughout the early endoderm and is important in the development of a number of organs including the liver , pancreas , and intestine.24 , 25 , 26 the specific role of this family in the stomach has yet to be determined , however , foxas are known to be involved in promoting pdx1 expression in the foregut ( figure 2 ) . because pdx1 is expressed only in the gastric antrum and not the more proximal corpus , foxa factors thus could be involved in regionalizing the stomach . gata4 and gata6 are involved in the specification of the extraembryonic endoderm28 , 29 , 30 and are expressed throughout the early definitive endoderm . during endodermal regionalization , both genes are expressed in the foregut . the expression domain of gata4 is particularly interesting because its anterior boundary resides at the future forestomach / glandular stomach boundary . potentially , gata4 may have an important role in specifying the glandular stomach or specifying the forestomach vs the glandular stomach ( figure 2 ) . consistent with the idea that gata4 is important for glandular stomach specification , gata4 null cells do not appear to be able to adopt gastric identity in chimeric embryos when they are competing with wild - type cells . sox2 is expressed broadly throughout the foregut from the most anterior pharyngeal endoderm to the future boundary of gastric antrum and duodenum . studies wherein expression of sox2 is reduced in developing endoderm have shown that it helps govern the development of a number of foregut organs including the stomach , esophagus , trachea , and lung.32 , 33 such experiments involved hypomorphic animals , so it will be interesting to know what the effects of complete loss of sox2 from early endoderm might be . perhaps sox2 has an even more critical role in anterior foregut and stomach specification than currently thought . the border between sox2 and cdx2 expression during development ( figure 2 ) resides at the prospective gastrointestinal junction and suggests that sox2 could define this boundary . misexpressing sox2 in cdx2-positive progenitors in the developing intestine increases expression of gastric - specific differentiation markers . interestingly , loss of cdx2 during early development causes a dramatic transformation of the prospective intestine into sox2-expressing esophageal - like progenitors and not gastric progenitors , indicating that sox2 is not a simple progastric , anti - intestine transcription factor . pdx1 is expressed regionally within the posterior foregut in the areas that give rise to the posterior stomach ( antrum / pylorus ) , anterior duodenum , dorsal and ventral pancreatic buds , and proximal extrahepatic biliary system.27 , 37 pdx1 expression can be used during development to distinguish antral gastric progenitors ( sox2gata4pdx1 ) from corpus progenitors ( sox2gata4pdx1 ) . loss of pdx1 causes aberrant antral stomach progenitors including pyloric defects and loss of gastrin - producing endocrine cells . definitive endoderm - specific knockout of hnf1 alters gene expression within caudal stomach progenitors , including causing loss of pdx1 and indian hedgehog ( ihh ) . the impact on gastric specification in these knockouts remains unclear , but recent in vitro studies intriguingly have implicated hnf1 in promoting antral stomach specification in organoid culture . to date , no specific gene has been shown to have expression restricted only to early gastric progenitors ; thus , it remains difficult to examine directly how the stomach is specified from other organs , the way , for example , cdx1 and cdx2 have been studied in intestinal specification . instead , investigators rely on more broadly expressed genes ( ie , expressed concomitantly in other organs besides the stomach ) such as sox2 , gata4 , and pdx1 to identify the factors defining the prospective gastric regions . further identification of transcripts that may have more restricted or specific expression to gastric progenitors ( particularly to the glandular stomach ) during early development could lead to the generation of new genetic tools to explore and characterize gastric specification or even to perform stomach - specific epithelial cell gene deletion because intestinal epithelial - specific deletion can be driven by villin - cre . however , there could be marked improvement in our understanding of stomach specification simply by manipulating gene expression in early endoderm with tools that already exist . for example , signaling pathways and transcription factors suspected of being involved in gastric development could be deleted via crosses to well - characterized mouse pedigrees that express foxa3- , sox17- , or shh- cre.41 , 42 , 43 summing up all that currently is known and can be inferred from published studies , we have proposed one possible signaling and epistasis model for specification of glandular stomach ( figure 2 ) . mesenchymal cross - talk , and the stomach does not seem to be an exception . for example , foundational experiments in chicks have shown that placing proventricular ( stomach region in chicks similar to the mammalian glandular stomach ) mesenchyme with gizzard ( anterior chicken stomach ) or esophageal endoderm induces proventricular gene expression and causes gland development in these normally nonglandular tissues.44 , 45 similarly , gizzard or esophageal mesenchyme can suppress proventricular gene expression and gland development in proventricular endoderm and promote squamous fates . interestingly , proventricular mesenchyme could not induce proventricular gene expression in intestinal endoderm ; hence , overlying mesoderm can instruct endoderm identity but only within restricted regions . although bmp signaling , principally deriving from the mesenchyme , influences gastric epithelial development , hedgehog signaling derived from the epithelium influences the mesenchyme . for example , in addition to their early role in foregut growth , hedgehog ( shh / ihh ) signals are produced by the gastric endoderm to support mesenchymal growth and differentiation , a pattern that is maintained in the adult.49 , 50 another example of a factor that originates from the mesenchyme and regulates the epithelium is fgf10 , likely via the fgf receptor 2b . fgf10 promotes epithelial proliferation and gland development.51 , 52 although it may not be required for adult homeostasis , it has been shown to inhibit parietal and chief cell differentiation in favor of the mucous neck cell type . in addition to the themes of epithelial hedgehog and mesenchymal bmp signaling that occur throughout the gastrointestinal tract , there have been some descriptions of signals more specific to gastric development vs other regions . for example , barx1 is a transcription factor that is restricted to the prospective esophageal and gastric mesoderm . the stomach intestinal boundary is disturbed such that ectopic cdx2 + intestinal epithelial cells can be found in the posterior stomach.54 , 55 in addition to the disrupted interorgan patterning , the division of intrastomach domains is altered . for example , h / k adenosine triphosphatase expressing cells are seen intermingled with pdx1 + cells , which in mice are normally exclusive to the corpus and antrum , respectively . bapx1 ( nkx3 - 2 ) , nkx2 - 5 , gata3 , six2 , nr2f2 ( chicken ovalbumine upstream promoter - transcription factor ii ) , and sox9 are other known transcription factors expressed in the posterior stomach mesenchyme and involved in specifying the pylorus.56 , 57 , 58 in the absence of those transcription factors , there is aberrant neuromuscular regulation of the pyloric sphincter , which in human beings can manifest as the relatively common condition known as pyloric stenosis.58 , 59 between the stage of endodermal specification and the stage of specific cell lineage commitment in the stomach , the gastric epithelium remains a simple epithelium with no obvious differentiation . at approximately e14.5e16.5 , markers representative of cell types such as endocrine , parietal , and chief cells begin to be expressed , and small glands begin to invaginate into the mesenchyme from the simple epithelium lining the lumen . between e16.5 and 2 weeks of postnatal development , most of the major cell types arise within the stomach , and the glandular stomach mostly becomes organized into its adult form . however , the murine stomach does not reach adult organization with full chief cell and endocrine cell lineage specification until 68 weeks postnatally . for most cell lineages in the stomach we have a poor understanding of pathways and factors involved in their specification and the progenitors from which they directly derive . for example , and this is truly remarkable when contrasted to the state of our understanding in the intestines , there is no specific factor that is known to be necessary or sufficient for specification of chief , parietal , pit , mucous neck , or isthmal cells . the markers used in gastric biology represent the terminal differentiation of those cells ( eg , atp4b , tff1 , pgc , and gif ) . the lack of this basic specification knowledge greatly hinders deciphering the molecular mechanisms underlying how gastric disease causes the loss or increase of any particular cell lineage . the developmental sequence between gastric epithelial progenitors in an adult gastric unit and the differentiated progeny that arise continuously throughout life also is unknown . it is entirely possible that all the mature cell types are specified from a single multipotent progenitor that persists throughout life , or , in turn , there might be numerous long - lived lineage - restricted progenitors62 , 63 ( figures 3 and 4 , and see detailed discussion later ) . the only stomach lineages with known genetic determinants and known progenitor markers are endocrine cells , which are controlled by the master regulators ascl1 and ngn3.65 , 66 ngn3 marks endocrine progenitor cells but not mature forms . ngn3 null embryos lack gastrin , somatostatin , and glucagon endocrine cell types , with largely reduced census of serotonin - positive cells , but enterochromaffin - like ( ecl ) and ghrelin populations still are present.65 , 66 ascl1 null embryos wholly lack gastrin , somatostatin , and glucagon - secreting endocrine cell types ( the former 2 missing from their usual niches in the stomach ) , and gastric serotonin and ghrelin endocrine cells are decreased in number . ascl1 null embryos die before ecl cells emerge developmentally ; however , it was noted that the vast majority of chromogranin a positive cells ( chromogranin a is a general marker of endocrine cells ) are missing in ascl1 null embryos , and ecl cells represent the majority of chromogranin - positive cells in the corpus . thus , if ascl1 is required for all chromogranin a positive cells to emerge , a conditional deletion in the adult also might show that ecl cells are ascl1-dependent , although this only can be speculated with current data . taken together , the data show that ascl1 and ngn3 are each required to specify gastrin , somatostatin , and glucagon - positive endocrine cells . the eventual emergence of ecl cells may be dependent on ascl1 but not ngn3 . serotonin - positive endocrine cells in the antrum also largely are lost in ascl1 and ngn3 mutants . a recent study showed that serotonin - positive cells in the corpus are bone marrow derived , mucosal - associated mast cells and not descendants from endodermal progenitors , an ngn3 lineage , or epithelial cells at all . if corpus serotonin - positive cells are not derived from the endoderm , those cells likely account for the presence of nonantral serotonin - positive cells in ascl1 mutants mentioned earlier . it is unclear how specific mature endocrine cell types arise from endocrine - committed progenitors during embryogenesis and adult homeostasis ; however , endocrine specification in the pancreas and intestine may serve as an illustrative model.68 , 69 endocrine - committed progenitors derived from ascl1- or ngn3-positive populations differentiate into individual endocrine cell types depending on the specific downstream transcription program that is enacted . there is indication that similar programs exist in the stomach because mice null for various transcription factors have defects in specific endocrine lineages . for example , pdx1 , nkx6.3 , pax4/6 , and arx all have been implicated in controlling differentiation of mature endocrine cell types in the stomach.38 , 70 , 71 , 72 although it is mostly not clear what controls the specification of nonendocrine cell lineages within the stomach , some factors have been implicated in maturation of those cell types . the transcription factor spdef has been shown to be crucial for antral deep mucous cell maturation . foxq1 is necessary for the expression of muc5ac in pit cells ( muc5ac is the key mucin protein secreted by these cells ) . xbp1 and mist1 ( bhlha15 ) are important for the ultrastructural maturation of chief cells.75 , 76 specifically , they coordinate the architectural changes necessary for these cells to become regulated secretory factories . in their absence , chief cells fail to generate a dense rough endoplasmic reticulum network and do not make large zymogen - containing vesicles . mucous neck cells , the progenitors for chief cells , emerge in rodents around the time of weaning in a process that depends in part on transforming growth factor and the epidermal growth factor receptor,77 , 78 although whether these play a role in maturation or specification is not known . the isthmus of the corpus epithelium contains a continuously proliferating cell population that lacks any differentiated nuclear and cytoplasmic features ( eg , secretory granules or specialized organelles ) . nucleotide analog labeling studies ( eg , h - thymidine or bromodeoxyuridine ) show that labeled nucleotides are incorporated most frequently in isthmal cells with those morphologically immature characteristics , and this cell lineage has been termed the granule - free stem cell . pulse - chase experiments with such analogs show that the labeled nucleotides spread bidirectionally from the isthmus . karam and leblond hypothesized that the granule - free stem cell directly gave rise to progenitors that were immature versions of each of the mature corpus lineages . some of the earliest cells to incorporate label were cells characterized by ultrastructural features of immature pit cells ( eg , scant but distinctive pit cell mucous granules ) . label spread more slowly in the other direction ( ie , toward the base and away from the gastric lumen ) . the cells that showed early incorporation of label in that direction commonly have early / immature mucous neck cell features . at 12 weeks after injection of labeled nucleotides , label appears in the prezymogenic chief cells at the top of the base , those with features characteristic of both mucous neck cells and zymogenic cells.76 , 80 it appears eventually , also in parietal cells and endocrine cells , first in the isthmus area.81 , 82 in pulse - chase experiments wherein the nucleotides are given only once as opposed to continuously label typically is not retained for longer than a few days in either the immature ( presumptive progenitor ) cells or in the granule - free cells . rather , label is retained long - term only in mature parietal , chief , and endocrine cells . the simplest interpretation of these observations is that the undifferentiated , granule - free isthmal cell is a constitutively active multipotent stem cell that can give rise to and replenish all the mature cell lineages ( figure 3 ) . other than such studies , wherein lineage relationships are inferred from morphology and labeled nucleotide migration patterns , there is little else known about transitions from the stem cell to progenitors and lineage - committed cells in the corpus . the limited state of understanding in the gastric corpus is in marked contrast to that in the small intestine , where numerous markers of crypt - based cells with stem cell potential have been identified over the past 10 years.83 , 84 , 85 , 86 , 87 strikingly , there is still neither a specific molecular marker nor a specific promoter whose expression is restricted to an undifferentiated isthmal cell in the corpus that has yet been identified . several studies using chimeric mice and mosaic silencing of an x - linked transgene in female mice suggest that stomach glands start off polyclonal but become monoclonal over time.62 , 88 , 89 , 90 these results thus support the single gastric unit stem cell hypothesis . however , bjerknes and cheng found patterns of mutant clones that showed that , as mice age , there might be other progenitor - progeny relationships outside the dogma of the single , long - lived , multipotent stem cell proposed by karam and leblond . in adult mice , bjerknes and cheng saw units that seemingly had stable labeling restricted to specific single lineages , suggesting that there also might be long - lived , lineage - committed progenitor cells rather than the transient ones hypothesized by karam and leblond . we have provided a cartoon to distinguish the 2 models ( ie , a multipotent , undifferentiated stem cell giving rise to all lineages vs multiple long - lived , lineage - committed progenitors , each fueling only their specific lineage ) ( figure 4 ) . genetic lineage tracing experiments that have been attempted in the stomach suffer from the caveat that the promoters used to drive lineage tracing also are expressed ( usually much more strongly ) in differentiated cells . for example , long - term lineage tracing in adult animals using the sox2 promoter suggested that some sox2-promoter - expressing cells have stem cell function with the capacity for self - renewal and differentiation into all lineages in the corpus . rare , highly sox2 + cells were suggested to be the most stem - like . interestingly , those cells localized to the base of corpus units , not the isthmus . sox2 protein can be found in many cell lineages throughout the corpus at mid - to - low levels and even can be used as a marker in human beings of gastric differentiation relative to intestinal.92 , 93 other lineage tracing studies have focused on marking mature chief cells using the tumor necrosis factor receptor superfamily member 19 ( tnfrsf19 or troy ) or muscle , intestine and stomach expression 1 ( mist1 ) promoters . long - term lineage tracing using those promoters suggested that chief cells also can act as stem cells and give rise to all the cell lineages within the corpus . mist1 protein and rna are almost exclusive to mature chief cells , and troy is restricted to a handful of chief and parietal cells . these results indicate that differentiated chief cells have the potential to serve as stem cells in some situations , albeit such functional stem cell activity in chief cells seems relatively rare , at least during homeostasis . recent studies have indicated that rare cells labeled with a mist1 knock - in allele also can be found in the isthmus of the corpus . these occasional , isthmus - localized cells that express the mist1 promoter could be another source of stemness in the corpus . however , the molecular / cellular identity of those cells is defined only by this spurious mist1 expression , given that neither the endogenous mist1 transcript nor the mist1 protein has been shown to be expressed outside of chief cells in wild - type mice . definitive lineage tracing studies in the stomach also have been hampered by a technical problem that does not affect other gastrointestinal organs to the same degree , such as small intestine and pancreas , where lineage tracing has been used to great effect . the vast majority of genetic lineage tracing tools use a modified cre recombinase that requires binding tamoxifen to be transported to the nucleus where it can activate reporter genes or other genetic tools ( cre ) . unfortunately , for gastric researchers , tamoxifen induces parietal cell death and chief cell metaplasia when delivered above a threshold dose.97 , 98 , 99 thus , inducible lineage tracing using cre with tamoxifen can be confounding in the stomach because it may induce nonhomeostatic patterns of differentiation with increased cellular plasticity . the stomach is also particularly sensitive to high doses of cre itself . it would be ideal to develop more stomach - lineage specific promoters and induce lineage tracing with methods such as tetracycline - inducible systems or estrogen receptor agonists that do not induce injury furthermore , any lineage tracing in the stomach should be performed with proper controls : mice homozygous for floxed alleles but lacking cre recombinase expression and mice with cre recombinase but with a nonfloxed allele of the gene of interest . to highlight how our understanding of stem cell dynamics in the intestine is more advanced than in the corpus , we point out how cre driven by the lgr5 promoter is an efficient marker of functional stem cell activity in the intestine . lgr5 is expressed at higher levels in the presumptive stem cells in the small intestine than in differentiated progeny . importantly , both the endogenous lgr5 transcript and lgr5 protein also are expressed preferentially in the presumptive stem cell . lgr5 can be used during homeostasis to trace labeled cells , and all cell lineages can be seen eventually to derive from lgr5-promoter expressing , crypt - resident ( presumptive stem ) cells with undifferentiated features . lgr5 promoter - based studies corroborate other studies that , together , make it seem incontrovertible that there is a population of constitutively active , long - lived , multipotent stem cells in the small intestine . although the gastric epithelial stem cell in the adult corpus remains unidentified , there has been some beginning characterization of the patterns of molecular and cellular differentiation of the various mature cell lineages deriving from that stem cell . one strong line of evidence supports an interesting differentiation pattern wherein mucous neck cells give rise to chief cells , a differentiation step that has been termed a transdifferentiation to chief cells.76 , 78 , 101 evidence supporting the lineage relationship between neck and chief cells is circumstantial , but varied and relatively abundant . for one , there are situations in which neck and chief cell markers are co - expressed . during postnatal maturation , after maturation , units in the corpus harbor similar transitional cells with characteristics of both cell populations by ultrastructural and gene expression analysis.76 , 80 , 101 , 102 when the stomach is injured , metaplastic cells arising from the chief cell lineage express both neck and chief cell markers.6 , 95 , 101 furthermore , lineage tracing studies using the tff2 promoter have suggested that parietal cells and mucous neck / chief cells are derived from a common progenitor pool . finally , slowing maturation of chief cells by deleting either mist1 or xbp1 leads to increased cells with neck - chief transitional characteristics.75 , 76 , 101 the surface mucous ( pit / foveolar ) cells clearly arise rapidly from a progenitor in the isthmus . the nature of the progenitor has not been established but must be either a committed pit - specific , long - lived progenitor or the canonical multipotent stem cell ( or both ) . interestingly , we have observed that decreased proliferation in the isthmal progenitor zone tends to have effects on pit cells more than the deeper glandular cells , indicating that much of the proliferation in the isthmus , at least under normal conditions , is directed toward surface mucous cell replenishment . as mentioned earlier , the transcription factor foxq1 is involved in pit cell differentiation because it is required for expression of the key component of the pit cell mucous granules ( muc5ac ) , although it is not required for specification of the lineage itself . a number of signaling pathways have been shown to be active during stomach homeostasis and affect cell behavior . notch signaling is active in the isthmus of the corpus and promotes proliferation within this region . ectopic notch signaling driven by a parietal cell - lineage specific promoter blocked differentiation and maintained progenitor characteristics in differentiating parietal cells . inhibition of the bmp signaling pathway promotes increased cell proliferation in the adult stomach : glands contained fewer parietal cells and more transitional cells ( cells with both neck and zymogenic chief cell characteristics similar to the metaplastic or transitional cells mentioned earlier ) at the base of the unit , indicating that bmp signals regulate progenitor proliferation and cell maturation in the corpus . the primary physiological role of gastrin is to promote acid secretion by activating ecl and parietal cells . absence of gastrin causes decreased cellular proliferation in the corpus and leads to generation of immature parietal and ecl cells,107 , 108 , 109 , 110 whereas overexpression of gastrin causes increased proliferation of those cell populations . parietal cell production of shh is an important regulator of gastrin production . in the absence of this source of shh , excess gastrin is produced by g cells , and pit cells in the corpus have increased proliferation . the antrum is considerably less complex then the corpus ( in organization and number of cell types ) . lee and leblond identified the most actively proliferating cells as also being the least differentiated ultrastructurally ( like the granule - free presumptive stem cell in the isthmus of the corpus ) . in the antrum , the isthmus is much nearer the base than in the corpus , in a pattern more resembling the large intestine . in pulse - chase experiments , labeled dna spreads both upward to the lumen and further down into the base from this isthmus zone ( figure 1 ) . in contrast to the corpus , markers and gene promoters have been shown to efficiently label cells with multipotent progenitor capacity . for example , as in the small intestine , lgr5 shows a pattern of homeostatic expression that is confined to a specific cell population that frequently and efficiently can be traced into progeny that include all the cell lineages in the antrum and cardia , but not the corpus . similarly , cck2r - based lineage tracing labeled as + 4 ( the designation of + 4 is borrowed from the intestine , wherein cells traditionally have been numbered from the most basal cell upward to the lumen ) antral cells that also has stem cell potential and was shown to give rise to lgr5 + antral cells . in addition , villin- and sox2-promoter based lineage tracing also label rare cells in antral glands that show functional stem cell characteristics.91 , 116 it is not yet clear what the relationship among all of these cell populations with stem cell capacity is yet . the lgr5 + cells clearly are not the granule - free , isthmal antral cells because they commonly are located at the very base of the antral unit , not the isthmus , and they show ultrastructural features of differentiation.113 , 114 the cck2r and lgr5 populations seem to be overlapping , at least functionally , but are distinct from each other . sox2 , on the other hand , is expressed in many cells , therefore it likely is not specific to a defined stem cell . it is possible that cells in the antrum are plastic , so that many cells can serve as stem cells even homeostatically . antral glands also undergo relatively frequent fission events , in which one gland gives rise to another,62 , 89 , 117 so perhaps some of the markers label cells that are not constitutive stem cells but that drive budding off of new glands . in sum , sox2 , lgr5 , and villin are not principally expressed in the zone where the least differentiated , most proliferative cells are . that is in contrast to the intestine where the lgr5-expressing ( crypt - base - columnar ) cells are the most proliferative and the least ultrastructurally differentiated cells . perhaps , thus , a marker of isthmal , antral stem cells that is equivalent to lgr5 in the intestine has yet to be identified in the stomach . in the antrum , inhibition of notch signaling promotes mucous and endocrine cell differentiation , whereas activating the pathway stops differentiation . bmp signaling , through bmpr1a , regulates the proliferation and differentiation of mucous cells in the antrum.100 , 119 in the absence of bmpr1a , antral mucous cells hyperproliferate and fail to express the mucin muc5ac . mutations in the bmp family are known to cause juvenile polyposis syndrome , which presents with polyps throughout the gastrointestinal tract , including the antrum . finally , given that lgr5 is expressed and may regulate stem cell activity in the antrum , there may be a role for wnt signaling in regulating antral homeostasis because lgr5 is a co - receptor for canonical wnt signals . although it is clear that tissue interactions between the gastric endoderm and mesoderm are important for gastric development , there is still scant knowledge about how naive endodermal progenitors become specified to the gastric progenitor state . there is equally poor understanding about the factors that control the specification of gastric lineages during development and adult homeostasis , other than some initial inroads into outlining the origins of endocrine lineages . many more studies are needed to determine which cell types have stem cell properties in the adult stomach ( in particular the corpus ) , and their relative contribution during homeostasis and disease / injury conditions . such studies will depend on the development of promoter - based tools that , similar to the intestine , are specific for stem cells and not expressed in differentiated cells . recent reports have described the derivation of mouse and human gastric organoids derived either from adult stomach94 , 122 , 123 , 124 , 125 , 126 or via differentiation from induced pluripotent stem cells . potentially through the manipulation of these cells , the field might have a new approach to better understand the pathways and factors controlling stemness and specification of gastric lineages . the generation of such new tools to study these processes is an important first step to exploring the mechanisms that control gastric specification .

gastric diseases cause considerable worldwide burden . however , the stomach is still poorly understood in terms of the molecular cellular processes that govern its development and homeostasis . in particular , the complex relationship between the differentiated cell types located within the stomach and the stem and progenitor cells that give rise to them is significantly understudied relative to other organs . in this review , we highlight the current state of the literature relating to specification of gastric cell lineages from embryogenesis to adulthood . special emphasis is placed on substantial gaps in knowledge about stomach specification that we think should be tackled to advance the field . for example , it has long been assumed that adult gastric units have a granule - free stem cell that gives rise to all differentiated lineages . here , we point out that there are also other models that fit all extant data , such as long - lived , lineage - committed progenitors that might serve as a source of new cells during homeostasis .

inflation , as proposed in early 1980s to address conceptual issues of the hot big bang cosmology @xcite , has become the most successful paradigm of describing the very early universe . its profound prediction of a nearly scale - invariant primordial power spectrum has been verified to high precision by the observations on the cosmic microwave background ( cmb ) in recent years @xcite . moreover , recently the bicep2 collaboration reported the detection of the cmb primordial @xmath0-mode polarization @xcite . this observation , if confirmed to be originated from primordial gravitational waves , will be another major significance for inflation . the success of inflation , however , is based on a series of assumptions including the existence of a sufficiently long period of quasi - exponential expansion realized by an as yet undetermined physical mechanism , such as to introduce a slow - roll scalar field or to modify gravity theories . an important question to be addressed is how to formulate the effective field description from fundamental theories . in the literature , there have been many attempts of realizing the ( generalized ) starobinsky model @xcite in the context of , namely , the supergravity descriptions @xcite , the approach of asymptotically safe gravity @xcite and the modified gravitational actions @xcite . recently , a new class of models was developed in @xcite , which suggested that inflation models with the same conformally described gauge invariance are observationally equivalent . specifically , a gravitational system involving a scalar field with a flattened potential can be derived by two - field theory with an approximate @xmath1 symmetry @xcite which is invariant under a gauge transformation . this class of models was dubbed as t - models later @xcite . the t - models , which can be realized in supergravity , predict small tensor - to - scalar ratio similar to starobinsky model . this original version of the t - models is however under danger because of the large @xmath0-mode detected by bicep2 @xcite . in this paper we study possible extensions of t - models which are invariant under this same gauge transformation . we investigate the properties of the t - models and find that they can be embedded into a broader class which includes specific typical examples that covers a larger portion on the @xmath2-@xmath3 plane . especially , taking the recent observation on large @xmath0-modes in consideration , we can seek for a simple chaotic inflation model with a power - law potential @xcite in such a class of conformally described models . this article is organized as follows . in section [ sec : model ] we briefly review the t - models and the gauge transformation under which the lagriangian is invariant . then , we extend it to a generalized description by introducing a non - trivial potential beyond the t - models . in section [ sec : general ] we focus on some specific examples and study their cosmological implications , especially the predictions on the @xmath2-@xmath3 relationship . we compare the predictions with the recent bicep2 data on tensor modes . we then conclude in section [ sec : conc ] . let us start by quickly reviewing the t - models proposed in @xcite . if we write down a non - minimally coupled lagrangian with two real scalar fields , @xmath4 \ , .\ ] ] the negative sign of @xmath5 field seems dangerous , but it will not bring any classical instability since it is not a physical degree of freedom . it is invariant under the following local gauge transformations : @xmath6 this gauge invariance tells us that we can fix the gauge by choosing an appropriate field @xmath7 and get the physical degree of freedom . it looks like a conformal symmetry under this gauge transformation , but it is not as the metric is not changed physically but only redefined @xcite . one can eliminate this degree of freedom by fixing a specific gauge , i.e. by choosing a specific function @xmath7 which may be arbitrary . a convenient choice is @xmath8 to realize this gauge fixing , it is also convenient to define a new field @xmath9 in terms of which @xmath5 and @xmath10 are written as @xmath11 and correspondingly , the lagrangian can be reformulated as@xmath12 \,.\ ] ] one can easily find this lagrangian is exactly the form of the starobinsky model @xmath13 in the einstein frame with @xmath14 @xcite . note that under the gauge condition ( [ gaugefix ] ) , slow - roll inflation occurs at @xmath15 , where an @xmath1 symmetry in field space is restored . the extension to this description , the so - called t - models @xcite , has a general potential as compared to ( [ conformalstar ] ) , @xmath16 \ , , \ ] ] where @xmath17 is a function of @xmath18 . we can see that except for this @xmath17 factor , all the other terms preserves an extra @xmath1 symmetry in the field space of @xmath5 and @xmath10 . inflation happens in the neighborhood of the limit @xmath19 , where the @xmath1 symmetry is restored . as inflation proceeds , @xmath18 deviates from 1 monotonously . and finally inflation ends as the @xmath1 symmetry is completely broken . to study this deviation , we define a new variable @xmath20 one can see from this definition that unless @xmath5 and @xmath10 are complex fields with different phases , a real @xmath9 satisfying ( [ gaugefix ] ) will generate @xmath21 . a typical t - model chooses a specific form for the function @xmath17 as @xmath22 . with the gauge condition ( [ gaugefix ] ) , the potential becomes simply @xmath23 the predictions for @xmath2 and @xmath3 are very close to that of the starobinsky model regardless the specific value of the exponent @xmath24 @xcite . that is , both the original starobinsky model and the t - models predict small tensor modes as is in tension with the recent bicep2 data . here we see that the @xmath1 symmetry plays a crucial rule in constructing the potential . if we preserve this symmetry in inflation , all the models generated from ( [ conformalt ] ) have similar predictions . however , as we will see in the next section , there exist other generalized models originating from this lagrangian that can give rise to different relations between @xmath2 and @xmath3 . in this section we construct a broader class of models beyond t - models . to do this we abandon the preservation of the @xmath1 symmetry of the field space even during the inflationary period , but still keep the gauge invariance ( [ xform ] ) . in this case , the general potential of the action is @xmath25 the @xmath26 factor is necessary to keep the gauge invariance of the entire lagrangian . after we choose the conformal gauge as ( [ gaugefix ] ) , this potential can be expressed solely by @xmath27 defined in ( [ def : z ] ) as @xmath28 we can see that if @xmath29 is a smooth function , there exist two second - order poles , @xmath30 . in the present work , we focus our interest on the case of real fields and hence the pole at @xmath31 will not be addressed . the existence of the pole at @xmath32 , however , would probably spoil the slow - roll requirements of inflationary cosmology due to the singular mathematical behavior around this position . in order to describe the dynamics of the inflationary phase , it is convenient to define the slow - roll parameters @xmath33 and @xmath34 as @xmath35 with @xmath36 \equiv \frac{g(z)}{\sqrt{6 } } \ , , \ ] ] and @xmath37 of which the values are required to be much less than unity under the slow - roll condition . however , one can easily observe that when @xmath38 is close to @xmath39 , @xmath40 and in turn @xmath33 would be in general @xmath41 and the slow - roll condition is not guaranteed , unless @xmath42 contains a first order pole at @xmath32 with a residue equal to ( or close to ) @xmath43 . a simple case is the t - models where @xmath44 @xcite . then both second order poles in ( [ v(z ) ] ) are canceled and the potential is simply @xmath45 . another important case is the original starobinsky model @xcite . the effective potential in ( [ starobinskylag ] ) can be recovered from ( [ v(z ) ] ) once we choose @xmath46 . our next step is to seek for more general models from the above requirements . the exact form of @xmath47 with @xmath48 is not clear except for its asymptotic behavior @xmath49 to preserve the slow - roll conditions . a non - zero limit of @xmath50 will give rise to a starobinsky - like model equivalent to @xmath51 with an arbitrary exponent @xmath52 . as the predictions in this case are disfavoured by the bicep2 result as well , we will not discuss it in detail . for further discussions , see for instance @xcite . for simplicity , let us just suppose that @xmath53 in this paper . even so , it is still difficult to determine the relation between @xmath33 and @xmath34 accurately . however , if @xmath54 is finite , we can make a tayler expansion of @xmath47 around @xmath55 as @xmath56 this yields @xmath57 up to the leading order of @xmath58 . after substituting it back into ( [ vslope ] ) , we can see that the starobinsky model is a special case when @xmath59 thus @xmath60 . if @xmath61 , we have to go to higher order in ( [ gexpansion ] ) . let us assume that the first @xmath62 terms of the taylor series are all zero , and ( [ gexpansion ] ) begins from @xmath63 then we find a solution @xmath64 \ , , \ ] ] which deviates from the starobinsky model only up to next - to - leading order . an interesting case occurs when @xmath47 is not an analytic function at @xmath65 and in the meanwhile @xmath54 is divergent . namely , we consider a toy model @xmath66 where @xmath65 is a removable singularity and @xmath67 is a positive parameter . the minus sign is to make sure that @xmath68 for small @xmath58 . this can still preserve the slow - roll conditions , but now we can not have a general relationship as ( [ eta^2 ] ) . a particular solution to ( [ vslope ] ) , up to leading order , is now given by @xmath69 this gives us an effective potential @xmath70 , a dynamical modification to the power index . with this modification one can calculate the slow - roll parameter @xmath33 as @xmath71 whose solution can be expressed by the lambert @xmath72 function , @xmath73 \ , .\ ] ] note that the above two different expressions are mathematically equivalent due to the definition of the lambert @xmath72 function . the subscript @xmath74 denotes the lower branch of the lambert function , where we have @xmath75 therefore , we can obtain the spectral index of the power spectrum @xmath3 in terms of the tensor - to - scalor ratio @xmath2 through the following relation : @xmath76 \left [ 1-\frac{\sqrt{3r}}{8\lambda w_{-1}\left(-\sqrt{3r}/\lambda \right ) } \right ] - \frac{r}{8 } \ , .\ ] ] it is easy to check that the traditional result obtained by the starobinsky model can be recovered under the limit @xmath77 : @xmath78 . the @xmath79-folding dependence can be found easily as @xmath80 where li@xmath81 denotes the logarithmic integral function . we can solve the inverse relation and derive @xmath82^{-1 } \ , .\ ] ] this can be taken back into ( [ xi - e1 ] ) to have a set of parametric equations of @xmath2 and @xmath3 depending on @xmath67 . we show this relation in the left panel of figure [ fig:2ex ] . from this plot , one can see that the value of the tensor - to - scalar ratio is in general very tiny unless one finely tune the parameter @xmath67 to be pretty small . -@xmath3 diagram for ( [ g - log ] ) . the planck constraints @xcite are shown , but the bicep2 ones are out of range . the thick line denotes the starobinsky model which corresponds to @xmath77 . the thin curves are for different values of @xmath67 : from the top , @xmath83 , 1 , 10 , @xmath84 and @xmath85 , respectively . the thin dotted and solid lines represents the @xmath79-folds respectively @xmath86 and 60 . ( right ) @xmath2-@xmath3 diagram for ( [ g(z ) ] ) . the blue contours are the recent bicep2 result . the diagonal lines correspond to different values of @xmath87 : from the top , @xmath88 , 0.1 , 1 , 2 ( thick ) , and 10 , respectively . the thin dotted and solid lines represents the @xmath79-folds respectively @xmath86 and 60.,title="fig:",width=312 ] -@xmath3 diagram for ( [ g - log ] ) . the planck constraints @xcite are shown , but the bicep2 ones are out of range . the thick line denotes the starobinsky model which corresponds to @xmath77 . the thin curves are for different values of @xmath67 : from the top , @xmath83 , 1 , 10 , @xmath84 and @xmath85 , respectively . the thin dotted and solid lines represents the @xmath79-folds respectively @xmath86 and 60 . ( right ) @xmath2-@xmath3 diagram for ( [ g(z ) ] ) . the blue contours are the recent bicep2 result . the diagonal lines correspond to different values of @xmath87 : from the top , @xmath88 , 0.1 , 1 , 2 ( thick ) , and 10 , respectively . the thin dotted and solid lines represents the @xmath79-folds respectively @xmath86 and 60.,title="fig:",width=302 ] now we explore another interesting extension of the conformally invariant inflation models , which is particularly of recent observable interest . as mentioned in section [ sec : intro ] , the recent bicep2 result indicates a large tensor - to - scalar ration @xmath2 . thus , it is an interesting question whether one can extend the conformal description to include the models which lead to a large value of @xmath2 consistent with the bicep2 observation . to be clear , we would like to reconstruct the form of @xmath89 by assuming @xmath90 where @xmath87 is a dimensionless parameter of @xmath41 . in this case , we can solve @xmath91 substituting it back into ( [ vslope ] ) , we then obtain @xmath92^{4/\mu } \ , , \ ] ] and further derive the effective potential for the inflaton field as @xmath93 from this expression , one can clearly find that this model is equivalent to chaotic inflation with a power - law potential of @xmath9 . in this regard , we point out that chaotic inflation can also be described by the conformally invariant theories under specific choices of the function @xmath94 , or @xmath95 equivalently . the number of @xmath79-foldings for inflation can be expressed by @xmath96 where we have chosen the number of @xmath79-foldings to be vanishing when @xmath97 . note that , in a realistic model this point corresponds to the true vacuum of the inflaton field after inflation and hence , there are several number of @xmath79-foldings overestimated in our expression ( which is associated with the preheating phase ) . however , this approximation would not alter the precise result and can greatly simplify the analytic analysis in the following . by solving ( [ n(z ) ] ) inversely , one can easily derive the variable @xmath38 as a function of @xmath98 : @xmath99 as well as the slow roll parameters @xmath100 this is as expected from the potential for chaotic inflation ( [ chaoticv ] ) . we explicitly show the predictions on the @xmath2-@xmath3 diagram with different values of @xmath87 in the right panel of figure [ fig:2ex ] . since the coefficient @xmath87 is a free parameter in the conformally invariant description for inflation models , we specifically consider several parameter choices by taking different values of @xmath87 . one can see that the parameter choices for @xmath101 lie in the center of the contour provided by bicep2 . in particular , when @xmath102 , which corresponds to the standard @xmath103 inflation model , can fit to the data very well . as indicated by the recent bicep2 data with a high level detection of the primordial tensor modes , it seems that a class of inflation models such as t - models as well as the starobinsky model , is disfavoured . thus , it is interesting to study whether the formalism of the inflation models which the t - models originates remains of theoretical interest . this issue has been carried out from different viewpoints , see e.g. @xcite for relevant discussions . in the present article , we have developed a generalized class of the t - models which breaks the approximate @xmath1 symmetry . we start from an arbitrary potential @xmath104 with @xmath105 as a dynamical field , which can describe the starobinsky model as well as t - models as specific and straightforward examples . we interestingly find that a larger class of more general inflation models can be embedded into this formalism . also , a larger portion on the @xmath2-@xmath3 plane can be covered . in particular , we have considered two concrete examples . one is a starobinsky - like model which admits a dynamical exponent , which generically predicts a small tensor - to - scalar ratio @xmath2 and hence is in tension with the recent bicep2 observation . in the other case , we have found that chaotic inflation model can also be embedded into the conformally invariant description . in this scenario , the power index of the derived chaotic inflation can be a non - integer value as is determined by the model parameter appeared in the original lagrangian.as a result , for this type of models , there exist enough parameter space to accommodate with the latest cosmological observations . we thank frederico arroja , qing - guo huang , takahiro tanaka and yingli zhang for useful discussions . we acknowledge the workshop `` new perspectives on cosmology '' at the asia pacific center for theoretical physics where part of this work was carried out . the work of yfc is supported in part by nserc and by funds from the canada research chair program . jg acknowledges the max - planck - gesellschaft , the korea ministry of education , science and technology , gyeongsangbuk - do and pohang city for the support of the independent junior research group at the asia pacific center for theoretical physics . jg is also supported by a starting grant through the basic science research program of the national research foundation of korea ( 2013r1a1a1006701 ) . sp thanks the gcoe bilateral international exchange program of kyoto university and the hospitality of the yukawa institute for theoretical physics at kyoto university for his visit . r. kallosh and a. linde , jcap * 1011 * , 011 ( 2010 ) [ arxiv:1008.3375 [ hep - th ] ] ; s. v. ketov and a. a. starobinsky , phys . d * 83 * , 063512 ( 2011 ) [ arxiv:1011.0240 [ hep - th ] ] ; j. ellis , d. v. nanopoulos and k. a. olive , phys . lett . * 111 * , 111301 ( 2013 ) [ arxiv:1305.1247 [ hep - th ] ] ; f. farakos , a. kehagias and a. riotto , nucl . b * 876 * , 187 ( 2013 ) [ arxiv:1307.1137 [ hep - th ] ] . y. -f . cai and d. a. easson , phys . rev . d * 84 * , 103502 ( 2011 ) [ arxiv:1107.5815 [ hep - th ] ] ; y. -f . cai and d. a. easson , int . j. mod . d * 21 * , 1250094 ( 2013 ) [ arxiv:1202.1285 [ hep - th ] ] ; y. -f . cai , y. -c . chang , p. chen , d. a. easson and t. qiu , phys . d * 88 * , 083508 ( 2013 ) [ arxiv:1304.6938 [ hep - th ] ] ; e. j. copeland , c. rahmede and i. d. saltas , arxiv:1311.0881 [ gr - qc ] . r. costa and h. nastase , arxiv:1403.7157 [ hep - th ] . s. ferrara , a. kehagias and a. riotto , arxiv:1403.5531 [ hep - th ] ; r. kallosh , a. linde , b. vercnocke and w. chemissany , arxiv:1403.7189 [ hep - th ] ; j. ellis , m. a. g. garcia , d. v. nanopoulos and k. a. olive , arxiv:1403.7518 [ hep - ph ] ; k. hamaguchi , t. moroi and t. terada , arxiv:1403.7521 [ hep - ph ] .

we describe extended theories which shares the gauge transformation symmetry of the t - models , and takes the t - models as well as starobinsky model as special cases . we derive a general relation between the two slow - roll parameters , and find that a large class of models can be embedded . such models include more general starobinsky - like inflation as well as the chaotic inflation with a large tensor - to - scalar ratio consistent with the bicep2 result . 1.2 cm 1.2 cm

Texas Gov. Rick Perry said on Sunday he would “make exactly the same decision” that resulted in a grand jury indicting him. Perry, who was indicted by a Travis County grand jury in Texas on Friday alleging he abused the powers of his office, told “Fox News Sunday” that the indictment was “not the way we settle political differences in this country.” The felony counts against the Republican governor stem from his attempt to pressure a Democratic district attorney in Travis County to step down by threatening to veto state funding for her office following her drunken driving arrest and conviction. “I very clearly, I very publicly, said as long as that individual was running that agency, I had lost confidence in her, the public had lost confidence in her,” the Republican governor said. (WATCH: The Sunday shows in 90 seconds) “I stood up for the rule of law in the state of Texas," he said. "And if I had to do it again, I would make exactly the same decision.” Perry said “across the board you’re seeing people weigh in and reflecting that this is way outside of the norm,” pointing out a tweet from one of President Barack Obama's former top aides, David Axelrod, who wrote that the indictment “seems pretty sketchy.” Perry has vowed to fight his indictment, calling it a "farce" during a news conference on Saturday. Read more about: Rick Perry, Texas, Indictments ||||| WASHINGTON (AP) — Texas Gov. Rick Perry on Sunday defended the veto that led a grand jury to indict him on two felony counts of abuse of power, noting that even some Democrats have questioned the move by prosecutors. FILE - In this Friday, Aug. 8, 2014, file photo, Texas Gov. Rick Perry delivers a speech to nearly 300 in attendance at the 2014 RedState Gathering, in Fort Worth, Texas. Perry was indicted on Friday,... (Associated Press) FILE - This Aug. 8, 2014, file photo shows Governor Rick Perry as he speaks at the 2014 Red State Gathering, in Fort Worth, Texas. Perry has been indicted for abuse of power after carrying out a threat... (Associated Press) "I stood up for the rule of law in the state of Texas, and if I had to do it again I would make exactly the same decision," Perry, a potential candidate for the 2016 Republican presidential nomination, said. Already the longest-serving governor in state history, Perry has made it clear that he plans to complete his third and final term in January as planned. In an interview with "Fox News Sunday," the governor noted that David Axelrod, a former adviser to President Barack Obama, had called the indictment "sketchy" while Harvard Law professor Alan Dershowitz had questioned the move. "Across the board you're seeing people weigh in and reflecting that this is way outside of the norm. This is not the way that we settle differences, political differences in this country," Perry said. "You don't do it with indictments. We settle our political differences at the ballot box." A Travis County grand jury on Friday indicted Perry for carrying out a threat to veto state funds to the local district attorney, an elected Democrat, unless she resigned following her arrest and conviction for drunken driving. That 2013 veto prompted a criminal investigation. Perry said he had lost confidence in the prosecutor and had been clear about his intentions to veto the funding. The governor said Sunday that the indictment reflected a larger problem of government agencies not following the rule of law, pointing to the Internal Revenue Service scandal in Washington and concerns about National Security Agency surveillance. Several Republicans have come to Perry's defense and the governor has received words of support from Louisiana Gov. Bobby Jindal, Texas Sen. Ted Cruz and former Florida Gov. Jeb Bush. "This is the criminalization of just the legislative function and when you do that you weaken democracy. This is certainly a political attack, and this is very bad precedent," said Rep. Michael Turner, R-Ohio, who appeared on NBC's "Meet the Press." Perry is the first Texas governor since 1917 to be indicted. The charges came as he has sought to reintroduce himself to Republican leaders and rank-and-file party members eager to win back the White House. Several stumbles during his presidential bid in 2012 led to his early departure from the race. Perry's veto cut $7.5 million in funding to the state's ethics watchdog housed in the county district attorney's office. A state judge assigned a special prosecutor to investigate the veto following a complaint filed by a left-leaning watchdog group, which accused Perry of trying to leverage his power to force the resignation of District Attorney Rosemary Lehmberg. That unit of public corruption investigators is based in Austin, a liberal haven in the mostly conservative state. Voters in the county reliably elect a Democrat to serve as district attorney. Perry said Saturday he was confident that he would prevail and said those responsible for this "farce of a prosecution" would be held accountable. Many Democrats criticized Perry's aggressive reaction to the indictment and accused him of trying to shift the blame. Yet state Sen. Wendy Davis, the face of the party in Texas who's running a high-profile campaign for governor, took a more cautious tone Saturday. "The charges that were brought down by the grand jury are very, very serious," Davis said, adding that she trusted the justice system to do its job. Tensions between Republicans and the public integrity unit have simmered for years. Conservatives have long grumbled that the unit operates through a partisan lens and targets Republicans. ___ Associated Press writer Douglass K. Daniel contributed to this report. ___ Follow Ken Thomas on Twitter: https://twitter.com/AP_Ken_Thomas

– Two days after being indicted Rick Perry is still calling the findings of the Texas grand jury little more than a political witch hunt, reports Politico. "I stood up for the rule of law in the state of Texas," he told Fox News Sunday. "And if I had to do it again, I would make exactly the same decision." The indictment, he said, as per the AP, is "not the way we settle political differences in this country. You don't do it with indictments. We settle our political differences at the ballot box." Perry claims he's not the only one skeptical of the case, pointing to longtime Obama operative David Axelrod, who tweeted that it was "sketchy." He's gotten support from high-profile Republicans—including those he could potentially face off against in the 2016 presidential race, Bobby Jindal, Ted Cruz, and Jeb Bush—and today got some more from Ohio Republican Michael Turner. "This is the criminalization of just the legislative function and when you do that you weaken democracy," Turner told Meet the Press. "This is certainly a political attack, and this is very bad precedent." Wendy Davis, a Democrat running for Perry's job, was more measured, calling the charges, "very, very serious."

Tim Tebow is joining “GMA” as a contributor The Heisman winner, who currently works as an analyst for ESPN’s SEC Network, becomes the latest person from the sports world to join “Good Morning America.” He’ll debut on Monday. “Legends of Korra” will be back in October The Nickelodeon series just ended its 3rd season two weeks ago. Season 4 begins Oct. 3. Mark Wahlberg’s “Shooter” movie is being adapted as a TNT series Wahlberg will serve as executive producer of the drama based on his 2007 film directed by Antoine Fuqua. Lifetime bringing back “True Tori” Tori Spelling’s reality show will return for a 2nd season on Oct. 21. ||||| The Daily Show with Jon Stewart fans may find that Saturday Night Live's new Weekend Update anchor looks familiar. Comedian Michael Che will be replacing Cecily Strong, who will remain as a cast member on SNL, and joining Colin Jost at the desk when season 40 begins on Sept. 27. Che joined SNL as a writer this past year, and will be leaving The Daily Show after just three months on the job, according to The Hollywood Reporter . The funnyman thanked The Daily Show via Twitter on Thursday night, Sept. 11, writing: "I wanna thank Jon & the entire @TheDailyShow staff for letting me do this. i had a FANTASTIC time there. 1st class all the way." i wanna thank Jon & the entire @TheDailyShow staff for letting me do this. i had a FANTASTIC time there. 1st class all the way — Michael Che (@CheThinks) September 12, 2014 In addition to these impressive accolades, the comedian has performed stand-up on Late Night With Seth Meyers and The Late Show With David Letterman. He alsohad his comedy on a special The Half Hour aired on Comedy Central The funnyman will make history when he takes a seat at the Weekend Update desk, as he will be the first black person ever to anchor the broadcast. SNL returns with a new season Sept. 27 with host Chris Pratt and musical guest Ariana Grande. Do you think Che is right for the job?

– NBC says a correspondent on Jon Stewart's Daily Show is joining Saturday Night Live. Comedian Michael Che will handle "Weekend Update" duties with Colin Jost during the upcoming 40th season of SNL, premiering Sept. 27, the network says. Che, who wrote for SNL last season, had joined Stewart's Comedy Central show earlier this year. He is replacing Cecily Strong on the "Weekend Update" desk; Strong will stay with SNL as a cast member. Che will be the first black anchor of "Weekend Update," ETOnline reports. (In other TV news, Tim Tebow has an interesting new gig.)

the absorption of iron is strictly controlled through hepcidin , while there are no efficient physiologic mechanisms to excrete iron from the body . under conditions where iron metabolism is disturbed , such as in transfusion - dependent patients with thalassemia major , myelodysplastic syndromes , aplastic anemia , or sickle cell disease , excessive iron deposition occurs in the liver , heart , and endocrine organs , resulting in reactive oxygen species ( ros ) through the fenton and haber weiss reaction . ros can attack components of cells and further induce organ dysfunction , such as liver fibrosis , cirrhosis , hepatic carcinoma , myocarditis , pericarditis , and other diseases . in the liver of chronic hepatitis c ( chc ) patients , iron deposition has been found in both hepatocytes and reticuloendothelial cells although the mechanism is not fully clarified . like other viruses , hepatitis c virus ( hcv ) needs constituents of host cells to proliferate , and iron is one of the most important constituents . many studies have explored the connection between iron overload and hcv life cycle with differing results . some studies have found that iron promotes hcv replication , while others have shown that iron suppresses hcv replication . most of the studies suggest the positive role of iron on hcv translation . to summarize the interactions between hcv and iron , and understand the mechanisms of iron overload in chc , we searched articles published in the pubmed databases up to january 28 , 2017 , to gain an in - depth understanding and knowledge of relevant areas . in the human body , iron is critical for maintaining the fundamental function of many proteins . iron in the diet is absorbed through divalent metal transporter 1 ( dmt1 ) , a multi - transmembrane protein , or heme carrier protein 1 on duodenal and jejunal enterocytes . it is then exported by the ferroportin ( fpn ) to bind to transferrin in the bloodstream , and taken to the erythroblasts for erythropoiesis . iron that is not utilized can also be stored as ferritin or hemosiderin in enterocytes , macrophages , and hepatocytes . there are no efficient physiologic mechanisms to excrete iron , a little iron ( about 2 mg per day ) is lost by sloughing of intestinal epithelial cells , desquamation of skin and urinary cells , blood loss , and sweat . iron homeostasis in the human body is mainly regulated by the hepcidin / fpn and iron - regulatory protein / iron - responsive element ( irp / ire ) systems . when iron levels increase , hepcidin negatively regulates iron levels by binding to the fpn and promoting the internalization and degradation of fpn . this reduces the amount of iron absorbed by enterocytes , released by hepatocytes , and recycled from macrophages , and finally reduces transferrin levels in the bloodstream . in contrast , when iron levels decrease , hepcidin is downregulated to improve transferrin levels . transferrin receptor 1 ( tfr1 ) and bone morphogenetic protein 6 receptor ( bmp-6r ) can sense transferrin saturation ( ts ) and tissue iron content , respectively , further regulating hepcidin concentration . hepcidin can also be affected by other factors , including inflammation , erythropoietic activity of the bone marrow , and the oxygen tension within hepatocytes . while hepcidin regulates systemic iron metabolism transcriptionally and posttranslationally , cellular iron metabolism is regulated by the irp / ire system posttranscriptionally . the irp / ire system alters the expression of iron - metabolism - related proteins , such as ferritin , fpn , hypoxia - inducible factor 2 ( hif2/epas1 ) , dmt1 , tfr1 , and other proteins . many studies have found iron deposition in the liver , and in both hepatocytes and reticuloendothelial cells . were the first to find elevated serum ferritin and iron levels in patients with chronic hepatitis ( both chronic hepatitis b and chc ) . subsequently , in 1999 , a study of 209 chc patients found liver iron accumulation detected by liver biopsy in 42.1% of patients , the majority of which was mild liver iron accumulation ( 35.4% of the 209 chc patients ) . those with liver iron accumulation had significantly higher levels of serum iron ( si ) , ferritin , and ts ; liver iron accumulation was also found to have a significant relationship with the severity of histological activity based on metavir classification and cirrhosis . in a study of 100 consecutive patients with hcv infection who underwent liver biopsy , 19 patients were found to be hepatic iron stain positive , which is associated with stage iii or iv fibrosis . fifty - five patients had at least one abnormal value of si , ferritin , or ts . in multivariate analysis , the only independent predictive factor of severe hepatic fibrosis was serum ferritin . however , elevated serum ferritin can also be caused by hepatic inflammation . in 1994 , a study of 123 chronic hepatitis patients ( including 63 chc patients ) found increased si , iron saturation , and ferritin in chc patients , while no evidence of hepatic iron accumulation could be found in any of these patients . in this study , serum ferritin was elevated in the absence of liver iron overload , which indicates that elevated serum ferritin may also be caused by inflammation itself . thus , elevated ferritin reflects hepatic iron accumulation , as well as hepatic inflammation , and also predicts severe hepatic fibrosis . in other words , hepatic iron accumulation can lead to elevated ferritin , while elevated ferritin is not only induced by hepatic iron accumulation but also caused by hepatic inflammation . thus , serum ferritin levels only serve as a reference to evaluate liver iron status in chc patients , and liver biopsy is the gold standard for diagnosis of iron overload . so far , plenty of studies have been devoted to exploring the mechanism as to how hcv leads to iron overload . it is generally accepted that hcv alters iron metabolism by reducing the level of hepcidin . fujita et al . measured hepcidin messenger rna ( mrna ) levels in liver samples from 56 patients with hcv infection , and revealed that the expression of hepcidin is strongly correlated with serum ferritin and the degree of iron deposition in liver tissues . the hepcidin - to - ferritin ratio was significantly lower in hcv(+ ) patients than hbv(+ ) patients or controls . girelli et al . detected s - hepcidin ( the 25-amino acid bioactive peptide in serum ) levels in 81 untreated chc patients and 57 controls with a rigorous definition of normal iron status and found that s - hepcidin was significantly lower in chc patients than in controls . in chc patients , s - hepcidin levels examined the determinants of serum hepcidin and liver hepcidin mrna levels and their association with histological lesions in 96 patients with chc and 30 controls ; they concluded that serum hepcidin was significantly lower in patients with chc compared to healthy controls , and that liver hepcidin mrna levels did not differ between patients and controls . a study using fl - n/35 transgenic mice harboring the hcv polyprotein also found decreased hepcidin expression in the liver , accompanied by an increase in fpn expression in the duodenum , spleen , and liver . this suggests that hcv proteins may directly lead to increased duodenal iron absorption , macrophage iron release , and hepatic iron accumulation . elevated duodenal fpn levels and a significant relationship between hcv and hepcidin in chc patients were also found by other studies . all of these studies suggest that hepcidin may play a pivotal role in the pathogenesis of iron overload in patients with chc . kohjima et al . analyzed iron - metabolism - related gene expression profiles in 100 patients with chc ( genotype 1b , n = 50 ; genotype 2 , n = 50 ) and 18 living donors of liver transplantation . they found that expression of genes related to iron absorption ( transferrin , and dmt1 ) , iron export ( fpn ) , cellular iron metabolism ( irp1 and irp2 ) , and hepcidin - regulation ( bmpr1 , bmpr2 , and hemojuvelin ) were significantly higher , indicating that hcv affects the expression of iron - metabolism - related genes , leading to iron accumulation in hepatocytes . besides , patients with a sustained virological response ( svr ) had significantly lower transcription and protein expression levels of hepcidin , fpn , bmpr2 , and hemojuvelin before therapy , indicating the importance of hepatocytic iron retention for viral response during pegylated interferon plus ribavirin treatment . almost all hcv proteins , including core , e1 , e2 , ns3 , ns4a , ns4b , and ns5a , have been shown to regulate hepcidin expression through signal transducer and activator of transcription 3 , mitogen - activated protein kinase , or bmp / smad signaling pathways , and increased histone deacetylase activity , which further clarifies the mechanism of decreased levels of hepcidin caused by hcv . like other viruses , hcv needs constituents of host cells to replicate and translate , and iron is one of the most important constituents . it is indispensable for several basic metabolic processes in viruses , as well as in mammalian cells , as described in many studies . were the first to analyze the effect of iron on hcv replication in vitro . in 2000 , they cultured a nonneoplastic hcv - infected human hepatocyte line ( ph5ch8 ) treated with feso4 and proved that iron can promote hcv replication in liver cells . in 2016 , foka et al . found that iron - overloaded macrophages was infected with hcv when co - cultured with hcv - infected human hepatoma cell line ( huh7.5 ) . these iron overloaded macrophages also enhanced hcv replication in co - cultured hcv - infected huh7.5 cells through reversed ferritin flow from macrophages to huh7.5 cells . macrophages without overloaded iron was also infected with hcv and enhance hcv replication in huh7.5 cells , but the rate of infection was slower and the effect on hcv replication was weaker . on the other hand , several studies have found that iron suppresses hcv replication . a study using huh7 cells in 2005 concluded that iron could inhibit hcv replication by inactivating the rna polymerase ns5b , without significant effect on translation . fillebeen et al . concluded that iron could decrease hcv replication by reducing the activity of ns5b in huh7.5.1 cells , similar to the result of the study in 2005 . a later study , in 2011 , again found that increased iron status and down - regulated hepcidin inhibited hcv replication . . this may be due to different cell types . besides , in clinical practice , chc with primary or secondary iron overload have different prognoses . chc patients with hereditary iron overload due to hemochromatosis gene mutations have increased svrs to antiviral therapy , when excess iron deposits in parenchymal cells and macrophages become iron deficient . in contrast , iron overload secondary to chc or other chronic liver diseases significantly aggravates the disease , when excess iron deposits in macrophages . it seems that the iron content of macrophages is associated with the clinical outcome of disease , because iron overload may impair the immune function of macrophages through oxidative stress . although the role of iron in promoting or suppressing hcv replication is debatable , there are few controversies about the effect of iron on hcv translation . apart from a group in the usa that reported that iron suppresses hcv translation through increasing heme oxygenase-1 in vitro and another group that found no effect of iron on hcv translation , all other studies confirm the positive role of iron on hcv translation , but the mechanisms are not fully understood . expression of hcv is predominantly controlled at the translational level , which involves the interaction between cellular translation initiation factors and a specific mrna stem - loop structure the internal ribosome entry site ( ires ) within the 5 untranslated region . iron is reported to stimulate the expression of eukaryotic initiation factor 3 ( eif3 ) , thus enhancing hcv ires - dependent translation both in hepg2 cells and hcv - infected patients , whereas iron chelation reverses it in vitro . another group also found that hepatic iron load promotes hcv translation initiation in vitro with the mechanism involving iron - dependent increased expression of eif3 . expression of another element , la protein , is also significantly increased by hepatic iron load which can promote hcv translation . expression of both eif3 and la protein can be partially inhibited by the iron chelator deferoxamine . cho et al . also found that iron changes the affinities of common cellular factors to hcv ires which modulates hcv ires - dependent translation . in summary , iron can regulate hcv ires - dependent translation by increasing expression levels of associated factors . translation of both hcv 1b and hcv 2b is significantly increased after iron treatment , while translation of hcv 6a shows little difference . compared with subtype 1b , hcv 6a has a modified eif3 binding site within hairpin iii . it is reported that hepatic iron levels are higher in patients infected with subtype 1b than those in patients infected with subtypes 2a or 2b , which may explain the different responses of hcv genotypes to iron overload . nowadays , liver biopsy is the gold standard for diagnosis of hepatic iron overload , and there are no uniform diagnostic criteria about extracellular iron concentration . most of the studies described in the paper used cell models incubated in ferric or ferrous iron solutions with maximum concentrations ranging from 50 to 300 mol / l , whether they reach the standard of iron overload is difficult to judge . therefore , whether these results from in vitro research could be suggestive to understand the effect of iron on hcv is still debatable . each part of iron metabolism , including absorption , restoration , recycling , and utilization , is regulated by hepcidin and the ire / irp system . there is no efficient way to eliminate iron from the body , so any abnormality in the process of iron metabolism may lead to excessive iron burden . the relationship between hcv and iron overload many studies have observed iron overload in patients with chc , and most suggest that decreased hepcidin expression , as well as increased hcv protein - mediated expression of other iron metabolism - related genes , play a role . as to the detailed mechanism of hcv proteins inducing iron overload , there is still much to discover . in turn , as an essential element for all living bodies , iron can also affect the life cycle of hcv . nearly all studies so far confirm the positive role of iron on hcv translation , while the role of iron in promoting or suppressing hcv replication is still unclear . more work is needed to understand this , and the mechanisms by which iron affects hcv life cycle . iron chelation therapy can reverse the negative effect of iron overload , which offers important information for clinical application . hcv reduces the levels of hepcidin , and elevates the levels of fpn , resulting in elevated iron absorbed by enterocytes and iron deposition in hepatocytes and macrophages . although the role of iron in hcv replication is disputable , it is strongly suggested the positive effect of iron on hcv translation by increasing expression of both eif3 and la protein , and changing the affinities of common cellular factors to hcv ires . hcv : hepatitis c virus ; fpn : ferroportin ; si : serum iron ; ts : transferrin saturation ; ires : internal ribosome entry site ; eif3 : eukaryotic initiation factor 3 ; : upregulated ; : downregulated . this work was supported by grants from the 215 project of beijing municipal commission of health and family planning ( no . 303 - 01 - 005 - 0068 ) and the basic - clinic cooperative foundation of capital medical university ( no . this work was supported by grants from the 215 project of beijing municipal commission of health and family planning ( no . 303 - 01 - 005 - 0068 ) and the basic - clinic cooperative foundation of capital medical university ( no .

objective : the aim of this study was to summarize the interactions between hepatitis c virus ( hcv ) infection and iron overload , and to understand the mechanisms of iron overload in chronic hepatitis c ( chc ) and the role iron plays in hcv life cycle.data sources : this review was based on data in articles published in the pubmed databases up to january 28 , 2017 , with the keywords hepatitis c virus , iron overload , iron metabolism , hepcidin , translation , and replication.study selection : articles related to iron metabolism , iron overload in patients with chc , or the effects of iron on hcv life cycle were selected for the review.results:iron overload is common in patients with chc . the mechanisms involve decreased hepcidin levels caused by hcv through signal transducer and activator of transcription 3 , mitogen - activated protein kinase , or bone morphogenetic protein / smad signaling pathways , and the altered expression of other iron - metabolism - related genes . some studies found that iron increases hcv replication , while other studies found the opposite result . most of the studies suggest the positive role of iron on hcv translation , the mechanisms of which involve increased expression levels of factors associated with hcv internal ribosome entry site - dependent translation , such as eukaryotic initiation factor 3 and la protein.conclusion:the growing literature demonstrates that chc leads to iron overload , and iron affects the hcv life cycle in turn . further research should be conducted to clarify the mechanism involved in the complicated interaction between iron and hcv .

KEVIN LAMARQUE/REUTERS U.S. President Barack Obama talks with Eliot Engel (D-NY) as he walks in before the State of the Union address to a joint session of Congress on Capitol Hill in Washington, January 25, 2011. WASHINGTON — In Congress, there is a Tea Party Caucus of conservative members and Black Caucus of African-American lawmakers. There is a Hispanic Conference, and even a Bike Caucus. On Tuesday night, when President Obama delivers his State of the Union address, Bronx Rep. Eliot Engel will highlight his role in an altogether different group of lawmakers. They’ve been called the Aisle Hogs. Presidents come and Presidents go, but during the annual State of the Union speech, one thing is certain: Engel, a Democrat, will be seated on the center aisle, perfectly positioned to shake hands with the President when he strides in and say goodbye when the President walks out. Rex / Rex USA/Rex / Rex USA Bronx Rep. Eliot Engel shakes hands with Obama during the president's previous State of the Union address. "I will be in my district somewhere in December and someone will say to me, 'I saw you on TV,'" Engel said Monday. "I'll think it was one of the many interviews I've done, but they'll say 'No. You were shaking the President's hand.' People remember me shaking the President's hand." Bronx Rep. Eliot Engel makes a phone call prior to the State of the Union Address in 2011. Engel is hardly the only lawmaker to hug the aisle, but he is the dean of this unique club, having grabbed his first center-aisle seat in 1989, just weeks after he entered Congress. A Mississippi congressman, former Rep. Sonny Montgomery, had invited Engel to sit with him so they could both try to say hello to the newly elected President George H.W. Bush, a friend of Montgomery's. Salon via Gawker President George W. Bush shakes hands with Eliot Engel, the U.S. Representative for New York's 16th congressional district, before the State of the Union Address in 2008. Engel remembers spotting an aisle seat and Montgomery telling him, "You better grab it before someone else does." "So I grabbed it, and I've been sitting there since," he said. Salon via Gawker President George W. Bush shakes hands with Eliot Engel, the U.S. Representative for New York's 16th congressional district, before the State of the Union Address in 2006. For rank-and-file lawmakers like Engel, the State of the Union is strictly festival seating — which means he has to arrive early and stick around to guarantee his prime spot. He said he would arrive on the House floor by 10 a.m. Tuesday and stake his claim, almost 12 hours before the speech. Salon via Gawker President George W. Bush shakes hands with Eliot Engel, the U.S. Representative for New York's 16th congressional district, before the State of the Union Address in 2003. But Engel won’t have to stay in his seat the entire time. He can leave for the bathroom, lunch, even for brief meetings near the chamber. A colleague will keep an eye on the spot. The congressman has meetings with constituent groups and an interview with MSNBC scheduled during his wait Tuesday. And when he's sitting, he said he'll catch up on reading. Salon via Gawker President Bill Clinton shakes hands with Eliot Engel, the U.S. Representative for New York's 16th congressional district, before the State of the Union Address in 2000. Engel said constituents like and have come to expect that he has a prime seat. "If they didn't see me, they'd think I was sick or something," he said. And now he is the undisputed king of the Aisle Hogs. Veteran Aisle Hog Rep. Dale Kildee (D-Mich.) retired; Reps. Dennis Kucinich (D-Ohio) and Jean Schmidt (R-Ohio) lost primaries. And Rep. Jesse Jackson (D-Ill.) Jr. resigned under an ethics cloud. The club isn't illustrious. Jackson just pleaded guilty to misusing campaign funds. Kucinich was an attention-seeker who never tried much to legislate. Republicans disliked Schmidt and Democrats hated her. But Engel makes no apologies for taking a prime seat. He called the speech "the height of American democracy" and said his small annual role remains a thrill for "a working-class kid from the Bronx." "To actually say hello to the President and shake his hand, I am much honored to do it, very honored to play a part," he said. [email protected] ||||| President Obama addresses a joint session of Congress with the final State of the Union speech of his first term. Jan. 24, 2012 President Obama addresses a joint session of Congress with the final State of the Union speech of his first term. Toni L. Sandys/The Washington Post Technology and partisanship have transformed the State of the Union over the past century. Here’s a look back. Technology and partisanship have transformed the State of the Union over the past century. Here’s a look back. Technology and partisanship have transformed the State of the Union over the past century. Here’s a look back. For the State of the Union squatters, the wait can be seven hours or more. You read the newspaper. You sign letters to constituents. You grumble about the rookies who think that — on this night, in this place — you can save a seat with a little paper sign instead of a bona fide, duly elected representative’s rear end. The payoff for all of that lasts about five seconds. But oh, those are five good seconds. There’s you, on national TV. And the leader of the free world seems to be laughing at your shared, private joke. “I said, ‘Don’t forget us in North Carolina!’ . . . And he would say, ‘How could I?’ ” said Rep. G.K. Butterfield (D-N.C.), asked what he actually says to President Obama when the two of them shake hands. “And we would erupt in laughter.” They’ll be there again Tuesday night, staking out seats close enough to touch Obama as he walks into the House chamber. From Eisenhower to Obama, presidents seem to have a penchant for some of the same lines in their State of the Union addresses. Whether it’s war or taxes or health care, there are themes that repeat again and again. Take a look back at almost 60 years of history in a little over two minutes. (Jason Aldag/Jason Aldag / The Washington Post) They’ve been around for at least 46 years. For the people on the aisle, the State of the Union is a rare night when a low-ranking legislator can score both a TV appearance and a personal audience with the president. Just try to ignore the elbows thrown by your colleagues. And be brief. “You can’t have a dissertation, you know what I mean? So it would be, ‘Stand by Israel, now,’ or ‘Stick with Israel, now,’ ” said Rep. Eliot L. Engel (D-N.Y.), recounting what he used to say to President George W. Bush. “Bush would usually say, ‘Oh, I believe that.’ ‘Oh, I will.’ ” The squatters on the House aisle are now a familiar part of the State of the Union ritual — a signal that the night has evolved from from a speech into a show, and then from the president’s show to more of an ensemble piece. On Tuesday, for instance, a variety of legislators have invited their own politically symbolic guests to sit in the House gallery and draw attention to a personal cause. Rep. Luis V. Gutierrez (D-Ill.) will bring an illegal immigrant. Rep. Steve Stockman (R-Tex.) will bring fiery anti-Obama rocker Ted Nugent. This is the newfangled way to grab some of the president’s spotlight. The old-fashioned way — dating at least to the late ’60s — has been to reach out and grab the president himself. “You would get a lot of calls from back home” afterward, said former representative Dale E. Kildee (D-Mich.), who first did it with President Jimmy Carter. A longer-serving member, Rep. William Natcher (D-Ky.), had invited Kildee to join him in waiting. There were cookies. And then, after Kildee had shaken the president’s hand, he found his own constituents looked at him in a different light. “People would say, ‘Gosh, I saw you shaking hands with the president.’ So you had that advantage,” Kildee recalled. He did it again and again, shaking hands with Democrats (“You’re doing really good in Flint,” he told President Bill Clinton, meaning Flint, Mich.) and Republicans. Most constituents didn’t mind these bipartisan handshakes. Kildee’s mother hated them. “She did not like Reagan. She said, ‘You don’t have to smile so much when you shake hands with him,’ ” Kildee said. After that, the congressman tried to look a little less happy while glad-handing the 40th president. “I was a little more neutral about that. Took my mother’s advice.” It was not always this way. In President Lyndon B. Johnson’s first State of the Union speech, members simply clapped and nodded as Johnson passed down the aisle. Three years later in 1967, two legislators reached out to shake his hand. Today, by contrast, there is so much competition for aisle seats that the House leadership must lay out ground rules. “Members will not be allowed to reserve seats prior to the joint session by placement of placards or personal items. Chamber Security may remove these items from the seats,” said a note sent out Monday by Rep. Kevin McCarthy (R-Calif.), the majority whip. “Members may reserve their seats only by physical presence.” The key is the wait. Members of Congress, as a class, don’t wait for much of anything. Not meetings. Not elevators. Not seats on a flight. On Capitol Hill, they ride in a special subway to an office building less than three blocks away. In this crowd, the aisle-seat squatters distinguish themselves by a simple tolerance for sitting still. “It’s been earlier and earlier, you know, as the years go by, because other people have caught on. Now it’s about 10 or 12 hours earlier,” said Engel, a congressman who might be best known for his years of presidential handshakes. He was so grateful to the legislator who introduced him to the aisle, former representative Gillespie “Sonny” Montgomery (D), that he traveled to Meridian, Miss., to attend Montgomery’s funeral in 2006. Then, finally, the president. You had better have something rehearsed. It could be a concern from folks back home. A joke from the campaign trail. (Butterfield and Obama talk about the time they were shaking hands at the same event and a voter with long fingernails somehow cut Butterfield deep enough to require a medic.) Or something totally unexpected. “Mr. President, I wish you peace,” said then-Rep. Dennis Kucinich (D-Ohio) when Bush walked by at the height of the Iraq war. Kucinich was a bitter critic of the war and of Bush. But he wanted Bush to know he understood the personal toll the conflict must have been taking. “ ‘Dennis,’ he said, ‘I really appreciate that,’ ” Kucinich recalled. “He said, ‘I know you mean that.’ ” This year, the ranks of the old-time squatters will be thinner. While stalwarts such as Reps. Sheila Jackson Lee (D-Tex.) and Al Green (D-Tex.) remain, Kucinich and former representative Jean Schmidt (R-Ohio), one of the few Republicans on the aisle, both lost races last year. Kildee retired after 36 years in Congress. “I’ll probably watch it on TV,” Kildee said. “I’ll see how I kind of looked,” he said, for all those years. Ed O’Keefe contributed to this report. by David A. Fahrenthold For the State of the Union squatters, the wait can be seven hours or more. You read the newspaper. You sign letters to constituents. You grumble about the rookies who think that — on this night, in this place — you can save a seat with a little paper sign instead of a bona fide, duly elected representative’s rear end. The payoff for all of that lasts about five seconds. But oh, those are five good seconds. There’s you, on national TV. And the leader of the free world seems to be laughing at your shared, private joke. “I said, ‘Don’t forget us in North Carolina!’ . . . And he would say, ‘How could I?’ ” said Rep. G.K. Butterfield (D-N.C.), asked what he actually says to President Obama when the two of them shake hands. “And we would erupt in laughter.” They’ll be there again Tuesday night, staking out seats close enough to touch Obama as he walks into the House chamber. They’ve been around for at least 46 years. For the people on the aisle, the State of the Union is a rare night when a low-ranking legislator can score both a TV appearance and a personal audience with the president. Just try to ignore the elbows thrown by your colleagues. And be brief. “You can’t have a dissertation, you know what I mean? So it would be, ‘Stand by Israel, now,’ or ‘Stick with Israel, now,’ ” said Rep. Eliot L. Engel (D-N.Y.), recounting what he used to say to President George W. Bush. “Bush would usually say, ‘Oh, I believe that.’ ‘Oh, I will.’ ” The squatters on the House aisle are now a familiar part of the State of the Union ritual — a signal that the night has evolved from from a speech into a show, and then from the president’s show to more of an ensemble piece. On Tuesday, for instance, a variety of legislators have invited their own politically symbolic guests to sit in the House gallery and draw attention to a personal cause. Rep. Luis V. Gutierrez (D-Ill.) will bring an illegal immigrant. Rep. Steve Stockman (R-Tex.) will bring fiery anti-Obama rocker Ted Nugent. This is the newfangled way to grab some of the president’s spotlight. The old-fashioned way — dating at least to the late ’60s — has been to reach out and grab the president himself. “You would get a lot of calls from back home” afterward, said former representative Dale E. Kildee (D-Mich.), who first did it with President Jimmy Carter. A longer-serving member, Rep. William Natcher (D-Ky.), had invited Kildee to join him in waiting. There were cookies. And then, after Kildee had shaken the president’s hand, he found his own constituents looked at him in a different light. “People would say, ‘Gosh, I saw you shaking hands with the president.’ So you had that advantage,” Kildee recalled. He did it again and again, shaking hands with Democrats (“You’re doing really good in Flint,” he told President Bill Clinton, meaning Flint, Mich.) and Republicans. Most constituents didn’t mind these bipartisan handshakes. Kildee’s mother hated them. “She did not like Reagan. She said, ‘You don’t have to smile so much when you shake hands with him,’ ” Kildee said. After that, the congressman tried to look a little less happy while glad-handing the 40th president. “I was a little more neutral about that. Took my mother’s advice.” It was not always this way. In President Lyndon B. Johnson’s first State of the Union speech, members simply clapped and nodded as Johnson passed down the aisle. Three years later in 1967, two legislators reached out to shake his hand. Today, by contrast, there is so much competition for aisle seats that the House leadership must lay out ground rules. “Members will not be allowed to reserve seats prior to the joint session by placement of placards or personal items. Chamber Security may remove these items from the seats,” said a note sent out Monday by Rep. Kevin McCarthy (R-Calif.), the majority whip. “Members may reserve their seats only by physical presence.” The key is the wait. Members of Congress, as a class, don’t wait for much of anything. Not meetings. Not elevators. Not seats on a flight. On Capitol Hill, they ride in a special subway to an office building less than three blocks away. In this crowd, the aisle-seat squatters distinguish themselves by a simple tolerance for sitting still. “It’s been earlier and earlier, you know, as the years go by, because other people have caught on. Now it’s about 10 or 12 hours earlier,” said Engel, a congressman who might be best known for his years of presidential handshakes. He was so grateful to the legislator who introduced him to the aisle, former representative Gillespie “Sonny” Montgomery (D), that he traveled to Meridian, Miss., to attend Montgomery’s funeral in 2006. Then, finally, the president. You had better have something rehearsed. It could be a concern from folks back home. A joke from the campaign trail. (Butterfield and Obama talk about the time they were shaking hands at the same event and a voter with long fingernails somehow cut Butterfield deep enough to require a medic.) Or something totally unexpected. “Mr. President, I wish you peace,” said then-Rep. Dennis Kucinich (D-Ohio) when Bush walked by at the height of the Iraq war. Kucinich was a bitter critic of the war and of Bush. But he wanted Bush to know he understood the personal toll the conflict must have been taking. “ ‘Dennis,’ he said, ‘I really appreciate that,’ ” Kucinich recalled. “He said, ‘I know you mean that.’ ” This year, the ranks of the old-time squatters will be thinner. While stalwarts such as Reps. Sheila Jackson Lee (D-Tex.) and Al Green (D-Tex.) remain, Kucinich and former representative Jean Schmidt (R-Ohio), one of the few Republicans on the aisle, both lost races last year. Kildee retired after 36 years in Congress. “I’ll probably watch it on TV,” Kildee said. “I’ll see how I kind of looked,” he said, for all those years. Ed O’Keefe contributed to this report.

– As you read this, there are already lawmakers sitting in the House chamber, just waiting for President Obama to arrive for his State of the Union address tonight. The aisle seats in the chamber have become hot commodities in recent years, with less-well-known legislators clamoring for a rare chance to, literally, reach out and touch the president—and be on TV, the Washington Post reports. The aisle seats are so sought-after, in fact, that House leaders have laid down some ground rules: For one thing, you have to actually be sitting in a seat in order to reserve it, meaning that your elected members of Congress wait about 10 to 12 hours, one congressman estimates, for just a few seconds with the president as he walks down the aisle. They're known as "aisle hogs," the New York Daily News notes. So what do they say to the president during those all-important few moments? Some, like Rep. GK Butterfield, keep it simple: "I said, 'Don't forget us in North Carolina!' ... And he would say, 'How could I?'" Others, like Rep. Eliot Engel (who's been hogging the aisle since 1989), have a specific topic in mind: "Stand by Israel, now," he used to tell George W. Bush. And staunchly anti-war Dennis Kucinich may have been a critic of Bush, but when he walked by during the Iraq war, Kucinich used his few seconds to tell the president, "I wish you peace." What's the payoff? A bit of recognition back home, explains former rep and longtime aisle sitter Dale Kildee. "People would say, 'Gosh, I saw you shaking hands with the president.' So you had that advantage." (Click to see some of the notable guests at this year's address.)

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Weather Service and Related Agencies Authorization Act of 1999''. SEC. 2. DEFINITIONS. For purposes of this Act, the term-- (1) ``Administrator'' means the Administrator of the National Oceanic and Atmospheric Administration; and (2) ``Secretary'' means the Secretary of Commerce. SEC. 3. NATIONAL WEATHER SERVICE. (a) Operations, Research, and Facilities.--There are authorized to be appropriated to the Secretary to enable the National Oceanic and Atmospheric Administration to carry out the Operations, Research, and Facilities activities of the National Weather Service $617,897,000 for fiscal year 2000 and $617,897,000 for fiscal year 2001, to remain available until expended. Of such amounts-- (1) $449,441,000 for fiscal year 2000 and $450,411,000 for fiscal year 2001 shall be for Local Warnings and Forecasts; (2) $2,200,000 for fiscal year 2000 and $2,200,000 for fiscal year 2001 shall be for Advanced Hydrological Prediction System; (3) $619,000 for fiscal year 2000 and $619,000 for fiscal year 2001 shall be for Susquehanna River Basin Flood Systems; (4) $35,596,000 for fiscal year 2000 and $35,596,000 for fiscal year 2001 shall be for Aviation Forecasts; (5) $4,000,000 for fiscal year 2000 and $4,000,000 for fiscal year 2001 shall be for Weather Forecast Offices (WFO) Facilities Maintenance; (6) $37,081,000 for fiscal year 2000 and $37,081,000 for fiscal year 2001 shall be for Central Forecast Guidance; (7) $3,090,000 for fiscal year 2000 and $3,090,000 for fiscal year 2001 shall be for Atmospheric and Hydrological Research; (8) $39,325,000 for fiscal year 2000 and $39,325,000 for fiscal year 2001 shall be for Next Generation Weather Radar (NEXRAD); (9) $7,573,000 for fiscal year 2000 and $7,573,000 for fiscal year 2001 shall be for Automated Surface Observing System (ASOS); (10) $38,002,000 for fiscal year 2000 and $38,002,000 for fiscal year 2001 shall be for Advanced Weather Interactive Processing System (AWIPS); and (11) $970,000 for fiscal year 2000 shall be for two 1,000- watt National Oceanic and Atmospheric Administration Weather Radio transmitters, to be located in Jasper and Marion Counties, Illinois, and nine 300-watt National Oceanic and Atmospheric Administration Weather Radio transmitters, to be installed in appropriate locations throughout the State of Illinois, and for maintenance costs related thereto. (b) Procurement, Acquisition, and Construction.--There are authorized to be appropriated to the Secretary to enable the National Oceanic and Atmospheric Administration to carry out the Procurement, Acquisition, and Construction activities of the National Weather Service $69,632,000 for fiscal year 2000 and $70,120,000 for fiscal year 2001, to remain available until expended. Of such amounts-- (1) $9,560,000 for fiscal year 2000 and $9,060,000 for fiscal year 2001 shall be for Next Generation Weather Radar (NEXRAD); (2) $4,180,000 for fiscal year 2000 and $6,125,000 for fiscal year 2001 shall be for Automated Surface Observing System (ASOS); (3) $22,575,000 for fiscal year 2000 and $21,525,000 for fiscal year 2001 shall be for Advanced Weather Interactive Processing System (AWIPS); (4) $11,100,000 for fiscal year 2000 and $12,835,000 for fiscal year 2001 shall be for Computer Facilities Upgrades; (5) $8,350,000 for fiscal year 2000 and $8,350,000 for fiscal year 2001 shall be for Radiosonde Replacement; (6) $500,000 for fiscal year 2000 shall be for National Oceanic and Atmospheric Administration Operations Center Rehabilitation; and (7) $13,367,000 for fiscal year 2000 and $12,225,000 for fiscal year 2001 shall be for Weather Forecast Office (WFO) Construction. (c) Duties of the National Weather Service.-- (1) In general.--To protect life and property (in all 50 States, the District of Columbia, and the Territories), the Secretary, through the National Weather Service, except as provided in paragraph (2), shall be responsible for-- (A) forecasts and shall serve as the sole official source of weather and flood warnings; (B) the issuance of storm warnings; (C) the collection, exchange, and distribution of meteorological, hydrological, climatic, and oceanographic data and information; (D) the preparation of hydrometeorological guidance and core forecast information; and (E) the issuance of marine and aviation forecasts and warnings. (2) Competition with private sector.--The National Weather Service shall not provide, or assist other entities to provide, a service if that service is currently provided or can be provided by commercial enterprise, unless-- (A) the service provides vital weather warnings and forecasts for the protection of life and property of the general public; or (B) the United States Government is obligated to provide such service under international aviation agreements to provide meteorological services and exchange meteorological information. (3) Amendments.--The Act of October 1, 1890 (26 Stat. 653) is amended-- (A) by striking section 3 (15 U.S.C. 313); and (B) in section 9 (15 U.S.C. 317), by striking ``, and it shall be'' and all that follows, and inserting a period. (4) Report.--Not later than 60 days after the date of the enactment of this Act, the Secretary shall submit to the Committee on Science of the House of Representatives and the Committee on Commerce, Science, and Transportation of the Senate a report detailing all National Weather Service activities which do not conform to the requirements of this subsection and outlining a timetable for their termination. (d) Closing of Local Weather Service Offices.--It is the sense of the Congress that the National Weather Service must fully take into account the dangerous and life threatening nature of weather patterns in Wind Zone IV, otherwise known as tornado alley, before making any determination on the closure of any of its local weather service offices. SEC. 4. ATMOSPHERIC RESEARCH. (a) Operations, Research, and Facilities.-- (1) In general.--There are authorized to be appropriated to the Secretary to enable the National Oceanic and Atmospheric Administration to carry out the Atmospheric Research Operations, Research, and Facilities environmental research and development activities of the Office of Oceanic and Atmospheric Research $173,250,000 for fiscal year 2000 and $173,250,000 for fiscal year 2001, to remain available until expended. (2) Climate and air quality research.--Of the amounts authorized under paragraph (1), $126,200,000 for fiscal year 2000 and $126,200,000 for fiscal year 2001 shall be for Climate and Air Quality Research, of which-- (A) $16,900,000 for fiscal year 2000 and $16,900,000 for fiscal year 2001 shall be for Interannual and Seasonal Climate Research; (B) $34,600,000 for fiscal year 2000 and $34,600,000 for fiscal year 2001 shall be for Long-Term Climate and Air Quality Research; (C) $69,700,000 for fiscal year 2000 and $69,700,000 for fiscal year 2001 shall be for Climate and Global Change; and (D) $5,000,000 for fiscal year 2000 and $5,000,000 for fiscal year 2001 shall be for Global Learning and Observations to Benefit the Environment (GLOBE). (3) Atmospheric programs.--Of the amounts authorized under paragraph (1), $47,050,000 for fiscal year 2000 and $47,050,000 for fiscal year 2001 shall be for Atmospheric Programs, of which-- (A) $36,600,000 for fiscal year 2000 and $36,600,000 for fiscal year 2001 shall be for Weather Research; (B) $4,350,000 for fiscal year 2000 and $4,350,000 for fiscal year 2001 shall be for Wind Profiler; and (C) $6,100,000 for fiscal year 2000 and $6,100,000 for fiscal year 2001 shall be for Solar-Terrestrial Services and Research. (b) Procurement, Acquisition, and Construction.--There are authorized to be appropriated to the Secretary to enable the National Oceanic and Atmospheric Administration to carry out the Atmospheric Research Procurement, Acquisition, and Construction environmental research and development activities of the Office of Oceanic and Atmospheric Research $10,040,000 for fiscal year 2000 and $14,160,000 for fiscal year 2001, to remain available until expended. Of such amounts-- (1) $5,700,000 for fiscal year 2000 and $8,000,000 for fiscal year 2001 shall be for the Geophysical Fluid Dynamics Laboratory Supercomputer; and (2) $4,340,000 for fiscal year 2000 and $6,160,000 for fiscal year 2001 shall be for the Advanced Composition Explorer (ACE) Follow-On Satellite/GEOSTORM. SEC. 5. NATIONAL ENVIRONMENTAL SATELLITE, DATA AND INFORMATION SERVICE. (a) Operations, Research, and Facilities.-- (1) In general.--There are authorized to be appropriated to the Secretary to enable the National Oceanic and Atmospheric Administration to carry out the Operations, Research, and Facilities environmental research and development and related activities of the National Environmental Satellite, Data and Information Service $103,092,000 for fiscal year 2000 and $103,092,000 for fiscal year 2001, to remain available until expended. (2) Satellite observing systems.--Of the amounts authorized under paragraph (1), $59,236,000 for fiscal year 2000 and $59,236,000 for fiscal year 2001 shall be for Satellite Observing Systems, of which-- (A) $2,000,000 for fiscal year 2000 and $2,000,000 for fiscal year 2001 shall be for Global Disaster Information Network (GDIN); (B) $4,000,000 for fiscal year 2000 and $4,000,000 for fiscal year 2001 shall be for Ocean Remote Sensing; and (C) $53,236,000 for fiscal year 2000 and $53,236,000 for fiscal year 2001 shall be for Environmental Observing Services. (3) Environmental data management systems.--Of the amounts authorized under paragraph (1), $43,856,000 for fiscal year 2000 and $43,856,000 for fiscal year 2001 shall be for Environmental Data Management Systems, of which-- (A) $31,521,000 for fiscal year 2000 and $31,521,000 for fiscal year 2001 shall be for Data and Information Services; and (B) $12,335,000 for fiscal year 2000 and $12,335,000 for fiscal year 2001 shall be for Environmental Data Systems Modernization. (b) Procurement, Acquisition, and Construction.-- (1) In general.--There are authorized to be appropriated to the Secretary to enable the National Oceanic and Atmospheric Administration to carry out the Procurement, Acquisition, and Construction environmental research and development and related activities of the National Environmental Satellite, Data and Information Service $413,657,000 for fiscal year 2000 and $476,183,000 for fiscal year 2001, to remain available until expended. (2) Systems acquisition.--Of the amounts authorized under paragraph (1), $410,612,000 for fiscal year 2000 and $473,803,000 for fiscal year 2001 shall be for Systems Acquisition, of which-- (A) $140,979,000 for fiscal year 2000 and $114,594,000 for fiscal year 2001 shall be for the procurement and launch of, and supporting ground systems for, Polar Orbiting Environmental Satellites (POES), K, L, M, N, and N'; (B) $80,100,000 for fiscal year 2000 and $113,600,000 for fiscal year 2001 shall be for the procurement and launch of, and supporting ground systems for, the National Polar-Orbiting Operational Environmental Satellite System (NPOESS); and (C) $189,533,000 for fiscal year 2000 and $245,609,000 for fiscal year 2001 shall be for the procurement and launch of, and supporting ground systems for, Geostationary Operational Environmental NEXT follow-on Satellites (GOES N-Q). (3) Construction.--Of the amounts authorized under paragraph (1), $3,045,000 for fiscal year 2000 and $2,380,000 for fiscal year 2001 shall be for National Oceanic and Atmospheric Administration Operations Center Rehabilitation Construction. SEC. 6. FACILITIES. There are authorized to be appropriated to the Secretary to enable the National Oceanic and Atmospheric Administration to carry out the Operations, Research, and Facilities environmental research and development and related activities required to meet recurring facilities operations costs associated with the David Skaggs Research Center in Boulder, Colorado, $3,850,000 for fiscal year 2000 and $3,850,000 for fiscal year 2001. SEC. 7. ELIGIBILITY FOR AWARDS. (a) In General.--The Administrator shall exclude from consideration for grant agreements made after fiscal year 1999 by the National Oceanic and Atmospheric Administration, under the activities for which funds are authorized under this Act, any person who received funds, other than those described in subsection (b), appropriated for a fiscal year after fiscal year 1999, under a grant agreement from any Federal funding source for a project that was not subjected to a competitive, merit-based award process, except as specifically authorized by this Act. Any exclusion from consideration pursuant to this section shall be effective for a period of 5 years after the person receives such Federal funds. (b) Exception.--Subsection (a) shall not apply to the receipt of Federal funds by a person due to the membership of that person in a class specified by law for which assistance is awarded to members of the class according to a formula provided by law. (c) Definition.--For purposes of this section, the term ``grant agreement'' means a legal instrument whose principal purpose is to transfer a thing of value to the recipient to carry out a public purpose of support or stimulation authorized by a law of the United States, and does not include the acquisition (by purchase, lease, or barter) of property or services for the direct benefit or use of the United States Government. Such term does not include a cooperative agreement (as such term is used in section 6305 of title 31, United States Code) or a cooperative research and development agreement (as such term is defined in section 12(d)(1) of the Stevenson-Wydler Technology Innovation Act of 1980 (15 U.S.C. 3710a(d)(1))). SEC. 8. INTERNET AVAILABILITY OF INFORMATION. The Administrator shall make available through the Internet home page of the National Oceanic and Atmospheric Administration the abstracts relating to all research grants and awards made with funds authorized by this Act. Nothing in this section shall be construed to require or permit the release of any information prohibited by law or regulation from being released to the public. SEC. 9. COMPLIANCE WITH BUY AMERICAN ACT. No funds authorized pursuant to this Act may be expended by an entity unless the entity agrees that in expending the assistance the entity will comply with sections 2 through 4 of the Act of March 3, 1933 (41 U.S.C. 10a-10c, popularly known as the ``Buy American Act''). SEC. 10. SENSE OF THE CONGRESS; REQUIREMENT REGARDING NOTICE. (a) Purchase of American-Made Equipment and Products.--In the case of any equipment or products that may be authorized to be purchased with financial assistance provided under this Act, it is the sense of the Congress that entities receiving such assistance should, in expending the assistance, purchase only American-made equipment and products. (b) Notice to Recipients of Assistance.--In providing financial assistance under this Act, the Secretary of Commerce shall provide to each recipient of the assistance a notice describing the statement made in subsection (a) by the Congress. SEC. 11. PROHIBITION OF CONTRACTS. If it has been finally determined by a court or Federal agency that any person intentionally affixed a label bearing a ``Made in America'' inscription, or any inscription with the same meaning, to any product sold in or shipped to the United States that is not made in the United States, such person shall be ineligible to receive any contract or subcontract made with funds provided pursuant to this Act, pursuant to the debarment, suspension, and ineligibility procedures described in section 9.400 through 9.409 of title 48, Code of Federal Regulations. Passed the House of Representatives May 19, 1999. Attest: JEFF TRANDAHL, Clerk.

National Weather Service and Related Agencies Authorization Act of 1999 - Authorizes appropriations for FY 2000 and 2001 to the Secretary of Commerce to enable the National Oceanic and Atmospheric Administration (NOAA) to carry out: (1) Operations, Research, and Facilities activities of the National Weather Service (NWS); (2) Procurement, Acquisition, and Construction activities of NWS; (3) Atmospheric Research Operations, Research, and Facilities environmental research and development activities of the Office of Oceanic and Atmospheric Research (OOAR); (4) Atmospheric Research Procurement, Acquisition, and Construction environmental research and development activities of OOAR; (5) Operations, Research, and Facilities environmental research and development and related activities of the National Environmental Satellite, Data, and Information Service (NESDIS); (6) Procurement, Acquisition, and Construction environmental research and development and related activities of NESDIS; and (7) Operations, Research, and Facilities environmental research and development and related activities required to meet recurring facilities operations costs associated with the David Skaggs Research Center in Boulder, Colorado. Revises requirements for the Secretary of Commerce's duties with respect to the NWS to include responsibilities for: (1) serving as the sole official source of weather and flood warnings; (2) issuing storm warnings; (3) collecting, exchanging, and distributing meteorological, hydrological, climatic, and oceanographic data and information;(4) preparing hydrometeorological guidance and core forecast information; and (5) issuing marine and aviation forecasts and warnings. Bars the NWS from providing or assisting other entities to provide a service that is currently provided or can be provided by commercial enterprise, unless: (1) the service provides vital weather warnings and forecasts for the protection of life and property of the general public; or (2) the U.S. Government is obligated to provide such service under international aviation agreements to provide meteorological services and exchange meteorological information. Directs the Secretary to report to the Committee on Science of the House of Representatives and the Committee on Commerce, Science, and Transportation of the Senate detailing all NWS activities which do not conform to requirements of this Act and outlining a timetable for their termination. Expresses the sense of the Congress that NWS must fully take into account the dangerous and life threatening nature of weather patterns in Wind Zone IV, otherwise known as tornado alley, before making any determination to close any of its local weather service offices. Requires the NOAA Administrator to exclude from consideration for grant agreements made after FY 1999 under the activities for which funds are authorized under this Act, any person who received funds (other than due to membership in a class specified by law for which assistance is awarded to class members according to a formula) appropriated for a fiscal year after FY 1999 under a grant agreement from any Federal funding source for a project that was not subjected to a competitive, merit-based award process. Makes such an exclusion effective for a period of five years after receipt of such Federal funds. Directs the Administrator to make available through NOAA's Internet home page the abstracts relating to all research grants and awards made with funds authorized by this Act. Prohibits any funds authorized pursuant to this Act from being expended by an entity unless such entity agrees, in expending such assistance, to comply with the Act of March 3, 1933, known as the Buy American Act. Expresses the sense of the Congress that entities receiving any equipment or products that may be authorized to be purchased with financial assistance provided under this Act should, in expending such assistance, purchase only American-made equipment and products. Requires the Secretary to provide to each recipient of such assistance a notice describing such statement. Prohibits any person who has been finally determined by a court or Federal agency to have intentionally affixed a label bearing a "Made in America" inscription or any inscription with the same meaning to any product sold in or shipped to the United States that is not made in the United States, from receiving any contract or subcontract made with funds provided pursuant to this Act pursuant to debarment, suspension, and ineligibility procedures.

success fail Jan AUG Sep 23 2014 2015 2016 2 captures 04 Jan 2015 - 23 Aug 2015 About this capture COLLECTED BY Organization: These crawls are part of an effort to archive pages as they are created and archive the pages that they refer to. That way, as the pages that are referenced are changed or taken from the web, a link to the version that was live when the page was written will be preserved. Then the Internet Archive hopes that references to these archived pages will be put in place of a link that would be otherwise be broken, or a companion link to allow people to see what was originally intended by a page's authors. The goal is to These crawls are part of an effort to archive pages as they are created and archive the pages that they refer to. 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Pope Francis celebrates mass with 4 homeless men on his 77th birthday Vatican News Agency ^ | December 17, 2013 Posted on by NYer Pope Francis turned 77 on Tuesday and celebrated Mass in the Santa Marta guesthouse with 4 homeless men, his closest collaborators and staff from the guesthouse, all of whom afterwards greeted him with a birthday song. Listen to this report by Susy Hodges: It was Pope Francis’s 77th birthday on Tuesday and those present at his morning Mass included Archbishop Pietro Parolin, the Secretary of State and Cardinal Angelo Sodano, the Dean of the College of Cardinals, together with staff from the Santa Marta guesthouse. The congregation also included the Almoner Monsignor Konrad Krajewski who brought with him 4 homeless men who live in the streets around the Vatican. After the mass, all those present wished the Pope a happy birthday and sang greetings to him before joining him for breakfast in the Vatican guesthouse. Today’s reading was centered on the genealogy of Jesus and the Pope used this in his homily to reflect on God’s enduring presence in our lives throughout history. He said “God wished to live out his life alongside us” and “took his surname from each of us.” “God,” the Pope continued, “has always walked alongside his people,” beginning with Abraham, Isaac and Jacob. He did not want to come to redeem us without coming to live among us and share our lives. The Pope said this long list of God’s people included “saints and sinners.” The latter included “high level sinners who committed serious sins and who didn’t listen” to God’s plans for them. Pope Francis said in addition to accompanying us in our lives our God follows us and in this way, he displays His humility, His patience and His love for us. He concluded his homily with “a Christmas wish” for all of us “to allow God to write our lives for us.” TOPICS: Catholic Current Events Ministry/Outreach KEYWORDS: catholic happybirthday popefrancis To: Tax-chick; GregB; Berlin_Freeper; SumProVita; narses; bboop; SevenofNine; Ronaldus Magnus; tiki; ... Happy Birthday, your Holiness, ping! by 2 posted onby NYer ("The wise man is the one who can save his soul. - St. Nimatullah Al-Hardini) To: NYer Ditto to His Eminence! To: NYer Actions speak louder than words. Well done. To: NYer A very Happy Birthday to Pope Francis! by 5 posted onby trisham (Zen is not easy. It takes effort to attain nothingness. And then what do you have? Bupkis.) by 6 posted onby trisham (Zen is not easy. It takes effort to attain nothingness. And then what do you have? Bupkis.) To: NYer The Pope is 77? The Church should find some 50 yr old next time. To: NYer OH that so sweet Happy Birthday Holy Father by 8 posted onby SevenofNine (We are Freepers, all your media bases belong to us ,resistance is futile) To: NYer Happy Birthday Pope Francis! by 9 posted onby Biggirl (“Go, do not be afraid, and serve”-Pope Francis) To: NYer The face of Christ. Think of St. Martin of Tours giving half his cloak to a beggar, and then Christ came to him in a dream wearing the half cloak. Picture the face of Christ in everyone. by 10 posted onby Salvation ("With God all things are possible." Matthew 19:26) To: Paladin2 This is young for a Pope. by 11 posted onby Salvation ("With God all things are possible." Matthew 19:26) To: Paladin2 The Church should find some 50 yr old next time. Ahhhh .. the notion that youth will provide a longer papacy. Our RC Bishop here in Albany NY just retired at age 75. It was while still working on the streets of the South End (of Albany) that Hubbard was appointed Bishop of the Roman Catholic Diocese of Albany. On March 27, 1977, at age 38, Hubbard became the youngest bishop in the country. Hubbard was an ultra progressive, called to "street" ministry. He floundered as bishop. His legacy is is a pile of lawsuits against abusive priests he appointed along with the closing of dozens of parishes and schools. Rare is the Bishop of Rome appointed at a young age, like JPII. There is much to be said about old age and wisdom. by 12 posted onby NYer ("The wise man is the one who can save his soul. - St. Nimatullah Al-Hardini) To: NYer And what happened after the birthday celebration? Were they turned out on the street again? I would hope the Pope would also try to find some way to house these men. by 13 posted onby murron (Proud Mom of a Marine Vet) To: murron I would hope the Pope would also try to find some way to house these men. What if they refused? What should he do? by 14 posted onby NYer ("The wise man is the one who can save his soul. - St. Nimatullah Al-Hardini) To: murron No room at the Vatican Inn? To: bonfire lol by 16 posted onby kjam22 (my newest music video:http://www.youtube.com/watch?v=l7gNI9bWO3s) To: NYer I would hope the Pope would also try to find some way to house these men. What if they refused? What should he do? Offer them the head coaching job at Texas... by 17 posted onby kjam22 (my newest music video:http://www.youtube.com/watch?v=l7gNI9bWO3s) To: NYer I think this is awesome. To: NYer Reason No. 45,876 if I were a Christian, I would only be Catholic. To: NYer Then there’s nothing he can do. But the article doesn’t mention that he offered and they refused. I would think that if he made the offer to stay with the Pope, at least one of them would take him up on his offer. by 20 posted onby murron (Proud Mom of a Marine Vet) To: NYer Happy birthday, Pope Francis! by 21 posted onby Tax-chick (I told you not to unplug that!) To: murron Your initial question is a valid one but is based on the premise that no such offer was made. It may seem odd but there are homeless people who choose to live this way. While working in Manhattan, I used to see various homeless individuals, some pushing grocery carts piled high with their personal belongings. Following the death of one of them, a news story noted that among the woman's belongings, the police found a bank book. The woman had $40,000 in her account. I'm sure the pontiff, through his almoner who visits the homeless on a regular basis, has offered shelter to those who are willing to accept it. In fact, he is known to personally visit the downtrodden at night. Pope Francis Reportedly Leaving Vatican at Night to Minister to Homeless of Rome Anonymously by 22 posted onby NYer ("The wise man is the one who can save his soul. - St. Nimatullah Al-Hardini) To: NYer I would like to think that he did. I’ve become a cynic in recent years. I see so many people who on the surface looks like they are doing good for people, but then realize that there are cameras broadcasting their good deeds, and then I realize that they were phony gestures just to make themselves good. I’m not saying that that is the case with the Pope. I do believe the Pope is sincere in his good works. I hope he did offer them shelter and that they refused. by 23 posted onby murron (Proud Mom of a Marine Vet) Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works. FreeRepublic , LLC, PO BOX 9771, FRESNO, CA 93794 FreeRepublic.com is powered by software copyright 2000-2008 John Robinson ||||| After Pope Francis got a cake and an impromptu tango flash mob for his 78th birthday Wednesday, he made sure Rome’s homeless got a gift, too -- sleeping bags emblazoned with the papal coat of arms. Interested in ? Add as an interest to stay up to date on the latest news, video, and analysis from ABC News. Add Interest The pontiff donated 400 of the sleeping bags to homeless people in the Italian capital, the Vatican said, continuing his tradition of helping the poor on his birthday. Members of the pope’s famed Swiss Guard and volunteers handed out hundreds of the sleeping bags Wednesday evening, stopping at railway stations and an area near a cemetery frequented by the homeless. “This is a gift for you from the pope on the occasion of his birthday,” they said as they passed out the sleeping bags, the Italian news agency ANSA reported. Francis, who is known for his humble, charitable lifestyle, also greeted eight homeless people bearing sunflowers during his Wednesday general audience. He marked his birthday last year by sharing breakfast and attending Mass with four homeless people. On Wednesday, he received more than 1,700 pounds of chicken meat the Vatican said would be distributed to soup kitchens. His chief alms-giver often carries out acts of charity in Francis’ name. The Vatican has started work on three showers for the homeless just off St. Peter’s Square after the Pope requested they be built, has given out checks to those in need across Rome -- and even has enlisted off-duty Swiss Guards to drive a stranded person home. Francis has reinvigorated the office of the Vatican almoner, entrusting the almoner, Konrad Krajewski, with hitting the streets daily in his name on mini-missions to help the poor. Krajewski told journalists last year that each morning, the pope sends him bundles of letters he has received from the faithful, along with notes like, “You know what to do,” or, “Go find them.” The Associated Press contributed to this report.

– Pope Francis spent his birthday last year by going to church with four homeless locals. This year he upped the ante, celebrating his 78th birthday on Wednesday by donating 400 sleeping bags—complete with an imprinted papal coat of arms—to homeless people around Rome, ABC News reports. Volunteers and Swiss Guard members handed out the birthday gifts in local railroad stations and near a cemetery where the homeless are known to congregate, telling recipients, "This is a gift for you from the pope on the occasion of his birthday," per ANSA. Next up on the pope's to-do list: completing three public showers right off St. Peter's Square.

Last winter’s snow accumulation in the mountains that provide state’s most important natural water system was just 5% of what is normal, study finds The Sierra Nevada snowpack that is a critical water source for California fell to a 500-year low last winter – far worse than scientists had estimated and underlining the severity of the current drought, according to new research. The snow accumulation in the mountains was just 5% of what is normal, inflating the risk of wildfires, drying up wells and orchards, and pushing communities into water rationing. Scientists had earlier thought that the snow pack was the lowest in 100 years, after a winter that was the warmest on record. Now it turns out it was actually the lowest in five centuries, according to research published in Nature Climate Change on Monday. “It was definitely a 500-year low. In the 500-year reconstruction, it was unprecedented,” said Valerie Trouet of the University of Arizona, who led the study. “When you are a climate scientist, first you get excited by the result. Then you realise the extreme level of the snowpack is not something to get excited about.” El Niño expected to hit US hard, but not enough to ease California drought Read more Snow surveyors have been trekking into the Sierra Nevada since the 1930s using gauges to measure the accumulation of snow pack, which provides almost a third of California’s surface water, at 108 observation stations. Trouet’s team studied two independent sets of records of tree rings, whose patterns reflect annual rainfall and temperatures. They found in the study of the 3,500 samples that 2015 was indeed the worst snowpack in 500 years – a situation that is unlikely to return for 1,000 years at lower elevations. California gets almost all of its precipitation in the winter months, and the Sierra Nevadas are the state’s most important natural water storage system. Come April, when the snow melts, the water flows into streams and reservoirs to be captured for the hot, dry months ahead. When the snowpack does not materialise, California faces shortfalls in water supply. Two factors aligned for the extreme low in the snow pack last year: winter temperatures too warm to allow formation of snow in the Sierras, especially at lower elevations, and a phenomenon known as the “Ridiculously Resilient Ridge”, the high pressure atmospheric formation over the north Pacific that blew storm tracks off course, preventing rains from reaching California. Last year was the hottest year on record. The warm temperatures, which prevented winter rains from turning to snow, were the bigger factor in the failure of the snow pack, Trouet said. The blasting temperatures also intensified the impact of the drought. But both high temperatures and a lack of rain would need to come into play for a recurrence of 2015’s dismal snow pack, and this year’s. “You need to have the coincidence of high temperature and low precipitation,” she said. At the moment, there is only a tiny chance of a recurrence of such extreme conditions in the coming centuries. But with winters continuing to warm under climate change, the likelihood of future low snow packs – and future punishing droughts – increase, she said. ||||| CNBC's Jane Wells takes a look at the Top Best Most expensive cities in America to buy beer. "Trees form a new ring every year," said Valerie Trouet, a researcher at the University of Arizona's Laboratory for Tree-Ring Research. "In a year with a wet winter, these trees will grow a lot, and form a wide ring. In years with dry winters, they will not grow a lot and and they will show a very narrow ring." The team examined the concentric rings that formed in the trunks of 1,500 blue oak trees from that region, paying particular attention to the width of each ring. They compiled measurements of these tree rings over the last several centuries and paired the data with an already published reconstruction of seasonal temperatures over the same amount of time. The results showed that the 2014-15 winter in California brought record low snow levels and record high temperatures—two factors that limited the amount of snowpack. The team published its results Monday in the journal Nature Climate Change. Read MoreSuper Bowl of software descends on San Francisco California is in its fourth year of drought, and the state has implemented water-rationing measures in cities and is struggling to keep crops irrigated. The low snowpack in the Sierras in the winter was an early indicator of how severe shortages would be this summer. "Snowpack is a natural water storage system," Trouet said. "When you have no precipitation in summer, you can access water from snowmelt." Trouet also said that the wildfires currently raging across the state can be directly linked to the extremely low snowpack levels, as well. "I am looking at the uncontrollable wildfires in California, and that is not a coincidence. It has been showed for more than a decade that there is a direct link between the amount of snowpack in the winter and the wildfire risk in the following summer." And if the climate continues to warm as it has, "chances of this happening again in the future are much higher than they were in the past," she said.

– As if California doesn't have enough water problems. Now scientists say the Sierra Nevada snowpack—which gives the state nearly a third of its surface water—is at a shocking 500-year low, the Guardian reports. That means California, now in its fourth year of drought, can't rely as much on winter snow accumulation in the mountains to fill streams and reservoirs during the hot summers. "It was unprecedented," says Valerie Trouet, who led the study published in Nature Climate Change. "When you are a climate scientist, first you get excited by the result. Then you realise the extreme level of the snowpack is not something to get excited about." Trouet's team reached their conclusion by analyzing rings in the trunks of 1,500 blue oak trees in the region, CNBC reports. Winter precipitation plays a big role in the trees' growth, she says, which can be measured by the width of each year's ring—and last year's was pretty darn thin. So how did it get this bad? Seems that last winter's record-high temperatures and lack of rain led to the dismally low snow accumulation. Trouet also warns that California's "uncontrollable wildfires" can be linked to the lack of Sierra Nevada snowmelt, which scientists had already figured was at a 100-year low. If the climate keeps warning, she adds, "chances of this happening again in the future are much higher than they were in the past." (See how LA is fighting drought with 96 million black plastic balls.)

the interplay between transport currents and magnetization dynamics continues to be a major research topic in ferromagnetic metal spintronics.@xcite the current understanding of this class of phenomena has been derived mainly from numerous studies of spin - transfer torques ( stts ) , which arise when spin polarized currents traverse _ non - collinear _ magnetic systems . stts can be exploited to achieve current - induced magnetization reversal and current - induced domain - wall motion , both of which have potentially important technological applications . there have been comparatively few studies of the influence of transport currents on magnetization in _ uniform _ ferromagnets , presumably because spin transfer torques vanish in these systems . yet , as pointed out independently by several researchers@xcite , current - induced reorientation of magnetization does occur in some uniform ferromagnets . the first experimental fingerprint of this phenomenon was uncovered by chernyshov _ et al._@xcite who demonstrated that an electric current alters magnetization reversal characteristics in strained ( ga , mn)as films with a single magnetic domain . stts can be considered to be one member of a family of current - induced torque ( cit ) effects by which transport currents influence magnetization in ferromagnetic or antiferromagnetic@xcite systems . the aim of this paper is to contribute to the theoretical analysis of current - induced torques in uniformly magnetized ferromagnets . in sec . ii we study the effect responsible for this type of torque , which we refer to as the ferromagnetic inverse spin - galvanic effect.@xcite in non - magnetic conductors the inverse spin - galvanic effect ( isge ) refers to current - induced spin density . since a non - zero spin - density already appears in the equilibrium state of a ferromagnet , the ferromagnetic inverse spin - galvanic effect has a distinct experimental signature . specifically , we find that in gyrotropic ferromagnets the magnetization direction is altered by a steady - state transport current . at a conceptual level , we associate this reorientation with a change in magnetic anisotropy in the presence of a transport current . an important implication of this connection is that the magnetic anisotropy energy in the transport steady state of a ferromagnet which exhibits the isge is _ not _ invariant under magnetization reversal , essentially because the applied current breaks time reversal invariance . at a practical level , we provide a concise analytical expression for the current - induced change in the magnetic anisotropy . this expression is suitable for evaluation from first principles because it requires the knowledge of only the band structure of the ferromagnet and the lifetime of the bloch states . at a technical level , our theory allows for the spatial inhomogeneities that inevitably occur in the _ magnitude _ of the ferromagnet s exchange field at atomic lenghtscales . in sec . iii we carry out quantitative calculations for the isge of strained ( ga , mn)as using a 4-band kohn - luttinger model . this calculation directly addresses the experiment by chernyshov _ et al._@xcite and corroborates their interpretation of the data . by computing the anisotropy field both in absence and in presence of an electric current , we find that in ( ga , mn)as magnetization reversal may in principle be achieved solely by electric means : the required critical current densities are in the order of @xmath0 and depend on the strain , mn concentration and hole density . sec . iv contains a brief summary and presents our conclusions . the main conclusions of our work coincide with those reached by manchon and zhang in their independent and previously published work described in ref . yet , our analysis highlights aspects that have not been emphasized previously . first , we assert that in ferromagnets with inversion symmetry , the current - induced spin - density vanishes _ to all orders _ in the strength of the spin - orbit interaction . second , when evaluating the current - induced spin polarization we include a contribution from interband coherence which can become quantitatively important in disordered ferromagnets such as ( ga , mn)as . third , we identify the current - induced transverse spin - density associated with the isge in ferromagnets as a consequence of a change in magnetic anisotropy in the presence of an electric current . we thus promote transport currents to the same status as temperature@xcite , gate voltages@xcite , strain@xcite and chemical processes@xcite , all of which are well - established control parameters for the tuning of magnetic anisotropy . in non - magnetic metals or semiconductors that are gyrotropic , _ i.e. _ non - centrosymmetric _ and _ chiral,@xcite a dc charge current is generically accompanied by a non - zero spin polarization.@xcite this phenomenon is sometimes referred to as the inverse spin galvanic effect ( isge).@xcite because of the advent of spintronics and subsequent attempts to control spin polarization by electric means , even in paramagnetic materials , the isge has received widespread experimental@xcite and theoretical@xcite attention . the isge is purely a consequence of symmetry since i ) current , which is odd under time reversal , is the dissipative response of a conductor to a dc electric - field , ii ) spin is also odd under time reversal and therefore allowed as part of the dissipative response , and iii ) axial vectors ( like spin ) and polar vectors ( like current ) are coupled in gyrotropic materials.@xcite the direction of the carriers spin is determined by the direction of the electric field as well as by the axis along which inversion symmetry is broken.@xcite the isge is sometimes viewed as a possible route toward the development of spintronics effects in paramagnetic materials that are as robust as effects like giant magnetoresistance that occur only in ferromagnetic materials . partly because spin - orbit interactions tend to be fairly weak , it appears to be difficult to make spin - galvanic effects in normal metals useful . in this section we turn the tables on this strategy by concentrating on the inverse spin - galvanic effect in _ magnetic _ conductors . in uniformly magnetized ferromagnets with inversion symmetry , the transport current is spin polarized because the conductivities of majority and minority spin channels are different . this familiar fact is unrelated to the isge . since spin - polarization is already present in the thermodynamic equilibrium state of a ferromagnet , the ferromagnetic isge is manifested not by the presence of a non - zero spin - density but instead by a change in magnetization direction in the non - equilibrium steady - state which is dependent on the magnitude and direction of the electric field . in this paper we formulate a theory of the isge in ferromagnets by evaluating the torque which acts on the collective magnetization of a magnetic conductor due to spin - orbit interactions in the presence of a transport current . when the current is set to zero , the torque we evaluate vanishes along easy ( and hard ) magnetization directions and is normally viewed@xcite as a precessional torque due to magnetocrystalline anisotropy fields . these torques are in turn associated with the magnetization - direction dependence of the magnetocrystalline anisotropy energy . at zero current , the anisotropy torques must change sign when the magnetization direction is reversed because time reversal symmetry requires that the anisotropy energy be invariant under reversal . the ferromagnetic isge in gyrotropic crystals may be viewed as a change in anisotropy torque due to a transport current . significantly , the isge torques are _ not _ odd under magnetization reversal . the ferromagnetic isge is reminiscent of the magnetoelectric phenomena that have been extensively studied in multiferroic materials,@xcite _ i.e. _ materials in which magnetism coexists with ferroelectricity . a common characteristic of multiferroic perovskites is the presence of canted magnetism that stems from the dzyaloshinskii - moriya interaction . since the direction of canting is determined by the symmetry of the crystal , one can envisage@xcite scenarios in which an electric - field - mediated reversal of the ferroelectric polarization causes a simultaneous reversal of the canting angle or of the magnetization . another interesting property of multiferroic materials is the coupling between ferroelectricity and antiferromagnetism.@xcite this coupling makes it possible to switch the magnetization of an exchange - biased ferromagnet by the application of an electric field . in spite of the contextual similarities , there are fundamental differences between the aforementioned phenomena and the ferromagnetic isge . for one thing , ferroelectricity occurs only in insulators while the isge occurs only in conductors . we evaluate the ferromagnetic isge microscopically within the framework of linear response theory ( fig . ( [ fig : bubbles]a ) ) : @xmath1 where @xmath2 is the current - induced spin density ( @xmath3 ) , @xmath4 is the applied electric field , and @xmath5 the dissipative spin - current response function : @xmath6 this linear response theory expression applies for time - independent uniform applied electric fields , and may be derived in the standard way@xcite by analytically continuing the imaginary@xcite part of @xmath7 , where @xmath8 @xmath9 is the matsubara frequency at temperature @xmath10 and @xmath11 is the frequency of the external field . in eq . ( [ eq : chi ] ) @xmath12 and @xmath13 are the @xmath14-dependent matrix - elements of the spin and velocity operators ( @xmath15 ) between bloch states ( @xmath16 ) in bands @xmath17 and @xmath18 . note that the bloch states are in general spinors in which orbital and spin degrees of freedom are entangled . @xmath19 is the retarded ( advanced ) green s function evaluated at the fermi energy @xmath20 , and @xmath21 is the quasiparticle lifetime . for simplicity we have ignored disorder vertex corrections to both velocity and spin operators . in the numerical calculations discussed in section iii we will in addition take the quasiparticle lifetime to be a phenomenological parameter which is independent of momentum and band labels . as we discuss below , the transverse components of the spin - density are directly related to the anisotropy field , which exerts a torque on the macrospin . on the same footing , the current - induced contribution to the transverse spin density is directly related to the current - induced contribution to the anisotropy field . for a ferromagnet with inversion symmetry @xmath22 irrespective of spin - orbit interaction strength , for essentially the same reasons as the isge vanishes in normal conductors with inversion symmetry.@xcite this property can be verified by recognizing that in presence of inversion symmetry the hamiltonian of the ferromagnet is invariant under @xmath23 , which implies that @xmath24 , @xmath25 and @xmath26 . consequently , the right hand side of eq . ( [ eq : chi ] ) vanishes after summing over all @xmath14 . from a crystal symmetry classification standpoint there are 21 non - centrosymmetric crystal classes , among which three ( @xmath27 , @xmath28 and @xmath29 ) are not gyrotropic . the occurence of the isge is therefore restricted to 18 crystal classes.@xcite the main objective of this section is to relate the ferromagnetic isge to a current - induced change in the magnetic anisotropy field , yet before we do so it is beneficial to pave the way by reviewing the nuances of magnetic anisotropy in electric equilibrium . in the absence of currents , magnetic anisotropy describes the dependence of the free energy of a ferromagnet on the direction of its magnetization.@xcite magnetic anisotropy originates from@xcite magnetic dipolar interactions and spin - orbit interactions . the former lead to shape anisotropy in non - spherical samples while the latter produce magnetocrystalline anisotropy by communicating the lack of rotational symmetry in the crystalline lattice to the spin degrees of freedom . in practice , magnetic anisotropy reveals itself in dynamical processes such as ferromagnetic resonance through an anisotropy field that forces the magnetization to precess unless it is along an easy or hard axis , _ i.e. _ along a direction in which the anisotropy energy is minimized or maximized . this precessional magnetization dynamics is properly characterized by the landau - lifshitz equation , @xmath30 , where @xmath31 is the direction of the ferromagnet s collective dynamical variable ( which may be chosen to be either the magnetization or the ferromagnetic exchange field ) and @xmath32 is an effective magnetic field , taken here to include reactive as well as dissipative processes.@xcite the anisotropy field may then be defined as the contribution to the non - dissipative part of the effective magnetic field which survives in the absence of true magnetic fields : @xmath33 where @xmath34 is the ground state energy of the ferromagnet in equilibrium ( we take zero temperature throughout ) and @xmath35 is the total spin ( magnetization@xmath36 volume ) of the ferromagnet . [ fig : cartoon ] when we discuss ( ga , mn)as in the following section , we will use spherical coordinates ( fig . [ fig : cartoon ] ) in which the anisotropy field may be written as @xmath37 where @xmath38 and @xmath39 are the azimuthal and the polar unit vectors , respectively . the longitudinal component of the anisotropy field is irrelevant because @xmath40 . in order to elaborate on the microscopic theory of the anisotropy field in a concrete way we work within the spin - density - functional theory of a magnetic material , in which the effective hamiltonian that describes the theory s kohn - sham quasiparticles can be expressed as @xmath41 in eq . ( [ eq : h_ks ] ) @xmath42 is the exchange effective - magnetic - field of the ferromagnet , @xmath31 is the direction of the exchange field , @xmath43 is the quasiparticle spin operator , @xmath44 captures spin - orbit interactions , and @xmath45 collects all spin - independent terms in the kohn - sham hamiltonian . in this work we characterize the macrostate of a ferromagnet by specifying the direction of the exchange field . @xmath31 is assumed to be uniform in space but the magnitude @xmath46 of the exchange field is allowed to have spatial dependence at the atomic lengthscale.@xcite we neglect dipolar interactions since they are not directly influenced by currents and can normally be cleanly separated from magnetocrystalline anisotropy . it follows that the zero - temperature anisotropy field is given by @xmath47 in eq . ( [ eq : h_an_eq ] ) we have used@xcite @xmath48 , where @xmath49 is the energy of the bloch state quasiparticles and @xmath50 is the equilibrium occupation factor at zero temperature . furthermore we have exploited the fact that @xmath51 since the number of electrons in the ferromagnet is invariant under rotations of the magnetization . this implies a @xmath31-dependence of the fermi energy,@xcite which is taken into account in the calculations of sec . ( [ eq : h_an_eq ] ) may be rewritten in a more informative manner using the feynman - hellmann theorem , which implies that @xmath52 then , @xmath53 where @xmath54 . for the envelope - function model we use in the next section , the magnitude of the exchange field is a spatially constant @xmath55 and the torque exerted by the anisotropy field is simply equal to the @xmath55 times the transverse spin - density divided by the total spin of the ferromagnet . in _ ab initio _ calculations , the magnitude of the exchange field always varies substantially on an atomic scale and , as we have emphasized previously,@xcite this variation must be accounted for . in this case the anisotropy field is evaluated by integrating the product of the exchange field magnitude and transverse spin density over space . ( [ eq : h_an_eq2 ] ) may be separated into azimuthal and polar components : @xmath56 if we neglect spatial variations of @xmath46 , eqs . ( [ eq : h_an_eq2 ] ) and ( [ eq : h_pt ] ) indicate that the torque created by the anisotropy field will vanish when the ( spin ) magnetization @xmath57 is parallel to the exchange field . conversely , whenever the direction of magnetization is misaligned with @xmath58 , the anisotropy field will be nonzero and will produce a torque on the magnetization . in transition metals spin - orbit interactions produce a misalignment between the exchange field and the magnetization , unless @xmath31 is pointing along some special crystalline direction that corresponds ( by definition ) to an easy or hard axis . a similar picture applies to local - moment ferromagnets as well , where due to spin - orbit coupling the direction of the local moments is generally misaligned with the direction of the itinerant spin density . one of the targets of this section is to present formulae that are useful for researchers working on both model systems as well as _ ab - initio _ electronic structure calculations . therefore , we digress to explain that eq . ( [ eq : h_an_eq2 ] ) is equivalent to the alternative expressions found in _ ab - initio _ studies . in first principles magnetic anisotropy theory@xcite eq . ( [ eq : fh ] ) has been approached from a different perspective . in such approach it is customary to choose the spin quantization axis along the direction of magnetization , so that @xmath59 is independent of @xmath31 . when this choice is made , the spin - orbit term in the hamiltonian becomes explicitly @xmath31-dependent . consequently , @xmath60 the anisotropy field is then evaluated combining eq . ( [ eq : so ] ) with the force theorem@xcite and a full - potential electronic - structure calculation.@xcite of course , the final result is invariant with respect to the choice of the spin quantization axis . in order to prove the equivalence of eqs . ( [ eq : fh ] ) and ( [ eq : so ] ) it is convenient to rewrite@xcite eq . ( [ eq : so ] ) as @xmath61\rangle\vert_{0}$ ] and @xmath62\rangle\vert_{0}$ ] . to see that these expressions agree with eq . ( [ eq : h_pt ] ) note that @xmath63=[{\cal h}-{\cal h}_{\rm kin}+{\bf\delta}\cdot{\bf s},{\bf s}]$ ] , that @xmath64\equiv 0 $ ] , and that @xmath65|a,{\bf k}\rangle=(\epsilon_{{\bf k},a}-\epsilon_{{\bf k},a})\langle a,{\bf k}|{\bf s}|a,{\bf k}\rangle = 0 $ ] . in this way the derivative of energy with respect to magnetization direction can be related to the exchange term in the kohn - sham equation rather than to the spin - orbit coupling term . ( [ eq : h_an_eq2 ] ) and ( [ eq : h_pt ] ) are recovered after using @xmath66=i\epsilon_{ijk } s_k$ ] to simplify @xmath67\rangle$ ] . we now show that the green s function expression we use to evaluate the ferromagnetic isge ( eq . ( [ eq : chi0 ] ) ) corresponds to the current - induced change in eq . ( [ eq : h_an_eq2 ] ) . we begin by mentioning that the application of an electric current can alter the magnetic anisotropy field , which leads to a current - induced torque on the magnetization . for an arbitrary orientation of the exchange field , the change is given by @xmath68 adopting the relaxation - time approximation , @xmath69 reads @xmath70 and for the change in the matrix elements we use @xmath71 with @xmath72 in eq . ( [ eq : state2 ] ) we have once again appealed to linear response theory and have used the fact that the electric field is uniform . recognizing the fact that the integration of equal - band green s functions gives rise to a factor of @xmath84 , @xmath85 yields the intraband piece of eq . ( [ eq : chi ] ) modulo a factor of @xmath86 . similarly , @xmath78 brings in the interband part of eq . ( [ eq : chi ] ) modulo a factor of @xmath86 ; in order to verify this we recall@xcite that @xmath87 in sum , we find @xmath88 which agrees with the isge expression for the current - induced spin density ( eq . ( [ eq : chi ] ) ) except for an overall normalization factor ( @xmath89 ) and the fact that the spin - operator is weighted by an spatially inhomogeneous magnitude of the exchange field . with the aim of making eq . ( [ eq : complete ] ) more manageable for first principles calculations , we will ignore the interband contribution as well as the @xmath90 term ; both omissions are justified in most metallic ferromagnets.@xcite in this case eq . ( [ eq : complete ] ) simplifies into @xmath91 where we have re - inserted @xmath92 . while approximate , eq . ( [ eq : simplified ] ) may provide a valid platform to explore current induced magnetization reversal in real gyrotropic ferromagnets with a single magnetic domain . in the next section we will describe in detail how a large @xmath93 can produce a large reorientation of the magnetization . if the spatial dependence of @xmath46 is negligible ( as it will be in the model studied in the next section ) , eq . ( [ eq : complete ] ) may be rewritten in a more compact way : @xmath94 where @xmath95 is the spin - current susceptibility introduced in eq . ( [ eq : chi ] ) . ( [ eq : link ] ) proves that the ferromagnetic isge describes the change in the magnetic anisotropy field due to a current . in other words , ferromagnetic isge determines how an electric current changes the location of the extrema in the micromagnetic energy functional . this is the central idea of this section . as a final sidenote , we point out that this section has concentrated on evaluating the change in magnetic anisotropy under a perturbation represented by @xmath96 , where @xmath97 is the electromagnetic vector potential . the anisotropy is evaluated by calculating the change in the expectation value of @xmath98 , thus leading to a rather standard linear response function calculation . we could in the same way calculate the change in the transverse spin - spin response function due to an electric field as indicated in fig . ( [ fig : three ] ) , in order to determine how small amplitude magnetic fluctuations are altered . if , however , we are interested only in uniform magnetization dynamics no additional information is obtained by doing this calculation . the key point is that the response to a transverse field @xmath99 is already built in our expression for the equilibrium anisotropy field ( eq . ( [ eq : h_an_eq2 ] ) ) , to _ all _ orders in @xmath99 . in other words , the reference ( unperturbed ) macrostate to which we apply a current contains a magnetization that is `` arbitrarily '' misaligned with the exchange field . hence , eq . ( [ eq : link ] ) along with eq . ( [ eq : h_an_eq2 ] ) offers a complete account of the nonequilibrium magnetic anisotropy of uniform magnetic states in the presence of a transport current . magnetoelectric phenomena in dilute magnetic semiconductors@xcite such as ( ga , mn)as have attracted special attention because these materials are more compatible with current microelectronics technology than metals . in addition , electric field control of magnetism has turned out to be more feasible in ( ga , mn)as than in conventional dense - moment metallic ferromagnets because of their small magnetization , high carrier spin polarization , strong spin - orbit interactions , and carrier - mediated ferromagnetism.@xcite in particular , the recent experiment@xcite by chernyshov _ on ( ga , mn)as wafers under compressive strain has demonstrated the ability of transport currents to reversibly _ assist _ the reorientation of magnetization in _ single - domain _ ferromagnets . as we demonstrate here this effect is dependent on having both spin - orbit interactions and broken inversion symmetry . in this section we compute the change in the magnetic anisotropy due to an electric current for a realistic model of ( ga , mn)as . our calculation is directly relevant to the experiment of chernyshov _ et al._. our results corroborate their interpretation of the data and predict the possibility of all - electric magnetization switching in ( ga , mn)as . our analysis is limited to zero temperature and neglects the shape anisotropy , which for typical mn doping concentrations is 10 - 100 times weaker than in conventional ferromagnets . the dependence of the magnetic anisotropy of ( ga , mn)as on doping , external electric fields , temperature and strain has been successfully explained@xcite by combining ( i ) a mean - field theory of the exchange coupling between localized mn moments and valence band carriers with ( ii ) a phenomenological four or six band envelope function model in which the valence band holes are characterized by luttinger , spin - orbit splitting and strain - energy parameters . the results presented below predict the rate at which these fields change with external electric field . in line with this we adopt the following hamiltonian for ga@xmath100mn@xmath101as : @xmath102 @xmath103 is the 4-band kohn - luttinger hamiltonian@xcite with luttinger parameters @xmath104 , @xmath105 and @xmath106 . @xmath107 is the spin operator projected onto the j=3/2 total angular momentum subspace at the top of the valence band . @xmath108 is the exchange field , @xmath31 denotes the orientation of the local moments , @xmath109 is the p - d exchange coupling parameter , @xmath110 is the spin of the mn ions , and @xmath111 is the mn concentration ( @xmath112 is the lattice constant of gaas ) . this four - band model is expected to be adequate for small and intermediate mn doping strengths . @xmath113 is the strain hamiltonian@xcite given by @xmath114\nonumber\\ & + & c_4 \left [ j_x \left(\epsilon_{yy}-\epsilon_{zz}\right ) k_x + c.p.\right],\end{aligned}\ ] ] where @xmath115 is the total angular momentum ( @xmath116 by the wigner - eckart theorem ) , @xmath117 are diagonal elements of the stress tensor , @xmath118 is the axial deformation potential and the parameter @xmath119 captures the strain - induced linear in @xmath120 spin - splitting of the valence bands in paramagnetic gaas . in eq . ( [ eq : strain ] ) the notation _ c.p . _ stands for cyclic permutations and @xmath121 for @xmath122 $ ] growth lattice - matching strains . the term proportional to @xmath123 is crucial for the occurrence of the ferromagnetic isge because it breaks inversion symmetry ( we are neglecting the intrinsic lack of inversion symmetry of the zinc - blende structure , which is relatively inconsequential ) , and it introduces chirality . ( a bulk , unstrained zinc - blende crystal is not gyrotropic because it corresponds to the @xmath27 symmetry point group . ) eq . ( [ eq : strain ] ) may be simplified to @xmath124 where @xmath125 is the purely axial strain component . in this paper we take @xmath126 ( compressive strain ) , which applies when ( ga , mn)as is grown on top of a gaas substrate . using eqs . ( [ eq : h_an_eq2 ] ) , ( [ eq : link ] ) and ( [ eq : model ] ) we evaluate the magnetic anisotropy field both with and without electric current ; the results are highlighted in figs . ( [ fig : h_an_eq1])- ( [ fig : critical ] ) . figs . ( [ fig : h_an_eq1 ] ) and ( [ fig : h_an_eq2 ] ) correspond to electrical equilibrium and illustrate @xmath127 for @xmath128 and @xmath129 for @xmath130 , respectively . the extrema of the micromagnetic energy functional are characterized by @xmath131 and by inspection we locate them at @xmath132 and @xmath133 where @xmath134 . for our parameters ( see figure captions ) the energy minima that define metastable magnetic configurations are found at @xmath135 . that is to say , the easy directions correspond to [ 100 ] , [ 010],[@xmath13600 ] and [ 0@xmath1360 ] , which are contained in the plane of the ( ga , mn)as wafer . for later reference , we consider an initial condition in which the magnetization is pointing along [ 100 ] . if a small static perturbation tilts it towards [ 110 ] , the negative anisotropy field ( @xmath137 for @xmath138 ) creates a torque that will , in conjunction with damping,@xcite turn the magnetization back to [ 100 ] . ( [ fig : intra vs inter ] ) illustrates how an electric current along [ 010 ] alters the azimuthal anisotropy field@xcite for fixed @xmath130 . the cosine - like shape is consistent with the dresselhaus symmetry of the @xmath123 term in the strain hamiltonian . if the system had a perfect dresselhaus symmetry the change in the micromagnetic energy functional under an electric current @xmath139 would read @xmath140 which means that a current along [ 010 ] ( [ 100 ] ) would tilt the steady - state magnetization direction along [ 010 ] ( [ @xmath14100 ] ) . using @xmath142 and @xmath143 it follows that @xmath144 , and hence a cosine - like dependence in @xmath145 is indeed expected for a current along [ 010 ] . we have verified that a current along @xmath146 gives rise to a sine - like dependence with the appropriate sign . nevertheless , eq . ( [ eq : dress ] ) is not exact because the magnetization vector introduces another preferred direction ; for instance , we find that an electric field pointing along @xmath147 ( i.e. [ 001 ] ) can also alter the steady - state spin orientation . this effect , which vanishes in the paramagnetic limit , highlights one instance in which the ferromagnetic and paramagnetic isges differ . another attribute of fig . ( [ fig : intra vs inter ] ) is that it determines the quantitative importance of interband contributions to the current - induced spin density in ( ga , mn)as . although normally neglected , interband transitions become quantitatively significant in strongly disordered ferromagnets . in particular , interband and intraband contributions are largely indistinguishable in ferromagnets with @xmath148 . we note parenthetically that neither intraband nor interband contributions display the smooth sinusoidal shape portrayed by their sum . in addition , we remark that reversing the sign of the axial strain ( i.e. making it tensile ) leads to a sign reversal of @xmath149 without substantial changes in its magnitude.@xcite fig . ( [ fig : h_an_neq1 ] ) demonstrates that a sufficiently strong current is able to rotate the magnetization by @xmath150 or @xmath151 . we explain this property by considering the case in which the equilibrium magnetization is pointing along [ 100 ] . if a small current is applied along [ 010 ] , then [ 100 ] is no longer an extremum of the micromagnetic energy functional ( because @xmath152 ) . the modified _ easy _ direction remains in the neighborhood of [ 100 ] since the restoring torque ( @xmath137 ) again crosses zero at @xmath138 . once the applied electric field exceeds a critical value ( @xmath153 in the present figure ) the @xmath137 region near [ 100 ] disappears completely and hence assisted by damping the magnetization eventually points along [ 010 ] . in other words , at ( and above ) the critical switching field the energy minimum that is nearest to [ 100 ] is located at [ 010 ] ( note that this direction remains stable when the current flows along [ 010 ] ) . once the magnetization is aligned with [ 010 ] , an equally strong electric current in the [ 100 ] direction will rotate it towards [ @xmath13600 ] . in this fashion it is possible to switch the direction of magnetization by @xmath151 solely by application of transport currents . the procedure sketched above accomplishes magnetization switching by application of two perpendicular current pulses , each of which forces a @xmath150 rotation . yet , it is also possible to achieve the @xmath154\to[{\bar 1}00]$ ] switching with a single _ unidirectional _ pulse , provided the electric field along [ 100 ] is ramped up sufficiently ( @xmath155 for the parameters of the present figure ) . in order to understand this , recall that @xmath156 . consequently , for a strong electric current [ @xmath14100 ] is the only easy direction ( [ 100 ] becomes a hard direction ) . the inequivalence between [ 100 ] and [ @xmath13600 ] does not violate any symmetry principles;@xcite in effect , an electric current breaks time reversal symmetry and can thus connect time - reversed magnetic states . using @xmath157 as the typical resistivity for ( ga , mn)as samples we deduce that @xmath158 corresponds approximately to a current density of @xmath159 , hence the critical switching current is on the order of @xmath0 . it is plausible that a detailed exploration of the parameter space comprised by the mn concentration @xmath160 , the hole density @xmath161 and the axial strain @xmath162 will enable lower critical currents , thereby diminishing the importance of the joule heating . as a word of caution , we note that the 4-band model employed here typically overestimates the effect of spin - orbit interactions , thus potentially leading to an underestimate of these critical currents . there is in addition some uncertainty associated with the use of a life - time approximation for bloch state quasiparticles in these strongly disordered metallic conducting ferromagnets . overall , the magnitude of the critical switching current depends on ( a ) the size of the equilibrium anisotropy barrier , ( b ) the extent to which inversion symmetry is broken and ( c ) the strength of spin - orbit interaction . in ( ga , mn)as the first two factors are tunable . on one hand , ( a ) may be optimized by choosing appropriate doping concentrations : in general lower mn density is beneficial ( fig . ( [ fig : critical ] ) ) , as it reduces the equilibrium anisotropy without significantly affecting the magnitude of isge . however , for very low mn concentrations a metal - insulator transition is impending , which hampers isge . on the other hand , ( b ) may be modified via strain engineering : as shown in fig . ( [ fig : critical ] ) , the critical current is ( roughly ) inversely proportional to the strength of the uniaxial strain that breaks inversion symmetry . the inverse proportionality may be understood on the basis of eq . ( [ eq : dress ] ) combined with the fact that the equilibrium anisotropy does not change to _ first _ order in @xmath162 ( because @xmath14-linear terms vanish after summing over all momenta ) . in this work we have presented a theory of the current - induced spin torques in uniform ferromagnets . the torques can be viewed as due to a difference between the magnetic anisotropy energy of a ferromagnet which carries no current and the magnetic anisotropy of a ferromagnet in the transport steady state , which give rise to a corresponding change in anisotropy effective magnetic fields . when the transport steady state is described using a relaxation time approximation , the current - induced contribution to the anisotropy field of a strongly metallic ferromagnet is given in energy units by @xmath163_{a , a}{\bf v}_{a , a}\cdot{\bf e } \ , \frac{\partial f_{{\bf k},a}}{\partial\epsilon_{{\bf k},a } } \ , \tau_{{\bf k},a}.\ ] ] where @xmath164_{a , a}$ ] is the spin - density weighted average of the exchange splitting of a particular state . we refer to the existence of this current - induced anisotropy field as the ferromagnetic inverse spin - galvanic effect . in bulk materials this current induced field is non - zero only in gyrotropic ferromagnets , _ i.e. _ only in ferromagnets that have broken inversion symmetry and are chiral . although uniform ferromagnetism may appear to be incompatible with broken inversion symmetry because of the the dzyaloshinskii - moriya interaction , the equilibrium magnetic anisotropy is often strong enough ( or at least can be engineered so that it is strong enough ) to prevent the formation of spiral magnetic states . as an illustration of our theory , we have estimated current induced torques in uniform ( ga , mn)as , which is not gyrotropic when it has pseudo - cubic symmetry but becomes gyrotropic when strained . since substrate - dependent strains are present in all ( ga , mn)as thin films , the strength of the ferromagnetic isge is expected to be strongly sample - dependent . we have concluded that it should _ a priori _ be feasible to design ( ga , mn)as samples in which it is possible to switch the magnetization purely by electrical means . for typical sample parameters the necessary switching currents are on the order of @xmath165 , but the value may be tuned by adjusting the doping concentration and the axial strain . at these critical currents the joule heating is not negligible ; 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( kluwer academic / plenum publishers , new york , 2000 ) . in the zero frequency limit the real part of @xmath173 is cancelled out by the diamagnetic response . this reflects the fact that in non - superconducting metals the current induced spin density is dissipative . liu , b. zhou , s.q . shen and b.f . zhu , phys . b * 77 * , 125345 ( 2008 ) . s.v . vonsovskii ( editor ) , _ ferromagnetic resonance _ ( pergamon press , oxford , 1966 ) . for reviews see _ e.g. _ p. bruno , in _ physical origins and theoretical models of magnetic anisotropy _ ( frerienkurse des forschungszentrums julich , julich , 1993 ) ; m.t . johnson , p.j.h . bloemen , f.j.a den broeder and j.j . de vries , rep . . phys . * 59 * , 1409 ( 1996 ) ; j. stohr , j. magn . magn . mater . * 200 * , 470 ( 1999 ) . d. steiauf , j. seib and m. fanhle , phys . b * 78 * , 020410(r ) ( 2008 ) . the sum of the single - particle kohn - sham eigenvalues does not account for the actual ground state energy of the ferromagnet because it neglects the double - counted hartree and exchange - correlation contributions . however , we invoke the _ force theorem _ which states that the extra terms will cancel when we one takes the difference in total energies between two macrostates with non - collinear exchange fields . see for instance a.r . mackintosh and o.k . andersen , _ electrons at the fermi surface _ ( ed . m. springford ) ( cambridge university press , cambridge , 1980 ) ; a.i . liechtenstein , m.i . katsnelson and v.a . gubanov , j. phys . f * 14 * , l125 ( 1984 ) ; m. weinert , r.e . watson and j.w . davenport , phys . b * 32 * , 2115 ( 1985 ) ; see also ref . [ ] . daalderop , p.j . kelly and m.f.h . schuurmans , phys . b * 41 * , 11919 ( 1990 ) . j. wunderlich , t. jungwirth , b. kaestner , a.c . irvine , k.y . wang , n. stone , u. rana , a.d . giddings , a.b . shick , c.t . foxon , r.p . campion , d.a . williams and b.l . gallagher , phys . lett . * 97 * , 077201 ( 2006 ) . x. wang , r. wu , d.s . wang and a.j . freeman , phys . b * 54 * , 61 ( 1996 ) . k. gilmore , y.u . idzerda and m.d . stiles , phys . 99 , 27204 ( 2007 ) . for reviews see _ e.g. _ a.h . macdonald , p. schieffer and n. samarth , nat . materials * 4 * , 195 ( 2005 ) ; t. jungwirth , j. sinova , j. masek , j. kucera and a.h . macdonald , rev . phys . * 78 * , 809 ( 2006 ) . n. nagaosa , j. sinova , s. onoda , a.h . macdonald and n.p . ong , arxiv:0904.4154 ( 2009 ) . strictly speaking eqs . ( [ eq : state2 ] ) and ( [ eq : trick ] ) are accurate only in absence of disorder . nevertheless , the connection between them remains intact in presence of impurities . the leading o(@xmath83 ) correction due to interband transitions would be captured by the second line of eq . ( [ eq : h_inter ] ) . i. stolichnov , s.w.e . riester , h.j . trodahl , n. setter , a.w . rushforth , k.w . edmonds , r.p . campion , c.t . foxon and b.l . gallagher , nature mater . * 7 * , 464 ( 2008 ) . h. ohno and t. dietl , j. magn . magn . mat . * 320 * , 1293 ( 2008 ) . m. abolfath , t. jungwirth , j. brum and a.h . macdonald , phys . b * 63 * , 054418 ( 2001 ) . t. dietl , h. ohno and f. matsukura , phys . b * 63 * , 195205 ( 2001 ) . j. zemen , j. kucera , k. olejnik and t. jungwirth , arxiv:0904.0993 ( 2009 ) . p. yu and m. cardona , _ fundamentals of semiconductors _ , 3rd ed . ( springer , new york , 2005 ) . m. silver , w. batty , a. ghiti and e.p . oreilly , phys . b * 46 * , 6781 ( 1992 ) . for an exhaustive list of symmetry - allowed strain terms see _ e.g. _ r. winkler , _ spin - orbit coupling effects in two - dimensional electron and hole systems _ ( springer , berlin , 2003 ) . in absence of damping the magnetization would keep precessing indefinitely . the combined action of the anisotropy field and damping is what ultimately drives the system to the minimum energy state . our discussion concentrates on @xmath174 . although @xmath175 too generally changes in presence of a current , it is not pertinent to the [ 100]@xmath176[010 ] or [ 100]@xmath176[@xmath14100 ] magnetization reorientations that we are interested in . it is known that in gaas quantum wells the strain - induced * k*-linear terms have negligible impact if the strain is compressive , yet they matter if the strain is tensile ( see _ e.g. _ ref . [ ] ) . this observation does not apply to bulk ( ga , mn)as . j. stohr , h.c . siegmann , a. kashuba and s.j . gamble , appl . . lett . * 94 * , 072504 ( 2009 ) . however , it has been suggested that sizeable rashba spin - orbit interactions arise in magnetic interfaces of rare earth metals such as gd , where the atomic spin - orbit coupling is strong . see o. krupin , g. bihlmayer , k. starke , s. gorovikov , j.e . prieto , k. dobrich , s. blugel and g. kaindl , phys . b * 71 * , 201403(r ) ( 2005 ) .

current - induced torques are commonly used to manipulate non - collinear magnetization configurations . in this article we discuss current - induced torques present in a certain class of collinear magnetic systems , relating them to current - induced changes in magnetic anisotropy energy . we present a quantitative estimate of their characteristics in uniform strained ferromagnetic ( ga , mn)as .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Millennium National Commission on Space Act''. SEC. 2. PURPOSE. It is the purpose of this Act to establish a National Commission on Space that will assist the United States-- (1) to define the long-range needs of the Nation that may be fulfilled through the peaceful uses of space; (2) to maintain the Nation's preeminence in space science, technology, and applications; (3) to promote the peaceful exploration and utilization of the space environment; and (4) to articulate goals and develop options for the future direction of the Nation's civilian space program in coordination with commercial space activities. SEC. 3. FINDINGS. The Congress finds and declares that-- (1) the National Aeronautics and Space Administration, the lead civilian space agency, as established in the National Aeronautics and Space Act of 1958 (42 U.S.C. 2451 et seq.), has conducted a space program that has been an unparalleled success, providing significant economic, social, scientific, and national security benefits, and helping to maintain international stability and good will; (2) the National Aeronautics and Space Act of 1958 (42 U.S.C. 2451 et seq.) has provided the policy framework for achieving this success, and continues to be a sound statutory basis for national efforts in space; (3) the United States has entered an era of international competition and cooperation in space, and therefore this Nation must strengthen the commitment of its public and private technical, financial, and institutional resources, so that the United States will not lose its leadership position during the coming decade; (4) the private sector is a major participant in the utilization of the space environment; (5) the Nation continues its commitment to a permanently manned space station in low Earth orbit, and future national efforts in space will benefit from the presence of such a station; (6) the separation of the civilian and military space programs is essential to ensure the continued health and vitality of both; and (7) the identification of long range goals and policy options for the United States civilian space program through a high level, representational public forum will assist the President and Congress in formulating future policies for the United States civilian space program. SEC. 4. ESTABLISHMENT OF COMMISSION. (a) In General.--The President shall, no earlier than February 1, 2001, and no later than May 1, 2001, establish, and appoint the members of, a National Commission on Space. (b) Membership.-- (1) Appointments.--The Commission shall consist of 15 members, appointed for the life of the Commission, of whom 10 shall be appointed as follows: (A) 3 members shall be appointed from a list of 6 individuals nominated by the Majority Leader of the Senate in consultation with the chairman of the Senate Committee on Commerce, Science, and Transportation. (B) 3 members shall be appointed from a list of 6 individuals nominated by the Speaker of the House of Representatives in consultation with the chairman of the House Committee on Science. (C) 2 members shall be appointed from a list of 4 individuals nominated by the Minority Leader of the Senate in consultation with the ranking member of the Senate Committee on Commerce, Science, and Transportation. (D) 2 members shall be appointed from a list of 4 individuals nominated by the Minority Leader of the House of Representatives in consultation with the ranking member of the House Committee on Science. (2) Chairman; vice chairman.--The President shall designate 1 of the members of the Commission appointed under this subsection to serve as Chairman, and 1 of the members to serve as Vice Chairman. The Vice Chairman shall perform the functions of the Chairman in the Chairman's absence. (c) Qualifications.-- (1) In general.--The members shall be selected from among individuals from Federal, State, and local governments, industry, business, labor, academia, and the general population who, by reason of their background, education, training, or experience, possess expertise in scientific, technological, and commercial pursuits, as well as the use and implications of the use of such pursuits. (2) Federal officers or employees.--Not more than 3 members may be employees of the Federal Government. (3) First time service.--Not less than 5 members shall be individuals who have never before been appointed to serve on a Commission established by the Federal Government. (d) Compensation.--Members who are not otherwise officers or employees of the United States shall be paid at a rate equal to the daily equivalent of the minimum rate of basic pay payable for level IV of the Executive Schedule under section 5315 of title 5, United States Code, for each day, including travel time, during which such members are engaged in the actual performance of the duties of the Commission. While away from their homes or regular places of business, such members shall be allowed travel expenses, including per diem in lieu of subsistence, in accordance with sections 5702 and 5703 of title 5, United States Code. (e) Ex Officio Members.--The President shall appoint 1 individual from each of the following Federal departments and agencies to serve as ex officio, advisory, non-voting members of the Commission (if such department or agency does not already have a member appointed to the Commission pursuant to subsection (a)): (1) National Aeronautics and Space Administration. (2) Department of State. (3) Department of Defense. (4) Department of Transportation. (5) Department of Commerce. (6) Department of Agriculture. (7) Department of the Interior. (8) National Science Foundation. (9) Office of Science and Technology Policy. (10) Department of Energy. (f) Congressional Advisory Members.--The President of the Senate shall appoint 2 advisory members of the Commission from among the Members of the Senate and the Speaker of the House of Representatives shall appoint 2 advisory members of the Commission from among the Members of the House of Representatives. Such members shall not participate, except in an advisory capacity, in the formulation of the findings and recommendations of the Commission. (g) Reimbursement of Expenses for Ex Officio and Congressional Members.--Members of the Commission appointed under subsection (e) or (f) shall not be entitled to receive compensation for service relating to the performance of the duties of the Commission, but shall be entitled to reimbursement for travel expenses incurred while in the actual performance of the duties of the Commission. (h) Staff.--The Commission shall appoint and fix the compensation of such personnel as it deems advisable. The Chairman of the Commission shall be responsible for-- (1) the assignment of duties and responsibilities among such personnel and their continuing supervision; and (2) the use and expenditures of funds available to the Commission. In carrying out the provisions of this subsection, the Chairman shall act in accordance with the general policies of the Commission. (i) Agency Assistance.--To the extent permitted by law, the Commission may secure directly from any executive department, agency, or independent instrumentality of the Federal Government any information it deems necessary to carry out its functions under this Act. Each such department, agency, and instrumentality shall cooperate with the Commission and, to the extent permitted by law and upon request of the Chairman of the Commission, furnish such information to the Commission. (j) Information-Gathering Activities.--The Commission may hold hearings, receive public comment and testimony, initiate surveys, and undertake other appropriate activities to gather the information necessary to carry out its activities under section 5 of this Act. (k) Detailed Employees.-- (1) Authority to detail.--Upon request of the chairman of the Commission, the head of any Federal department or agency may detail any of the personnel of the department or agency to the Commission to assist it in carrying out its duties under this Act. (2) Reimbursement.--Any Federal Government employee may be detailed to the Commission with or without reimbursement, and any such detail shall be without interruption or loss of civil service status or privilege. (l) Support and Assistance.-- (1) Support.--The Office of Science and Technology Policy shall provide support services to the Commission. (2) Assistance.--The Comptroller General of the United States may provide assistance, including the detailing of employees, to the Commission in accordance with an agreement entered into with the Commission. (m) Other Authority.--The Commission may procure by contract, to the extent funds are available, the temporary or intermittent services of experts or consultants pursuant to section 3109 of title 5, United States Code. The Commission shall give public notice of any such contract before entering into that contract. (n) Applicability of FACA.--Except as otherwise provided in this Act, the Commission is subject to the Federal Advisory Committee Act (5 U.S.C. App.). (o) Funding.--There are authorized to be appropriated to the Commission $2,500,000 for fiscal year 2001, and $5,000,000 for fiscal year 2002, to carry out its duties under this Act. (p) Sunset.--The Commission shall cease to exist 60 days after it has submitted the plan required by section 5(c) of this Act. SEC. 5. STUDY AND REPORT. (a) Study.--The Commission shall study existing and proposed space activities and formulate an agenda for the United States civilian space program. The Commission shall identify long range goals, opportunities, and policy options for United States civilian space activity for the next 20 years. In carrying out this responsibility, the Commission shall take into consideration-- (1) the Nation's plans for a permanently manned space station in low Earth orbit; (2) present and future scientific, economic, social, environmental, and foreign policy needs of the United States, and methods by which space science, technology, and applications initiatives might address those needs; (3) the adequacy of the Nation's public and private capability in fulfilling the needs identified in paragraph (2); (4) how a cooperative interchange between Federal agencies on research and technology development, and technology transfer programs can benefit the civilian space program; (5) opportunities for, and constraints on, the use of outer space toward the achievement of Federal program objectives or national needs; (6) current and emerging issues and concerns that may arise through the utilization of space research, technology development, and applications; (7) the Commission shall analyze the findings of the reviews specified in paragraphs (1) through (6) of this subsection, and develop options and recommendations for a long range national civilian space policy plan. (b) Estimates of Requirements.--Options and recommendations submitted in accordance with subsection (c) of this section shall include, to the extent appropriate, an estimate of costs and time schedules, institutional requirements, and statutory modifications necessary for implementation of such options and recommendations. (c) Report.--Within 15 months after the date of the establishment of the Commission, the Commission shall submit to the President and to the Committee on Commerce, Science, and Transportation of the Senate and the Committee on Science of the House of Representatives, a long range plan for United States civilian space activity incorporating the results of the studies conducted under this section, together with recommendations for such legislation as the Commission determines to be appropriate. D23/

Requires the Commission to identify long range goals, opportunities, and policy options for U.S. civilian space activity for the next 20 years and to develop options and recommendations for a long range national civilian space policy plan. Authorizes appropriations.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Indian and Alaska Native Foster Care and Adoption Services Amendments of 2001''. SEC. 2. AUTHORITY OF INDIAN TRIBES TO RECEIVE FEDERAL FUNDS FOR FOSTER CARE AND ADOPTION ASSISTANCE. (a) Children Placed in Tribal Custody Eligible for Foster Care Funding.--Section 472(a)(2) of the Social Security Act (42 U.S.C. 672(a)(2)) is amended-- (1) by striking ``or (B)'' and inserting ``(B)''; and (2) by inserting before the semicolon the following: ``, or (C) an Indian tribe (as defined in section 479B(e)) or an intertribal consortium if the Indian tribe or consortium is not operating a program pursuant to section 479B and (i) has a cooperative agreement with a State pursuant to section 479B(c) or (ii) submits to the Secretary a description of the arrangements (jointly developed or developed in consultation with the State) made by the Indian tribe or consortium for the payment of funds and the provision of the child welfare services and protections required by this title''. (b) Programs Operated by Indian Tribal Organizations.--Part E of title IV of the Social Security Act (42 U.S.C. 670 et seq.) is amended by adding at the end the following: ``SEC. 479B. PROGRAMS OPERATED BY INDIAN TRIBAL ORGANIZATIONS. ``(a) Application.--Except as provided in subsection (b), this part shall apply to an Indian tribe that elects to operate a program under this part in the same manner as this part applies to a State. ``(b) Modification of Plan Requirements.-- ``(1) In general.--In the case of an Indian tribe submitting a plan for approval under section 471, the plan shall-- ``(A) in lieu of the requirement of section 471(a)(3), identify the service area or areas and population to be served by the Indian tribe; and ``(B) in lieu of the requirement of section 471(a)(10), provide for the approval of foster homes pursuant to tribal standards and in a manner that ensures the safety of, and accountability for, children placed in foster care. ``(2) Determination of federal share.-- ``(A) Per capita income.-- ``(i) In general.--For purposes of determining the Federal medical assistance percentage applicable to an Indian tribe under paragraphs (1) and (2) of section 474(a), the calculation of an Indian tribe's per capita income shall be based upon the service population of the Indian tribe as defined in its plan in accordance with paragraph (1)(A). ``(ii) Consideration of other information.--An Indian tribe may submit to the Secretary such information as the Indian tribe considers relevant to the calculation of the per capita income of the Indian tribe, and the Secretary shall consider such information before making the calculation. ``(B) Administrative expenditures.--The Secretary shall, by regulation, determine the proportions to be paid to Indian tribes pursuant to section 474(a)(3), except that in no case shall an Indian tribe receive a lesser proportion than the corresponding amount specified for a State in that section. ``(C) Sources of non-federal share.--An Indian tribe may use Federal or State funds to match payments for which the Indian tribe is eligible under section 474. ``(3) Modification of other requirements.--Upon the request of an Indian tribe or tribes, the Secretary may modify any requirement under this part if, after consulting with the Indian tribe or tribes, the Secretary determines that modification of the requirement would advance the best interests and the safety of children served by the Indian tribe or tribes. ``(4) Consortium.--The participating Indian tribes of an intertribal consortium may develop and submit a single plan under section 471 that meets the requirements of this section. ``(c) Cooperative Agreements.--An Indian tribe or intertribal consortium and a State may enter into a cooperative agreement for the administration or payment of funds pursuant to this part. In any case where an Indian tribe or intertribal consortium and a State enter into a cooperative agreement that incorporates any of the provisions of this section, those provisions shall be valid and enforceable. Any such cooperative agreement that is in effect as of the date of enactment of this section, shall remain in full force and effect subject to the right of either party to the agreement to revoke or modify the agreement pursuant to the terms of the agreement. ``(d) Regulations.--Not later than 1 year after the date of enactment of this section, the Secretary shall, in full consultation with Indian tribes and tribal organizations, promulgate regulations to carry out this section. ``(e) Definitions of Indian Tribe; Tribal Organizations.--In this section, the terms `Indian tribe' and `tribal organization' have the meanings given those terms in subsections (e) and (l) of section 4 of the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450b), respectively.''. (c) Effective Date.--The amendments made by this section take effect on the date of enactment of this Act without regard to regulations to implement such amendments being promulgated by such date.

Indian and Alaska Native Foster Care and Adoption Services Amendments of 2001 - Amends part E (Foster Care and Adoption Assistance) of title IV of the Social Security Act to provide for Federal foster care maintenance payments to qualifying Indian tribal plans designed for foster and adoptive care of an Indian child.Sets forth Federal assistance (including medical assistance) eligibility requirements for such programs operated by Indian tribal organizations.

The 32-year-old Norwegian man who allegedly went on a shooting spree on the island of Utoya has been identified as Anders Behring Breivik, according to multiple reports. The Daily Mail and Sky News were among those to report the suspect's name. According to witnesses, the gunman was dressed as a police officer and gunned down young people as they ran for their lives at a youth camp. Police said Friday evening that they've linked the youth camp shooting and Oslo bombing. Breivik is believed to have acted alone. Norwegian TV2 reports that Breivik belongs to "right-wing circles" in Oslo. Swedish news site Expressen adds that he has been known to write to right-wing forums in Norway, is a self-described nationalist and has also written a number of posts critical of Islam. A Twitter account for Breivik has surfaced, though it only has one post, this quote from philosopher John Stuart Mill: "One person with a belief is equal to the force of 100 000 who have only interests." The tweet was posted on July 17. On a Facebook account that Norwegian media outlets have attributed to Breivik, he describes himself as having Christian, conservative views. He says he enjoys hunting, the games World of Warcraft and Modern Warfare 2, and lives in Oslo. He also lists political analysis and stock analysis as interests. ||||| (CNN) -- As Norway struggles to come to terms with its greatest loss of life in decades, all eyes are on the man charged in the explosion in central Oslo and the deadly shooting rampage at a youth camp. While police have not officially named him, Norwegian television and newspaper reports have identified the suspect as 32-year-old Anders Behring Breivik, of Norwegian origin. A picture is emerging, gleaned from official sources and social media, of a right-wing Christian fundamentalist who may have had an issue with Norway's multi-cultural society. Norwegian and international news outlets have run photographs of a blond man with blue-green eyes and chiseled features, dressed in a preppy style. A victim who was shot during the attack at the youth camp on Utoya island told CNN Saturday that he had seen pictures of Breivik taken from what is believed to be his Facebook page and shown on NRK and TV2. The victim said he recognized the man from the news reports as the gunman. Breivik is a member of the Oslo Pistol Club and has three weapons registered in his name, according to leading Norwegian newspaper VG, citing Norway's official weapons register. They are a Glock pistol, a rifle and a shotgun, VG reported. NRK reports that Breivik does not have a military background and was exempt from Norway's mandatory military service. He has not had any special military training, it adds on its website. He was a youth and adult member of the conservative Fremskrittspartiet (FrP) or Progress Party, VG newspaper reports, remaining involved until 2007. The party's most prominent manifesto pledge is to minimize immigration. His membership was confirmed by a senior party member, Jonas Kallmyr, who is quoted by VG as saying that encountering Breivik was "like meeting Hitler before World War II." The leader of the Progress Party, Siv Jensen, told Norwegian broadcaster TV2 News she was "horrified" to learn that the suspect was a former member of her party. "But this is first and foremost an attack against the entire nation. It has affected all of us," she said, saying that her party members stood in solidarity with the youth movement of the Labour Party. A post in Breivik's name on an online forum, Document.no, from December 2009, talks about non-Muslim teenagers being "in an especially precarious situation with regards to being harassed by Islamic youth." "I know of many hundred occasions where non-Muslims have been robbed, beaten up and harassed by Islamic gangs," the post reads. "I had a best friend between the ages of 12-17 who was a Pakistani, so I was one of the many protected, cool 'potatoes' that had protection. But this also made me see the hypocrisy up close and personal and made me nauseous." Such anti-Islamic sentiment is nothing new in Norway or other European nations, where there has been resistance against increasing numbers of Muslims and their practices. About 3% of Norway's population in 2010 -- 144,000 people -- were Muslim, but that was expected to more than double to 6.5% over the next 20 years, according to a report released earlier this year by The Pew Forum on Religion and Public Life. That is one of the largest percentage increases in Muslim populations across all of Europe, thanks in part to fertility rates significantly higher than those of non-Muslims. Another post in Breivik's name in October 2009 advises "Hans", described as the founder of Document.no, to "develop an alternative to the violent extreme Norwegian Marxist organisations Blitz, SOS Rasisme and Rod Ungdom" -- all left-wing movements in Norway. "The conservatives dare not openly express their viewpoints in public because they know that the extreme Marxists will trump them. We cannot accept the fact that the Labour Party is subsidising these violent "Stoltenberg jugend", who are systematically terrorising the politically conservative," the post reads. He is making a reference to the youth movement of Prime Minister Jens Stoltenberg, who heads the Labour Party. A Twitter account attributed to Breivik by Norwegian newspaper Aftenposten has only one message, dated July 17. "One person with a belief is equal to the force of 100,000 who has only interests," it says, adapting a quote from 19th-century British philosopher John Stuart Mill. Police have not ruled out the possibility that other people may have helped the suspect. "The official questioning is starting now," Roger Andresen, a police official, told reporters during a news conference Saturday. The suspect was cooperating with police, making it clear he wanted to explain himself, Andresen said. Norway's police website said the suspect is currently charged with breaking paragraph 147a of the penal code -- a terrorism offense, with a maximum sentence of 21 years. The statement said he was charged in both the Utoya attack and the bombing of government buildings in Oslo, and that the charges might change. "The suspect has never been arrested by the police before," it said. Two addresses connected to the suspect are being searched, police said. One of them is believed to be an apartment in Oslo and the other a farm in Hedmark. NRK reports that Breivik is registered as having run a company that produced "vegetables, melons, roots and tubers" -- an industry which allows access to large amounts of fertilizer, the broadcaster notes, which can be used for explosives. An employee at a Norwegian agricultural cooperative told CNN that the man identified in media reports as the suspect in Friday's attacks bought six tons of fertilizer from her company in May. Oddmy Estenstad, of Felleskjopet Agr, said she did not think the order was strange at the time because the suspect has a farm, but after the Oslo attack she called police because she knew the material can be used to make bombs. "We are very shocked that this man was connected to our company," said Estenstad. "We are very sad about what happened." More details on the man are sure to emerge in the coming hours and days. But what many Norwegians find hard to comprehend is that the chief suspect in the massacre appears to be one of their own. Stoltenberg stressed that whoever was behind the attacks must be dealt with properly. "It is very important that those who are responsible -- one or several persons -- are sentenced according to Norwegian law, in the Norwegian system of justice," he said. "Norway is a small country but it is a proud country. We are all very close, especially in times like this." CNN's Laura Smith-Spark and Cynthia Wamwayi contributed to this report. ||||| Norwegian massacre gunman was a right-wing extremist who hated Muslims Suspect named by Norwegian media as Anders Behring Breivik Police believe he is not connected to Islamist organisations Claims he boasted online about having talks with English Defence League 'Loner' lived with mother in a wealthy suburb and is well-educated Reports say he attended same school as Norway's crown prince Posted on Twitter: 'One person with a belief is equal to the force of 100,000 who have only interests' Farm business gave him easy access to fertiliser - an ingredient used in bomb-making Police say he is a 'very demanding suspect' Suspect: Norwegian media reported that Anders Behring Breivik has been arrested The man responsible for the massacre in Norway was a member of a Swedish nazi forum which encourages attacks on government buildings. It was also revealed by local police that he had extreme right wing views who hated Muslims. According to Swedish website Expo Anders Behring Breivik is a member of 'Nordisk' which has 22,000 members and focuses on political terrorism. Officers also found a series of raving internet posts by the 32-year-old, who has been charged with two counts of terrorism after gunning down children on the island of Utoya and detonating a bomb in Oslo yesterday. Media reports in Norway described Breivik as a 'loner', who lived with his mother in a wealthy suburb of west Oslo, was well-educated and enjoyed hunting. Only a few days ago he set up a Twitter account and posted a single message: 'One person with a belief is equal to the force of 100,000 who have only interests'. It is attributed to the English philosopher John Stuart Mill, whose concept of liberty justified the freedom of the individual in opposition to unlimited state control. The account appears to have only been set up a few days ago. On his Facebook profile, Breivik describes himself as a Christian and a conservative. It also listed interests such as body-building and freemasonry. Breivik is believed to have grown up in Oslo, and studied at the Oslo School of Management. He later appears to have moved out of the city and established Breivik Geofarm, a company believed to be an organic farm. Arrested: Anders Behring Breivik callously opened fire on groups of teenagers on the island of Utoya Suspect: Further photographs of Anders Behring Breivik, such as this one where he is carrying a weapon, have emerged It specialised in melons and root vegetables. There is speculation among the media in Norway that this may have allowed him easy access to fertiliser, an ingredient used in bomb-making . Along with the farm, he also appears to own a flat in Oslo. Breivik had no military background except for ordinary national service and no criminal record. It is thought that the 32-year-old is a former member of Labour's opposition youth party, Fremskrittspartiet. Police at the home of Breivik, a farm at Ostre Asta near Oslo, where he allegedly planned the entire massacre He is reported to have attended the same Smestad primary school as Norway's crown prince. He is later said to have attended schools in Oslo's Gaustad and the Handelsgymnasium. Classmate Michael Tomola, who knew Breivik from the age of 13 to 16, said: 'He was rather introverted at school, even though he was a good student. I'm very surprised by this. I had a good impression, although he became very engaged in subjects he cared for. He got very extreme about things he cared for.' According the website Atlantic.com, Breivik expressed extremist Islamophobic views on forums and criticised immigration policies. He argued on a Swedish news website that the media were not critical enough about Islam and claimed that Geert Wilders' Party for Freedom in the Netherlands was the only 'true' party of conservatives. Web: Breivik's sole tweet, posted last week, is attributed to the English philosopher John Stuart Mill - whose concept of liberty justified the freedom of the individual in opposition to unlimited state control He said that socialism was breaking down traditions, culture, national identity and other societal structures and that this in turn made society weak and confused. He claimed to admire the Norwegian Second World War hero Max Manus, a highly decorated sailor who was an expert in sinking Nazi ships. It has also been reported he boasted about conversations with unnamed members of the far-right English Defence League and the organisation Stop the Islamification of Europe. He is said to have spoken to them about the success of provocative street actions leading to violence. It is claimed he wrote on a blog two years ago: 'I have on some occasions had discussions with SIOE and EDL and recommended them to use certain strategies. 'The tactics of the EDL are now to 'lure' an overreaction from the Jihad Youth/Extreme-Marxists, something they have succeeded in doing several times already.' Breivik's Facebook profile listed his favourite books as The Trial by Franz Kafka and Nineteen Eighty-Four by George Orwell. His favourite TV show was named as Dexter - a series about a Miami police forensics expert who moonlights as a serial killer of criminals whom he believes have escaped justice. Police officer Roger Andresen said today: 'He is clear on the point that he wants to explain himself.' Andersen said the suspect posted on websites with Christian fundamentalist tendencies. He did not describe the websites in any more details. Crime scene: The 32-year-old Norwegian is said to have used this white van to drive onto the island of Utoya National police chief Sveinung Sponheim said he was talking to them and has admitted to firing weapons on the island. It was not clear if he had confessed to anything else he is accused of. Police said he retained a lawyer, who did not want to be named 'He has had a dialogue with the police the whole time, but he's a very demanding suspect,' Sponheim said. He also told public broadcaster NRK that the suspected gunman's Internet postings 'suggest that he has some political traits directed toward the right, and anti-Muslim views, but if that was a motivation for the actual act remains to be seen'. Six foot tall and blond Breivik is reported to have arrived on the island of Utoya dressed as a policeman and opened fire after beckoning several young people over in his native Norwegian tongue. Reports suggest he was also seen loitering around the site of the bomb blast in Oslo two hours before the island incident. Suspect: The 32-year-old Norwegian Anders Behring Breivik, who has been arrested after the attacks Police said later that the suspect had right-wing and anti-Muslim views, but the motive for the attacks was unclear. The Norwegian daily Verdens Gang quoted a friend as saying he became a rightwing extremist in his late 20s. It said he expressed strong nationalistic views in online debates and had been a strong opponent of the idea that people of different cultural backgrounds can live alongside each other. An official said the gunman used both automatic weapons and handguns, and that there was at least one unexploded device at the youth camp that a police bomb disposal team and military experts were working on disarming. Some 92 are believed to have been killed - seven in Oslo and 84 on Utoya Island, 50 miles north of the capital. Initially it was not known what were the motives of the gunman and architect of the car bomb - whether they or the single person had been radicalised and was part of a militant Muslim group waging Jihad or was trying to further a home-grown political cause. But it now appears Breivik was behind both attacks, a fact that it took police hours to realise as the mayhem ensued. The incidents come as social tensions with Norway heighten in recent months over the country’s perceived stance on Islamic issues. Fatal: Seven people were killed in the Oslo bomb blast (pictured) Though a long-standing Nato member, Norway has not attracted many enemies because it has tended to stay out of international conflicts. However, it has recently increased its military presence in Muslim countries such as Afghanistan or Libya, a move bound to anger fanatics. There was anger among some of the 150,000 Muslims living in Norway when a newspaper reproduced the controversial Danish cartoons of the Prophet Mohammad in January last year. Last night ‘Helpers of the Global Jihad’ posted a message on the internet claiming the bombing was ‘only the beginning’ of the retaliation over the cartoons. But this has been dismissed by some commentators as a publicity stunt. Other Scandinavian countries have faced radical Islamic attacks in the past. Violence erupted in Denmark after a newspaper published a cartoon of the Prophet wearing a turban in the shape of a bomb in 2005. And last December an Islamic suicide bomber, who was radicalised in Britain, set off a bomb in Stockholm. Police would not speculate on who was responsible for the attack or whether international groups were involved. But the country is also in the midst of grappling with a homegrown terror plot linked to al-Qaeda. Two suspects are in jail awaiting charges. Last week, a Norwegian prosecutor filed terror charges against an Iraqi-born cleric for threatening Norwegian politicians with death if he is deported from the Scandinavian country. The indictment centred on statements that Mullah Krekar - the founder of the Kurdish Islamist group Ansar al-Islam - made to various news media, including American network NBC. Jihadist groups have also made recent threats to Norway over plans to expel Mullah Krekar, the founder of the Kurdish Islamist group Ansar al-Islam. Norway's support of NATO's mission in Libya also earned it enemies, Bob Ayers, a former U.S. intelligence officer, told AP. 'Norwegians are in Afghanistan. They're in Tripoli. They reprinted the cartoons,' he said. Many intelligence analysts said they had never heard of Helpers of Global Jihad, which took initial credit. Ansar al-Islam also took credit on some jihadist web sites. And Ayers said it appeared more than one person was involved. Wrecked: The blast in Oslo was outside a government office Asked at a press conference in Tripoli about Libya's reaction to the events in Oslo, government spokesman Moussa Ibrahim said, 'We never support any acts of terrorism whatsoever.' But he suggested NATO's policies could have prompted the attack, saying, 'NATO is planting terrorism in the hearts of many. This is unfortunate and sad.' Authorities in Norway and other Scandinavian countries have focused on anti-terrorism tactics that frustrate countries like the U.S. that are more aggressive about making arrests. Scandinavian authorities fight terrorism by disrupting plots, sometimes telling suspects they know what they're up to, and warning them of the consequences. Terror convictions are also difficult to get because of scepticism in Scandinavian courts toward cases built on intent - as most terrorism trials are - and a demand for more evidence than in the U.S. and many other places. Europe has been the target of numerous terror plots by Islamist militants. The deadliest was the 2004 Madrid train bombings, when shrapnel-filled bombs exploded, killing 191 people and wounding about 1,800. A year later, suicide bombers killed 52 rush-hour commuters in London aboard three subway trains and a bus. And in 2006, U.S. and British intelligence officials thwarted one of the largest plots yet - a plan to explode nearly a dozen trans-Atlantic airliners. In October, the U.S. State Department advised American citizens living or travelling in Europe to take more precautions following reports that terrorists may be plotting attacks on a European city. Some countries went on heightened alert after the May 2 killing of Osama bin Laden. Intelligence analysts said they doubted the attack was linked to bin Laden's death. ||||| As the death toll mounts in the most horrific violence Norway has seen since World War II, local police have arrested the suspected perpetrator of both the bombing and the shooting at a children's summer camp. His name is Anders Behring Breivik, a 32-year-old man reportedly spotted at the scene of the bombing. Police believe he was acting alone. According to multiple news reports in Norway and Sweden, Brievik belonged to Oslo's extreme right wing. He was a frequent poster in Norwegian right-wing online forums, the accounts said, and had two guns registered to his name. He also appears to have launched a social media presence just days before the attacks. In Breivik's Facebook account, now removed, the suspect identifies himself as a Christian conservative. However, that was far from his only interest. Breivik also listed himself as a fan of World of Warcraft, Modern Warfare 2, bodybuilding and stock analysis. The account, which appeared to have only been started last week, was mostly filled with music videos. Breivik, who listed himself as single, said he had completed "3,000 hours of study in micro and macro finance, religion." Breivik appears to have started a Twitter account on the same day as he launched his Facebook presence, July 17. The account, which has not been removed, has just one tweet to its name. It's a quote from the philosopher John Stuart Mill: "One person with a belief is equal to the force of 100 000 who have only interests." The attacks may well have been politically motivated. The bombing took place outside a building where the Prime Minister, who wasn't present, has an office. And the purpose of the summer camp on the island of Utoya was to teach teenagers about politics.

– The snapshot emerging of 32-year-old Anders Behring Breivik, the suspect in Norway's twin attacks: He is a self-described nationalist who posted in extreme right forums in Norway. He often complained about Islam ("I know of many hundred occasions where non-Muslims have been robbed, beaten up and harassed by Islamic gangs" reads one sample) and Norway's immigration policy. He is thought to be a single, well-educated loner who lived with his mother in Oslo. He ran some kind of a farm, which gave him access to large amounts of fertilizer that could be used to make bombs. According to his now-removed Facebook profile, he likes Dexter, the video games World of Warcraft and Modern Warfare 2, body-building, and hunting. His favorite books are 1984 and Kafka's the Trial. His lone post on Twitter is a John Stuart Mill quote: "One person with a belief is equal to the force of 100,000 who have only interests." See more at CNN, Mashable, the Daily Mail, and the Huffington Post. (With the death toll approaching 100, police aren't ruling out a second shooter.)

variability of the complex systems enable those systems to respond to different environmental and intrinsic inputs in a whole spectrum of reactions and effects . heart rate variability reflects the possibility of the cardiovascular system to adapt to the whole spectrum of different more or less demanding tasks and situations . heart rate variability is reduced in many pathological conditions and most altered after myocardial infarction and in the failing heart , besides the other pathological conditions ( 1 , 2 ) . it is an important predictor in risk stratification and early prediction of cardiac autonomic neuropathy ( 3 , 4 ) . the importance of the monitoring of heart rate variability during surgical procedures and anaesthesia have been recognized . poincar plot is a visual presentation of time series of signal and has been used for quantifying of the parameters of heart rate variability ( 5 ) . sd1 represents the standard deviation of the variability of the signal in short terms , while sd2 represents standard deviation of the long term rr interval ( 6 ) . proposed physiological explanations of the significance of parameters are listed elsewhere ( 1 , 7 ) . there have been many clinical trials performed aiming to assess if there could be found significant differences of the effects of different anaesthetic agents ( 8,9,10 ) . besides two main linear methods of analysis ( time domain indices and frequency - domain indices ) there have been many new nonlinear methods of analysis evolving . some linear measures appropriate for short - time recordings are shown in the table 1 . linear measures of hrv in time - domain and frequency domain analysis ( modified from heart rate variability : standards of measurement , physiogical interpretation and clinical use circulation 1996 ) surgery and anaesthetics influence significat changes of homeostasis what is reflected in changes of haemodynamic variables ( 9 , 10 , 11 ) . after obtaining approval of ethics committee and informed consent sixtyfour patients of asa i and asa ii status , who were scheduled for elective abdominal surgery were randomized to two groups : group 1(balanced anaesthesia with inhalatory anaesthetic sevoflurane ) and group 2 ( balanced anaesthesia with inhalatory anaesthetic isoflurane ) . patients with cardiovascular disease , diabetes mellitus , arrhythmias , endocrine and neurologic conditions and therapy with medications that may affect heart rhythm were not included in the trial . fortyfive minutes before induction of anaesthesia patients were given midazolam ( dormicum , f. hoffman - la roche ltd basel , switzerland ) in the dosis of 7,5 mg . in the preinduction period patients were given opioid fentanyl 2gkg-1 ( fentanyl janssen - cilag , belgium ) . five minutes later induction was started by thiopentone ( thiopental sodium , rotexmedica gmbh germany ) which was administered in the doses range of 4 - 6 mg kg-1 . upon induction of anaesthesia and ventilation by face mask for five minutes orotracheal intubation was performed after administration of tracrium ( tracrium , glaxosmithkline uk ) in the dosis of 0,5 mg kg -1 , and later on maintenance of anaesthesia was performed by balanced technique . the recordings of electrocardiogram , recorded by holter ecg recorder ( trillium 3000 holter system , forest medical , usa ) , and after excluding artifacts were put to analysis by trillium hrvfreq 4.01 , 2006 software ( forestmedical , llc , east syracuse , usa ) . upon obtaining time series of the signal by exporting nn intervals it was possible to perform analysis with kubios hrv software v.2.1 , 2012 ( biosignal analysis and medical imaging group , department of applied physics , university of eastern finland , kuopio , finland ) for nonlinear indices . power spectra were determined in nine 5-minutes segments , in preinduction period - tpre , after administration of opioid -t1 , after induction t2 , after orotracheal intubation - t3 period , during balanced anaesthesia with administration of two different inhalation anaesthetics : sevoflurane or isoflurane (t4-t7 ) , and in postoperative period two hours after emergence tpost . data were presented as mean values of logarhitmic values of the total power spectrum values ( tp ) , mean values of the logarhitmic(nautural logarhitm ) values of power spectrum of low frequencies ( lf ) , mean values of the logarithmic values of power spectrum of high frequencies ( hf ) . statistical analysis was performed with 2-test for gender , student t - test for age , mann - whitney test for bmi data , and one - way repeated analysis of variance ( anova ) for parameters of hemodynamic and heart rate variability parameters . analysis was performed by statistical package ibm statistics spss v22.0 ( chicago , illinois , usa ) . results of analysis of demographic data have not shown statistically significant differences between the groups ( table 2 ) . results of the analysis of haemodynamic parameters have shown variations of hemodynamic variables in both groups , with slight decrease of the values of mean arterial pressure in both groups after administration of induction agent thiopental and changes in heart rate , but there was no statistically significant differences ( table 3 ) . demographic data . results are presented as means and standard deviation in brackets logarithmic values ( native logarithm ) of the tp , lf , hf spectra and sd1 and sd2 value . analysis of the changes of the values of the power of total spectrum ( tp ) , low frequency ( lf ) and high frequency ( hf ) spectra , demonstrated alterations of the power of all spectral parameters in both groups , which was most visible after induction , without statistically significant differences between the groups . results of anlysis of hamodynamic parameters are shown in the diagrams in figure 1 , results of the analysis of heart rate variability and poincar plot descriptors ( sd1 and sd2 ) in figure 2 , while some of the diagrams of poincar plot from different periods of perioperative time are shown in figure 3 . diagram of hamodynamic parameters ( mean arterial pressure and heart rate ) diagram of the spectral components and nonlinear geometric measures in time periods : a ) logarithmic values of tp spectrum , b ) logaritmic values c ) logaritmic values of hf spectrum , d ) values of sd1 and sd2 for both groups poincar plot in different perioperaive periods in different subjects : a)preinduction period , b)immediately after induction,(c , d , e , f , g ) intraoperatively , h ) in the early postoperative period stress reaction to surgical procedure and general anaesthesia have strong impact on the dynamic stability of the variability of physiological functions . there have been numerous published papers on the topic of possible influence of different anaesthetic agents on the parameters of heart rate variability ( 8,9,10,11,12 ) . coworkers who studied the effects of induction of anaesthesia by thiopentone have shown decrease of the power of total spectrum and individual components of the spectrum but no significant changes in the relationship between the spectral components , what suggested that there were no changes in the balance of autonomic nervous system(9 ) . and coworkers also examined the effects of three induction anaesthetic techniques on heart rate variability ( 10 ) . they have shown that induction of anaesthesia both with thiopental and nitrous oxide and etomidate and nitrous oxide were associated with decrease of the powers of total spectrum , low frequency and high frequency spectra , with more evident decrease of low frequency spectrum ( lf ) with thiopental in regard to etomidate ( 10 ) . tanaka s. and coworkers investigated effects of different inhalation anaesthetics and did not find sympathetic activation in patients who were administered sevoflurane unlike to those who received desflurane and isoflurane ( 11 ) . in the trial performed by kato m. and coworkers , who investigated the effects of inhalation anaesthesia with isoflurane with different inhalatory concentrations it was shown that all components of the heart rate variability were decreased in dose depnedent manner , but with more effects on the high - frequency and mid - frequency components ( 12 ) . ebert tj et al . described that sevoflurane could have such pharmacological profile that does not elict profound heart rate changes ( 13 , 14 ) . variations of heart rate in children who were administered sevoflurane as inhalation anaesthesia during induction could be described as withdrawal of parasympathetic tone ( 15 ) . results of our trial have shown variations of hemodynamic variables in both groups , with decrease of the values of mean arterial pressure in both groups after administration of induction agent , thiopental and consecutive changes in heart rate , with no statistically significant difference between the groups . analysis of the changes of the logarhitmic values of power of total spectrum , of low frequency ( lf ) and high frequency ( hf ) spectra , has shown reductions of the power of all spectral parameters in both groups , with most visible decrease after induction , without statistically significant differences between the groups . analysis of the descriptors of poincar plot , sd1 and sd2 demonstrated variations of the values of the descriptors sd1 and sd2 without statistically significant differences between the groups . short- term heart rate variability parameters measured in frequency - domain , in perioperative period in patients who underwent elective abdominal surgical procedures of moderate stress while general anaesthesia was performed using balanced technique in which the induction agent was the same ( thiopentone ) while the inhalatory components were two different anaesthetic agents : sevoflurane and isoflurane , have shown variable changes of all spectral components of the total spectrum of heart rate variability in both groups . the most visible changes of hrv parameters were evident in periinduction period , without statistically significant differences between the groups .

introduction : heart rate variability which denotes variations of the length of consecutive heart cycles has been suggested to reflect the modulation of heart rate by autonomic nervous system.methods:sixty four patients of asa i and asa ii status scheduled for elective abdominal surgical procedures were randomly allocated to group 1 and group 2 . premedication and induction of anaesthesia were performed with same agents . after orotracheal intubation maintenance of balanced anaesthesia was based on administration of same induction agents , opioids and muscle relaxant while delivery of gaseous mixture with sevoflurane in the group 1 ( n=32 ) and isoflurane in the group 2(n=32 ) . haemodynamic parameters were monitored in perioperative and electrocardiogram was recorded by holter ecg recorder , while the analysis of the parameters were performed by corresponding softwares . data were presented as mean values of logarithmic ( natural logarithm ) values of the power of the total spectrum of heart rate variability(tp ) , mean values of the logarithmic values of low frequency band ( lf ) , mean values of the logarithmic values of high frequency range(hf ) , and mean values of sd1 and sd2 parameters.results:analysis of the values of hemodynamic parameters has shown changes of haemodynamic parameters during perioperative period without significant statistical differences between the groups . analysis of the logarhitmic values of parameters of heart rate variability of frequency domain has shown changes of the total spectrum power and lf and hf spestra with variations of the values of total power spectrum and individual components of the spectrum of heart rate variability during the balanced anaesthesia with administration of two different inhalation anaesthetics , without statistically significant differences between the groups.conclusion:the results have shown that during balanced anaesthesia with two different inhalation anaesthetics there are variations of haemodynamic variables and parameters of heart rate variability without statistically significance that could show the difference between the groups and different agents administered .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Continued Free Association with Palau Act of 2012''. SEC. 2. APPROVAL OF AGREEMENT. Title I of Public Law 99-658 (48 U.S.C. 1931 et seq.) is amended by adding at the end the following: ``SEC. 105. COMPACT 15TH ANNIVERSARY SECTION 432 REVIEW AGREEMENT. ``(a) In General.--The Agreement and appendices signed by the United States and the Republic of Palau on September 3, 2010 (in this section referred to as the `Agreement'), in connection with section 432 of the Compact of Free Association between the Government of the United States of America and the Government of Palau (48 U.S.C. 1931 note; Public Law 99-658) (in this section referred to as the `Compact of Free Association'), are approved-- ``(1) except for the extension of Article X of the Agreement Regarding Federal Programs and Services, and Concluded Pursuant to Article II of Title Two and section 232 of the Compact of Free Association; and ``(2) subject to the provisions of this section. ``(b) Funding Provisions.-- ``(1) Infrastructure maintenance.--The amounts to be provided by the United States and Palau in fiscal year 2011 under section 2(a) of the Agreement shall be provided in fiscal year 2013, in addition to the amounts otherwise to be provided under that section in that fiscal year. ``(2) Fiscal consolidation fund.--The amounts to be provided by the United States under section 3 of the Agreement in fiscal years 2011 and 2012 shall be provided in fiscal years 2012 and 2013, respectively, and the amount so provided by the United States under that section in fiscal year 2012 shall be reduced by $411,000. ``(3) Infrastructure projects.--The amounts to be provided by the United States under section 5 of the Agreement in fiscal years 2011 through 2016 shall be provided in fiscal years 2012 through 2017, respectively. ``(c) Approval of Amendments to Compact Subsidiary Agreements.-- Congress consents to the amendments to the Compact subsidiary agreements referred to in sections 7 and 8 of the Agreement . ``(d) Application of Related Law.--Section 105(f)(1)(B)(ix) of the Compact of Free Association Amendments Act of 2003 (48 U.S.C. 1921d(f)(1)(B)(ix) shall be applied by substituting `2024' for `2009'. ``(e) Authorization of Appropriations.-- ``(1) Postal services.--There are authorized to be appropriated to the Department of the Interior $1,500,000 for each of fiscal years 2012 through 2024 for postal services related to Palau, the Federated States of Micronesia, and the Marshall Islands, to remain available until expended. The Department of the Interior may transfer funds made available pursuant to this paragraph to the United States Postal Service so long as domestic postage may be used for mail to Palau, the Federated States of Micronesia, and the Marshall Islands. ``(2) Continuation of other appropriations.--Appropriations to the Federal entities referred to in paragraphs (1), (3), and (4) of section 221(a) of the Compact of Free Association, and the successors to such Federal entities, to which appropriations have been made available in fiscal year 2011, may be made through fiscal year 2024 to carry out the purposes of those paragraphs, and shall remain available until expended. ``(3) Full faith and credit.--Section 236 of the Compact applies to the commitments of the United States under sections 1, 2(a), 3, 4(a), and 5 of the Compact Review Agreement, and to the amounts necessary to conduct the audits required by Appendix D to the Compact Review Agreement, to the same extent as such section 236 applies to the Compact. Section 215 of the Compact shall be applied to such commitments and amounts by substituting `2011' for `1981'. ``(f) Oversight and Report to Appropriate Congressional Committees.-- ``(1) Finding.--The Congress finds that the Government of Palau is eligible for certain United States domestic programs. ``(2) Annual report.-- ``(A) Report.--The Secretary of the Interior, because of the Secretary's jurisdiction with respect to the administration of financial assistance under the Compact, shall, not later than March 1 of each year, submit to the Committee on Energy and Natural Resources of the Senate and to the Committee on Foreign Affairs and the Committee on Natural Resources of the House of Representatives, a report on the use and effectiveness of financial, technical, and other assistance provided to Palau under any United States domestic program described in paragraph (1). ``(B) Consultation.--In preparing each report required by subparagraph (A) with respect to a domestic program, the Secretary of the Interior shall consult with the Federal agency or agencies with jurisdiction over that domestic program.''. SEC. 3. OFFSETS. (a) Repeal of Prior Authorization for Civil Administration of Trust Territory of the Pacific Islands.--Section 3 of the Act of June 30, 1954 (68 Stat. 330, 82 Stat. 1213, chapter 423) is repealed. (b) Global Health Programs.--Chapter 1 of part I of the Foreign Assistance Act of 1961 (22 U.S.C. 2151 et seq.) is amended by adding at the end the following: ``SEC. 136. LIMITATION ON USE OF FUNDS. ``(a) Limitation.--None of the funds made available to carry out this chapter or chapter 10 for global health activities for fiscal year 2012 and each fiscal year thereafter through fiscal year 2024 may be used to provide assistance to the People's Republic of China for such activities. ``(b) Amount of Reduction.--The total amount that may be obligated for global health activities for a fiscal year in subsection (a) is $2,000,000 less than the total amount made available for such activities for such fiscal year. ``(c) Applicability.--This section applies notwithstanding any other provision of law enacted after the enactment of this section.''. (c) Climate Change Funds.--Chapter 4 of part II of the Foreign Assistance Act of 1961 (relating to the economic support fund) (22 U.S.C. 2346 et seq.) is amended by adding at the end the following: ``SEC. 535. LIMITATION ON USE OF FUNDS. ``(a) Limitation.--None of the funds made available to carry out this chapter for climate change activities for fiscal year 2012 and each fiscal year thereafter through fiscal year 2024 may be used to provide assistance to the People's Republic of China for such activities. ``(b) Amount of Reduction.--The total amount that may be obligated for climate change activities for a fiscal year in subsection (a) is $4,500,000 less than the total amount made available for such activities for such fiscal year. ``(c) Applicability.--This section applies notwithstanding any other provision of law enacted after the enactment of this section.''. (d) Prohibition on Funding for Development Innovation Ventures (DIV) Program.--Section 667 of the Foreign Assistance Act of 1961 (22 U.S.C. 2427) is amended by adding at the end the following: ``(c)(1) None of the funds made available for fiscal years 2012 and 2013 to the United States Agency for International Development may be used for the Development Innovation Ventures (DIV) program or any successor program. ``(2) The total amount that may be obligated by the United States Agency for International Development for a fiscal year in subsection (a) is $28,200,000 less than the total amount made available for such Agency for such fiscal year. ``(3) This subsection applies notwithstanding any other provision of law enacted after the enactment of this subsection.''. (e) IMET.--Section 542 of the Foreign Assistance Act of 1961 (22 U.S.C. 2347a) is amended-- (1) by striking ``There are authorized'' and inserting the following: ``(a) In General.--There are authorized''; and (2) by adding at the end the following: ``(b) Limitation on Use of Funds.-- ``(1) Limitation.--None of the funds made available to carry out this chapter for fiscal year 2012 and each fiscal year thereafter through fiscal year 2024 may be used to provide assistance to Argentina. ``(2) Amount of reduction.--The total amount that may be obligated under this chapter for a fiscal year in subsection (a) is $4,500,000 less than the total amount made available for such activities for such fiscal year. ``(3) Applicability.--This subsection applies notwithstanding any other provision of law enacted after the enactment of this subsection.''. (f) UNESCO.--Chapter 3 of part I of the Foreign Assistance Act of 1961 (22 U.S.C. 301 et seq.) is amended by adding at the end the following: ``SEC. 308. LIMITATION ON USE OF FUNDS. ``(a) Limitation.--None of the funds made available for fiscal year 2012 and each fiscal year thereafter through fiscal year 2024 for United States assessed contributions to the United Nations may be used for such contributions to the United Nations Educational, Scientific and Cultural Organization. ``(b) Amount of Reduction.--The total amount that may be obligated for a fiscal year in subsection (a) for United States assessed contributions to the United Nations is $4,500,000 less than the total amount made available for such contributions for such fiscal year. ``(c) Applicability.--This section applies notwithstanding any other provision of law enacted after the enactment of this section.''. (g) United States Institute of Peace.--Section 1710 of the United States Institute of Peace (22 U.S.C. 4609) is amended by adding at the end the following: ``(e) Limitation on Obligation of Funds.-- ``(1) Limitation.--The total amount that may be obligated to carry out this title for fiscal year 2012 and each fiscal year thereafter through fiscal year 2024 is $6,811,000 less than the total amount made available for such purpose for such fiscal year. ``(2) Applicability.--This subsection applies notwithstanding any other provision of law enacted after the enactment of this subsection.''.

Continued Free Association with Palau Act of 2012 - Approves, with specified exceptions, the agreement and appendices signed by the United States and the Republic of Palau on September 3, 2010, in connection with the Compact of Free Association between the United States and Palau. Extends funding for: (1) infrastructure maintenance and projects, (2) the Fiscal Consolidation Fund (at a reduced level for FY2012), and (3) specified federal entities. Assents to specified amendments to the Compact subsidiary agreements. Authorizes appropriations to the Department of the Interior for postal services related to Palau, the Federated States of Micronesia, and the Marshall Islands. States that Congress finds that Palau is eligible for certain U.S. domestic programs. Prohibits specified funds from being used for: (1) assistance to China or Argentina, (2) the development innovation ventures program, and (3) contributions to the United Nations Educational, Scientific and Cultural Organization (UNESCO).

high heels are recognized as a part of fashion and have been developed into various designs1 and have become very popular among women . women under 30 years of age prefer higher heels even though they wear them for extended periods2 . high heels are preferred by women for esthetic reasons , but if they are worn for a long time , they cause back pain by fatiguing the lumbar muscles3 . nevertheless , according to research , women in their 20 s , prefer to wear 7 cm heels4 . in general , high heels over 6 cm increase lumbar muscle fatigue resulting in high back pain3 . the muscle activity of the erector muscle of the spine while wearing high heels increased muscle activity5 , 6 . this research has demonstrated that patients with back pain have higher muscle activity than people without back pain7 . this indicates a higher risk of back pain when people wear high heels for extended periods . the cost of treating back pain in our modern society is expensive , and it is quite common8 . in addition , people with back pain tend to avoid physical activities in order to minimize pain , which causes extensor muscular atrophy and deterioration , resulting in increased pain over time10 . the above research results indicate that deterring the weakening of extensor muscles and improving muscular strength can prevent or reduce back pain . therefore , recent studies regarding the effects of strength exercise for muscles around the waist have been performed , and in particular , studies on the effect of lumbar stabilization exercises have been performed as therapeutic approach for deep muscles of the waist with the goal of reducing or preventing back pain . brill and couzens11 mentioned that lumbar stabilization exercise is effective for balancing posture and strengthening of paraspinal muscles . among muscles involved in lumbar stabilization , multifidus and transversus abdominis contract earlier than other muscles in all the movements of the human body , and secure stabilization of the spine and thus , lumbar stabilization exercise not only increases stabilization of the spine and pelvis by strengthening the deep muscles of the trunk13 . lumbar stabilization exercise includes pelvic tilting , abdominal drawing , bridge exercise and four - point kneeling15 . bridge exercise can retrain fine motor and gross motor coordination in the proper ratio . this results in stabilization of the trunk and increase of muscular strength of the lower limbs and hips . kong18 claimed that while the bridge exercise in prone position increases abdominal muscle activity in the standing posture more than bridge exercise in supine or bridge exercise on the therapeutic ball , it decreases muscle activity of the erector muscle of the spine . on the other hand , there are not enough studies on whether lumbar stabilization exercise has a direct effect on actual daily life movement . insufficient studies have been performed on the effect of paraspinal muscles on muscular strength while lumbar stabilization exercises are performed . because the purpose of exercise is to perform daily life activities functionally by improving muscular strength , it is very important to understand the functional change of paraspinal muscles during functional activities after lumbar stabilization exercises are performed . therefore , the purpose of this study is to find out the effects of bridge exercises which are regarded as effective as lumbar stabilization exercises on paraspinal muscles during functional activities . in particular , this study was intended to demonstrate how paraspinal muscles are affected in women who do a significant amount of walking in high heels . the subjects of this study were 30 female students who go to s university located in busan . the subjects understood the purpose and intention of this subject and signed written consent forms . women were chosen who had not previously experienced back pain , nervous system diseases , pain or hypofunction on upper and lower limbs , or undergone surgical treatment in the previous 6 months . the subjects were randomly categorized into groups of 10 in bridge exercise in supine position , 10 in bridge exercise in prone position , and 10 in control group . the average age of subjects in the bridge exercise in supine group was 21.8 , the average height was 159.8 cm , and the weight was 56.4 kg . the average age of subjects in the bridge exercise in prone group was 21.5 , the average height was 164.9 cm , and the weight was 57.8 kg . the average age of subjects in the control group was 22.2 , the average height was 161.5 cm , and the weight was 55.3 kg . there was no difference in general characteristics among the groups ( table 1table 1.the general characteristic of subjectsvariablesbes ( n=10)bep ( n=10)control ( n=10)age ( years)21.8 0.821.5 1.022.2 1.0height ( cm)159.8 4.2164.9 6.6161.5 6.0weight ( kg)56.4 5.957.8 10.855.3 9.6mean sd . bes : bridge exercise in supine ; bep : bridge exercise in prone ) . bes : bridge exercise in supine ; bep : bridge exercise in prone in this study , surface electromyogram ( 4d - mt & emd-11 , relive , korea ) was used for measurement of muscle activity . to measure muscle activity of paraspinal muscles , we revealed the body parts for electrode pad placement , and then removed hair and wiped the skin to reduce skin resistance against surface electromyography signals . this electrode is disposable , soft gel type , 30 mm in external diameter , 22 mm electrode size , round in shape and with a conductivity of ag / agcl . the attachment part of the surface electrode was the paraspinal muscle , which is 2 cm apart to the left and the right from spinous process of c7 , t7 , and l519 . the sampling rate of the electromyogram signal was set at 1,000 hz , 60 hz analog notch filter , and 20500 hz digital band pass filters were used to extract the electromyogram signal . after sampling electromyogram signal with 1,000 samples / sec , we digitized it by using integrated analysis program . the average value of rms ( root mean square ) was used for the paraspinal muscle activity . after linear filtering data value for 5 seconds , rms average value for 3 seconds excluding the first and last seconds was calculated . the high heels used in this study were set back heels with 7 cm height according to the standard suggested by3 . we researched the effect of bridge exercise by measuring muscle activity of paraspinal muscles while the subjects walked in high heels before and after bridge exercises . for measuring the strength of abdominal muscles , all subjects were asked to lie down , to bend their knees at 90 and to put their feet on the ground . next , they stretched their arms forward and lifted their upper trunk until their fingertips barely touched their knees , and maintained the position . we measured how many seconds transpired until they could nt stay the motion , and the value was recorded and compared . the posture of the bridge exercise in supine position with the abdominal muscle drawing - in method applied started when the subjects lay straight , bent their knee joints at 90 , spread both feet and knees at shoulder width , put their soles parallel on the ground , and put both hands comfortably parallel on the ground . when the tester said raise your hips , the subjects raised their pelvis . when they heard when the instruction put your hips down was given , they put their pelvis down and rested for 30 seconds . the tester instructed the subjects to exhale while lowering their abdomen toward the ground during the exercises . five repetitions of this process were considered as 1 set , and a total of 3 sets were performed . the posture of the bridge exercise in prone position began with the subjects lying face down with their elbows bent at 90. they supported their body weight by using forearm and toes , their neck was drawn slightly , and they stared straight ahead . stay , they maintained their position for 30 seconds . when they heard put down , they put their body back down and had a 30 second break . to reduce errors of posture during exercise , they stayed in the neutral posture to prevent bending the lumbar area . five repetitions of this process were considered as 1 set , and a total 3 sets were performed . data analysis was performed using one - way anova to demonstrate the different general characteristics among the groups and the difference of muscle strength and paraspinal muscle activity . subsequently paired comparison t - test was performed to find out whether the bridge exercise had an effect on muscle strength of the straight muscles of the abdomen and on paraspinal muscle activity . to demonstrate the difference of change amount among the groups , analysis of covariance ( ancova ) the muscle strength of rectus abdominis muscle before bridge exercises the in supine group was 26.6 seconds , the prone group was 31.7 seconds , and the control group was 36.5 seconds . the paraspinal muscle activity of cervical spine , the bridge exercise in supine group was 91.1mv , the bridge exercise in prone group was 84.6mv , and the control group was 81.2mv . there was no significant difference in paraspinal muscle activity of cervical spine among the groups . the paraspinal muscle activity of thoracic parts , the bridge exercise in supine group was 119.8mv , the bridge exercise in prone group was 124.1mv , and the control group was 126.3mv . there was no statistically significant difference in paraspinal muscle activity of thoracic parts among the groups . the paraspinal muscle activity of lumbar parts , the bridge exercise in supine group was 86.9mv , the bridge exercise in prone group was 79.6mv , and the control group was 94.9mv . there was no statistically significant difference in paraspinal muscle activity of lumbar parts among the groups ( table 2table 2.the difference of muscle strength and muscle activity among the groupsvariablesbesbepcontrolstrength ( sec)26.6 16.831.7 22.436.5 24.7activity ( mv)cervical91.1 31.984.6 30.381.2 26.2thoracic119.8 31.1124.1 36.4126.3 29.5lumbar86.9 33.079.6 25.494.9 36.3mean sd . bes : bridge exercise in supine ; bep : bridge exercise in prone ) . bes : bridge exercise in supine ; bep : bridge exercise in prone the change of muscle strength of rectus abdominis muscle after exercise , the bridge exercise in supine group increased muscle strength from 26.6 seconds before exercise to 34.4 seconds after exercise , which showed a significant increase ( p<0.05 ) . the bridge exercise in prone group significantly increased muscle strength from 31.7 seconds before exercise to 42.5 seconds after exercise , which showed a significant increase ( p<0.05 ) . the bridge exercise in the control group slightly decreased from 36.5 seconds to 34.9 seconds after exercise , but no statistically significant difference was demonstrated . the comparison of aspect of change among the three groups showed that while the bridge exercise in supine group and the bridge exercise in prone group increased , the control group decreased ( p<0.05 ) ( table 3table 3.the changes of rectus abdominis muscle strength after bridge exercise ( unit : sec)grouppre - exercisepost - exercisebes*26.6 16.834.4 19.0bef*31.7 22.442.5 24.6control36.5 24.734.9 22.9mean sd . bes : bridge exercise in supine ; bep : bridge exercise in pronebes = bep > control by ancova test*p<0.05 ) . regarding the paraspinal muscle activity of cervical spine while the subjects were walking on the treadmill with high heels , the bridge exercise in the supine group decreased from 91.1mv before exercise to 89.6mv after exercise ; the bridge exercise in the prone group also decreased from 84.6mv before exercise to 84.2mv after exercise with no significant statistical difference ; and the control group decreased from 81.2mv before exercise to 80.1mv after exercise , with no significant statistical difference as well . the comparison of aspect of change among the three groups in the paraspinal muscle activity of cervical spine showed no statistical difference among the groups . regarding the paraspinal muscle activity of thoracic parts , the bridge exercise in supine group significantly decreased from 119.8mv before exercise to 89.5mv after exercise ( p<0.05 ) , and the bridge exercise in the prone group also significantly decreased from 124.1mv before exercise to 93.7mv after exercise ( p<0.05 ) . however , the control group decreased from 126.3mv before exercise to 112.6mv after exercise , but there was no statistical difference . the comparison of aspect of change among the three groups in the paraspinal muscle activity of thoracic parts all showed a decreasing tendency , but there was no statistical difference among the groups . regarding the paraspinal muscle activity of lumbar parts , the bridge exercise in supine group decreased from 86.9mv before exercise to 83.0mv after exercise , and the control group decreased from 94.9mv before exercise to 94.5mv after exercise , but both groups showed no statistical difference . however , the bridge exercise in prone group significantly decreased from 79.6mv before exercise to 54.7mv after exercise ( p<0.05 ) . the comparison of aspect of change among the three groups in the paraspinal muscle activity of lumbar parts showed that the bridge exercise in the prone group decreased more than the control group ( p<0.05 ) ( table 4table 4.the changes of spinal muscle activity after bridge exercise ( unit : mv)areagrouppre - exercisepost - exercisecervicalbes91.1 31.989.6 31.9bep84.6 30.384.2 22.3control81.2 26.280.1 27.4thoracicbes*119.8 31.189.5 21.1bep*124.1 36.493.7 35.2control126.3 29.5112.6 34.8lumbarbes86.9 33.083.0 30.2bep*79.6 25.454.7 14.5control94.9 36.394.5 35.7mean sd . bes : bridge exercise in supine ; bep : bridge exercise in pronebep > control by ancova test*p<0.05 ) . bes : bridge exercise in supine ; bep : bridge exercise in prone bes = bep > control by ancova test mean sd . bes : bridge exercise in supine ; bep : bridge exercise in prone bep > control by ancova test high heels have become popular for their aesthetic aspect , but wearing them for a long time can pose a risk for fatigue and pain in the lower back muscles3 . the height of the heels can affect changes in the position of the body joints and center of gravity , which requires a large amount of kinetic and mechanical compensation on other body structures , such as the spine20 . a large amount of compensation from the structures around the spine can cause lower back pain , and as the lower back pain becomes more severe , cross - sectional decrease and atrophy may occur in muscles around the spine21 . various approaches to treatment are being proposed today since pain and reduced muscle mass can cause limitations in physical activity that causes difficulties in activities of daily life22 . with respect to this , brill and couzens11 reported that maintaining a well - balanced posture and strengthening lower back muscles through lumbar stabilization exercises can be effective in treating lower back pain . most of the previous studies focused on finding effective exercise routines by comparing the level of trunk muscle activities achieved through lumbar stabilization . however , studies on the effects of these exercise routines on actual functional activities are still lacking . accordingly , the present study measured the level of abdominal muscle activities from applying different types of bridge exercise , which is effective for lumbar stabilization , and the study aimed to use the findings in examining the changes in the level of activity in the muscles near the spine during the functional activity of walking on a treadmill while wearing high heels . as a result , this study revealed that , as compared to the control group , both the bes and bep groups showed significant increase in the muscle strength of rectus abdominis muscles after bridge exercise . lumbar stabilization requires coordinated contractions of anterior , posterior , and lateral muscles of the spine23 , 24 . in addition , weakening of the abdominal muscles can cause lower back pain by increasing anterior pelvic tilt and lumbar lordosis25 . bridge exercises require motor control and balance , and because spinal stabilization requires enough strength to prevent anterior pelvic tilt and lumbar lordosis , muscle activity in the rectus abdominis muscle may have increased . studies by kavcic et al.26 and kim et al.27 reported that rectus abdominis muscle activity was highly correlated with bridge exercise , which was consistent with the findings in this study that found a significant increase in rectus abdominis muscle activity during bridge exercise . in order to identify the functional role of bridge exercise , the present study measured the differences between the groups in activities of muscles near the spine from walking on a treadmill wearing high heels , before and after bridge exercise . both the bes and bep groups showed no significant differences in muscles near the cervical vertebrae . however , both groups showed significant decrease in the muscles near the thoracic vertebrae . also , the bep group showed a significant decrease in the activities of muscles near the lumbar vertebrae , but the bes group showed no significant change . a study by stevens et al.28 reported that bridge exercise resulted in a significant decrease in the activities of the thoracic vertebrae muscles , which was consistent with the present study that found significant decrease in the activities of the muscles near the lumbar vertebrae following bridge exercise . moreover , it is believed that decrease in the activities of muscles near the lumbar vertebrae may be attributed to prevention of anterior pelvic tilt by strengthening the abdominal muscles through bridge exercises , and minimizing hyperextension of the trunk by reducing lumbar lordosis that resulted in reduced tension . in summarizing the findings in this study , it is believed that as the supporting surface area decreased , somatosensory information that is input proportionately to the cross - sectional area that the body touches during bridge exercise also decreased , which caused the muscles to become more tense , which resulted in significant changes in the muscle strength of abdominal muscles . many women wear high heels for long hours for aesthetic reasons and due to work requirements . for these women , abdominal muscle strengthening through bridge exercise can help prevent anterior pelvic tilt and decrease lumbar lordosis , which could play a role in reducing tension in the muscles around the spine . by doing so , the frequency of lower back pain can be reduced by relieving excessive muscle tension and limiting unnecessary muscle use during functional movement .

[ purpose ] the purpose of this research is to investigate the effect of the method of bridge exercise on the change of rectus abdominis muscle and the muscle activity of paraspinal muscles while doing treadmill walking with high heels . [ subjects and methods ] the subjects of this research are healthy female students consisting of 10 persons performing bridge exercises in a supine group , 10 persons performing bridge exercises in a prone group , and 10 persons in a control group while in s university in busan . bridge exercise in supine position is performed in hook lying position . bridge exercise in prone position is plank exercise in prostrate position . to measure the strength of rectus abdominis muscle , maintaining times of the posture was used . to measure the muscle activity of paraspinal muscles , emg ( 4d - mt & emd-11 , relive , korea ) was used . [ results ] the strength of rectus abdominis muscle of both bridge exercises in the supine group and bridge exercises in the prone group increases significantly after exercise . the muscle activity of paraspinal muscle such as thoracic parts and lumbar parts in bridge exercises in the prone group decreases statistically while walking on a treadmill with high heels . muscle activity of thoracic parts paraspinal muscle and bridge exercises in the supine group decreased significantly . [ conclusion ] according to this study , we noticed that bridge exercise in a prone position is desirable for women who prefer wearing high heels as a back pain prevention exercise method .

gingival enlargement ( ge ) is an overgrowth characterized by an expansion and accumulation of the connective tissue with seldom increase in a number of cells . it is a heterogeneous group of disorders causing esthetic , functional , masticatory and psychological disturbances . the etiopathogenesis of ge is poorly understood but can be directly or indirectly attributed to factors like plaque accumulation , inadequate nutrition or systemic hormonal stimulation . ge is also evidenced in blood dyscrasias or may result from factors like inflammation , drugs and inheritance . idiopathic gingival fibromatosis ( igf ) is a rare hereditary condition with no definite cause . the overgrowth varies from mild enlargement of an isolated inter dental papillae to segmental or uniform and marked enlargement affecting one or both the jaws . it is known to affect 1 in 3/4 of a million and can present as a single entity or as part of a syndrome . clinically the enlargement exhibits a normal color , is firm , non - hemorrhagic , non - exudative and asymptomatic . igf is synonymous with nomenclatures like gingivomatosis , elephantiasis gingivae , diffuse fibroma , familial elephantiasis , hereditary gingival hyperplasia , hereditary gingival fibromatosis ( hgf ) , congenital familial fibromatosis . it 's syndromic association can be autosomal dominant or recessive and has been evidenced in zimmerman - laband , murray - puretic - drescher , rutherford , cowden , cross and ramon syndromes , to name a few . the hgf gene has been mapped to 2p21-p22 ( hgf1 ) and the locus has been localized to 37 cm and chromosome 5q13-q22 ( hgf2 ) . recently , a mutation in the son of sevenless-1 gene has been linked to non - syndromic enlargements , but unequivocal evidence has not been established . the treatment of gingival fibromatosis is of prime importance as it can cause difficulty in mastication , phonetics , esthetics , malposition of teeth and can lead to considerable cosmetic and psychological concerns . traditional surgical procedures using scalpel and blade causes discomfort , elicits more bleeding and has patient cooperation issues . the use of diode laser for gingivectomy seems to address the above issues to a large extent . we present a case of recurrent ipsilateral idiopathic ge affecting the buccal and lingual / palatal aspect of maxillary and mandibular arches on the right side and its management using conventional external bevel gingivectomy and diode laser . a middle aged indian male patient reported to the department of periodontics , government dental college and hospital , hyderabad , india with a chief complaint of swelling of the gums in the upper and lower jaws on the right side of the face since 1 year . patient gave the history of similar lesion in the maxillary right jaw 15 years back and was treated at the same institute . there was no relevant medical , family or drug history and the patient is a known smoker for the past 20 years . on visual examination , the overgrowth extended from 11 to 18 in the maxilla and 32 - 48 in the mandible . the lesion appeared pale pink in color , was diffuse , firm and fibrotic with a smooth surface [ figures 2 and 3 ] . inflammatory changes secondary to local plaque and calculus deposits was evident and periodontal probing elicited bleeding and presence of pseudo pockets . frontal view showing right facial asymmetry pre - operative photograph showing the enlargement on buccal / labial sides pre - operative photograph showing the enlargement on lingual side complete blood picture was within normal limits on a hemogram . the orthopantamograph showed crestal bone loss in the maxilla and horizontal bone loss in the mandible extending from distal aspect of 44 to mesial aspect of 48 [ figure 4 ] . following phase i therapy , gingivectomy using external bevel incisions was planned on the buccal aspects of the maxillary and mandibular gingiva and diode laser was used for excision of the enlarged tissue on the lingual / palatal aspect . incisions on the buccal aspect were made using the kirkland knives and orban 's knife was used for interdental incisions . after arresting bleeding , a periodontal dressing ( coe - pak , gc america inc . patient was recalled after 2 weeks , periodontal dressing was removed and next surgical phase involving the lingual / palatal side using diode laser was carried out [ figure 5 ] . the diode laser had a wavelength of 940 nm and was used at 3 watts in continuous mode . no recurrence was observed at 1 year post surgery [ figures 6 and 7 ] . use of diode laser for excision of enlarged tissue one year post surgery ( buccal view ) one year post surgery ( lingual view ) the orthopantamograph showed crestal bone loss in the maxilla and horizontal bone loss in the mandible extending from distal aspect of 44 to mesial aspect of 48 [ figure 4 ] . following phase i therapy , gingivectomy using external bevel incisions was planned on the buccal aspects of the maxillary and mandibular gingiva and diode laser was used for excision of the enlarged tissue on the lingual / palatal aspect . incisions on the buccal aspect were made using the kirkland knives and orban 's knife was used for interdental incisions . after arresting bleeding , a periodontal dressing ( coe - pak , gc america inc . patient was recalled after 2 weeks , periodontal dressing was removed and next surgical phase involving the lingual / palatal side using diode laser was carried out [ figure 5 ] . the diode laser had a wavelength of 940 nm and was used at 3 watts in continuous mode . no recurrence was observed at 1 year post surgery [ figures 6 and 7 ] . use of diode laser for excision of enlarged tissue one year post surgery ( buccal view ) one year post surgery ( lingual view ) the present report describes as case of ipsilateral igf in a middle aged adult patient , recurring after a gap of 15 years . as there was no contributing family , medical , prenatal or drug histories , a diagnosis of igf the etiology of igf is poorly understood and has been attributed to congenital or hereditary factors . disturbances in the homeostatic equilibrium between synthesis and degradation of collagen and/or alterations in fibroblast function and proliferation have also been drawn in the etiopathogenesis of igf . the enlargement is confined to fibroblasts in the gingiva and does not involve the periodontal ligament . it occurs peripheral to the alveolar bone in the attached gingiva . in such cases , periodontitis and therefore , oral hygiene maintenance and supportive periodontal care is of paramount importance not only to minimize the periodontal involvement but also to prevent or delay the recurrence . there is a tendency for these lesions to recur after surgery but the time taken for recurrence is unpredictable and could range from months to years . one study reported no recurrence in 14 years in patients with good oral hygiene whilst mild recurrence was evident in another study 20 months post surgery due to poor plaque control . in the present case report the histopathology of the enlarged tissue consisted of increased collagen fiber bundles , irregular elongated retepegs in the stromal tissue with sparse cellularity and multiple small blood vessels . another reason for delayed recurrence in the present report could be linked to sparse cellularity of the lesion as greater the number of fibroblasts , more likely for the lesion to recur . various treatment modalities for the management of igf include external or internal bevel gingivectomy in association with gingivoplasty , an apically positioned flap , electrocautery and the use of lasers . the most effective method for removing the enlarged tissue when there is no attachment loss and all the pocketing is false , is the conventional external bevel gingivectomy . the present case was treated using external bevel gingivectomy on the labial / buccal gingiva of maxillary / mandibular arches and diode laser was used to excise the excess tissue on the lingual / palatal sides . the use of laser reduced the amount of bleeding , lowered pain during and after the procedure and significantly decreased the quantity of local anesthetic used . it also led to better visibility thereby reducing the chair side time resulting in minimized operator fatigue and better patient acceptance . henceforth , psychological counseling should be part of the comprehensive treatment plan for such patients , especially those belonging to the younger age group . moreover , the benefits of the surgery in eliminating the masticatory difficulties , providing access for better oral hygiene maintenance and significant improvement of phonetics and esthetics should not be underestimated . these views are in accordance with those of lobo et al . and shetty et al . the benefits of the surgery outweigh the risks of recurrence and should be employed whenever deemed crucial . patient education , periodic recall and proper oral hygiene maintenance reduce and delay the chances of recurrence . further studies at cellular , molecular and genetic levels are required to understand the etiology and pathogenesis of this bizarre condition .

idiopathic gingival fibromatosis is a relatively rare condition characterized by the proliferation of the gingival tissues resulting in masticatory , esthetics , phonetics and psychological disturbances . the severity of the overgrowth can range from a solitary isolated mass to a more generalized and diffused enlargement . the etiopathogenesis of this bizarre condition is poorly understood and has been attributed to various factors . it can present as a single disorder or may manifest as part of a syndrome . this case reports an ipsilateral diffused idiopathic gingival enlargement in a middle aged adult recurring after a gap of 15 years . external bevel gingivectomy on the buccal aspects of maxillary and mandibular gingiva and diode laser for excision of the enlarged tissue on the lingual / palatal aspect was carried out to eliminate the excessive tissue . periodic recalls showed maintenance of good oral hygiene and 1 year follow - up revealed no recurrence .

peritoneal metastases from lung cancer are a rare event . in this paper , we report the case of a patient with adenocarcinoma of the lungs who had isolated peritoneal metastases at the time of diagnosis . we report a 55-year - old female who presented with shortness of breath , decreased effort tolerance , cough , and weight loss . her initial chest x - ray and subsequent chest ct showed a 12 9 8 cm mass in the middle lobe of the right lung . the histopathological examination of her biopsy material was consistent with a thyroid transcription factor-1 positive lung adenocarcinoma . in the abdomen , the patient was administered chemotherapy based on carboplatin - paclitaxel - bevacizumab , but only with a partial response . therefore , a second - line treatment based on pemetrexed was administered for 9 courses , and a clinical and radiological response was observed . the chemotherapy was stopped and the patient did not exhibit any symptoms of progression while waiting for a new evaluation . the incidence of peritoneal involvement of lung cancer without metastases in other parts of the body is scarcely encountered in clinical practice . out of the different types of lung cancers , adenocarcinoma and large cell carcinoma immunohistochemical staining patterns were important in the differential diagnosis with the other etiologies for peritoneal metastasis and the mesothelioma . lung cancer represents one of the most common malignant diseases worldwide and the major cause of cancer - related deaths , accounting for 25% of all cancer deaths , and with a 5-year - survival rate of 1020% . approximately 4050% of the patients with lung cancer manifest metastases at the time of diagnosis . the most common regions of metastases are the pleura , lung parenchyma , skeletal system , liver , brain , and the adrenal glands . metastases in unusual locations like the small intestine and the colon have been reported ; however , peritoneal metastases are a rare event . we report the case of a patient with adenocarcinoma of the lungs who had isolated peritoneal metastases at the time of diagnosis . our patient was a 55-year - old female , who manifested shortness of breath , decreased effort tolerance , cough , and weight loss that began a few months earlier . she had no significant past medical history and never smoked or abused alcohol . on physical examination , she had stable vital signs and had no cyanosis , edema or lymphadenopathy . she had an increased air entry , dullness to percussion , and a reduced tactile vocal fremitus on the right side . she also had a normal blood count , basic metabolic panel , liver function tests , and coagulation profile . a subsequent chest ct demonstrated a 12 9 8 cm mass in the middle lobe of the right lung ( fig . 1 ) . based on the above findings , malignancy was suspected and bronchoscopy was performed , which showed a blunting at the carina , mucosal tram lines in both bronchi , and an external compression of the right lung , but endobronchial lesions were not observed . the histopathological examination of ct - guided transthoracic biopsy material was consistent with the thyroid transcription factor-1 ( tff-1 ) positive lung adenocarcinoma , and no epidermal growth factor receptor - activating mutations or echinoderm microtubule - associated protein like 4-anaplastic lymphoma kinase translocations were detected . distal organ metastases were not detected with whole - body bone scintigraphy and cranial ct ; in the abdomen , a 5.3 cm mass was identified ( fig . an exploratory laparotomy was performed which demonstrated several nodules in the greater omentum and the peritoneum ( the largest lesion was 0.5 cm in diameter ) . 3 ) and was negative for ck20 . those histologic findings corresponded with the primary lung cancer diagnosis and yielded an additional diagnosis of peritoneal metastases . the patient was administered a chemotherapy based on carboplatin ( auc 6 ) , paclitaxel ( 200 mg / m ) and bevacizumab ( 15 mg / kg ) every 3 weeks . following 6 courses of this treatement , a radiological evaluation was scheduled . a partial response was obtained and maintenance with bevacizumab was initiated . at 6 months after treatment , the patient presented brain metastases and received 30 gy of palliative whole - brain radiotherapy . therefore , a second line of chemotherapy based on pemetrexed ( 500 mg / m ) was administered every 3 weeks . today , the patient is no longer undergoing chemotherapy and has not shown any symptoms of progression while waiting for a new evaluation . the common sites of distant metastases in patients with lung cancer have been reported to be in the brain , the bones , the liver , and the adrenal glands . occasionally , lung cancer spreads to the stomach , the small and large intestines , pancreas , eye , skin , and even the breasts , but the incidence of peritoneal involvement without metastases in other parts of the body is hardly encountered in clinical practice [ 2 , 4 ] . although the frequency of peritoneal metastases in the autopsy series is 2.716% , we are talking about 12% in clinical studies [ 5 , 6 ] . out of the different types of lung cancers , adenocarcinoma and large cell carcinoma are more likely to metastasize to the peritoneum and account for more than 80% of the cases with peritoneal metastases [ 2 , 4 , 6 ] . clinically , peritoneal carcinomatosis is usually asymptomatic in the early stages , making early detection less likely . in recent years and with the increasing availability of novel technologies like ct scans , pet scans and ultrasonographies , peritoneal carcinomatosis can be diagnosed more accurately ( our patient was diagnosed using an abdomen ct ) . however , signs and symptoms including abdominal distress , distension pain together with respiratory distress , ileus , ascite , peripheral edema , nausea , and vomiting were described during the late stages of the disease [ 2 , 5 ] . despite the fact that lung cancer can be diagnosed before the peritoneal metastases become symptomatic , the symptomatic metastases may be the first clinical presentation of an unknown lung cancer . asymptomatic metastases may even be the first manifestation if incidentally discovered during exploratory laparotomy for another reason . the other most common etiologies for peritoneal metastasis are pelvic or abdominal malignancies while primary tumors are rare . peritoneal metastases in male patients are usually caused by cancers of the gastrointestinal tract , including the stomach , colon and pancreas , while in females , the most common metastases are caused by ovarian carcinomas . as such , immunohistochemical staining patterns are important in the differential diagnosis . for this , the most commonly accepted immunohistochemical markers are reported to be ck5/6 , ck7 , ck20 and ttf-1 . as in the current case , the immunophenotype demonstrated to be positive for ttf-1 and ck7 staining , but negative for ck20 [ 1 , 3 ] . furthermore , the distinction between epithelioid mesothelioma and lung adenocarcinoma remains a significant diagnostic challenge . in a patient with peritoneal metastases and primary lung adenocarcinoma , a possible metastatic pleural mesothelioma must first be ruled out by checking the immunohistochemical pattern of the antibodies that are used in the pathological examination . thus , the combination of carcinoembryonic antigen , calretinin , each wilms tumor 1 or thrombomodulin was suggested to be the best panel of immunohistochemical markers . the histology of the lung cancer , the molecular pathology , age , performance status , comorbidities and the patient 's preferences should be taken into account when deciding on the treatment strategy . for peritoneal metastases of non - small cell lung cancer ( nsclc ) , platinum - based combination chemotherapy prolongs survival , improves quality of life , and controls symptoms in patients with a ps 01 . treatment with a tyrosine kinase inhibitor ( erlotinib or gefitinib ) should be prescribed to patients with tumors bearing an activating epidermal growth factor receptor mutation . patients with nsclc harboring an alk rearrangement should be considered for crizotinib , a dual alk and met tyrosine kinase inhibitor . for patients who present metastatic small - cell lung cancer , 46 cycles of etoposide plus cisplatin or carboplatin are recommended [ 8 , 9 ] . peritoneal metastases are indicative of disseminated disease , and prognosis is extremely poor . the median survival following peritoneal carcinomatosis ranges from 15 days to 2 months [ 5 , 6 ] . in conclusion , metastases to the peritoneum are rarely encountered during the clinical course of lung cancer and they are usually accompanied by other systemic metastases . the case presented here is unusual , as the patient developed isolated peritoneal involvement without distant metastases . radiological investigations , followed by biopsy and immunohistochimy , are the best diagnostic tools for confirming and identifying the primary lung cancer diagnosis .

introductionperitoneal metastases from lung cancer are a rare event . in this paper , we report the case of a patient with adenocarcinoma of the lungs who had isolated peritoneal metastases at the time of diagnosis.case reportwe report a 55-year - old female who presented with shortness of breath , decreased effort tolerance , cough , and weight loss . her initial chest x - ray and subsequent chest ct showed a 12 9 8 cm mass in the middle lobe of the right lung . the histopathological examination of her biopsy material was consistent with a thyroid transcription factor-1 positive lung adenocarcinoma . in the abdomen , a 5.3-cm mass was identified . a biopsy and immunohistochemistry revealed a lung adenocarcinoma . the patient was administered chemotherapy based on carboplatin - paclitaxel - bevacizumab , but only with a partial response . six months later , the patient showed brain metastases . therefore , a second - line treatment based on pemetrexed was administered for 9 courses , and a clinical and radiological response was observed . the chemotherapy was stopped and the patient did not exhibit any symptoms of progression while waiting for a new evaluation.discussionthe incidence of peritoneal involvement of lung cancer without metastases in other parts of the body is scarcely encountered in clinical practice . out of the different types of lung cancers , adenocarcinoma and large cell carcinoma are most likely to metastasize in the peritoneum . immunohistochemical staining patterns were important in the differential diagnosis with the other etiologies for peritoneal metastasis and the mesothelioma . peritoneal metastases are indicative of a disseminated disease and prognosis is extremely poor .

COTTONWOOD - Cottonwood Police were dispatched to a disorderly call around 5 p.m. Wednesday for a male subject punching signs and throwing rocks at cars in the area of SR 89A and Cove Parkway, according to a news release from the department. Thursday, October 13, 2016 Read More SAN TAN VALLEY - Levi Douglas Jones is booked in the Pinal County Jail with a cash-only $1 million bond and waits extradition to Yavapai County for his connection in the early Monday shooting death of a Camp Verde man. Thursday, October 13, 2016 Read More CLARKDALE - An ailing 100-year old water system without historical mapping needs repair, so what could go wrong? As residents of Clarkdale's Mountain Gate subdivision learned, "Murphy's Law" could deliver an unplanned five-to-seven hour long water outage Tuesday morning. Thursday, October 13, 2016 Read More The Verde Valley and Sedona hosts various running events throughout the year. Whether they are long marathons or short 5Ks, they all aim at living a healthy lifestyle and being part of a community. Thursday, October 13, 2016 Read More After an Oct. 5 Yavapai County Board of Supervisors executive session, where the board considered action in pending litigation in Arizona Cattle Growers Association v. Yavapai County, the supervisors unanimously approved the amount of $10.39 per acre at full cash value for tax years 2016 and 2017. Thursday, October 13, 2016 Read More VERDE VALLEY - For the past five years, the non-profit Verde Watershed Restoration Coalition (VWRC) has hosted conservation crews for seasonal restoration work in the Verde Valley. This year's mission began Sept. 19 as 40 conservation crew members work to improve water quality in the Verde and Gila River Watersheds. Thursday, October 13, 2016 Read More I support comprehensive immigration reform and would have voted for the 2013 bill that addressed our immigration issues in a bipartisan manner. Thursday, October 13, 2016 Read More As Sheriff, I have seen what a porous border brings to Arizona. My deputies seized millions of dollars of drugs and seen the aftermath of battles between rival drug and human smuggling organizations. Thursday, October 13, 2016 Read More VERDE VALLEY - If removing oneself from a college's District Governing Board was as simple as saying "I resign," then Yavapai College became short one board member as of Tuesday. But a resignation letter must be given to Yavapai County School Superintendent Tim Carter for it to become official, so District 3 Representative Al Filardo is still on the board. Wednesday, October 12, 2016 Read More CAMP VERDE - A Phoenix man has been arrested in connection with the shooting death of a 31-year-old Camp Verde man early Monday morning. Wednesday, October 12, 2016 Read More CAMP VERDE - Andre Alicen Caron appeared before Yavapai County Superior Court Judge Michael Bluff in Camp Verde Monday for a pretrial conference and possible change of plea, but a six-week continuance was requested. Wednesday, October 12, 2016 Read More VERDE VALLEY - Verde Valley Newspapers, Inc., received 14 awards at the annual Western News&Info; Editorial Seminar on Friday, Oct. 7. Wednesday, October 12, 2016 Read More CLARKDALE - One dozen participants gathered at the Verde Valley Community Town Hall to discuss "Financing Arizona's Future" during a public forum Sept. 28 at the Yavapai College Clarkdale campus. Wednesday, October 12, 2016 Read More On Oct. 22, the organization plans to package 300,000 meals at the Verde Valley Fairgrounds utilizing the support of more than 660 volunteers! Wednesday, October 12, 2016 Read More CAMP VERDE - It is believed that a Phoenix man is responsible for the shooting death of a 31-year-old Camp Verde man early Monday morning. Monday, October 10, 2016 Read More Camp Verde Marshal's Office is looking for Phoenix resident Levi Jones in connection with a homicide early Monday at the Circle K in Camp Verde on Main Street, said CVMO Commander Jacqui MacConnell. Monday, October 10, 2016 Read More VERDE VALLEY - Joining the list of endangered species in the Verde Valley are signs reading: "For Rent". Saturday, October 8, 2016 Read More JEROME - Like its namesake, the Mine Cafe requires a downward descent to score treasure - - and considering the buzz on social media, it may have begun a gold rush all of its own. Saturday, October 8, 2016 Read More CLARKDALE - Tuesday, Clarkdale Town Council and interested public will hear the latest soil test results from Freeport Mineral Corporation as the United Verde Soil Program begins steps to remediate toxic residue tied to historic copper smelting operations in the area. Saturday, October 8, 2016 Read More When elected, I look forward to helping promote the educational advancement needs of all students throughout the County. Saturday, October 8, 2016 Read More I am running for re-election to provide a voice that reflects the concerns of District 2 constituents and refuse to be a rubber stamp for the bureaucracy. Saturday, October 8, 2016 Read More Judge Bill Lundy of the Verde Valley Justice Court issued the following felony complaints: Saturday, October 8, 2016 Read More As the movie Deepwater Horizon plays across screens throughout America, the real-life aftermath plays across the mind of Ed Martinez of Cottonwood. Thursday, October 6, 2016 Read More Hope Marie Olszewski was sentenced to three years in prison and five years of probation Monday by Judge Joseph C. Butner at Yavapai Superior Court in Camp Verde for her role in a home invasion that took the life of Gus Terrell Finklea. Thursday, October 6, 2016 Read More Arizona Town Hall officials conducted a public forum at the Yavapai College campus in Clarkdale Sept. 28 titled "Arizona and Mexico" to allow local residents' voices to be heard state wide. Thursday, October 6, 2016 Read More Wednesday, Sept. 28, representatives from PathfinderHealth ACO presented Elaine Bremner, executive director, with a substantial donation of $13,738.00 in support of the programs provided by the Verde Valley Senior Center to all communities of this area. Thursday, October 6, 2016 Read More The Cottonwood Public Library currently has over 80 volunteers on its roster, but a portion of those are snow-birds who return back to their second homes for the summer. Thursday, October 6, 2016 Read More Lori Drake Age: 46 Years in Verde Valley: I am a fourth generation Verde Valley resident. I was born and raised in Cottonwood, living in Phoenix for only a short time during college. My husband has been a Verde Valley resident for almost 40 years. Thursday, October 6, 2016 Read More Jonathan P Jauregui Age: 51 Years in Arizona/Verde Valley: 51 years/11 years Occupation: Letter Carrier U.S.P.S. Thursday, October 6, 2016 Read More Anthony Lozano Age: 71 Years in Arizona/Verde Valley: 71 years Occupation: 30 years in education; secondary occupations in construction and mining Thursday, October 6, 2016 Read More Pastor Robb Williams Age: 49 Years in Arizona/Verde Valley: My wife Sarah and I have lived in Arizona for 24 years, and we have lived in Cottonwood for since January 2007. Thursday, October 6, 2016 Read More Amanda M. Worth Age: 36 Years in Arizona/Verde Valley: I lived in Jerome for over 14 years, having moved here from my home state of Michigan in June of 2002 Thursday, October 6, 2016 Read More City Council met at their chambers Tuesday afternoon to discuss special event liquor licenses, street closures for Walking on Main, and to review the continuation of the Titled Earth Event for 2017. Thursday, October 6, 2016 Read More A 17-year-old female named Melody Murphy, of Cottonwood, has been reported missing by her mother. Thursday, October 6, 2016 Read More Cory Lynn White, of Cottonwood, made an appearance Monday before Judge Michael Bluff at Yavapai Superior Court in Camp Verde with her new defense attorney Tony J. Gonzales for case management hearings. Tuesday, October 4, 2016 Read More Many of you remember the homeless man who walked the streets of Cottonwood wearing a parka - and wonder what happened to him. Tuesday, October 4, 2016 Read More Around 9:30 a.m. Monday, a loaded cement truck traveling southbound on SR 89A experienced a mechanical malfunction, causing part of the frame to break and emptying one of three containers of cement powder, according to Clarkdale Police Chief Randy Taylor. Tuesday, October 4, 2016 Read More The driver of an 80s model Chevy Blazer lost control of the brakes and crashed into the bollards in front of the Jerome Fire Station Saturday, according to Fire Chief Rusty Blair. Tuesday, October 4, 2016 Read More Volunteers from Copper Canyon Fire & Medical Authority and the Red Cross installed 71 new smoke alarms to homes in the Verde Lakes neighborhood Saturday. Tuesday, October 4, 2016 Read More ||||| Daughter Diana Young Long tells the story of the recovery of her father's remains. Diana Young Long, center, with her husband, Greg Long, and family and friends pay their respects during the burial service for Herbert V. Young Jr., a U.S. Army Air Forces pilot during World War II, at the Prescott National Cemetery on Wednesday. (Photo: Charlie Leight, The Arizona Republic) PRESCOTT, Ariz. — She was in the womb when her dad went to war, an infant when he died. So there was no awareness that anti-aircraft rounds blasted his B-24 bomber, sending it spiraling in flames into the jungles of New Guinea. Just a hole in her life. Growing up fatherless. Secretly wondering what he was like and whether, despite a death certificate, he might someday show up. Seven decades elapsed. Then, in March, Diana Young Long got a call from the Army: Some of her father's remains had been recovered from the jungle wreckage and identified with DNA evidence. He was coming home with full military honors. Wednesday afternoon, with bagpipes playing at Prescott National Cemetery, 1st Lt. Herbert V. "Buddy" Young Jr. was buried. "It's been real emotional," says Young, 71, her eyes full of tears. "I always wanted a dad. But I had my mom and my brother. So there were the three of us." COLLECTING MEMORIES The odyssey has many chapters, many mysteries. And time has erased most of the details. They were both born in Jerome — Zoeleen McLain and Herbert Young — and grew up classmates at Clarkdale High School. Buddy, a heartthrob, was captain of the football and basketball teams. Zoe was Miss Prescott. The exact date is uncertain, but they married in 1941, just months before the Japanese attack on Pearl Harbor. Like thousands of young Americans, Buddy signed up to fight. He joined the U.S. Army Air Forces and became a pilot. Military records show he earned his wings at Williams Field, the old flight-training center in Mesa, and joined the 5th Air Force Command, 90th Bomber Group, 321st Bombardment Squadron. In a black-and-white photo, apparently taken before Buddy shipped out, the sweethearts resemble Hollywood film stars. Zoe was two months pregnant. Joyce McLain Peters, Zoe's sister, recalls Buddy's letters from overseas — thoughtful and funny. In some of them, he talked about the unborn child his wife was carrying. "He was just such a sweet, clever, handsome guy," adds Joyce, who still lives in Prescott. "I thought the world of him." By April 10, 1944, according to family lore, Buddy Young had flown 300 hours of combat missions and was scheduled to come home. Instead, he volunteered to fill in as co-pilot next to 1st Lt. Bryant E. Poulson aboard a B-24 bomber nicknamed "Hot Garters." "I always heard he was not supposed to be flying," Diana says softly. Poulson and his 11-man crew led the squadron's attack that day against Japanese installations at Hansa Bay on the northern coast of Papua New Guinea. A declassified account from the battle was written by 1st Lt. George R. Anderson, who was No. 2 in the flight formation at 10:45 a.m. "Lt. Poulson had apparently settled down on his bomb run, and I would say about 30 seconds before his release, point ack-ack started to burst all around him. Number two engine seemed to be hit and flames came back way past the tail . ... I saw the bombs being salvoed. Lt. Poulson then started a gradual turn to the left and I saw the bombs being salvoed. ... "The left wing folded up and the plane disintegrated. It was at approximately 10,000 feet. Five parachutes were seen to open. I followed the plane down and continued to circle until all five chutes were on the ground. The plane was still burning on the ground when we left the scene, and we could see two of the men moving about." Over the next few days, searches proved fruitless. Weeks later, however, Guineans near Nubia Village told an Australian military officer that four fliers had survived the crash, though badly burned. A report by Lt. W.A. Macgregor says natives described how an enemy patrol captured the men: "After binding the Americans, the Japanese beat them with pieces of timber and tried to induce the natives to do so. The natives say they refused." The prisoners were marched toward a Japanese base. Villagers recounted that one American, unable to continue, was shot. Over the ensuing days, another was beaten to death. A third apparently died of injuries. A fourth was shot. There is no account of the fifth parachutist. All 12 crewmen were listed as missing in action. Two years later, they were presumed dead. A non-profit uncovered Buddy Young’s remains after it began to investigate WWII crash sites in Papua New Guinea. (Photo: Final Search and Recover Report) BRINGING HIM HOME Back in Arizona, Diana collected snippets of information that a child hears growing up. She stayed sometimes with her father's parents, but Grandma struggled with Buddy's death and couldn't talk much about him. Zoeleen remarried, divorced and married again. But for Diana, stepdads never filled the fatherly void. The remark does not come out as a complaint, but a matter of fact. She lived a full life, including 20 years as a cosmetologist and 20 more in banking. She retired in Lake Almanor, Calif., with her husband, Greg Long. Remnants of a wrecked bomber 7,000 miles away were faint history. Diana was unaware that PacificWrecks, a non-profit organization dedicated to researching World War II crashes and battles, had begun collaborating with the Army on recovery expeditions in 2001. Over the next 13 years, according to military records, a series of at least four archaeological excavations were carried out, each one uncovering remains along with artifacts such as belt buckles, coins and ammunition. Graves of at least two parachutists were located. Diana said she learned of the discoveries several years ago. She'd waited a lifetime and was not impatient. Finally, this spring, the U.S. Army advised her that bones and teeth were being compared with DNA samples taken from Buddy's sister before she died. Did Diana want to know the results? Zoeleen and Buddy Young married in 1941. After Pearl Harbor was attacked, Buddy signed up for the Air Force. (Photo: Courtesy of family) She begins to cry, thinking of the next phone call: The DNA matched. Her father was coming home. Weeks ago, there was a ceremony at Diana's home in California. Along with medals, the Army gave Diana a thick book containing detailed military records of the crash and subsequent recovery efforts. About 300,000 Americans died in World War II combat, and more than 70,000 were unaccounted for. As Diana paged through the volume this week, grateful for a tangible keepsake of the dad she never knew, her face clouded with melancholy. "I just find it extremely sad," she says. "A waste. Not just him, but all of these young men dying." On Wednesday, nearly 100 attended her father's interment, about 20 family members among them. A bugler played taps. The honor guard delivered a 15-gun salute. Pastor Bob Hanson, a veteran who served in Korea and Vietnam, read Psalm 23. "Now he's back in these beautiful mountains and valleys where he grew up," the minister said, "surrounded by people who love him." His casket was lowered into the ground. A gravestone lay nearby with Buddy's name and a brief epitaph: "Killed in Action April 10, 1944. Welcomed home Oct. 15, 2014" There is one last chapter: Next spring, unidentified remains and relics from the crash site are to be buried in a single grave at Arlington National Cemetery. Wagner also reports for The Arizona Republic Read or Share this story: http://usat.ly/1sYIVHp

– Herbert "Buddy" Young's family says he was scheduled to come home after putting in 300 combat-mission hours when he subbed as co-pilot in a B-24 bomber called "Hot Garters" on April 10, 1944. The WWII plane was shot down over the jungles of Papua New Guinea, and for more than 70 years, Young was MIA. The Verde Independent reports his wife was two months pregnant when he was shipped overseas; his now-71-year-old daughter, Diana Young Long, received the closure she had been looking for all these years in March: Her dad's remains had been found, USA Today reports. Young was brought home with full military honors, and his family held a funeral on Wednesday, complete with a 15-gun salute, bagpipers, and a bugler playing taps. The plane was on the offense against Japanese installations at Hansa Bay when it was hit, and a service member in another plane said he saw five parachutes open and drop to the ground, where "we could see two of the men moving about." They couldn't find their comrades, though, and natives later told the Australian military that four of the men had survived, then been taken away by the Japanese and either died from their injuries or were brutally murdered. Long gave up thinking her father would be found, but a nonprofit group joined up with the Army and started searching for cold-case WWII crashes. Near where her dad's plane had gone down, search teams found coins, ammo, belt buckles—and soldier remains, some of which had DNA that matched Young's sister. His gravestone in Arizona's Prescott National Cemetery now reads: "Killed in Action April 10, 1944. Welcomed home Oct. 15, 2014."

SECTION 1. SHORT TITLE. This Act may be cited as the ``Antibiotic Resistance Prevention Act of 2001''. SEC. 2. FINDINGS. The Congress finds as follows: (1) The discovery in the 1940s of antimicrobial drugs, such as penicillin and streptomycin, led to ground breaking treatment of day-to-day illnesses and fatal diseases. (2) Drug-resistant pathogens have developed because many physicians and other health professionals have historically overprescribed antimicrobial drugs. (3) Antimicrobial resistance can be spurred by patients seeking antibiotics for viruses rather than bacterial infections. Antibiotics are effective only for bacterial infections, not viral infections. (4) Patients who fail to finish their prescribed doses of antibiotics leave themselves vulnerable to certain bacteria, strengthening antibiotic resistance. (5) Microbes that have increasingly built up resistance to antibiotics include the microbes involved in pneumonia; ear infections and meningitis; skin, bone, lung, and bloodstream infections; urinary tract infections; food borne infections; and infections transmitted in health care settings. (6) Many other pathogens are also becoming resistant to conventional treatments, including the bacteria that cause tuberculosis and gonorrhea; the fungi that cause yeast infections; and the parasites that cause malaria. (7) A substantial but as yet undetermined percentage of all antibiotics produced in the United States are used in animals, with estimates ranging from 40 to 80 percent. A substantial percentage of these antibiotics are used nontherapeutically in feed or in the water of farm animals to make them grow faster, while only about 20 percent of antibiotic feed additives are used to treat established infections. (8) This usage of antibiotics in farm animals, at levels too low to cure bacterial diseases but high enough to control them, is creating selective pressure on bacteria, causing them to develop resistance to the antibiotics. (9) Antibiotic resistant bacteria selected in animals can reach humans and pass their resistance to bacteria pathogenic to humans or, if pathogenic themselves, can cause disease that is not easily treatable, prolonging recovery. (10) Statistics have shown that antibiotic resistance can cause the total costs of inpatient care to be more than double the direct costs of such care. (11) Expenses incurred by hospitals around the Nation have risen to nearly $1.3 billion per year as a result of six ordinary types of resistant bacteria. (12) The Institute of Medicine, the American Society for Microbiology, the World Health Organization, the Congressional Office of Technology Assessment, and the General Accounting Office each have found that the Nation should improve surveillance for mounting antimicrobial resistance problems; prolong the useful life of antimicrobial drugs; develop new drugs; and utilize other measures, such as improved vaccines, diagnostics, and infection control measures, to prevent and control antimicrobial resistance. SEC. 3. DEPARTMENT OF HEALTH AND HUMAN SERVICES; FUNDING FOR TOP PRIORITY ACTION ITEMS UNDER PUBLIC HEALTH ACTION PLAN TO COMBAT ANTIMICROBIAL RESISTANCE. (a) In General.--For the purpose of carrying out the top priority action items designated in the Antimicrobial Resistance Action Plan, but only to the extent that the activities involved are within the jurisdiction of the Department of Health and Human Services (as determined under Federal laws other than this Act), there are authorized to be appropriated such sums as may be necessary for each of the fiscal years 2002 through 2006. Such authorization is in addition to other authorizations of appropriations that are available for such purpose. (b) Top Priority Action Items.--For purposes of this Act, the term ``top priority action items'' are action items designated by number in the Antimicrobial Resistance Action Plan and included (by reference to such numbers and to the categories used in such Plan) in the following list: (1) In the category ``Surveillance'', the following action items: (A) Action Item #2, described in the Plan as follows: ``With partners, design and implement a national AR surveillance plan that defines national, regional, state, and local surveillance activities and the roles of clinical, reference, public health, and veterinary laboratories. The plan should be consistent with local and national surveillance methodology and infrastructure that currently exist or are being developed.''. (B) Action Item #5, described in the Plan as follows: ``Develop and implement procedures for monitoring patterns of antimicrobial drug use in human medicine, agriculture, veterinary medicine, and consumer products.''. (2) In the category ``Prevention and Control'', the following action items: (A) Action Item #25, described in the Plan as follows: ``Conduct a public health education campaign to promote appropriate antimicrobial use as a national health priority.''. (B) Action Item #26, described in the Plan as follows: ``In collaboration with many partners, develop and facilitate the implementation of educational and behavioral interventions that will assist clinicians in appropriate antimicrobial prescribing.''. (C) Action Item #39, described in the Plan as follows: ``Evaluate the effectiveness (including cost- effectiveness) of current and novel infection-control practices for health care and extended care settings and in the community. Promote adherence to practices proven to be effective.''. (D) Action Item #58, described in the Plan as follows: ``In consultation with stakeholders, refine and implement the proposed FDA framework for approving new antimicrobial drugs for use in food-animal production and, when appropriate, for re-evaluating currently approved veterinary antimicrobial drugs.''. (E) Action Item #63, described in the Plan as follows: ``Support demonstration projects to evaluate comprehensive strategies that use multiple interventions to promote appropriate drug use and reduce infection rates, in order to assess how interventions found effective in research studies can be applied routinely and most cost-effectively on a large scale.''. (3) In the category ``Research'', the following action items: (A) Action Item #70, described in the Plan as follows: ``Provide the research community genomics and other powerful technologies to identify targets in critical areas for the development of new rapid diagnostics methodologies, novel therapeutics, and interventions to prevent the emergence and spread of resistant pathogens.''. (B) Action Item #75, described in the Plan as follows: ``In consultation with academia and the private sector, identify and conduct human clinical studies addressing AR issues of public health significance that are unlikely to be studied in the private sector (e.g., novel therapies, new treatment regimens, and other products and practices).''. (C) Action Item #76, described in the Plan as follows: ``Identify, develop, test, and evaluate new rapid diagnostic methods for human and veterinary uses with partners, including academia and the private sector. Such methods should be accurate, affordable, and easily implemented in routine clinical settings (e.g., tests for resistance genes, point-of-care diagnostics for patients with respiratory infections and syndromes, and diagnostics for drug resistance in microbial pathogens, including in nonculture specimens).''. (D) Action Item #77, described in the Plan as follows: ``Encourage basic and clinical research in support of the development and appropriate use of vaccines in human and veterinary medicine in partnership with academia and the private sector.''. (4) In the category ``Product Development'', the following action items: (A) Action Item #79, described in the Plan as follows: ``Create an Interagency AR Product Development Working Group to identify and publicize priority public health needs in human and animal medicine for new AR products (e.g., innovative drugs, targeted spectrum antibiotics, point-of-care diagnostics, vaccines and other biologics, anti-infective medical devices, and disinfectants).''. (B) Action Item #80, described in the Plan as follows: ``Identify ways (e.g. financial and/or other incentives or investments) to promote the development and/or appropriate use of priority AR products, such as novel compounds and approaches, for human and veterinary medicine for which market incentives are inadequate.''. The 13 action items specified in this subsection all have top priority under the Plan, regardless of their order on the list. (c) Antimicrobial Resistance Action Plan.--For purposes of this Act, the term ``Antimicrobial Resistance Action Plan'' means the plan that-- (1) is entitled ``A Public Health Action Plan to Combat Antimicrobial Resistance''; and (2) was developed by an interagency Task Force on Antimicrobial Resistance, created in 1999, that-- (A) is cochaired by the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health; and (B) in addition includes-- (i) the Agency for Healthcare Research and Quality and the Health Resources and Services Administration; (ii) the Health Care Financing Administration; (iii) the Environmental Protection Agency; and (iv) the Department of Agriculture, the Department of Defense, and the Department of Veterans Affairs. (d) AR.--For purposes of this Act, the term ``AR'' means antimicrobial resistance.

Antibiotic Resistance Prevention Act of 2001 - Authorizes appropriations for FY 2002 through 2006 for carrying out certain top priority action items designated in the Antimicrobial Resistance Action Plan (developed by an interagency Task Force on Antimicrobial Resistance in 1999) and within the jurisdiction of the Department of Health and Human Services.

our laboratory has been examining the mechanisms whereby chemicals are mutagenic in short - term in - vitro assays yet are not carcinogenic in 2-year rodent bioassays . previous studies indicated that mutagenic carcinogens increased the amount of cell turnover in the target organ , but that mutagenic noncarcinogens failed to do so . the present study compares the incidence of cell proliferation in specific regions of the kidney , which is the site of carcinogenicity , with cell proliferation induced in a nontarget tissue , the liver , by the mutagenic renal tubular carcinogen tris(2,3-dibromopropyl)phosphate ( tris ) . renal tubular adenocarcinoma induced by tris was the only tumor type identified in male f344 rats , and it was localized in the outer medulla . male f344 rats were fed a diet containing 0 , 50 , or 100 ppm tris for 14 days . these doses were identical to the doses given in the national toxicology program cancer bioassay . replicating cells were labeled with bromodeoxyuridine administered by an osmotic minipump and identified in tissue sections from liver and kidney using immunohistochemical techniques . examination of liver sections showed no chemically related increases in cell proliferation above control for either dose group . however , in the kidney , tris induced significant cell proliferation that was localized in the renal outer medulla region , the target area for carcinogenesis . the labeling index ( number of labeled cells / total number of cells counted ) in the kidneys of tris - exposed rats was increased approximately 4-fold in the outer medulla and was not increased in the cortex or inner medulla . the results of this study suggest an association between the chemically - induced renal cell proliferation and the renal carcinogenicity of tris.imagesfigure 2.figure 2 .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Preparing Excellent Teachers Act of 2006''. SEC. 2. FINDINGS. Congress finds the following: (1) The shortage of qualified teachers in the United States has reached critical levels. (2) Education experts predict that over the next decade, the United States will need more than 2 million new teachers. (3) In urban districts, nearly 50 percent of new teachers leave teaching during their first five years. (4) These numbers have a direct impact on the quality of the education of the children of the United States. SEC. 3. GRANTS FOR TEACHER MENTORING PROGRAMS. (a) Authority to Make Grants.--The Secretary of Education may make grants in accordance with subsections (d) and (e) to States and local educational agencies to assist such States and agencies, in cooperation with universities and colleges in accordance with subsection (b), to establish and support teacher mentoring programs in schools for the purpose of attracting and training teachers of exceptional ability who are mid-career professionals or recent college graduates. (b) Eligibility to Participate in Program.--To be eligible to participate in a teacher mentoring program under this section, a mid- career professional or recent college graduate shall be enrolled in a masters degree program in education or teaching in a university or college that-- (1) has entered into a written agreement relating to such program with the State or local educational agency that is the recipient of a grant under this section; (2) is located in such State or local educational agency; and (3) is accredited by the Council of Higher Education Accreditation and the accrediting agency in the State, if any. (c) Practical Experience.-- (1) In general.--A mid-career professional or recent college graduate who participates in a teacher mentoring program shall, under the supervision of an experienced mentor teacher, complete not fewer than ten months teaching a class containing not more than 30 students and not fewer than 10 students in a school chosen by the State or local educational agency that is the recipient of a grant under this section. (2) Experienced mentor teacher defined.--In this subsection, the term ``experienced mentor teacher'' means a teacher who-- (A) has at least five years teaching experience teaching in a school in the State or local educational agency that is the recipient of a grant under this section; and (B) has a masters degree in education or teaching. (d) Teacher Certification.--As a condition of receiving a grant under this section, a university or college shall award to a mid-career professional or recent college graduate who successfully completes a teacher mentoring program a teacher certification that is valid in the State or local educational agency in which such university or college is located. (e) Amount, Number, and Distribution of Grants.-- (1) Amount.--A grant under this section shall be in an amount that is 50 percent of the cost of establishing and supporting a teacher mentoring program in a State or local educational agency, but such grant may not exceed $2,500,000. (2) Number.--The Secretary may not make more than ten such grants each fiscal year, beginning with fiscal year 2007. (3) Distribution.--A State or local educational agency may receive not more than two grants each fiscal year. (f) Duration of Program.--A teacher mentoring program under this section shall be for a period of one academic year. (g) Agreement With Teachers for Placement in a School.--A mid- career professional or recent college graduate who successfully completes a teacher mentoring program under this section shall agree in writing to placement as a teacher in a school chosen by the State or local educational agency. Such placement shall be for a period of five academic years beginning with the academic year that begins after the successful completion by such professional or graduate in the teacher mentoring program. (h) Application.--To receive a grant under this section, a State or local educational agency shall submit to the Secretary an application at such time, in such manner, and containing such information as the Secretary may prescribe. (i) Competitive Basis for Selection.--The Secretary shall award grants to States and local educational agencies on a competitive basis. (j) Authorization of Appropriations.--There are authorized to be appropriated to the Secretary $25,000,000 for each of fiscal years 2007 through 2011 to carry out this section. Amounts appropriated are authorized to remain available until expended, and may be used by the Secretary to make additional grants, in accordance with this section, in a fiscal year beginning with fiscal year 2012.

Preparing Excellent Teachers Act of 2006 - Authorizes the Secretary of Education to make grants to states and local educational agencies to establish and support teacher mentoring programs to attract and train teachers of exceptional ability who are mid-career professionals or recent college graduates. Places limits on the amount, number, and distribution of such grants.

even though cases of ovarian cancer do not occur frequently , this disorder does not take the leading position in the structure of cancer pathology . however , it remains to be one of the unsolved problems of the medicine . according to the estimates of the international agency of cancer research there are nearly 239,000 of new cases of ovarian cancer registered annually in the world , and the standard incidence index equals to 6.1 per 100,000 of population ( 1 ) . at the same time , the increasing number of ovarian cancer patients has been increasing in many countries in the last decades . poor prognosis of the disease , despite the advances in diagnosis and treatment , causes a major medical and public health concern ( 24 ) . epidemiological studies of ovarian cancer conducted recently in kazakhstan ( 5 , 6 ) show that the dynamics of incidence indexes are raising , though the component analysis particularly , the one taking into consideration ethnic characteristics , has never been conducted . component analysis of the dynamics of malignant tumors in kazakhstan has been performed generally in all localizations ( 7 ) , with the cancer of the esophagus ( 8) and malignant tumors of the cns ( 9 ) . the study of the dynamics of malignant tumors is essential for planning and management of drug treatment for policy - makers . during this process for example , to what extent the increase in incidence is associated with aging of the population , and to what extent - to an increased risk of developing the disease due to the emergence of new or intensification of existing epidemiological factors . undoubtedly , identification and solution of such problems over the study period in this population are necessary , unless significant changes in registration and the quality of diagnosis could have occurred ( 10 ) . growth of incidence of the ovarian cancer is the result of accumulation of elements of complex combinations of different component structures . investigation of changes in the incidence of ovarian cancer in dynamics represents scientific and practical interest , especially with the component analysis . performance of such analysis for the study of individual components of the change in incidence , influencing its level , will allow oncology service management to identify the factors leading to the occurrence of ovarian cancer , and to organize targeted cancer control . the aim of the study was to perform component analysis of the dynamics of incidence of ovarian cancer of the female population of kazakhstan from 1999 to 2009 taking into account their ethnic background . the major source of the information on the incidence of the ovarian cancer was primary data on registered patients with malignant tumors in the whole country . the data of the committee of statistics of the ministry of national economy of the republic of kazakhstan on the female population was also used as the source of information ( 11 ) . retrospective study ( 19992009 ) incidence rates were calculated according to generally accepted methods of health statistics ( 12 , 13 ) and are represented by 100,000 ( 00000 ) of the corresponding female population . the study was approved by the local ethical committee and administrative permission was obtained from jsc astana medical university . the information may be shared for research purposes only if a requesting organization provides the data security and under takes all the necessary actions in making unable the identity of respondents , in concordance with the principles of the world medical association ( wma ) declaration of helsinki ethical principles for medical research involving human subjects , adopted by the 18th wma general assembly in helsinki , finland , in june 1964 . the dynamics of the ovarian cancer in the female population of kazakhstan was studied based on the guidelines of dvoyrin and axel ( 10 ) . this method of analysis allows segmentation of growth of the number of the diseased belonging to the same population , but at different time . the first three components are related to the changes in population number , age structure of population , and the combined influence of these factors . the fourth component is determined only by the change of the risk index of the malignant ovarian tumor and the other three components are related to the risk associated with the population growth , changes in its age structure and the resulting effect of all three factors . many researchers understand the term a disease risk as the whole complex of reasons that can lead to increase , reduction or stabilization of morbidity indexes . the component method used for analysis of the dynamics of the number of ovarian cancer patients was performed on cases that occurred from 1999 to 2009 among the entire female population , including females of kazakh and russian nationalities , as the studied ethnic groups still take a leading position in both the number of the female population and among the ovarian cancer patients . mathematical calculations for component analysis of morbidity dynamics for malignant tumor ovarian in population of kazakhstan were produced using microsoft excel program and are presented in the relevant tables . the following symbols and abbreviations were used in this article : pij the incidence of ovarian cancer at certain age in the i- th and in the j - th years , nij population size at certain age in the ith to j - th years , pj and nj crude incidence rate and the total population size in the j - th year respectively , j=1 the start year of observation , j=2 the final year of observation , nijnj = sij the proportion of patients aged i in the total population size in the j - th year , asp the age structure of the population , si structural indexes , rp risk of progressing , noc the number of ovarian cancer cases , pn population number , eni the expected number of infected . demographic change of the population is one of the most important epidemiological factors that influence the occurrence of cancers in the population , in particular ovarian cancer in women . thus , the number of total female population of the country over the study period ( 19992009 ) increased from 7 752 100 ( 1999 ) up to 8 185 900 ( 2009 ) , while the number of women of kazakh nationality increased and population of russian women decreased ( fig . 1 ) . change in the size of female population of kazakhstan for 19992009 the age structure of the female population has changed over this period in the individual age groups ( fig . 2 ) . thus , the proportion of women increased in general population for the 5059 age group ( 3.2% ) and 70 years and older ( 0.6% ) years , kazakh women aged 4049 ( + 2.9% ) , 5059 ( + 2.2% ) , 6069 ( + 0.5% ) and in russian women aged 5059 ( + 3.8% ) and 70 years and older ( + 1.4% ) . the change in age structure of the female population ( a total , b kazakh , c russian ) in kazakhstan for 1999 to 2009 ( % ) the results of the component analysis of the dynamics in the number of ovarian cancer patients in all kazakh and russian female population of kazakhstan since 1999 to 2009 is presented in tables 1 and 2 . component analysis of ovarian cancer incidence growth in kazakhstan component analysis of the dynamics of ovarian cancer incidence growth in kazakhstan the analysis of morbidity of the ovarian cancer in dynamics showed the growth of indexes , with the total increase in 2009 compared to 1999 caused by the changes in the age structure of the population , the disease risk and the combined influence of the age structure and the disease risk . at the same time , the growth of indexes among russian female population is mainly caused by the changes associated with risk of infection ( =p=+0.81 + 2.03 respectively ) , and for kazakh females it is mostly caused by changes in the age structure of the population ( =b=+0.91 ) . the internationally recognized epidemiological patterns say that with the population growth and the changes in its age structure the number of patients should grow as well . it can be concluded from the researches that in general the dynamics of the number of patients with ovarian cancer for the entire female population of kazakhstan can be caused by the following factors ( table 3 ) . components of increase in the number of cases of ovarian cancer in kazakhstan growth population number p=+22.1% ( kazakh p=+46.1 , russian p=259.3% ) ; changes in the age structure of the population a=+32.7% ( kazakh a=+15.7% , russian a=+130.8% ) . combined effect of changes in population number and its age structure pa=+1.8% ( kazakh pa=+7.2% , russian pa=19.2% ) . combined effect of changes in the disease risk and population number pr=+2.0% ( kazakh pr=+3.5% , russian pr=36.3% ) . combined effect of changes in the disease risk and age structure of the population ar=+5.1% ( kazakh ar=+3.5% , russian ar=36.3% ) . combined effect of the changes in the disease risk of the population and its age structure par=+0.3% ( kazakh par=+0.6% , russian the total increase in the absolute number of patients overall ( all nationalities ) equals the sum of components : n2n1=+38 + 57 + 3 + 63 + 4 + 9 + 0= = + 174 or + 25.4% in comparison with the primary number of patients ( 174686100=25.4% ) . at the same time , the components of the growth in the percentage at the primary level are equal for the whole female population : + 5.6 + 8.3%+0.5%+14.4%+9.1%+0.5%+1.3%+0.1%=+25.4%+11.0% the overall increase for kazakh female population equals to : n2n1=+62 + 37 + 10 + 18 + 5 + 3 + 1= = + 135 or + 57.9% compared to 1999 ( 135233100=57.9% ) , the components were : + 26.6%+15.7%+4.2%+46.5%+7.6%+2.0%+1.4%+0.4%+11.4%=+57.9% the overall increase for russian female population equals to : n2n1=52 + 264 + 497 + 91= = + 20 or + 5.7% compared to the original number of patients ( 20353100=5.7% ) . according to that , the components of growth in percent of the initial level were equal to : 14.7%+7.4%1.1%8.4%2.1%+14.0%+2.5%0.4%+14.0%=+5.7% thus , ovarian cancer in kazakhstan is characterized by the increase in the number of patients due to the changes in total number and the structure of the population ( for the entire female population + 14.4% of the total growth of + 25.4% ; for kazakh female population + 46.5 of the total growth + 57.9% and for russian female population 8.4% of the total growth of + 5.6% ) . the actual growth of ovarian cancer cases is significant and is equal to + 9.1% for the whole population , + 7.6% for kazakh women and + 14.0% for russian women . the components are grouped into 3 classes , one of which represents different kinds of changes in the population ( p+a+pa ) , the second one shows only the growth of disease risk ( r ) and the third the relationship between these factors ( pr+ar+par ) . therefore , to characterize the cumulative effect of changes in population or the disease risk the components of the 1st and 2nd class the effect of influence of the 3rd class components should be added : ( p+a+pa)+(pr+ar+par)r+(pr+ar+par ) ( p+a+pa)+(pr+ar+par ) if the overall increase in the number of ovarian cancer patients for the female population ( 174 ) is taken as 100% , the increase associated with the disease risk is + 43,4% ( ( + 9.1 + 0.5 + 1.3 + 0.1)25.4100 ) and with pure risk growth it equals to + 36.0% . for kazakh women the growing number of the disease risk ( 135=100% ) will be + 19.7% ( ( + 7.6 + 2.0 + 1.4 + 0.4)57.9100 ) , and with pure increased risk of + 13.1% , respectively , and for russian women ( 20=100% ) the growth of ovarian cancer risk will be 247.7% ( ( + 14.02.1 + 2.50.4)5.6100 ) , and with pure increased risk + 246.8% . various component structures in ovarian cancer at different times or in different groups of the female population at the same time period may provide important information for the construction of epidemiological hypotheses about possible causal role of environmental factors . thus , the number of patients with ovarian cancer in the whole country is increasing . the growth is mainly caused by population growth , the combined effect of changes in population number and its age structure , the changes if infection risks , the combined effect of changes in the infection risks and age structure of the population . the results of the component analysis of the dynamics of ovarian cancer infections in kazakhstan are recommended to use when planning anti - cancer activities of ovarian cancer . the number of patients with ovarian cancer has been steadily increasing in the republic of kazakhstan . it was found that the increase in the number of patients with this malignant disease is caused mainly by the change in the total number and age structure of the population , and their combined action , as well as the increase of risk of developing the disease due to the emergence of new or intensification of existing epidemiological risk factors . the results of the component analysis of the dynamics of ovarian cancer cases in kazakhstan are recommended to use when planning anti - cancer activities of ovarian cancer . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .

background : we examined epidemiological aspects of dynamic changes in incidence of ovarian cancer in women of kazakh and russian nationalities in kazakhstan.methods:the material of investigation was primary data on registered patients with malignant ovarian tumors in the whole country . the study was conducted during the period of 19992009 . evaluation of changes in ovarian cancer incidence in the female population of kazakhstan was performed using component analysis.results:the number of patients with ovarian cancer in the whole country is increasing . this increase is due to several major reasons , including population growth ( all females p=+22.1% , females of kazakh nationality p=+46.0% and females of russian nationality p=259.3% ) , changes in the age structure ( all females a=+32.7% , females of kazakh nationality a=+27.1 and females of russian nationality a=+130.8 ) , and changes in risks of developing the disease ( all females r=+36.0% , females of kazakh nationality r=+13.1% and females of russian nationality r=+246.8%).conclusion : this investigation was the first epidemiological study of dynamics of ovarian cancer by component analysis in women of kazakh and russian nationalities in kazakhstan . implementation of the results of the study is recommended in management of anti - cancer activities for ovarian cancer .

associated with string theory and higher dimensional universes , there has been a renewed interest in higher dimensional solutions to einstein field equations , among the most interesting being black rings @xcite , kk bubbles as well as black strings . one simple way to lift the 4d schwarzschild black hole to a 5d black string is to add an extra flat dimension . in other words it is possible to uniformly extend the 4d black hole with @xmath0 horizon into the fifth dimension producing a hypercylindrical black hole @xmath1 @xcite . a striking fact related to black strings is their generic instability and final fate and whether these end up as black holes or different objects is still not well understood @xcite , @xcite . in this sense it is interesting testing more general black string solutions both static and non - static . some generalizations are obtained by applying a boost to the string solution , dotating the string with the momentum along the fifth coordinate @xcite . in this work we derive and report a generalized black string solution with mass , arbitrary tension and an additional parameter related to deformation from spherical symmetry . to generate a generalized black string solution we take as seed the zipoy - vorhees ( zv ) family of solutions and then lift it to 5d by the procedure introduced in @xcite,@xcite . particular cases are the static black string with arbitrary tension of c. h. lee @xcite and the gregory - laflamme black string @xcite . trapped surfaces and horizons , as well as the mass and string tension parameters , are analyzed and discussed . we briefly explain the idea of the generating technique ( see details in @xcite ) . let us consider the 5d vacuum einstein action , @xmath2 where the hatted quantities mean the fifth dimensional version of the scalar curvature @xmath3 , the metric tensor @xmath4 and the gravitational newton constant @xmath5 and @xmath6 is the fifth coordinate . the equations of motion derived of the variation of action ( [ s5d ] ) coincide with the einstein - scalar coupled equations in four dimensions . for a static line element given in weyl coordinates , @xmath7 and a minimaly coupled scalar field @xmath8 , these field equations are given by @xmath9 let us consider the zv solution @xcite in weyl coordinates ( for a discussion on zipoy - voorhees solution see @xcite ) , with the line element ( [ a1 ] ) and the metric functions given by : @xmath10^ { \frac{q}{2 } } , \nonumber\\ \sigma&=&\frac{1}{2}\ln\left[\frac{(r_{+}+r_{-})^{2}-4m^{2}}{4r_{+}r_{- } } \right]^{\frac{q^{2}}{4 } } , \nonumber\\ r_{\pm } ^{2}&=&\rho^{2}+(z \pm m)^{2}. \label{a1.1}\end{aligned}\ ] ] zv solution is characterized by two free parameters @xmath11 and @xmath12 related to mass and spherical - symmetry deformation , respectively . for @xmath13 we recover schwarzschild solution while if @xmath14 it represents the darmois solution @xcite . adding the scalar field in order to use the generating algorithm of @xcite,@xcite @xmath15,\ ] ] where the scalar field is a solution of laplace s equation @xmath16 , we obtain the spacetime with a scalar field @xmath8 , expressed as @xmath17 with @xmath18.\ ] ] the above solution is an exact solution of the einstein - scalar equations ( [ field_eqs ] ) . using now the method described in @xcite , and considering the metric ( [ a3 ] ) as seed , we lift the solution to five dimensions : @xmath19 explicitly @xmath20 where @xmath21 transforming the metric ( [ a6 ] ) to the schwarzschild - like coordinates @xmath22 , with @xmath23 we obtain : @xmath24 where @xmath25 and @xmath26 . this solution is a generalized 5d black string characterized by three free parameters : @xmath27 , @xmath12 and @xmath11 . note that to recover transverse spherical symmetry , we must choose @xmath28 in ( [ a8 ] ) . doing so the term with @xmath29 does not appear in @xmath30 and @xmath31 , obtaining an element proportional to @xmath32 : @xmath33 the case @xmath34 and @xmath13 corresponds to the black string @xcite , @xmath35 in the case @xmath36 and @xmath37 solution ( [ a8 ] ) becomes @xmath38 -dt^{2},\ ] ] having in square brackets the schwarzschild line element with the euclidean signature . by analytic continuation of the 2-sphere in ( [ kk ] ) to a 2-de sitter making @xmath39 and @xmath40 we get the expression of the 5d kk - bubble of nothing @xcite @xmath41 + d \psi^{2}.\ ] ] another interesting particular case is the black string with arbitrary tension @xcite . performing in ( [ sph ] ) the coordinate transformation @xmath42 the metric is transformed into : @xmath43 + d^{\frac{4}{\sqrt{3}}a}d \omega^{2},\ ] ] where @xmath44 . parametrizing with @xmath45 related to @xmath46 by @xmath47 the metric ( [ a22 ] ) is written as @xmath48 in this parametrization the solution has only two free parameters @xmath49 and we identify it as the black string with arbitrary tension previously derived in @xcite and studied in @xcite . notice that we have given a much simpler derivation of the solution . rod structure of the 4d zipoy - vorhees solution , width=325,height=151 ] rod structure of the 5d black string generated from zipoy - vorhees and inserting a finite rod with scalar charge @xmath50 in the interval @xmath51 in the fifth dimension . the bold dotted line along @xmath52 is a rod with negative mass density ( conical singularity).,width=325,height=151 ] it is illustrative to sketch briefly how the generation method works in terms of the rod - structure @xcite , @xcite . the zv seed solution , eqs . ( [ a1])-([a1.1 ] ) , is characterized by the rod - structure shown in fig . it differs from schwarzschild only in the mass density along the killing directions : for schwarzschild the density in the interval @xmath53 $ ] along the @xmath54 direction is 1 , while for zv the density is @xmath55 . in the intervals @xmath56 $ ] and @xmath57 $ ] along @xmath52 the density is also @xmath55 ( @xmath13 for schwarzschild ) . introducing the scalar field @xmath8 and then lifting to 5d in terms of the rod structure amounts to introduce into the fifth dimension a rod of density @xmath58 . the rod structure of the 5d black string , eqs . ( [ a6])-([a6.1 ] ) , is ( shown in fig . [ fig2 ] ) the following : there is a density @xmath58 in the interval @xmath53 $ ] along the @xmath59 direction . a conical singularity along the @xmath52 direction is shown as the negative density @xmath60 in the interval @xmath53 $ ] ( bold dotted line ) ; also there is a positive density of @xmath55 in the intervals @xmath61 $ ] and @xmath57 $ ] along the @xmath52 direction . the density is @xmath62 in the interval @xmath53 $ ] along the @xmath54 direction ; to have a physical horizon , if one wants to keep calling the system a black string , the density along the timelike direction should be positive , i.e. @xmath63 . the invariant that defines trapped or marginally trapped surfaces for the generated solution ( [ a8 ] ) is analyzed in what follows . trapped surfaces @xmath64 and located horizons corresponding to the spacetime ( [ a8 ] ) , are determined by the scalar @xmath65 ( see @xcite ) . to calculate it , we fix the coordinates @xmath66 and denote the local coordinates on the surface @xmath64 by @xmath67 . the function @xmath68 , gives the canonical volume element of the surfaces @xmath64 . introducing @xmath69 , @xmath70 and defining @xmath71 the invariant @xmath65 for the obtained solution amounts to @xmath72 for the solution of our interest , @xmath73\ ] ] and therefore , @xmath65 is obtained as @xmath74[r - m(1-\cos\theta)]\}^{a^{2}+ \frac{q^{2}}{4}-3}[{\tilde v}_{,r}]^{2 } } { r^{a^{2}+\frac{q^{2}}{4}+\frac{a}{\sqrt{3}}+\frac{q}{2}+1 } ( r-2m)^{a^{2}+\frac{q^{2}}{4}-\frac{a}{\sqrt{3}}-\frac{q}{2}+1}}\ ] ] with @xmath75m^2r- ( 1+a^2 + \frac{q^{2}}{4}+q ) \sin^2{\theta}m^3 \nonumber\\ & = & ( r - m)[2r(r-2m)+m^{2}\sin^{2}\theta(a^{2}+ \frac{q^{2}}{4}+1)]-mq[r^{2}-2mr+m^{2}\sin^{2}\theta],\end{aligned}\ ] ] let us analyze the marginally trapped surfaces defined when @xmath76 as well as the singularities if @xmath65 diverges . to determine those values of @xmath65 cancelations in the denominator coming from @xmath77 should be taken into account . assuming that @xmath78 and @xmath79 , then there exists a singularity at @xmath80 since the exponent of @xmath81 in the denominator of ( [ a12 ] ) is always positive , @xmath82 . also there are two marginally trapped surfaces at @xmath83 , nevertheless these are wrapped or hidden by the naked singularity located at @xmath84 . depending on the values of @xmath27 and @xmath12 , in the product of @xmath85 and @xmath86 may be cancelations that define horizons that coincide with the naked singularity @xmath84 . another kind of marginally trapped surfaces that overlap the singularity in some regions , arise from the real root @xmath87 of the third degree polynomial @xmath85 . these surfaces when @xmath88 do not cover completely the singularity due to the dependence on @xmath89 . then the situation when @xmath88 is that for some ranges of @xmath89 the singularity is hidden but coming from other direction the singularity is naked , i.e. the singularity is partially naked ( or partially dressed ) . for the black string with arbitrary tension ( @xmath90 ) , @xmath65 amounts to @xmath91 the solution is singular at @xmath84 unless @xmath13 ( @xmath92 ) , case in which it possesses a horizon at @xmath84 ( @xmath93 ) . in any other case ( @xmath94 ) there is a naked singularity at @xmath84 that hides horizons at @xmath95 . the @xmath65 diverges at @xmath80 showing the singularity there . in the case @xmath34 and @xmath13 that we recover the black string solution @xcite , it possesses a horizon at @xmath84 as the expression for @xmath65 shows , @xmath96 in this case the naked singularity disappears and instead a horizon is located at @xmath84 . with respect to the analysis of the singularities we have attempted to draw penrose diagram to dilucidate the global structure of the solutions . however , due to the reduced symmetry of the line element ( [ a8 ] ) the metric function @xmath30 does not depend only on @xmath81 but also on @xmath89 . even if one drops the @xmath89 dependence , by fixing the angle , the integration to be performed involve hypergeometric functions , and the analysis by this method does not produce a clear picture . on the other hand , the information one obtains by studying the scalar @xmath65 , is essentially the same that can be obtained from the kretschmann scalar . to characterize the 5d black string we need to determine the mass and tension of the source using the asymptotic expansion of the metric functions @xmath97 and @xmath98 of ( [ a8 ] ) , @xmath99 comparing with the asymptotic form of metric around a stationary matter source as given in @xcite , @xcite : @xmath100 the mass and string tension of the 5d black string ( [ a8 ] ) are identified then as ( we are considering @xmath101 ) @xmath102 therefore when ( [ a1 ] ) is lifted to 5d , by means of the scalar field @xmath103 , the string tension changes in @xmath104 , that can modify the tension and even make it vanish by calibrating @xmath105 , however , from the rod - structure we learned that @xmath106 in order to have a horizon . in the case @xmath34 and @xmath13 we recover the black string solution @xcite , with @xmath107 . the case @xmath108 and @xmath37 corresponds to a black string with @xmath109 . in this paper by equiping first the 4d zipoy - vorhees solution with a scalar field , we lifted it to five dimensions ; the so generated 5d solution is a black string characterized by three free parameters : mass , tension and deformation parameter . there is a physical spacetime singularity at @xmath80 . moreover , the horizons do not cover completely the naked singularity at @xmath84 , except in the case that @xmath84 is the horizon itself . therefore , in 5d the cosmic censorship conjecture does not hold . the static black string with arbitrary tension is a particular case when there is transversal spherical symmetry . the stability of the 5d generalized black string deserves further analysis , particularly to acquaint how the deformation parameter @xmath27 can affect the stability of the solution , since it modifies the string tension . we have seen that the three parameter generalizations of the black string solutions are singular . this may well be an indicator that the black strings are unstable in the sense of @xcite , @xcite . a.f . acknowledges the support of the basque government grant gico7/51-it-221 - 07 and the spanish science ministry grant fis2007 - 61800 . n. b. would like to thank the colleagues of upv / ehu for warm hospitality . l. a. lpez acknowledges conacyt - mxico for a ph . d. grant . partial support of conacyt - mexico project 49182-f is also acknowledged .

starting with a zipoy - voorhees line element we construct and study the three parameter family of solutions describing a deformed black string with arbitrary tension .

previous articles ( mcbride et al . , 1992 , 1996 ; millar et al . , 1996 ; goping et al . , 1998 ) these include isolation of rat heart mitochondria , transcription - translation of plasmids encoding vdac and preornithine carbamyl transferase ( poct ) , and import of s - labeled translation products into mitochondria in vitro . recombinant glutathione s - transferase ( gst)human tom201 - 29 ( formerly named gst-30htom20 ) , lacking the nh2-terminal transmembrane segment of htom20 , was expressed in topp2 cells and purified ( schleiff et al . , 1997 ) . protein immobilized on glutathione - sepharose 4b was washed and suspended in 20 mm napo4 , ph 7.4 , 150 mm nacl , 1 mm dithiothreitol , 0.5 mm cacl2 , and incubated with 5 g / ml thrombin for 18 h at 4c , generating htom201 - 29 with an extra gly residue at the nh2 terminus derived from the thrombin cleavage site . the mixture was passed through a mono s hr 5/5 column and protein was eluted with a linear gradient ( buffer a , 10 mm mes , ph 5.0 ; buffer b , 10 mm 3-cyclohexylamino-1-propane sulfonic acid , ph 10 , 500 mm nacl ) . peak fractions containing htom201 - 29 were resolved on a superdex 200 column in 10 mm hepes , ph 7.0 , and 100 mm nacl . fractions containing the purified protein were dialyzed against the same buffer containing 5 mm dtt and the protein concentrated to 1.5 mg / ml . plasmid encoding gst - htom201 - 29 was manipulated by standard recombinant dna procedures to substitute cys at htom20 codon position 100 with ser and to introduce ser - cys after gly at the thrombin cleavage site . the thrombin cleavage product , htom201 - 29/n - gsc / c100s , was generated and purified as above . approximately 100 nm large unilamellar vesicles ( luvs ) ( lipid composition : pc , phosphotidylcholine ; pe , phosphotidylethanolamine ; pi , phosphotidylinositol ; ps , phosphotidylserine ; pc / pe / pi / ps at molar ratios of 55:28:13:3 or pc / pe / pi / ps / pe - bmps at molar ratios of 54.5:27.5:13:3:1 ) were prepared in 170 mm sucrose , 20 mm tris acetate , ph 7.0 , and 2 mm cacl2 ( shahinian and silvius , 1995 ) . luvs containing -maleimidopropionic acid n - hydroxysuccinimide ester of pe ( pe - bmps ) were incubated for 12 h at 4c with htom201 - 29/n - gsc / c100s ( 10-fold molar excess relative to pe - bmps ; coupling efficiency , 8595% ) followed by two 30 min incubations with excess luvs generated in medium lacking sucrose ( 100 mm nacl , 20 mm tris acetate , ph 7.0 , and 2 mm cacl2 ) to competitively remove unincorporated htom20 . sucrose - loaded luvs containing the covalently attached cytosolic domain of htom20 were recovered by centrifugation at 50,000 g for 60 min in a beckman 75ti rotor . previous articles ( mcbride et al . , 1992 , 1996 ; millar et al . , 1996 ; goping et al . , 1998 ) these include isolation of rat heart mitochondria , transcription - translation of plasmids encoding vdac and preornithine carbamyl transferase ( poct ) , and import of s - labeled translation products into mitochondria in vitro . recombinant glutathione s - transferase ( gst)human tom201 - 29 ( formerly named gst-30htom20 ) , lacking the nh2-terminal transmembrane segment of htom20 , was expressed in topp2 cells and purified ( schleiff et al . , 1997 ) . protein immobilized on glutathione - sepharose 4b was washed and suspended in 20 mm napo4 , ph 7.4 , 150 mm nacl , 1 mm dithiothreitol , 0.5 mm cacl2 , and incubated with 5 g / ml thrombin for 18 h at 4c , generating htom201 - 29 with an extra gly residue at the nh2 terminus derived from the thrombin cleavage site . the mixture was passed through a mono s hr 5/5 column and protein was eluted with a linear gradient ( buffer a , 10 mm mes , ph 5.0 ; buffer b , 10 mm 3-cyclohexylamino-1-propane sulfonic acid , ph 10 , 500 mm nacl ) . peak fractions containing htom201 - 29 were resolved on a superdex 200 column in 10 mm hepes , ph 7.0 , and 100 mm nacl . fractions containing the purified protein were dialyzed against the same buffer containing 5 mm dtt and the protein concentrated to 1.5 mg / ml . plasmid encoding gst - htom201 - 29 was manipulated by standard recombinant dna procedures to substitute cys at htom20 codon position 100 with ser and to introduce ser - cys after gly at the thrombin cleavage site . the thrombin cleavage product , htom201 - 29/n - gsc / c100s , was generated and purified as above . approximately 100 nm large unilamellar vesicles ( luvs ) ( lipid composition : pc , phosphotidylcholine ; pe , phosphotidylethanolamine ; pi , phosphotidylinositol ; ps , phosphotidylserine ; pc / pe / pi / ps at molar ratios of 55:28:13:3 or pc / pe / pi / ps / pe - bmps at molar ratios of 54.5:27.5:13:3:1 ) were prepared in 170 mm sucrose , 20 mm tris acetate , ph 7.0 , and 2 mm cacl2 ( shahinian and silvius , 1995 ) . luvs containing -maleimidopropionic acid n - hydroxysuccinimide ester of pe ( pe - bmps ) were incubated for 12 h at 4c with htom201 - 29/n - gsc / c100s ( 10-fold molar excess relative to pe - bmps ; coupling efficiency , 8595% ) followed by two 30 min incubations with excess luvs generated in medium lacking sucrose ( 100 mm nacl , 20 mm tris acetate , ph 7.0 , and 2 mm cacl2 ) to competitively remove unincorporated htom20 . sucrose - loaded luvs containing the covalently attached cytosolic domain of htom20 were recovered by centrifugation at 50,000 g for 60 min in a beckman 75ti rotor . standard protein import was conducted by combining rat heart mitochondria with human vdac synthesized in reticulocyte lysate . in this system , the preprotein translocation pore can be jammed by partially importing a chimeric protein containing a matrix - targeting signal fused to dihydrofolate reductase ( dhfr ) . unfolding of the dhfr moiety on the cytosolic side of the outer membrane is prevented by the high - affinity dhfr active site inhibitor , methotrexate ( mtx ; eilers and schatz , 1986 ; vestweber et al . , 1989 ) . in the presence of mtx , excess podhfr ( sheffield et al . , 1990 ) , a chimeric protein consisting of the matrix targeting signal of poct fused to dhfr and purified from expressing bacteria , blocked import and processing of poct ( fig . 1 a , lower panel , lanes 3 and 4 ) , whose processed form otherwise acquires resistance to external trypsin ( fig . in addition to inhibition of poct import , podhfr / mtx inhibited outer membrane insertion of ytom70(1 - 29)dhfr ( fig . 1 b ) , also designated pomd29 , a chimeric protein comprised of the transmembrane signal - anchor domain of yeast tom70 fused to dhfr , whose insertion into the outer membrane of heart mitochondria in vitro has been documented previously ( li and shore , 1992 ; mcbride et al . , 1992 ) . ytom70(1 - 29)dhfr is inserted into the outer membrane in the nin - ccyto orientation ( li and shore , 1992 ; mcbride et al . , 1992 ) and therefore , its import in the absence of competing podhfr was unaffected by mtx ( not shown ) . in contrast to poct and ytom70(1 - 29)dhfr , import and membrane insertion of vdac in this system , assessed by the temperature - sensitive acquisition of resistance to alkaline extraction ( fujiki et al . , 1982 ; goping et al . 1 a , upper panel , compare lanes 7 and 8) , was relatively unaffected by podhfr / mtx ( fig . 1 a , upper panel , lanes 8 and 9 ) . the slight reduction in vdac import at 5 min effected by podhfr / mtx may relate to the fact that preproteins like podhfr can stimulate recruitment of tom20 into the translocation complex , thereby competitively reducing the amount of free tom20 in the membrane that is available for interaction with vdac ( rapaport et al . , 1998 ) . the failure of partially translocated podhfr / mtx to block membrane insertion of vdac suggested that vdac may bypass the requirement for the tom40 translocation pore during import . to address this question further , import of vdac was examined using isolated yeast mitochondria containing a temperature - sensitive mutant of tom40 ( kassenbrock et al . , 1995 ) . in contrast to control mitochondria , temperature - sensitive tom40 mitochondria were incapable of importing the matrix preprotein form of cytochrome oxidase subunit va ( cox va ) at the nonpermissive temperature ( 37c ) , as judged by the failure of pcox va to be processed by the mitochondria at 37c ( fig . 1 c , lane 4 ) , while processing of pcox va was observed at the permissive temperature of 23c . in contrast to pcox va , membrane insertion of vdac occurred at both 23 and 37c ( fig . 1 c ) . the slight decrease in membrane insertion of vdac at 37c compared with 23c was similar for both wild - type and temperature - sensitive tom40 mitochondria ( fig . 1 c ) , suggesting that this difference was related to events other than the temperature - sensitive phenotype of tom40 . the cytosolic domain of htom20 , htom201 - 29 , when included as a soluble entity in excess in the import reaction , inhibited import of poct ( fig . 1 a , lower panel , compare lanes 8 and 10 ) , presumably because it sequestered the preprotein through direct protein interaction ( schleiff et al . , 1997 ) and prevented transfer of the preprotein to the translocation machinery . htom201 - 29 can also physically interact with vdac ( schleiff et al . , 1997 ) . in distinct contrast to poct , however , htom201 - 29 did not interfere with insertion of vdac into the outer membrane . 1 a , upper panel , compare lanes 8 and 10 ) , suggesting that potential interactions between vdac and htom201 - 29 in the import reaction must be readily reversible . moreover , the difference in response of poct and vdac to htom201 - 29 in the import reaction suggested a potential fundamental difference in the import pathways of the two proteins . however , the results also imply that a complex of vdac and soluble htom201 - 29 can make contact with the mitochondrial surface in vitro , a suggestion that is compatible with the observed binding of the cytosolic domain of htom20 to lipid surfaces in vitro ( schleiff and turnbull , 1998 ; fig . 2 a ) . to assess the possibility that htom20 can mediate direct insertion of vdac into a membrane lipid bilayer , synthetic luvs were created in which the cytosolic domain of htom20 was linked to the bilayer surface via covalent attachment to pe - pmbs ( fig . 2 a ) . to that end , the protein was modified to contain a unique cys at the nh2 terminus of htom201 - 29 ; the other cys located at codon position 100 was converted to ser . these changes did not influence the ability of the receptor to interact with either vdac or poct in vitro ( data not shown ) . the liposomes had a phospholipid composition similar to that of total mitochondrial outer membrane in rat liver ( de kroon et al . , 1997 ) . under the conditions used for mitochondrial protein import reactions with vdac synthesized in reticulocyte lysate such liposomes were found to efficiently insert the protein , as determined by acquired resistance to extraction at alkaline ph or with urea ( fig . moreover , the resulting import product was resistant to treatment with trypsin ( lane 4 ) , reflective of vdac in native membranes ( colombini et al . , 1996 ; mannella , 1997 ) . luvs bearing the htom20 cytosolic domain did not translocate poct , as judged by the failure of poct to acquire resistance to trypsin ( fig . 2 b , lower panel ) , nor did they insert ytom70(1 - 29)dhfr , as judged by its extractability from liposomes with 7 m urea ( not shown ) . furthermore , vdac that associated with luvs lacking the htom20 cytosolic domain exhibited facile interliposomal transfer ( fig as expected , vdac that was inserted into the luv lipid bilayer by the htom20 cytosolic domain did not transfer to subsequently added protein - free luvs . in contrast , poct that bound to luvs containing the htom20 cytosolic domain could subsequently transfer to protein - free luvs , but slower than poct that bound to luvs lacking htom20 ( t1/2 , 15 versus 1 min ; fig . this finding is consistent with the ability of htom20 to physically interact with poct ( schleiff et al . , 1997 ) . moreover , the relatively slow dissociation of poct from the htom20 cytosolic domain explains the ability of excess htom201 - 29 to inhibit import of poct into mitochondria in vitro ( fig . finally , vdac that had been inserted into luvs by the htom20 cytosolic domain was examined for its ability to transport a physiological substrate of this channel protein , atp ( rostovtseva and colombini , 1997 ; lee et al . , 1998 ) . p]atp before the import reaction , and the subsequent release of atp was measured at various times after the initiation of the reaction . insertion of a single functional vdac channel into the vesicle would be predicted to release encapsulated atp . release of radioactive atp commenced immediately upon initiation of vdac insertion into liposomes ( fig . egress of atp was dependent on functional vdac , inhibited by a known antagonist , nadh ( zizi et al . , 1994 ) , and required the presence of the htom20 cytosolic domain on the liposome surface to integrate vdac into the lipid bilayer . in contrast , the control protein poct did not stimulate atp export from luvs alone or luvs with htom20 ( fig . the first indication that a -barrel protein like vdac might not require a complex preprotein translocation machinery for insertion into a membrane lipid bilayer came with the observation that purified detergent - solubilized vdac can spontaneously integrate into planar lipid bilayers as a functional entity . moreover , in this system insertion is cooperative as a result of self - mediated stimulation ( xu and colombini , 1996 ) . although the lag period for this insertion was relatively long , the results suggest an inherent ability of the molecule to partition into a lipid bilayer , but presumably this is because the detergent - extracted entity is in a favorable state for lipid bilayer integration . however , in normal physiology , other considerations apply : the question of membrane specificity ; the problem of competing interactions of vdac with other proteins , specific or otherwise ; the necessity to maintain a conformation of soluble vdac after release from the ribosome that is compatible with subsequent membrane insertion ; and the requirement for a mechanism to catalyze vdac insertion upon contact with the mitochondrial outer membrane . in the import reaction documented here , the appropriate translocation - competent conformation for vdac may be supplied by chaperones / factors present in reticulocyte lysate ( smith et al . the only other minimum requirement was provided by htom20 on the surface of the membrane . while it is impossible to rule out any involvement of the tom40 translocation pore , its contribution to vdac membrane insertion was not detected in the assays described here , whereas its influence on import of matrix poct and pcox va , and on membrane insertion of outer membrane tom70(1 - 29)dhfr was pronounced . in addition to its role as a receptor in directing newly synthesized vdac exclusively to the mitochondrial outer membrane within the context of a whole cell , our results suggest that htom20 is capable of catalyzing direct insertion of the protein into the lipid bilayer . the receptor may accomplish this simply by bringing vdac into close proximity to the bilayer and/or by triggering release of presumptive chaperones or other factors from vdac that otherwise maintain the protein water - soluble . in either scenario , vdac may spontaneously insert into the proximate bilayer . alternatively , or in addition , htom20 may play a direct role in guiding the conformational change that allows the transbilayer -barrel channel to form . soluble cytosolic domain of htom20 stimulates insertion of vdac into the outer membrane of rat heart mitochondria in vitro by a pathway that is independent of the preprotein translocation pore . ( a ) s - labeled transcription - translation products of human vdac and rat poct in reticulocyte lysate were subjected to standard protein import reactions in the presence of purified rat heart mitochondria for the indicated times at 4c ( lanes 2 and 7 ) or 30c ( lanes 1 , 36 , and 811 ) in the absence ( lane 1 ) or presence ( lanes 211 ) of mitochondria . also included in the reactions were 15 g purified podhfr ( sheffield et al . , 1990 ) and 2 mm mtx ( lanes 4 , 6 , 9 , and 11 ) , or 15 g purified cytosolic domain of htom20 , htom201 - 29 ( lanes 5 , 6 , 10 , and 11 ) . at the end of the reactions , the mitochondria were either treated with trypsin ( poct , lanes 711 ; mcbride et al . , 1992 ) or extracted with 0.1 m naco3 , ph 11.5 ( alkali , vdac lanes 811 ; goping et al . , 1998 ) . the bar graph quantifies the radioactive bands from import reactions of vdac at 30 min , using a power macintosh 7200/120 and nih image v1.61 image analysis software . shown the bar numbers refer to the lane numbers in the vdac ( 30 min ) fluorogram . ( b ) import ( 30 min ) of [ s]vdac , [ s]poct , and [ s]ytom70(1 - 29)dhfr ( previously called pomd29 ; mcbride et al . , alkaline - resistant vdac and ytom70(1 - 29)dhfr and processed poct were analyzed and quantified as in a. ( c ) same as a , except that import of [ s]vdac or yeast [ s]pcox va was conducted using mitochondria isolated ( daum et al . , 1982 ) from wild - type saccharomyces cerevisiae ( strain d273 - 10b ) or from a yeast strain ( kky3.3 ) harboring a temperature sensitive mutation in tom40 ( kassenbrock et al . , 1995 ) , and incubated at the nonpermissive ( 37c ) or permissive ( 23c ) temperatures for tom40 for 60 min before conducting import reactions . import was for 30 min at 4 , 23 , or 37c , as indicated . p , precursor form of cox va ; m , mature form of cox va . ( a ) schematic illustration of covalent coupling of cytosolic domain of htom20 ( htom-201 - 29/n - gsc / c100s ; see materials and methods ) to the pe - pmbs incorporated into preformed luvs . ( b ) standard protein import reactions contained sucrose - loaded luvs ( diameter 100 nm ; 0.02 mm lipid ; 1.0 mol% pe - pmbs ) , with or without covalently attached htom20 ( 90 nm ) , and were incubated for 10 min at room temperature with [ s]vdac or [ s]poct . after a 20-fold dilution with reaction medium , the luvs were recovered by centrifugation at 170,000 g in an airfuge . recovery of sucrose - loaded luvs after centrifugation in all reactions was > 95% , as judged by incorporation of 0.1 mol% rhodamine - labeled pe and detection by fluorescence . the pellets were subjected to extraction with 0.1 m naco3 , ph 11.5 ( alkali ; goping et al . 1998 ) , or with 8 m urea , 40 mm hepes , ph 7.0 ( urea ) . alternatively , reactions were cooled to 4c and incubated with trypsin ( 1.0 g ) for 20 min , followed by incubation for 20 min with 10 g soybean trypsin inhibitor before dilution and recovery of luvs . final liposomal pellets were subjected to 10% sds - page and the products were visualized by fluorography . ( c ) import reactions were conducted with [ s]vdac or [ s]poct in the presence of sucrose - loaded luvs ( 0.07 mm lipid ) with or without attached cytosolic domain of htom20 . after 10 min , a 10-fold molar excess of plain lipid vesicles lacking sucrose was added for the indicated time periods , the sucrose - loaded vesicles were isolated by centrifugation as described above , and the associated [ s]vdac or [ s]poct was quantified by scintillation counting ( expressed as percent of total input ) . shown sucrose - loaded luvs with or without covalently attached htom20 and containing 1.8 mm [ p]atp ( 20 ci / mol ) were incubated in a standard protein import reaction ( goping et al . , 1998 ) with vdac or poct transcription - translation products in the presence or absence of 1 mm nadh . at the indicated times , 20 vol of import reaction medium was added , the luvs were collected by centrifugation , and radioactivity in the supernatant was determined as in fig . 2 b. shown are the average of the normalized results of three determinations with standard deviations ( maximum radioactivity = 2,100 cpm ) . the range of total encapsulated atp released from luvs - tom20 by vdac at 15 min was 510% .

insertion of newly synthesized proteins into or across the mitochondrial outer membrane is initiated by import receptors at the surface of the organelle . typically , this interaction directs the precursor protein into a preprotein translocation pore , comprised of tom40 . here , we show that a prominent -barrel channel protein spanning the outer membrane , human voltage- dependent anion - selective channel ( vdac ) , bypasses the requirement for the tom40 translocation pore during biogenesis . insertion of vdac into the outer membrane is unaffected by plugging the translocation pore with a partially translocated matrix preprotein , and mitochondria containing a temperature - sensitive mutant of tom40 insert vdac at the nonpermissive temperature . synthetic liposomes harboring the cytosolic domain of the human import receptor tom20 efficiently insert newly synthesized vdac , resulting in transbilayer transport of atp . therefore , tom20 transforms newly synthesized cytosolic vdac into a transmembrane channel that is fully integrated into the lipid bilayer .

the search for exoplanets through direct imaging has led to many serendipitous detections of brown dwarfs and low - mass stellar companions ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? these surveys tend to target young , bright stars whose potential companions would still be warm and bright in the infrared ( e.g. , * ? ? ? brown dwarfs , having higher temperatures than planetary - mass companions of the same age , are significantly brighter and therefore easier to detect . while brown dwarf companions are not the primary focus of direct imaging searches , they are useful in their own right for a better understanding of substellar atmospheres and for comparing competing formation models ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? @xcite reports the discovery of a bound low - mass companion to hd 984 , a bright , nearby ( @xmath7 pc ) f7v star of mass @xmath81.2 m@xmath9 @xcite and a temperature of @xmath10 k @xcite . with an age estimate of 30200 myr ( @xmath11 myr at a 95% confidence level ) derived from isochronal age , x - ray emission and rotation @xcite , and consistent with previous age estimates @xcite , hd 984 is ideal for direct imaging campaigns to search for young substellar objects . the results presented in @xcite finds hd 984 b at a separation of @xmath12 ( @xmath13 au ) based on the @xmath14 observations with naco @xcite in 2012 july , and the @xmath15 band observations with sinfoni @xcite in 2014 september , both mounted on ut4 on the very large telescope ( vlt ) at cerro paranal , chile . comparing the sinfoni spectrum to field brown dwarfs and low - mass star in the nasa infrared telescope facility ( irtf ) library , @xcite conclude the companion to be a m@xmath16 object @xcite . the paper reports an estimated mass of @xmath17 m@xmath18 , overlapping the brown dwarf and low - mass star regime . this mass range corresponds to a mass - ratio of @xmath19 . @xcite note that future observations in the @xmath20 band could provide additional constraints on the surface gravity of the companion , which could help place the system in the lower or higher range of the age estimate of @xmath11 myr . competing theories of companion formation are reliant upon observational studies to verify their models . systems like hd 984 b , with low mass - ratios are particularly interesting for understanding brown dwarf and low - mass companion formation . @xcite find a flat mass - ratio distribution for solar type stars , which they state to be consistent with formation via fragmentation on small scales , however their sample does not extend below @xmath21 . furthermore , the long baseline of observations of hd 984 b allows for better determination of the companion s orbit . this is necessary for understanding formation scenarios , given their dependence on separation , as some suggest disk instability is responsible for companion formation at large ( @xmath22 au ) separations and protostellar core fragmentation at small ones ( @xmath23 au ) ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? finally , characterizing young binary star systems like hd 984 is important for future observations with jwst and@xmath24or 30-m class telescopes that could discoverer lower mass exoplanets , giving insight of planet formation in binary systems . hd 984 was observed as one of the targets of the gemini planet imager exoplanet survey ( gpies , @xcite ) , an ongoing survey of over 600 nearby young stars with nearly 900 hours dedicated time on the 8-meter gemini south telescope using the gemini planet imager ( gpi , * ? ? ? * ) , a coronagraphic adaptive optics integral field spectrograph and imaging polarimeter . using near - infrared imaging spectroscopy ( 0.92.4 ) and advanced imaging and post - processing techniques , gpi detects thermal emission from exoplanets and brown dwarfs at angular separations of @xmath25@xmath26 from their parent star . we present new spectroscopic observations of hd 984 b at @xmath20 ( 1.121.35 , @xmath27 ) and @xmath28 ( 1.501.80 , @xmath29 ) bands with gpi , from which we derive the first orbit estimate and update luminosity , magnitude and mass measurements . in section [ obsv ] we describe the gpi observations . basic reductions are explained in section [ redu ] . section [ psfsub ] details the point spread function ( psf ) subtraction technique . astrometry is discussed in section [ astrometry ] , orbital fitting in section [ orbitp ] and spectral and photometric analyses are presented in section [ analysis ] . finally , we conclude in section [ conc ] . hd 984 was observed with the gpi integral field spectrograph ( ifs , * ? ? ? * ; * ? ? ? * ) on 2015 august 30 ut during the gpies campaign ( program gpies-2015b-01 , gemini observation i d : gs-2015b - q-500 - 982 ) at gemini south . the gpi ifs has a field - of - view ( fov ) of @xmath30 arcsec@xmath31 with a plate scale of @xmath32 miliarcseconds / pixel and a position angle offset of @xmath33 @xcite . coronographic images were taken in spectral mode in the @xmath20 and @xmath28 bands . observations were performed when the star was close to the meridian at an average airmass of 1.1 so as to maximize fov rotation for angular differential imaging ( adi , * ? ? ? * ) and minimize the airmass during observations . twenty - three exposures of 60 seconds of one coadd each were taken in the _ h _ band and 23 exposures , also of 60s and one coadd , were followed up in the @xmath20 band ; the @xmath20 band data was acquired with the @xmath28 band apodizer due an apodizer wheel mechanical issue . two @xmath28 band exposures and five @xmath20 band exposures were rejected due to unusable data quality . total fov rotation for _ h _ band was @xmath34 and a total rotation of @xmath35 was acquired with _ average dimm seeing for @xmath28 and @xmath20 band sequences was @xmath36 and @xmath37 respectively , higher than the median seeing of @xmath38 . the windspeed averages for @xmath28 and @xmath20 bands were 2.5 m s@xmath39 and 1.9 m s@xmath39 . images for wavelength calibration were taken during the daytime at zenith and short exposure arc images were acquired just before the sequences at the target elevation to correct for instrument flexure @xcite . the images were reduced using the gpi data reduction pipeline @xcite v1.3.0 ] . using primitives in the pipeline , raw images were dark subtracted , argon arc image comparisons were used to compensate for instrument flexure @xcite , the spectral data cube was extracted from the 2d images @xcite , bad pixels were interpolated in the cube and distortion corrections were applied @xcite . a wavelength solution was obtained using arc lamp images taken during the day prior to data acquisition . four satellite spots , psf replicas of the star generated by the pupil - plane diffraction grating @xcite , were used to measure the location of the star behind the coronagraphic mask for image registration at a common centre , and to calibrate the object flux to star flux @xcite . after the initial data reduction , each slice of each data cube , which were each flux normalized using the average maximum of a gaussian fit on the four calibration spots , were spatially magnified to align diffraction - induced speckles using the pipeline - derived spot positions to determine the star position . the images were then unsharp masked using a @xmath40 pixel kernel to remove the seeing halo and background flux , and were psf subtracted using the tloci ( template locally optimized combination of images ) algorithm @xcite . tloci uses _ a priori _ planet spectral information to optimize the least squares - based subtraction algorithm to maximize planet detection when using data acquired with the simultaneous spectral differential imaging ( ssdi , * ? ? ? * ; * ? ? ? * ) and the adi @xcite techniques . t8 and l0 templates created from the brown dwarf spectroscopic survey @xcite were used for these reductions . the tloci pipeline was run in a 6 pixel ( 85 mas ) width annulus of increasing size with an inner gap to avoid the coronagraph focal plane mask . the idl ` invert.pro ` algorithm , which uses a gaussian elimination method , was used to invert the correlation matrix with the single value decomposition cutoff algorithm which shows limited gains in the signal - to - noise ratio ( snr ) for gpi data . two annuli , one with a width of 5 pixels interior to the subtraction zone inner annuli , and another of a 10 pixel width exterior to the subtraction zone outer annuli , are used for the reference pixels to derive the correlation matrix ( pixels in the subtraction zones are not included in the correlation matrix to avoid the algorithm to fit the planet ) . once all the data cubes had been psf subtracted , a final 2d image was obtained by performing a weighted - mean of the 37 slices , using the input template spectrum and image noise to maximize the object s snr . final images for @xmath20 and @xmath28 bands shown in figure [ finalimages ] . while the initial discovery was obtained by performing both an ssdi and adi subtractions , to avoid spectral cross - talk bias , only a less aggressive adi - only subtraction ( reference images are selected if they have less than 30% of the substellar object flux in a 1.5 @xmath41 diameter aperture centred at the object position ) was used for spectral and astrometry extractions . [ cols= " < " , ] + lccccc distance & pc & @xmath7 & & & 1 + age & myr & 30200&&&2 + m@xmath42 & & @xmath43 & @xmath44 & @xmath45&3 + m@xmath46 & & @xmath47 & & @xmath48&3 + spectral type & & f7v & m@xmath16 & m@xmath0 & 4 + temperature & k & @xmath10 & @xmath49&@xmath1&5 + @xmath50 & dex & @xmath51 & @xmath52&@xmath53&2 + mass & & @xmath81.2@xmath54 & @xmath55 to @xmath56 m@xmath6 & @xmath4 to @xmath57 m@xmath6 & 2 + semi major axis@xmath58 & au & & & @xmath59 + period@xmath58 & yrs & & & @xmath60 + inclination@xmath58 & deg & & & @xmath61 + eccentricity@xmath58 & & & & @xmath62 + [ props ] our new observations of hd 984 b with the gemini planet imager have built upon the results presented by @xcite and provided a more comprehensive understanding of this young substellar companion . here we summarize the characterization we have achieved in our analysis . all numerical results can be found in table [ props ] . with a three year baseline between the first epoch of @xcite astrometry and the new gpi astrometry presented in this work , we derive the first constraints on all of the orbital parameters for this system using a rejection sampling technique . continued astrometric monitoring of hd 984 b with gpi will help to further constrain these orbital parameters , and reduce the effects of any systematic biases between measurements obtained from different instruments . the gpi observations were also used to investigate the photometric and spectroscopic properties of hd 984 b , which were compared to predictions of evolutionary models and to other substellar objects spanning a range of spectral types and ages . from the integrated _ j _ and _ h _ band spectra , and knowing the distance to the object , we measure an absolute magnitude which is used with dusty evolutionary models to derive a luminosity , mass and temperature . complementing our gpi _ jh _ spectrum with the sinfoni _ k _ band spectrum presented in @xcite , we estimated the spectral type of hd 984 b from spectral templates constructed from a large number of near - infrared spectra of low - mass stars and brown dwarfs . to account for spectral covariances , the spectra were split into high and low spatial frequencies and binned according to the correlation length measured within each spectrum . the best spectrum match was further used to calculate an effective temperature using empirical spectral type - to - temperature relations . while the results from the fit to the unfiltered and low frequency spectra were consistent in terms of the derived spectral type , the high frequency component did not help constrain the spectral type due to the lack of sharp spectral features . this method however , may prove useful to match spectral features with @xmath63 band data , where narrow spectral features , such as co , can be identified and fitted . splitting the spectra in these cases will allow for better noise statistics and improved @xmath64 analysis . the surface gravity of hd 984 b was also investigated , as a low surface gravity could have been used to provide a further constraint on the age and mass of the system . the five best fitting objects to the _ jhk _ spectrum of hd 984 b had a mix of gravity classifications . with this ambiguous result , several photometric and spectral indicators were also computed to look for additional evidence of low surface gravity . none of these indicators suggested a low surface gravity for hd 984 b , and we therefore do not assign a gravity classification to the spectral type . hd 984 b is one of the latest of a growing number of brown dwarf and low - mass companions discovered via direct imaging , often serendipitously during searches for exoplanets . as demonstrated for this object , substellar companions discovered in these campaigns can be rapidly characterized with an integral field spectrograph , and preliminary constraints on orbital parameters can be derived with a relatively short baseline between epochs . with the many ongoing surveys using extreme adaptive optics instruments such as gpi , sphere , and scexao , there is ample opportunity to discover and characterize new substellar objects in the near future . although one of object alone can not prove a rule , continued identification and characterization of this class of objects will undoubtedly further our understanding of their formation . we would like to thank dr . tiffany meshkat for providing the sinfoni @xmath63 band spectra . this research has benefited from the spex prism library and spex prism library analysis toolkit , maintained by adam burgasser at http://www.browndwarfs.org/spexprism , the montreal brown dwarf and exoplanet spectral library , maintained by jonathan gagn , and the simbad database , operated at cds , strasbourg , france . this paper is based on observations obtained at the gemini observatory , which is operated by the association of universities for research in astronomy , inc . , under a cooperative agreement with the nsf on behalf of the gemini partnership : the national science foundation ( united states ) , the national research council ( canada ) , conicyt ( chile ) , ministerio de ciencia , tecnologa e innovacin productiva ( argentina ) , and ministrio da cincia , tecnologia e inovao ( brazil ) . this publication additionally makes use of data products from the two micron all sky survey , which is a joint project of the university of massachusetts and the infrared processing and analysis center / california institute of technology , funded by the national aeronautics and space administration and the national science foundation . portions of this work were performed under the auspices of the u.s . department of energy by lawrence livermore national laboratory under contract de - ac52 - 07na27344 . supported by nasa grants nnx11ad21 g and nnx15ad95/nexss ( r.j.d.r . , j.r.g , j.j.w , t.m.e , p.g.k . ) and nx14aj80 g ( e.l.n . , s.b , f.m . ) , and nsf grants ast-0909188 and ast-1313718 ( r.j.d.r . , t.m.e . , p.g.k . )

we present new observations of the low - mass companion to hd 984 taken with the gemini planet imager as a part of the gemini planet imager exoplanet survey campaign . images of hd 984 b were obtained in the _ j _ ( 1.121.3 ) and _ h _ ( 1.501.80 ) bands . combined with archival epochs from 2012 and 2014 , we fit the first orbit to the companion to find an 18 au ( 70 year ) orbit with a 68% confidence interval between 14 and 28 au , an eccentricity of 0.18 with a 68% confidence interval between 0.05 and 0.47 , and an inclination of 119 with a 68% confidence interval between 114 and 125 . to address considerable spectral covariance in both spectra , we present a method of splitting the spectra into low and high frequencies to analyze the spectral structure at different spatial frequencies with the proper spectral noise correlation . using the split spectra , we compare to known spectral types using field brown dwarf and low - mass star spectra and find a best fit match of a field gravity m@xmath0 spectral type with a corresponding temperature of @xmath1 k. photometry of the companion yields a luminosity of @xmath2/@xmath3 dex , using dusty models . mass estimates , again from dusty models , find an age - dependent mass of @xmath4 to @xmath5 m@xmath6 . these results are consistent with previous measurements of the object .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Freedom's Way National Heritage Area Act''. SEC. 2. FINDINGS AND PURPOSES. (a) Findings.--Congress finds that-- (1) the cultural and natural legacies of the region encompassing 34 communities in Massachusetts and 6 communities in New Hampshire have made important and distinctive contributions to the national character of America; (2) these legacies were the foundation of communities in this region, and by according appropriate recognition and protection these legacies can help sustain the quality of life in the future; (3) particularly significant legacies are-- (A) the early settlement of the United States and the early evolution of democratic forms of government; (B) the development of intellectual traditions of the philosophies of freedom, democracy, and conservation; (C) the evolution of social ideas and religious freedom; (D) the role of immigrants and industry in contributing to ethnic diversity; (E) Native American and African American resources; and (F) the role of innovation and invention in the cottage industries; (4) the communities in this region know the value of their legacy, but need a cooperative framework and technical assistance to achieve important goals by working together; (5) the National Park Service is responsible for advocating the protection and interpretation of the Nation's cultural and historic resources; (6) within this distinctive area of New Hampshire and Massachusetts there is a Federal interest to support the development of a regional framework to assist the Commonwealth of Massachusetts and the State of New Hampshire, other local organizations and governments, and private citizens to conserve, protect, and bring recognition to this heritage for the educational and recreation benefit of this and future generations of Americans; (7) significant examples of such resources include-- (A) Walden Pond State Reservation; (B) Minute Man National Historical Park; (C) Shaker Villages in Shirley and Harvard; (D) Wachusett Mountain State Reservation, Fitchburg Art Museum, and Barrett House in New Ipswich; and (E) Beaver Brook Farms and Lost City of Monson in Hollis; (8) the Freedom's Way Heritage Association, Inc., would be an appropriate entity to oversee the development of the Freedom's Way National Heritage Area; and (9) the study entitled ``Freedom's Way Heritage Area Feasibility Study'', prepared by the Freedom's Way Heritage Association, Inc., and the Massachusetts Department of Environmental Management, demonstrates the sufficient assemblage of nationally distinctive historical resources necessary to establish the Freedom's Way National Heritage Area. (b) Purposes.--The purposes of this Act are-- (1) to foster a close working relationship with all levels of government, the private sector, and the local communities in Massachusetts and New Hampshire; (2) to empower communities and organizations in these 2 States to preserve the special historic identity of the region and with it the identity of the Nation; and (3) to provide for the management, preservation, protection, and interpretation of the natural, historical, and cultural resources of the region for the educational and inspirational benefit of future generations. SEC. 3. DEFINITIONS. For the purposes of this Act: (1) Association.--The term ``Association'' means the Freedom's Way Heritage Association, Inc. (2) Heritage area.--The term ``Heritage Area'' means the Freedom's Way National Heritage Area established by section 4. (3) Plan.--The term ``Plan'' means the Cultural Heritage and Management Plan required by section 6. (4) Secretary.--The term ``Secretary'' means the Secretary of the Interior. SEC. 4. FREEDOM'S WAY NATIONAL HERITAGE AREA. (a) Establishment.--There is established in the Commonwealth of Massachusetts and in the State of New Hampshire the Freedom's Way National Heritage Area. (b) Boundaries.--Except as otherwise provided in section 6, the boundaries of the Heritage Area shall include all of those lands depicted on a map entitled ``Freedom's Way National Heritage Area'', numbered ____ and dated ____. The map shall be on file in the appropriate offices of the National Park Service. The Secretary shall publish in the Federal Register, as soon as practical after the date of the enactment of this Act, a detailed description and map of the boundaries established under this subsection. Boundaries may be revised if proposed in the Plan, approved by the Secretary as provided in section 8(b), and placed on file in accordance with this subsection. SEC. 5. ADMINISTRATION AND MANAGEMENT. (a) Administration.--The Heritage Area shall be administered in accordance with the provisions of this Act. (b) Management Entity.--The management entity of the Heritage Area shall be the Freedom's Way Heritage Association, Inc. SEC. 6. MANAGEMENT PLAN. (a) Plan Requirements.--The Association shall prepare and submit for review and approval by the Secretary, a Cultural Heritage and Management Plan for the Heritage Area that presents comprehensive recommendations and strategies for the conservation, funding, management, and development of the Heritage Area. The Plan shall-- (1) take into consideration current Federal, State, county, and local plans and involve residents, public agencies, and private organizations in the Heritage Area, but shall coordinate those plans and present a unified historic preservation and interpretation plan; (2) include a description of actions that units of government and private organizations are recommended to take to protect the resources of the Heritage Area; and (3) identify existing and potential sources of Federal and non-Federal funding for the conservation, management, and development of the Heritage Area, and include-- (A) an inventory which includes any property in the Heritage Area that should be conserved, restored, managed, developed, or maintained because of the natural, cultural, recreational or historic significance to the themes of the Heritage Area; (B) a recommendation of policies for resource management and protection that consider and detail the application of appropriate land and water management techniques, including the development of intergovernmental cooperative agreements to manage and protect the historical, cultural, and natural resources and recreation opportunities of the Heritage Area in a manner consistent with supporting compatible economic revitalization efforts; (C) a program of strategies and actions to implement the Plan, including identification of the roles of agencies and organizations which are party to the implementation of the Plan, identification of specific restoration and construction plans or goals, and identification of a program of public involvement, annual work plans and reports, and the role of the Association; (D) an analysis of ways in which Federal, State, and local programs may best be coordinated to promote the purposes of this Act; (E) an interpretive and educational plan for the Heritage Area; (F) any revisions proposed by the Association to the boundaries of the Heritage Area and requested by the affected local government; and (G) a process to provide public access to the Association for the purpose of attempting to informally resolve any disputes arising from the Plan. (b) Approval of Plan.--The Secretary shall approve or disapprove the Plan in accordance with section 8(b). SEC. 7. AUTHORITIES, PROHIBITIONS, AND DUTIES OF THE ASSOCIATION. (a) Authorities.--The Association may, for purposes of preparing and implementing the Plan, use Federal funds made available through this Act-- (1) to make grants to the Commonwealth of Massachusetts, its political subdivisions, or both, the State of New Hampshire, its political subdivisions, or both, nonprofit organizations, and other persons; (2) to enter into cooperative agreements with or provide technical assistance to the Commonwealth of Massachusetts, its political subdivisions, or both, the State of New Hampshire, its political subdivisions, or both, nonprofit organizations, and other organizations; (3) to hire and compensate staff; (4) to obtain money from any source and to participate in any program or law requiring the recipient of such money to make a contribution in order to receive such money; and (5) to contract for goods and services. (b) Prohibition of Acquisition of Real Property.--The Association may not use Federal funds received under this Act to acquire real property or any interest in real property. Nothing in this Act shall preclude the Association from acquiring real property or any interest in real property using other funds intended for that purpose. (c) Duties of the Association.--The Association shall carry out the following duties: (1) Prepare and submit to the Secretary for approval a plan as described in section 6 not later than 3 years after the date of the enactment of this Act. If the Plan is not submitted to the Secretary as required under this paragraph within the specified time, the Heritage Area shall no longer qualify for Federal funding until the Plan is submitted and approved by the Secretary. (2) Give priority to the implementation of actions, goals, and strategies set forth in the Plan, including assisting units of government and others in-- (A) carrying out the programs that recognize and protect important resource values within the Heritage Area; (B) encouraging, by appropriate means, economic viability in the Heritage Area consistent with the goals of the Plan; (C) establishing and maintaining interpretive exhibits in the Heritage Area; (D) developing recreational and educational opportunities in the Heritage Area; (E) increasing public awareness of and appreciation for the natural, historical, and cultural resources of the Heritage Area; (F) restoring historic buildings that are located within the boundaries of the Heritage Area relating to the themes of the Heritage Area; and (G) ensuring that clear, consistent, and appropriate signs identifying public access points and sites of interest are posted throughout the Heritage Area. (3) Prepare and implement the Plan while considering the interests of diverse units of government, businesses, private property owners, and nonprofit groups within the Heritage Area. (4) Conduct Association meetings open to the public at least quarterly regarding the development and implementation of the Plan. (5) Submit an annual report to the Secretary for any fiscal year in which the Association receives Federal funds under this Act, setting forth its accomplishments, its expenses and income, including the entities to which it made grants during the year for which the report is made. (6) Make available for audit for any fiscal year in which it receives Federal funds under this Act, by the Congress, the Secretary, and appropriate units of government, all records and other information pertaining to the expenditure of such funds and any matching funds; and require, for all agreements authorizing expenditure of Federal funds by other organizations, that the receiving organizations make available for such audit all records and other information pertaining to the expenditure of such funds. SEC. 8. DUTIES AND AUTHORITIES OF THE SECRETARY. (a) Technical and Financial Assistance.-- (1) In general.--The Secretary may, upon the request of the Association, provide technical and financial assistance to the Heritage Area to develop and implement the approved Plan. In assisting the Heritage Area, the Secretary shall give priority to actions that in general assist in-- (A) conserving the significant natural, historic, and cultural resources of the Heritage area; and (B) providing educational, interpretive, and recreational opportunities consistent with the purposes of the Heritage Area. (2) Spending for nonfederally owned property.--Federal funds made available by the Secretary to the Association may be spent directly on nonfederally owned property identified in the Plan, or listed or eligible for listing on the National Register of Historic Places. (3) Other assistance.--The Secretary may enter into cooperative agreements with public and private organizations for the purposes of implementing this subsection. (b) Approval and Disapproval of Plan.-- (1) In general.--The Secretary shall approve or disapprove the Plan not later than 90 days after receiving the Plan. (2) Criteria for approval.--In determining whether to approve the Plan, the Secretary shall consider whether-- (A) the Association has afforded adequate opportunity, including public hearings, for public and governmental involvement in the preparation of the Plan; (B) the resource protection and interpretation strategies contained in the Plan, if implemented, would adequately protect the historic and cultural resources of the Heritage Area; and (C) the Secretary has received adequate assurances from the appropriate state and local officials whose support is needed to ensure the effective implementation of the State and local aspects of the Plan. (3) Action following disapproval.--If the Secretary disapproves the Plan, the Secretary shall advise the Association in writing of the reasons therefor and shall make recommendations for revisions to the Plan. The Secretary shall approve or disapprove a proposed revision within 60 days after the date it is submitted. (c) Approval of Amendments.--Substantial amendments to the Plan shall be reviewed by the Secretary and approved in the same manner as provided for the original Plan. The Association shall not use Federal funds authorized by this Act to implement any amendments until the amendments are approved by the Secretary. SEC. 9. DUTIES OF OTHER FEDERAL AGENCIES. Any Federal entity conducting or supporting activities directly affecting the Heritage Area shall consider the potential effect of the activity on the purposes and the Plan, and shall consult with the Association with respect to the activity, and to the extent practicable conduct or support such activities to avoid adverse effects on the purposes of the Heritage Area. SEC. 10. RELATIONSHIP TO LAND USE REGULATION AND PRIVATE PROPERTY. (a) Land Use Regulation.--The Association shall provide assistance and encouragement to State and local governments and to private organizations and individuals to protect and promote the resources and values of the Heritage Area. Nothing in this Act is intended to abrogate in any way the authority of State or local governments. Nothing in this Act may be construed to provide any authority to the Association to regulate any use of land under this or any other law, nor to grant any zoning or land use authority to the Association. (b) Private Property.--The Association shall be an advocate for land management practices consistent with the purposes of the Heritage Area. This Act provides no authority to the Association to abridge the rights of any person with regard to private property. Nothing in this Act is intended to abrogate in any way any State or local authority regarding private property. Nothing in this Act shall impose any additional burden on any property owner by the listing of his property pursuant to section 6(a)(3)(A). SEC. 11. AUTHORIZATION OF APPROPRIATIONS. (a) In General.--There is authorized to be appropriated for the purposes of this Act not more than $1,000,000 for any fiscal year. Not more than a total of $10,000,000 may be appropriated for the Heritage Area under this Act. (b) Matching Funds.--Federal funding provided under this Act may not exceed 50 percent of the total cost of any assistance or grant provided or authorized under this Act. SEC. 12. SUNSET. The authority of the Secretary to provide assistance under this Act shall terminate on the day occurring 15 years after the date of the enactment of this Act.

Freedom's Way National Heritage Area Act - Establishes in Massachusetts and New Hampshire the Freedom's Way National Heritage Area.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Elder Justice Reauthorization Act''. SEC. 2. FINDINGS. Congress finds the following: (1) According to the American Journal of Public Health, at least 10 percent of older Americans experience elder abuse. (2) Victims of elder financial abuse are estimated to lose at least $2.9 billion a year. (3) Victims of elder abuse are three times more likely to end up in a hospital and four times more likely to end up in a nursing home than nonvictims. (4) Adult protective services which operate in all 50 States to help prevent elder abuse and investigate cases have no dedicated Federal funding or any designated Federal agency home. (5) Underreporting of elder abuse cases, especially financial abuse, remains a major issue combined with a dearth of comprehensive and reliable data which collectively leads to a vast underestimation of the real amount of elder abuse in the Nation. (6) Differences in State laws and practices in the areas of abuse, neglect, and exploitation of older adults lead to significant disparities in prevention, protective and social services, treatment systems, and law enforcement, and lead to other inequities. (7) Starting with the 1974 enactment of the Child Abuse Prevention and Treatment Act, the Federal Government has played an important role in promoting research, training, public safety, data collection, the identification, development, and dissemination of promising health care, social, and protective services, and law enforcement practices, relating to child abuse and neglect, domestic violence, and violence against women. The Federal Government should promote similar efforts and protections relating to elder abuse, neglect, and exploitation. (8) The Federal Government should provide leadership to assist States and communities in their efforts to prevent elder abuse, including the promotion of coordinated planning between all levels of government and nongovernment entities and generating and sharing knowledge relevant to protecting elders. (9) The problem of elder abuse, neglect, and exploitation requires a comprehensive approach that-- (A) recognizes the statutory role of State and local adult protective services and long-term care ombudsman programs to respond to elder abuse; (B) integrates the work of health, legal, and social service agencies and organizations; (C) emphasizes the need for prevention, detection, reporting, investigation, assessment and treatment, and prosecution of elder abuse, neglect, and exploitation at all levels of government; (D) ensures that sufficient numbers of properly trained personnel with specialized knowledge are in place to treat, assess, and provide services related to elder abuse, neglect, and exploitation, and carry out elder protection duties; (E) ensures there is cultural competency to address the unique needs of a diverse older adult population with respect to elder abuse; and (F) balances an elder's right to self-determination with society's responsibility to protect elders. (10) The future well-being of millions of older adults may be challenged by elder abuse and a coordinated and comprehensive Federal response is needed. Elder abuse prevention is a sound investment that can produce savings to the Medicare and Medicaid programs in the future. (11) A victim of elder abuse is never the same after being victimized. SEC. 3. REAUTHORIZATION OF THE ELDER JUSTICE ACT OF 2009. (a) Amendments to the Social Security Act.-- (1) Each of the following provisions of the Social Security Act is amended by striking ``2014'' and inserting ``2019'': (A) Section 2024(2) (42 U.S.C. 1397k-3(2)). (B) Section 2042(a)(2) (42 U.S.C. 1397m-1(a)(2)). (C) Section 2042(b)(5) (42 U.S.C. 1397m-1(b)(5)). (D) Section 2042(c)(5) (42 U.S.C. 1397m-1(c)(5)). (E) Section 2043(b)(2) (42 U.S.C. 1397m-2(b)(2)). (2) Each of the following provisions of the Social Security Act is amended by striking ``and 2014'' and inserting ``through 2019'': (A) Section 2031(f)(3) (42 U.S.C. 1397l(f)(3)). (B) Section 2041(d)(3) (42 U.S.C. 1397m(d)(3)). (C) Section 2043(a)(2)(C) (42 U.S.C. 1397m- 2(a)(2)(C)). (3) Section 2045 of the Social Security Act (42 U.S.C. 1397m-4) is amended by striking ``October 1, 2014'' and inserting ``2 years after the completion of grants made to States under section 2042''. (b) Amendments to the Patient Protection and Affordable Care Act.-- Section 6703(b) of the Patient Protection and Affordable Care Act (42 U.S.C. 1395i-3a(b)) is amended in each of paragraphs (1)(C) and (2)(C), by striking ``2014'' and inserting ``2019''.

Elder Justice Reauthorization Act Reauthorizes the Elder Justice Act of 2009 and funding for its programs through FY2019. Amends the Patient Protection and Affordable Care Act to reauthorize through FY2019: (1) the National Training Institute for Federal and State Surveyors, and (2) grants by the Secretary of Health and Human Services to state agencies that perform surveys of skilled nursing facilities or nursing facilities.

After a triple digit swoon into negative territory, the Dow closed higher, up 80 at 15,040, and the S&P 500 rose to 1622, up 13, recovering after slipping beneath its 50-day moving average at 1605, and bouncing off support in the 1598 area. Ader said the Treasury market ultimately signals the expectation is for a weak jobs report. "Uncertainty is not something the markets deal with, and they (the Fed) took a central bank approach, and not a market approach," he said. Ader said the Fed may have boxed itself in, creating a market that will now not easily let go of quantitative easing. "What's going to be the easiest way to get the patient off this drug? Is it cold turkey or is it methadone?" he asked. "Today's action reveals we don't know how to handle this." Mesirow Financial economist Diane Swonk said its possible the Fed could start to pare back bond purchases starting in September, but she also does not see a growth outlook as rosy as the Fed or some other economists for the second half of the year. "I think the issue is we haven't seen the full effects of the sequester and people have gotten this false sense of security that it's not out there, and the reality is it is out there," she said. "There's going to be job reductions. Some government employment is going to be reduced." Maki also believes the full impact of the sequester, or automatic spending cuts, have not been felt and he is expecting growth of just two percent for the second half. LaVorgna, however, expects the Fed to taper in September, and he sees the economy improving from the current sluggish sub-2 percent growth in the second quarter. "The economy is fundamentally healthy. The building blocks for continued growth are there, and that's why the second half of the year should be better," he said. "I think we finally get to the promised land of 3 percent growth." But he expects May's jobs report to be weaker than consensus, at just 125,000, and he notes May has been especially weak for the last several years. Swonk expects to see 140,000 nonfarm payrolls, and she said the number has become overly important to markets. "In the near term, it will shape market expectations because it's gotten this out-sized weighting and that's unfortunate because the reality is they are taking everything into account. It's not just one number. It's not just one month. The market likes to distill it down to simplicity," she said. Swonk said the markets have been impacted by uncertainty, due to the dissonance within the Fed, with some officials saying bond purchases should be wound down now and others saying several months of confirming economic data are necessary. "They're all singing in the chorus about how they don't like fiscal drag…they've all come pretty much in line about that issue. The dissonance is about timing issues and that's what they're going to have to come to consensus on, and most of them thinking it would be nice not to have this much longer. The earliest is September and it's still just calibrating." Credit Suisse economist Jonathan Basile expects to see 150,000 jobs added in May, and he said if that is the number, the Fed will still talk about tapering since clearly some officials favor it sooner rather than later. "We have to think about what they're tapering. Is it MBS (mortgage-backed securities).Is it Treasurys? Is it both? Does the housing market really need the MBS purchases to receive support. Look what's happening to housing. You have more buyers than sellers and prices are going up. Do the training wheels still need to be on the housing market…with the Fed's MBS purchases?" Basile said Credit Suisse expects to see tapering, starting in September, with the Fed paring back its purchases of Treasurys to $35 billion and its mortgage purchases to $30 billion a month. Even with tapering, the Fed still has a hefty easing program underway and has more than $3 trillion in securities already on its balance sheet. But Basile's questions about mortgage-backed purchases highlight an issue on Wall Street, and that is there is little consensus about what the Fed intends to do and what it means for market pricing. CRT's Ader surveyed market participants Thursday and found they are unclear about what the Fed might do. He said a majority believes the Fed will cut back on Treasury purchases and mortgage purchases equally, but a good number believe it could cut back just on Treasurys and others see it ending just mortgage purchases. Ader's survey also showed that 76 percent believed tapering would begin this year, but most did not expect it before September. A third thought it would begin in either September or October. "The market is confused in here," he said. ||||| In this May 29, 2013 photo, job seeker Craig Cline of Lincolnwood, Ill., right, meets with Jeremy Skeeters, left, and Lindy Hammel, of Aflac Insurance Co. during a career fair in Rolling Meadows, Ill.... (Associated Press) U.S. employers added 175,000 jobs in May, steady hiring but below the more robust pace that took place during the autumn and winter. The Labor Department says the unemployment rate rose to 7.6 percent from 7.5 percent in April. The increase occurred because more people began looking for work, a good sign. The government said the economy added 12,000 fewer jobs in April and March. Employers have added an average of 155,000 jobs in past three months, below the average of 237,000 created from November through February. The modest gains likely mean the Federal Reserve will continue its bond purchases. The Fed has said it will maintain its pace of bond purchases until the job market improves substantially. The purchases have helped drive down interest rates and boost stock prices.

– The unemployment rate ticked up a notch in May: It had been expected to remain at 7.5%, but instead went up to 7.6%, the Wall Street Journal reports. But, the AP notes, that's because more people are looking for work, which is a good thing. And while 169,000 new jobs were expected to have been created, today's jobs report revealed the very slightly sunnier number of 175,000. The Journal journos' take seems to be: not great, but also not terrible. And perhaps a bit anticlimactic, considering CNBC earlier reported this could be the most important jobs report in years, one that could shape market expectations for months and even "clarify the Fed's next policy move." (But CNBC did note it could just reaffirm the status quo.) The AP thinks the Fed will continue its bond purchases based on these numbers. More less-than-exciting news: The jobs added in April and March were revised downward by 12,000.

SECTION 1. PURCHASE OF SETTLEMENT COMMON STOCK OF COOK INLET REGION. (a) In General.--Section 7(h) of the Alaska Native Claims Settlement Act (43 U.S.C. 1606(h)) is amended by adding at the end the following: ``(4) Cook Inlet Regional Corporation.--(A) In this paragraph: ``(i) The term `Cook Inlet Regional Corporation' means Cook Inlet Region, Incorporated. ``(ii) The term `nonresident distribution right' means the right of owners of nonvillage shares to share in distributions made to shareholders pursuant to subsections (j) and (m). ``(iii) The term `nonvillage shares' means shares of Settlement Common Stock owned by stockholders who are not residents of a Native village. ``(iv) The term `nonvoting security' means a security, for only the nonresident rights that attach to a share of Settlement Common Stock, that does not have attached voting rights. ``(B) Cook Inlet Regional Corporation may, by an amendment to its articles of incorporation made in accordance with the voting standards under section 36(d)(1), purchase Settlement Common Stock of Cook Inlet Regional Corporation and all rights associated with the stock from the shareholders of Cook Inlet Regional Corporation in accordance with any provisions included in the amendment that relate to the terms, procedures, number of offers to purchase, and timing of offers to purchase. ``(C) Subject to subparagraph (D), and notwithstanding paragraph (1)(B), the shareholders of Cook Inlet Regional Corporation may, in accordance with an amendment made pursuant to subparagraph (B), sell Settlement Common Stock of the Cook Inlet Regional Corporation to the Corporation. ``(D) No purchase or sale may be made pursuant to this paragraph without the prior approval of the board of directors of Cook Inlet Regional Corporation. Except as provided in subparagraph (E), each purchase and sale made under this paragraph shall be made pursuant to an offer made on the same terms to all holders of Settlement Common Stock of the Cook Inlet Regional Corporation. ``(E) To recognize the different rights that accrue to any class or series of nonvillage shares, an amendment made pursuant to subparagraph (B) shall authorize the board of directors (at the option of the board) to offer to purchase-- ``(i) nonvillage shares, including nonresident distribution rights, at a price that includes a premium, in addition to the amount that is offered for the purchase of other village shares of Settlement Common Stock of the Cook Inlet Regional Corporation, that reflects the value of the nonresident distribution rights; or ``(ii) nonvillage shares without the nonresident distribution rights associated with the shares. ``(F) Any shareholder who accepts an offer made by the board of directors pursuant to subparagraph (E)(ii) shall receive, with respect to each nonvillage share sold by the shareholder to the Cook Inlet Regional Corporation-- ``(i) the consideration for a share of Settlement Common Stock offered to shareholders of village shares; and ``(ii) a nonvoting security. ``(G) An amendment made pursuant to subparagraph (B) shall authorize the issuance of a nonvoting security that-- ``(i) shall, for purposes of subsections (j) and (m), be treated as a nonvillage share with respect to-- ``(I) computing distributions under those subsections; and ``(II) entitling the holder of the share to the proportional share of the distributions made under those subsections; ``(ii) may be sold to Cook Inlet Regional Corporation; and ``(iii) shall otherwise be subject to the restrictions under paragraph (1)(B). ``(H) A share of Settlement Common Stock purchased pursuant to this paragraph shall be canceled on the conditions that-- ``(i) a nonvillage share with the nonresident rights that attach to such a share that is purchased pursuant to this paragraph shall be considered to be-- ``(I) an outstanding share; and ``(II) for the purposes of subsection (m), a share of stock registered on the books of the Cook Inlet Regional Corporation in the name of a stockholder who is not a resident of a Native village; ``(ii) any amount of funds that would be distributable with respect to a nonvillage share or nonvoting security pursuant to subsection (j) or (m) shall be distributed by Cook Inlet Regional Corporation to the Corporation; and ``(iii) a village share that is purchased pursuant to this paragraph shall be considered to be-- ``(I) an outstanding share; and ``(II) for the purposes of subsection (k), shares of stock registered on the books of the Cook Inlet Regional Corporation in the name of a resident of a Native village. ``(I) Any offer to purchase Settlement Common Stock made pursuant to this paragraph shall exclude from the offer-- ``(i) any share of Settlement Common Stock held, at the time the offer is made, by an officer (including a member of the board of directors) of Cook Inlet Regional Corporation or a member of the immediate family of the officer; and ``(ii) any share of Settlement Common Stock held by any custodian, guardian, trustee, or attorney representing a shareholder of Cook Inlet Regional Corporation in fact or law, or any other similar person, entity, or representative. ``(J)(i) The board of directors of Cook Inlet Regional Corporation, in determining the terms of an offer to purchase made under this paragraph, including the amount of any premium paid with respect to a nonvillage share, may rely upon the good faith opinion of a recognized firm of investment bankers or valuation experts. ``(ii) Notwithstanding any other law, Cook Inlet Regional Corporation, a member of the board of directors of Cook Inlet Regional Corporation, and any firm or member of a firm of investment bankers or valuation experts who assists in a determination made under this subparagraph shall not be liable for damages resulting from terms made in an offer made in connection with any purchase of Settlement Common Stock if the offer was made-- ``(I) in good faith; ``(II) in reliance on a determination made pursuant to clause (i); and ``(III) otherwise in accordance with this paragraph. ``(K) The consideration given for the purchase of Settlement Common Stock made pursuant to an offer to purchase that provides for the consideration may be in the form of cash, securities, or a combination of cash and securities, as determined by the board of directors of Cook Inlet Regional Corporation, in a manner consistent with an amendment made pursuant to subparagraph (B). ``(L) Sale of Settlement Common Stock in accordance with this paragraph shall not diminish a shareholder's status as a Native or descendant of a Native for the purpose of qualifying for those programs, benefits and services or other rights or privileges set out for the benefit of Natives and Native Americans. Proceeds from the sale of Settlement Common Stock shall not be excluded in determining eligibility for any needs-based program that may be provided by a Federal, State, or local agency.''. (b) Conforming Amendment.--Section 8(c) of the Alaska Native Claims Settlement Act (43 U.S.C. 1607(c)) is amended by striking ``(h)'' and inserting ``(h) (other than paragraph (4))''.

Amends the Alaska Native Claims Settlement Act to authorize the Cook Inlet Regional Corporation (Cook Inlet Region, Incorporated) to purchase its shareholder-held common stock.

mary s hospital approved the protocol for this study ( approval number hc09eisi0059 ) . for the dm and igt groups , men or women who were aged between 20 and 70 years all of the igt and dm ( type 2 ) subjects had received a formal diagnosis according to the world health organization guidelines at the department of endocrinology . the endocrinologist referred potential candidates who agreed to undergo a prescreening ncs evaluation of the right sural and superficial peroneal nerves . only those with normal ncs values ( sensory nerve action potential [ snap ] values > 10 v ) were enrolled . clinical characteristics were recorded at the time of enrollment . to rule out the presence of other possible causes of peripheral polyneuropathy , igt and dm participants underwent laboratory tests of thyroid hormones , lipid profile , and vitamin levels , in addition to routine glucose tests , on the same day that the ncs was performed . participants in the igt and dm groups were assessed using the toronto clinical scoring system ( tcss ) ( 16 ) . reflex and sensory tests , including pinprick , temperature , light touch , vibration , and position sensation , were performed as part of the tcss . healthy volunteers with no known risk factors of neuropathy or abnormality upon neurologic examination were enrolled as the hc group . a prescreening ncs was performed to confirm normal snap values in the sural and superficial peroneal nerves . subjects who met the following criteria were excluded : 1 ) skin lesion or edema of the lower extremities that would interfere with ncs procedures ; 2 ) previous diagnosis or clinical symptoms that would indicate the presence of mononeuropathy or entrapment neuropathy of the lower extremities ; a history of 3 ) alcohol drinking > 170 g / week 4 ) substance abuse , 5 ) use of medications such as chemotherapeutic or antituberculosis drugs ; and 6 ) a former diagnosis of other systemic conditions related to peripheral polyneuropathy , other than that caused by diabetes in the two hyperglycemic groups . all ncss were performed with viking select electromyography ( viasys healthcare , nicolet biomedical inc . , madison , wi ) at the setting of 20 hz for the lower filter , 3 khz for the higher filter for sensory studies , and 5 hz10 khz for motor studies . a sweep speed of 2 ms / division and sensitivity of 20 v / division were used for the distal sensory nerves . all ncss were performed with 10-mm - diameter silver chloride cup electrodes ( viasys healthcare ) . ncss of the right sural , superficial peroneal , median sensory , and tibial motor nerves were performed . delayed responses were obtained with minimum f - response latencies from the right tibial and median nerve , along with h - reflex latencies from tibial nerve stimulation . the mdc nerve was assessed with antidromic electrical stimulation performed 10 cm proximal to the recording electrodes ( 6 ) ; the mp nerve was assessed with orthodromic stimulation at 14 cm ( 5 ) , and the ds nerve conduction was performed with electrical stimulation applied 10 cm from the recording electrodes ( 4 ) . signal averaging of 510 responses was used when snaps were too small to be obtained with a single stimulation . a follow - up of ncs evaluation of the right leg in the igt ( n = 5 ) and dm ( n = 5 ) groups was performed to document any longitudinal changes of the distal sensory nerves . we compared the clinical , laboratory parameters , blood pressure , and tcss between the igt and dm group using the unpaired t test . side - to - side differences in the ncs values were tested using the paired t test . to compare the demographic features and ncs parameters of the three groups we performed ancova with adjustments for the covariates of age , bmi , and folate . abnormal responses were defined as those beyond the limit of the normal range values of mean 2 sds from the logarithmic transformed values ( 17 ) and were calculated for each distal sensory nerve . we performed the cochran - armitage trend test to compare the number of subjects with abnormal responses among the three groups . all statistical analyses were performed using sas software ( sas institute , inc . , cary , nc ) . for the dm and igt groups , men or women who were aged between 20 and 70 years were recruited . all of the igt and dm ( type 2 ) subjects had received a formal diagnosis according to the world health organization guidelines at the department of endocrinology . the endocrinologist referred potential candidates who agreed to undergo a prescreening ncs evaluation of the right sural and superficial peroneal nerves . only those with normal ncs values ( sensory nerve action potential [ snap ] values > 10 v ) were enrolled . to rule out the presence of other possible causes of peripheral polyneuropathy , igt and dm participants underwent laboratory tests of thyroid hormones , lipid profile , and vitamin levels , in addition to routine glucose tests , on the same day that the ncs was performed . participants in the igt and dm groups were assessed using the toronto clinical scoring system ( tcss ) ( 16 ) . reflex and sensory tests , including pinprick , temperature , light touch , vibration , and position sensation , were performed as part of the tcss . healthy volunteers with no known risk factors of neuropathy or abnormality upon neurologic examination were enrolled as the hc group . a prescreening ncs was performed to confirm normal snap values in the sural and superficial peroneal nerves . subjects who met the following criteria were excluded : 1 ) skin lesion or edema of the lower extremities that would interfere with ncs procedures ; 2 ) previous diagnosis or clinical symptoms that would indicate the presence of mononeuropathy or entrapment neuropathy of the lower extremities ; a history of 3 ) alcohol drinking > 170 g / week 4 ) substance abuse , 5 ) use of medications such as chemotherapeutic or antituberculosis drugs ; and 6 ) a former diagnosis of other systemic conditions related to peripheral polyneuropathy , other than that caused by diabetes in the two hyperglycemic groups . all ncss were performed with viking select electromyography ( viasys healthcare , nicolet biomedical inc . , madison , wi ) at the setting of 20 hz for the lower filter , 3 khz for the higher filter for sensory studies , and 5 hz10 khz for motor studies . a sweep speed of 2 ms / division and sensitivity of 20 v / division were used for the distal sensory nerves . all ncss were performed with 10-mm - diameter silver chloride cup electrodes ( viasys healthcare ) . ncss of the right sural , superficial peroneal , median sensory , and tibial motor nerves were performed . delayed responses were obtained with minimum f - response latencies from the right tibial and median nerve , along with h - reflex latencies from tibial nerve stimulation . the mdc nerve was assessed with antidromic electrical stimulation performed 10 cm proximal to the recording electrodes ( 6 ) ; the mp nerve was assessed with orthodromic stimulation at 14 cm ( 5 ) , and the ds nerve conduction was performed with electrical stimulation applied 10 cm from the recording electrodes ( 4 ) . signal averaging of 510 responses was used when snaps were too small to be obtained with a single stimulation . a follow - up of ncs evaluation of the right leg in the igt ( n = 5 ) and dm ( n = 5 ) groups was performed to document any longitudinal changes of the distal sensory nerves . all ncss were performed with viking select electromyography ( viasys healthcare , nicolet biomedical inc . , madison , wi ) at the setting of 20 hz for the lower filter , 3 khz for the higher filter for sensory studies , and 5 hz10 khz for motor studies . a sweep speed of 2 ms / division and sensitivity of 20 v / division were used for the distal sensory nerves . all ncss were performed with 10-mm - diameter silver chloride cup electrodes ( viasys healthcare ) . ncss of the right sural , superficial peroneal , median sensory , and tibial motor nerves were performed . delayed responses were obtained with minimum f - response latencies from the right tibial and median nerve , along with h - reflex latencies from tibial nerve stimulation . the mdc nerve was assessed with antidromic electrical stimulation performed 10 cm proximal to the recording electrodes ( 6 ) ; the mp nerve was assessed with orthodromic stimulation at 14 cm ( 5 ) , and the ds nerve conduction was performed with electrical stimulation applied 10 cm from the recording electrodes ( 4 ) . signal averaging of 510 responses was used when snaps were too small to be obtained with a single stimulation . a follow - up of ncs evaluation of the right leg in the igt ( n = 5 ) and dm ( n = 5 ) groups was performed to document any longitudinal changes of the distal sensory nerves . we compared the clinical , laboratory parameters , blood pressure , and tcss between the igt and dm group using the unpaired t test . side - to - side differences in the ncs values were tested using the paired t test . to compare the demographic features and ncs parameters of the three groups we performed ancova with adjustments for the covariates of age , bmi , and folate . abnormal responses were defined as those beyond the limit of the normal range values of mean 2 sds from the logarithmic transformed values ( 17 ) and were calculated for each distal sensory nerve . we performed the cochran - armitage trend test to compare the number of subjects with abnormal responses among the three groups . all statistical analyses were performed using sas software ( sas institute , inc . , cary , nc ) . each group comprised 50 participants ( n = 150 ) . the characteristics and laboratory parameters of the hyperglycemic subjects baseline demographic and clinical characteristics of the hc , igt , and dm groups tcss scores from 75% of the igt participants and 83% of the dm participants displayed positive symptoms or signs . all participants in the hc group were preselected after confirmation that their tcss scores were 0 ; thus , comparisons of total scores and subscores were performed only between the two hyperglycemic groups ( table 1 ) . the statistical analysis showed no side - to - side differences in ncs values for all tested nerves in any of the test groups ( results not shown ) . although all of the ncs values were within the normal range , the two hyperglycemic groups showed significant differences in their ncs values obtained for the sural and median sensory nerves compared with the hc group ( table 2 ) . comparison of the nerve conduction results of sensory , motor nerves , and late responses in the hc , igt , and dm groups the snap amplitudes of the three distal sensory nerves were significantly smaller in the dm group than in the hc group . even after adjustment of the covariates of age and bmi , the dm group still showed these differences ( table 3 ) in the mdc and ds . in the igt group , the snap amplitudes of the mdc and ds nerves , but not of the mp nerve , were significantly smaller than those of the hc group ( table 3 ) . after adjustment of age and bmi , these differences in snap amplitudes were only observed in the left ds nerve . after adjustment of folate , age , and bmi , no statistical difference was observed between the igt and dm group in the mdc and ds snap amplitudes ( supplementary table 1 ) ; this was similar to findings before adjustment . results of the mp , ds , and mdc nerves in the hc , igt , and dm groups the findings from the three distal sensory nerves showed abnormal ncs responses in 20 ( 41% ) and 8 ( 16% ) of the dm and igt participants , respectively . statistical analysis showed a significant increase in the number of subjects with abnormal snap responses for the distal sensory nerves with disease progression from hc to igt to dm ( table 4 ) . hc , igt , and dm group participants who showed bilateral ncs values that fell below the normal range for the distal sensory nerves at the 2-year follow - up assessment , snap amplitudes of the mdc and ds nerves in the igt group were significantly smaller compared with those assessed 2 years earlier ( supplementary table 2 ) . a similar trend was observed in the dm group , although it did not reach statistical significance . tcss scores from 75% of the igt participants and 83% of the dm participants displayed positive symptoms or signs . all participants in the hc group were preselected after confirmation that their tcss scores were 0 ; thus , comparisons of total scores and subscores were performed only between the two hyperglycemic groups ( table 1 ) . the statistical analysis showed no side - to - side differences in ncs values for all tested nerves in any of the test groups ( results not shown ) . although all of the ncs values were within the normal range , the two hyperglycemic groups showed significant differences in their ncs values obtained for the sural and median sensory nerves compared with the hc group ( table 2 ) . comparison of the nerve conduction results of sensory , motor nerves , and late responses in the hc , igt , and dm groups the snap amplitudes of the three distal sensory nerves were significantly smaller in the dm group than in the hc group . even after adjustment of the covariates of age and bmi , the dm group still showed these differences ( table 3 ) in the mdc and ds . in the igt group , the snap amplitudes of the mdc and ds nerves , but not of the mp nerve , were significantly smaller than those of the hc group ( table 3 ) . after adjustment of age and bmi , these differences in snap amplitudes were only observed in the left ds nerve . after adjustment of folate , age , and bmi , no statistical difference was observed between the igt and dm group in the mdc and ds snap amplitudes ( supplementary table 1 ) ; this was similar to findings before adjustment . results of the mp , ds , and mdc nerves in the hc , igt , and dm groups the findings from the three distal sensory nerves showed abnormal ncs responses in 20 ( 41% ) and 8 ( 16% ) of the dm and igt participants , respectively . statistical analysis showed a significant increase in the number of subjects with abnormal snap responses for the distal sensory nerves with disease progression from hc to igt to dm ( table 4 ) . hc , igt , and dm group participants who showed bilateral ncs values that fell below the normal range for the distal sensory nerves the statistical analysis showed no side - to - side differences in ncs values for all tested nerves in any of the test groups ( results not shown ) . although all of the ncs values were within the normal range , the two hyperglycemic groups showed significant differences in their ncs values obtained for the sural and median sensory nerves compared with the hc group ( table 2 ) . comparison of the nerve conduction results of sensory , motor nerves , and late responses in the hc , igt , and dm groups the snap amplitudes of the three distal sensory nerves were significantly smaller in the dm group than in the hc group . even after adjustment of the covariates of age and bmi , the dm group still showed these differences ( table 3 ) in the mdc and ds . in the igt group , the snap amplitudes of the mdc and ds nerves , but not of the mp nerve , were significantly smaller than those of the hc group ( table 3 ) . after adjustment of age and bmi , these differences in snap amplitudes were only observed in the left ds nerve . after adjustment of folate , age , and bmi , no statistical difference was observed between the igt and dm group in the mdc and ds snap amplitudes ( supplementary table 1 ) ; this was similar to findings before adjustment . results of the mp , ds , and mdc nerves in the hc , igt , and dm groups the findings from the three distal sensory nerves showed abnormal ncs responses in 20 ( 41% ) and 8 ( 16% ) of the dm and igt participants , respectively . statistical analysis showed a significant increase in the number of subjects with abnormal snap responses for the distal sensory nerves with disease progression from hc to igt to dm ( table 4 ) . hc , igt , and dm group participants who showed bilateral ncs values that fell below the normal range for the distal sensory nerves at the 2-year follow - up assessment , snap amplitudes of the mdc and ds nerves in the igt group were significantly smaller compared with those assessed 2 years earlier ( supplementary table 2 ) . a similar trend was observed in the dm group , although it did not reach statistical significance . the objectives of this study were to investigate the ncs results of the most distal sensory nerves ( the mp , ds and mdc nerves ) in dm and igt subjects who otherwise displayed normal values from their routine ncs evaluations . even after adjustment of age and bmi , the dm group exhibited significant ncs differences compared with the hc group in the ds and mdc nerves . in addition , ncs assessments of these three distal nerves together showed that 16 and 40% of igt and dm subjects displayed abnormal snap responses . we used the tcss , a valid instrument that reflects the clinical symptoms and signs of diabetic polyneuropathy ( 16 ) . the tcss is designed to emphasize subtle sensory symptoms and deficits rather than motor symptoms . although participants in the two hyperglycemic groups displayed mild neuropathic symptoms and signs , we were able to detect significant ncs changes in the most distal sensory nerves in the igt and dm groups . notably , although a statistical analysis revealed no significant differences in the tcss scores between these two groups , the dm group displayed more advanced ncs findings in the distal sensory nerves than the igt group . an analysis of the clinical characteristics of these two hyperglycemic group showed that the dm group had more prolonged exposure to hyperglycemia , as evidenced in their higher fasting blood glucose level , higher hba1c , and longer duration of hyperglycemia . folate levels in the dm group , although within the normal range , were significantly reduced compared with those recorded for the igt group . a recent report has suggested the role of folate in type 1 diabetes ( 19 ) ; however , further studies will be necessary to determine whether the reduced levels of folate observed in dm play a role in dpn . values within normal reference ranges were found for other factors known to be related to the incidence of dpn , including blood pressure , elevated triglyceride level , bmi ( 20 ) , and lipid profiles ( 21 ) . other anthropometric factors that may affect ncs results , such as age , height , and sex , were similar in both groups . in consideration of these factors , we suggest that the advanced ncs findings in the distal sensory nerves of the dm group may be attributable to the more prolonged glycemic exposure . electrodiagnostic tests are objective and validated tests of peripheral polyneuropathy ( 2 ) . among the various ncs measures available , the sural snap amplitude is reported to show the earliest alteration in dpn ( 22 ) . the ds nerve , which is the distal portion of the sural nerve , also manifested these early changes in the igt and dm groups , confirming previous findings that dpn is a length - dependent process , with the earliest abnormalities appearing at the ends of the longest nerve fibers , which extend to the toes . because of their superficial position , distal sensory nerves of the feet can be prone to injury or entrapment , but these injuries usually manifest as unilateral abnormalities . because dpn is a symmetric disease , abnormal snaps can be observed on both sides ; therefore , we think that the bilateral abnormal responses observed in these distal sensory nerves are more closely related to occult dpn changes than to focal trauma or entrapment . recent studies have suggested that the prevalence of polyneuropathy is increased in igt ( 10,11,14 ) and even in impaired fasting glucose ( 23 ) compared with normal glucose tolerance . results of the current study were in accordance to these previous studies and showed that there were significantly more patients with abnormal ncs responses of the most distal sensory nerves in the igt group than in the hc group . in addition , supplementary ncs studies of igt patients ( supplementary table 2 ) at 2 years of follow - up indicated that these ncs parameters show gradual deterioration with smaller values . although we did not include individuals with impaired fasting glucose , the issue whether the most distal sensory nerves can reflect the early dpn changes in this group is a topic that needs to be addressed in future studies . certain limiting factors of this study need to be considered : first , the hc participants were significantly younger than those in the two hyperglycemic groups . although age is known to have a significant effect on ncs parameters , ncs changes are known to be more prominent in those older than 60 years ( 24 ) . however , most subjects in all of the three groups were aged 4060 years , and reference values are usually provided for this age group as a whole . also , even after adjustment of age and bmi , significant differences in the ncs values of the distal sensory nerves were detected in the dm group compared with the hc group . second , the early stages of dpn are postulated to involve small fibers first ; in igt patients , this may , but not always , manifest as painful neuropathy ( 10 ) . the methods used to measure nerve conduction in this study primarily assess the large fibers ; therefore , the results do not provide information on the extent of small - fiber involvement . further studies that assess the dysfunction of small , unmyelinated fibers are warranted . it is important to diagnose dpn at the earliest stage possible , because early intervention for prediabetic patients is reported to slow or even halt the progression of dpn ( 25 ) and to prevent the occurrence of more debilitating consequences such as foot ulceration and amputation . current guidelines ( 2 ) mandate that no further ncss are necessary when unilateral ncss of the lower extremities , which include the sural nerve , reveal normal findings . however , according to the results of our study , hyperglycemic subjects , including igt patients , already display changes in the most distal sensory nerves , despite mild symptoms or equivocal clinical findings and normal results on conventional ncs studies . the results of this study confirm previous reports on the clinical utility of assessing these nerves in hyperglycemic patients ( 49,15 ) . also , these results are clinically significant in that this is the first study to date that has performed ncss of all three distal sensory nerves simultaneously and compared the results among igt , dm , and hc groups . our results indicate that assessment of the distal sensory nerves can help to detect occult abnormalities in dm and igt patients , possibly even before conventional studies and clinical scales show positive findings .

objectivethis study evaluated the nerve conduction study ( ncs ) parameters of the most distal sensory nerves of the lower extremities namely , the medial dorsal cutaneous ( mdc ) , dorsal sural ( ds ) , and medial plantar ( mp ) nerves in diabetic ( dm ) and impaired glucose tolerance ( igt ) patients who displayed normal findings on their routine ncss.research design and methodsstandard ncss were performed on healthy control ( hc ) , dm , and igt groups ( n = 147 ) . the bilateral ncs parameters of the mdc , ds , and mp nerves were investigated . the toronto clinical scoring system ( tcss ) was assessed for the dm and igt groups.resultsthe mean tcss scores of the igt and dm groups were 2.5 2.3 and 2.8 2.2 , respectively . no significant differences between the two groups were observed . after adjustment of age and bmi , the dm group showed significant ncs differences in ds and mdc nerves compared with the hc group ( p < 0.05 ) . these differences were also exhibited in the left ds of the igt group ( p = 0.0003 ) . more advanced ncs findings were observed in the dm group . bilateral abnormal ncs responses in these distal sensory nerves were found in 40 and 16% of dm and igt patients , respectively.conclusionsthese results showed that the simultaneous assessment of the most distal sensory nerves allowed the detection of early ncs changes in the igt and dm groups , even when the routine ncs showed normal findings .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Vested Worker Protection Act of 2002''. SEC. 2. SAFE HARBOR IN EVENT OF REDUCTION IN FUTURE BENEFIT ACCRUALS WHERE PLAN PROVIDES NOTICE AND ELECTION TO CONTINUE BENEFIT ACCRUALS UNDER FORMER PLAN INSTEAD OF AMENDED PLAN. (a) In General.--Paragraph (1) of section 411(b) of the Internal Revenue Code of 1986 (relating to defined benefit plans) is amended by adding at the end the following new subparagraph: ``(I) Safe harbor upon reduction in future benefit accruals.-- ``(i) In general.--An applicable pension plan that adopts an amendment which has the effect of reducing the rate of future benefit accrual of 1 or more participants shall be treated as not meeting the requirements of this paragraph unless such plan provides each participant who is, as of the date of the adoption of the plan amendment, a fully vested participant with-- ``(I) written notice which meets the requirements of section 4980F, and ``(II) an election to continue to accrue benefits under such plan, determined under the terms of such plan as in effect immediately before the effective date of such plan amendment. ``(ii) Protected accrued benefit.--For purposes of clause (i), an accrued benefit shall include any early retirement benefit or retirement-type subsidy (within the meaning of subsection (d)(6)(B)(i)), but only with respect to a participant who satisfies (either before or after the effective date of the amendment) the conditions for the benefit or subsidy under the terms of the plan as in effect immediately before such date. ``(iii) Timing of election.--Except as provided in regulations, the election required by clause (i)(II) shall be provided at least 90 days before the effective date of the amendment. ``(iv) Exemption upon showing of distress criteria.--This subparagraph shall not apply with respect to any plan amendment if the plan sponsor, prior to the date of the adoption of the amendment, demonstrates to the satisfaction of the Secretary that, under regulations of the Secretary, requirements-- ``(I) applicable with respect to the adoption of the plan amendment, and ``(II) similar to the requirements of clause (i), (ii), or (iii) of section 4041(c)(2)(B) of the Employee Retirement Income Security Act of 1974 applicable with respect to a distress termination, are met by each employer required (under the terms of the plan as in effect immediately before the adoption of the plan amendment) to make contributions under the plan. ``(v) Fully vested participant.--For purposes of this subparagraph, the term `fully vested participant' means a participant who under the plan has a nonforfeitable right to the participant's entire accrued benefit. ``(vi) Applicable pension plan.--The term `applicable pension plan' means-- ``(I) a defined benefit plan, or ``(II) an individual account plan which is subject to the funding standards of section 412, which had 100 or more active participants who had accrued a benefit under the plan (whether or not vested) as of the last day of the plan year preceding the plan year in which the plan amendment becomes effective. Such term shall not include any governmental plan (within the meaning of section 414(d)) or any church plan (within the meaning of section 414(e)) with respect to which the election provided by section 410(d) has not been made.''. (b) Excise Tax on Failure To Offer Election.-- (1) In general.--Chapter 43 of subtitle D of the Internal Revenue Code of 1986 (as amended by section 2 of this Act) is amended further by adding at the end the following new section: ``SEC. 4980G. FAILURE TO OFFER ELECTION TO CONTINUE BENEFIT ACCRUALS UNDER FORMER APPLICABLE PENSION PLAN IN EVENT OF REDUCTIONS IN FUTURE BENEFIT ACCRUALS. ``(a) Imposition of Tax.--There is hereby imposed a tax on the failure of any applicable pension plan to meet the requirements of subsection (d). ``(b) Amount of Tax.-- ``(1) In general.--The amount of the tax imposed by subsection (a) shall be 50 percent of the lesser of-- ``(A) the reduction in the future employer benefit cost for the plan attributable to the plan amendment referred to in subsection (d) (determined, as provided in regulations of the Secretary, as of the date of the adoption of such plan amendment), or ``(B) the amount of the excess pension assets in such plan, determined as of the effective date of the amendment. ``(2) Future employer benefit cost.--For purposes of paragraph (1)(A), the term `future employer benefit cost' for a plan means the present value of future accruals, by current participants and beneficiaries, of benefits derived from employer contributions (within the meaning of section 411(c)(1)). ``(3) Excess pension assets.--For purposes of paragraph (1), the term `excess pension assets' has the meaning given to such term by section 420(e)(2). ``(c) Liability for Tax.--The following shall be liable for the tax imposed by subsection (a): ``(1) In the case of a plan other than a multiemployer plan, the employer. ``(2) In the case of a multiemployer plan, the plan. For purposes of the preceding sentence, all multiemployer plans of which the same trust forms a part shall be treated as 1 plan. For purposes of this paragraph, if not all persons who are treated as a single employer for purposes of this section have the same taxable year, the taxable years taken into account shall be determined under principles similar to the principles of section 1561. ``(d) Election To Continue Benefit Accruals Under Former Applicable Pension Plan In Event of Reductions in Future Benefit Accruals.--In the case that an applicable pension plan adopts an amendment which has the effect of reducing the rate of future benefit accrual of 1 or more participants, the requirements of this subsection are met if the plan administrator provides each fully vested participant with-- ``(1) written notice which meets the requirements of section 4980F, and ``(2) an election to continue to accrue benefits under such plan, determined under the terms of such plan as in effect immediately before the effective date of such plan amendment. ``(e) Timing of Election.--Except as provided in regulations, the election required by subsection (d) shall be provided at least 90 days before the effective date of such amendment. ``(f) Protected Accrued Benefit.--For purposes of this section, an accrued benefit shall include any early retirement benefit or retirement-type subsidy (within the meaning of section 411(d)(6)(B)(i)), but only with respect to a participant who satisfies (either before or after the effective date of the amendment) the conditions for the benefit or subsidy under the terms of the plan as in effect immediately before such date. ``(g) Exemption upon Showing of Distress Criteria.--This section shall not apply with respect to any plan amendment if the plan sponsor, prior to the date of the adoption of the amendment, demonstrates to the satisfaction of the Secretary that, under regulations of the Secretary, requirements-- ``(1) applicable with respect to the adoption of the plan amendment, and ``(2) similar to the requirements of clause (i), (ii), or (iii) of section 4041(c)(2)(B) of the Employee Retirement Income Security Act of 1974 applicable with respect to a distress termination, are met by each employer required (under the terms of the plan as in effect immediately before the adoption of the plan amendment) to make contributions under the plan. ``(h) Definitions.--For purposes of this section-- ``(1) Applicable pension plan.--The term `applicable pension plan' means-- ``(A) a defined benefit plan, or ``(B) an individual account plan which is subject to the funding standards of section 412, which had 100 or more active participants who had accrued a benefit under the plan (whether or not vested) as of the last day of the plan year preceding the plan year in which the plan amendment becomes effective. Such term shall not include any governmental plan (within the meaning of section 414(d)) or any church plan (within the meaning of section 414(e)) with respect to which the election provided by section 410(d) has not been made. ``(2) Fully vested participant.--The term `fully vested participant' means a participant who has under the plan a nonforfeitable right to the participant's entire accrued benefit.''. (2) Clerical amendment.--The table of sections for chapter 43 of subtitle D of such Code (as amended by section 2 of this Act) is amended further by adding at the end the following new item: ``Sec. 4980G. Failure to offer election to continue benefit accruals under former applicable pension plan in event of reductions in future benefit accruals.''. SEC. 3. EFFECTIVE DATES. (a) In General.--The amendments made by this Act shall apply to plans and plan amendments taking effect after 60 days after the date of the enactment of this Act. (b) Special Rule.--The period for providing any notice required by the amendments made by this Act shall not end before the date which is 90 days after the date of the enactment of this Act.

Vested Worker Protection Act of 2002 - Amends the Internal Revenue Code to mandate that an "applicable pension plan" adopting any amendment that reduces rates of future benefits provide: (1) written notice meeting certain requirements to participants; and (2) that the participants be offered the chance to elect to continue to accrue benefits under the terms in effect immediately before the amendment. Defines "accrued benefit" as an early retirement benefit or retirement-type subsidy meeting certain standards. Defines "applicable pension plan" as a defined benefit plan or an individual account plan with at least 100 active participants meeting certain funding standards and other restrictions.Requires plans to inform participants of the option of staying under the old terms at least 90 days before the effective date of the amendment. Exempts a plan from the above requirements if its sponsor can show the Secretary of the Treasury that each employer contributing to the plan meets certain distress termination conditions under regulations of the Secretary.Imposes an excise tax on plans that adopt amendments decreasing benefits and do not let participants elect to continue to accrue benefits under the old terms. Makes the plan liable for such tax in the case of a multiemployer plan, and the employer liable in any other case.

strange stars are hypothetical compact stars which are built entirely or almost entirely of strange quark matter ( containing light @xmath3 , @xmath4 , and @xmath5 quarks and possibly electrons ) . the hypothesis of strange stars is based on the idea of @xcite that the strange quark matter is the absolutely stable form of matter even at zero pressure . the hypothesis can not be definitely confirmed or refuted by available theories and experimental data . strange stars are attracting permanent attention ( see , e.g. , a recent review of * ? ? ? * ) . one can not exclude that at least some stars , which are currently thought to be neutron stars , are in fact strange stars . the theories predict the existence of bare strange stars ( with the strange matter extended to the very surface ) and strange stars with a thin crust of normal matter extended not deeper than the neutron drip point ( e.g. , * ? ? ? the normal crust may occur , for instance , due to accretion of normal matter onto a bare strange star . strange stars of masses @xmath6 much lower than the `` canonical '' neutron - star mass , @xmath7 , are predicted to have radii @xmath8 km , essentially smaller than the radii of neutron stars . however , strange stars with @xmath7 have nearly the same radii , @xmath9 km , as typical neutron stars . we will show that strange stars with crusts could be potentionally distinguished from neutron stars by their oscillation spectra . oscillations of strange stars have been analyzed by a number of authors . @xcite studied three types of quadrupole oscillations of strange stars and hybrid neutron stars . they found some differences in oscillation frequencies of such stars . also , they demonstrated that the damping times of oscillations are sensitive to the model of strange matter . recently @xcite showed that the combined knowledge of the frequency of emitted gravitational waves and the mass or radius of a compact object would allow one to discriminate between a strange star and a neutron star and set stringent bounds on the parameters of quark matter . both groups of authors analyzed global oscillations of strange stars . in this paper we focus on pressure oscillations ( p and f modes ) of strange star crusts . in our previous papers @xcite we have studied oscillations localized in a neutron star crust due to large multipolarity @xmath10 . here we show that acoustic oscillations in a strange star crust are very specific even for low @xmath0 because of a huge density jump at the interface between the normal crust and the quark core . because a strange star crust is very thin ( a few hundred meters for a strange star of mass @xmath11 ) , the approximation of plane - parallel layer can be used . then the space - time metric in the crust can be written as @xmath12 where the local time @xmath13 and the local depth @xmath14 are related to the schwarzschild time @xmath15 and the circumferential radius @xmath16 by @xmath17 @xmath18 is the circumferential radius of the stellar surface , @xmath19 and @xmath20 are spherical angles , @xmath21 is the gravitation radius , and @xmath6 is the gravitational mass of the star . the metric ( [ metric ] ) is locally flat and allows us to use the newtonian hydrodynamic equations for a thin envelope with the gravitational acceleration @xmath22 the pressure in the strange star crust is mostly determined by degenerate electrons and is almost independent of temperature @xmath23 . accordingly , we can use the same zero - temperature equation of state ( eos ) for the equilibrium structure of the crust and for perturbations . we will neglect the buoyancy force and study pressure modes . we will also neglect elastic stresses which are unimportant for crust oscillations in the frequency range of interest ( they would be important for lower frequencies @xmath24 hz ) . the linearized hydrodynamic equations ( for a non - rotating star ) for the velocity potential @xmath25 ( so that the oscillation velocity is @xmath26 ) can be rewritten as ( see , e.g. , the monograph by * ? ? ? * ) @xmath27 where @xmath28 is the squared sound speed . the potential @xmath25 can be presented in the form @xmath29 where @xmath30 is an oscillation frequency , and @xmath31 is a spherical function ( see , e.g. , @xcite ) . an unknown function @xmath32 obeys the equation @xmath33 where @xmath34 . the requirement of vanishing lagrange variation of the pressure at the surface implies @xmath32 to be bounded as @xmath35 . because the strange quark matter at the interface between and crust and the quark core is very dense and almost incompressible , we impose the condition @xmath36 , which means the vanishing radial displacement at the crust bottom @xmath37 . in other words , we study oscillations of the crust alone . following standard prescription we will call the modes without radial nodes of @xmath32 by f modes , and the modes with nodes by p modes . in analogy with the oscillation problem for neutron star crusts @xcite , the oscillation problem for strange star crusts is self - similar . taking the equilibrium pressure @xmath38 as an independent variable in eq.([f ] ) we come to the equation for an eigenvalue @xmath39 ; this equation contains the scaling parameter @xmath40 . accordingly , the eigenfrequencies can be written as @xmath41 here , @xmath42 are functions which can be calculated numerically . note , that for @xmath43 ( radial oscillations ) the eigenfrequency is proportional to the gravity @xmath44 . for the polytropic eos , the squared sound speed is @xmath45 and eq . ( [ f ] ) transforms to @xmath46 the eos of a strange star crust can be well approximated by the polytropic eos with the index @xmath47 . thus , eq . ( [ f_polytrop ] ) with @xmath47 will be used below for an analytical consideration of the oscillation problem . the frequencies @xmath30 refer to the local crust reference frame ( see eq . ( [ metric ] ) ) . the frequencies @xmath48 of oscillations detected by a distant observer are @xmath49 for radial oscillations ( @xmath43 ) eq.([f_polytrop ] ) is simplified , @xmath50 the solution bounded at the surface ( @xmath51 ) is @xmath52 where @xmath53 is a constant , and @xmath54 is a bessel function of the first kind ( see , e.g. , * ? ? ? . then the eigenfrequencies are given by the equation @xmath55 formally , the solution contains the eigenfrequency @xmath56 which corresponds to @xmath57 ( i.e. , to a meaningless vanishing oscillation velocity ) . in addition , the equation gives an infinite number of eigenfrequencies , @xmath58 where @xmath59 is an @xmath60th zero of @xmath54 . for a given @xmath61 and a given maximum density in the crust , @xmath62 , the crustal depth @xmath63 , and @xmath30 is proportional to @xmath44 , in agreement with the general relation ( [ scaling ] ) . note , that a mode labeled by @xmath60 has @xmath60 nodes of @xmath32 . at @xmath47 we have @xmath64 for @xmath60 from 1 to 5 . for @xmath65 the difference of neighboring values is @xmath66 ( and it is slightly larger @xmath67 for @xmath60=1 ) . accordingly , the eigenfrequencies are approximately equidistant . this feature can be used to distinguish such oscillations from other ones ( see section [ subsecstarparams ] ) . the problem of non - radial oscillations of a thin polytropic layer was studied by @xcite . following those studies let us introduce @xmath68 and @xmath69 in eq . ( [ f_polytrop ] ) . then eq . ( [ f_polytrop ] ) reduces to @xmath70 the solution to this equation bounded at @xmath35 is @xmath71 , where @xmath53 is a constant and @xmath72 is the kummer function ( see , e.g. , * ? ? ? the boundary condition @xmath36 leads to the equation @xmath73 for a not very large multipolarity @xmath74 , the value of @xmath75 is small , and the long - wavelength approximation applies which simplifies problem . the eigenfrequency of the fundamental mode can be determined using asymptotic series expansions , which give @xmath76.\ ] ] the respective eigenfunction is @xmath77 @xcite . in this case matter elements move nearly horizontally ; the ratio of the radial to the horizontal velocity components can be estimated as @xmath78 . the p modes can be studied numerically . however , they have relatively high frequencies , so that @xmath79 in eq . ( [ f ] ) . neglecting @xmath80 , we come to the same equation as for radial oscillations . thus , higher modes of non - radial oscillations have almost the same frequencies ( [ radfreq ] ) and radial parts ( [ radmodes ] ) of the velocity potential @xmath32 , as radial oscillations ( see section [ subsecradosc ] ) . these results can also be obtained using the asymptotes of the kummer function . in these cases the velocity is mostly radial ; the ratio of the radial to the horizontal velocity components can be estimated from eq . ( [ f_polytrop ] ) as @xmath81 . we define the oscillation damping time ( in the local stellar reference frame ) as @xmath82 where the oscillation energy is @xmath83\,{\rm d}z\ ] ] and @xmath84 here , @xmath85 , @xmath86 and @xmath87 are oscillation energy loss rates owing to the emission of electromagnetic and gravitation waves and owing to the viscous dissipation . to estimate the gravitational radiation rate ( for @xmath88 ) we employ the multipole expansion formula @xcite @xmath89 ^ 2}\ , \frac{gr}{\omega}\ , \left(\frac{\omega\,r}{c}\right)^{2l+1}\ , \,i_{\rm grav}^2,\ ] ] where @xmath90 the electromagnetic damping rate ( for @xmath91 ) calculated in the model of a frozen - in dipolar magnetic field disturbed by oscillations , with the vacuum boundary conditions at the stellar surface @xcite , is given by @xmath92 ^ 2 } \nonumber \\ & \times & \left\{\frac{2\,(l+1)\,f(0)/r - f^{\prime}(0)}{r\,\omega}\right\}^2 , \label{elmag_zatuh}\end{aligned}\ ] ] where @xmath93 is the magnetic field strength at the magnetic pole . the presence of the magnetosphere can change the emission power @xcite , but we neglect this effect . the viscous damping of oscillations was studied by @xcite who showed that @xmath94 where @xmath95 and @xmath96 is the shear viscosity . note , that the viscous damping can be additionally enhanced by thin viscous layers near weak first - order phase transitions associated with transformation of nuclides in dense matter . the viscosity in these layers can be diffusive or turbulent ; we neglect this additional dissipation in our calculations . taking the equilibrium pressure @xmath38 as the integration variable in eq . ( [ e ] ) we obtain @xmath97 where @xmath98 is the pressure at the crust bottom , and @xmath99 . note , that for given eos , @xmath62 , @xmath100 , and the root - mean - square radial displacement at the surface , the energy scales as @xmath101 . as will be shown in section [ secnumres ] , the viscous damping dominates at @xmath43 and @xmath102 . dipole modes decay usually owing to electromagnetic radiation . depending on the magnetic field strength , modes with @xmath103 damp mainly under the action of either electromagnetic or gravitational radiation . let us consider the oscillation damping for a polytropic eos for which the equilibrium density is @xmath104 . in this case , the damping rate via gravitational radiation is evaluated analytically and the oscillation energy ( for a given rms amplitude of radial surface displacements ) is independent of @xmath0 . the results are outlined below . the oscillation damping of a fundamental mode comes mainly from horizontal motions of the matter . accordingly , it is sufficient to take @xmath105 . then @xmath106 and @xmath107 note that for a given root - mean - square radial displacement @xmath108 at the surface , the normalization constant is @xmath109 ( as follows from eq . ( [ fundfreq ] ) ) . accordingly , the energy is independent of @xmath0 . p modes ( with at least one radial node ) of not very large multipolarity @xmath110 are accompanied by nearly radial velocities of the matter . their velocity potential @xmath111 and oscillation frequencies are almost the same as for radial oscillations . thus , their energy can be estimated as @xmath112 for the same root - mean - square radial displacement on the surface the energy is independent of @xmath0 . one has @xmath113 the last equality is obtained using eq . ( [ radmodes ] ) for the function @xmath111 . all numerical results are presented for a strange star of the gravitational mass @xmath114 , the circumferential radius @xmath115 km , and the crust depth @xmath116 m. the results can easily be rescaled to other strange star models ( with the same eos and the same maximum density of the normal matter ) using the scaling relation ( [ scaling ] ) . eigenfrequencies have been determined from eq . ( [ f ] ) ( with the boundary conditions @xmath36 and @xmath111 bounded at @xmath117 ) by the runge - kutta method . figure [ fig_freq ] shows oscillation eigenfrequencies calculated for a distant observer as a function of multipolarity @xmath0 . crosses are plotted for the eos of the accreted matter @xcite with the accurate treatment of phase transitions ( see , e.g. , * ? ? ? lines are for the polytropic eos ( @xmath47 ) , which describes the normal matter composed of @xmath118fe nuclei and ultrarelativistic electrons . the density at the crust bottom is @xmath119 g @xmath120 for the accreted crust and @xmath121 g @xmath120 for the polytropic one . note , that the polytropic eos accurately describes most of eigenfrequencies , but oscillations of the accreted crust have two specific additional branches ( shown by thinner lines in figure [ fig_freq ] ) known as density discontinuity g modes ( see , e.g. , * ? ? ? these oscillations are caused by buoyancy forces associated with phase transitions ; they are present in neutron stars and in strange stars with crust . for a vanishing shear modulus of the matter in the vicinity of a phase transition , the frequencies of such modes can be estimated as @xcite @xmath122 where @xmath123 is the depth of the phase transition , @xmath124 is the density jump , and @xmath125 is the density just after the jump . the parameters of such modes are sensitive to the model of accreted matter , to the shear modulus of this matter , etc . note that the distinctness of phase transitions in the accreted crust is still not clear they could be smoothed ( which would affect the respective g mode oscillation frequencies ) . therefore , we will not include density discontinuity g modes in our analysis and will study other oscillation branches in the polytropic approximation . figure [ fig_ssvsns ] shows the frequencies of oscillations of a strange star and a neutron star of the same mass @xmath114 and radius @xmath115 km . both stars are assumed to have an accreted crust . for the strange star , the crust depth is chosen to be @xmath116 m. details of calculations of neutron star oscillations are described by @xcite . if @xmath126 , oscillations are localized in a thin surface layer of the depth @xmath127 ; then both the strange star and the neutron star have the same oscillation spectrum . for lower @xmath0 the oscillations can penetrate into the layers of the depth @xmath128 , and the oscillation spectra of the strange star and the neutron star are seen to become different . let us focus on oscillations of the crust of strange stars . for not very large @xmath129 the frequencies of fundamental modes depend linearly on @xmath0 , but for p modes ( with at least one radial node ) the frequencies are approximately constant and equidistant . this feature is in good agreement with analytical results of sections [ subsecradosc ] and [ subsecnonradosc ] . for higher @xmath0 the @xmath0-dependence of the frequencies becomes more complicated because of the violation of the long - wave approximation ( which requires @xmath130 ) . finally , for @xmath131 , the oscillations are localized in the outer layers of the crust , and their frequencies become the same as for neutron stars . oscillations of strange stars with crust have several specific features which can be used to distinguish them from oscillations of neutron stars . * the frequencies of fundamental modes have linear dependence on @xmath0 . * the frequencies of p modes ( with at least one radial node ) are approximately equidistant and have very weak dependence on @xmath0 . figure [ fig_dump ] shows the damping time of oscillations , rescaled for a distant observer ( @xmath132 ) . the crust temperature ( important for the viscous damping ) is assumed to be @xmath133 k and the magnetic field strength at the magnetic poles is @xmath134 g. for higher @xmath23 the viscous damping time becomes larger . the damping time is seen to vary by many orders of magnitude , from @xmath135 years for the fundamental mode with @xmath136 to @xmath137 s for the mode with at least 2 radial nodes of @xmath32 and @xmath138 . this huge difference is produced by several damping mechanisms . in particular , radial oscillations ( @xmath43 ) decay exclusively through the viscous dissipation ( generating neither gravitational nor electromagnetic radiation ) . they damp slowly , with @xmath139 year . the modes with @xmath140 undergo powerful electromagnetic damping which greatly decreases the damping time ( figure [ fig_dump ] ) . fundamental modes have low frequencies . accordingly , they mainly undergo the viscous damping and do not damp efficiently via the emission of electromagnetic and gravitation waves . their damping times are relatively large , up to @xmath141 years . the exclusion is provided by the modes with @xmath142 and 4 , which decay quicker via the emission of electromagnetic waves . for p modes ( with at least one radial node ) the picture is different . the modes with @xmath143 decay primarily though the electromagnetic channel . because neither oscillation frequency nor @xmath32 depend on @xmath0 ( see section [ subsecnonradosc ] ) , the @xmath0-dependence of the dissipation time is fully determined by the electromagnetic energy losses ( see eq . ( [ elmag_zatuh ] ) ) . for higher multipolarity @xmath102 , the electromagnetic and gravitational emissions are strongly suppressed by large @xmath0 ( see eqs . ( [ grav_zatuh ] ) and ( [ elmag_zatuh ] ) ) and the viscous damping prevails . as a result , the damping times become approximately constant due to a weak @xmath0-dependence of oscillation frequencies and radial parts @xmath32 of the velocity potential . note that for lower @xmath144 g , the main damping mechanism of modes with @xmath145 consists in the emission of gravitational waves , while the electromagnetic channel is important only for dipole modes . to conclude , the fundamental modes and all radial oscillations have damping times exceeding 1 year and have better chances to be detected . the modes with @xmath102 have also relatively large damping times @xmath146 year , but it could be difficult to excite and detect them owing to large multipolarity . let us assume that some oscillation frequencies are detected and corresponding modes are identified . the frequencies of pressure modes ( in the local stellar reference frame ) are given by eq . ( [ radfreq ] ) . then the measured frequencies @xmath147 would give us the value of @xmath148 the frequencies of fundamental models are given by eq.([fundfreq ] ) . if @xmath149 were measured , it would provide us with the value of @xmath150 formally , we need to detect only one mode of each type to infer the values of @xmath151 or @xmath152 , but detecting several modes would give more confidence to the results . having @xmath151 and @xmath152 , we could obtain the value of @xmath153 without any additional assumption on the value of @xmath62 . note that @xmath154 , the mean density of the star . let us assume that we can deduce the value of @xmath62 form the theory or from interpretation of some observations . then the crust depth @xmath155 could be calculated for a given eos . for the polytropic eos it can be estimated as @xmath156 where @xmath157 cms@xmath158 and @xmath159 g@xmath120 . in that case we would obtain two equations ( for @xmath151 and @xmath152 ) for two important unknown stellar parameters , the mass @xmath6 and the radius @xmath160 , and could determine these parameters . if we do not know @xmath62 , we would be unable to determine @xmath6 and @xmath160 , but could constrain them taking into account that @xmath62 can not exceed the neutron drip density @xmath161 g@xmath120 ( for the accreted envelope ) . substituting @xmath162 into ( [ h ] ) and @xmath155 into ( [ c ] ) we would obtain the upper limit on @xmath160 . with this upper limit , we could easily derive the upper limit on @xmath6 from the value of @xmath163 . if , on the other hand , the mass @xmath6 is known from independent observations ( e.g. , the star enters to a binary system ) then the equations for @xmath151 and @xmath152 would allow one to determine @xmath160 and @xmath155 . note , that we do not include density discontinuous g modes into our analysis . the frequencies of these modes depend on many factors ( such as the densities of phase transitions , associated density jumps , etc . ) . the uncertainties of such factors would complicate the theoretical interpretation of measured g mode frequencies . however , if observed , g modes could provide some useful additional information . for instance , the number of such modes for a fixed @xmath164 is equal to the number of phase transitions @xmath165 ( this statement is strict only in the absence of other sources of buoyancy ) . this number could bound the maximum crust density @xmath62 in the region between theoretically predicted @xmath165-th and @xmath166-th phase transitions and impose then better bounds on the inferred values of @xmath6 and @xmath160 . we have studied pressure oscillations of strange star crusts . our main conclusions are as follows . \(1 ) the oscillations are almost insensitive to the various modifications of the eos in the normal crust . the polytropic eos provides approximately the same eigenfrequencies as the eos of the accreted crust , except for density discontinuous g modes , which are absent for the polytropic eos ( see section [ secnumres ] and figure [ fig_freq ] ) . ( 2 ) the oscillation problem for acoustic modes is self - similar ( in the plane - parallel approximation ) . once the problem is solved for one stellar model , it can easily be rescaled to strange star models with any mass and radius ( but the same eos and the maximum crust density ; see section [ secformal ] ) . \(3 ) for a thin polytropic crust , the oscillation problem is solved analytically ( sections [ subsecnonradosc ] and [ subsecradosc ] ) . \(4 ) the oscillation spectrum of a strange star crust is _ specific_. the frequencies of fundamental modes depend linearly on @xmath0 ; the frequencies of p modes are almost independent of @xmath0 . these features are _ unmistakable seismic signatures of strange stars with crust _ ( section [ secnumres ] ) . \(5 ) a detection and identification of one fundamental mode and one p mode would enable one , in principle , to infer the mass and radius of a strange star ( if the maximum crust density is known ) or at least to obtain corresponding upper limits ( section [ subsecstarparams ] ) . therefore , oscillation modes of strange stars with crust are potentially good tools to distinguish these strange stars from neutron stars and to determine their masses and radii . the oscillation frequencies could be detected by radio - astronomical methods very precisely . a search for these oscillation modes could be useful . some of them do not damp quickly and can survive for a long time ( section [ secnumres ] ) . pressure modes are robust because they are relatively independent of the thermal state of the crust , and they should not be strongly affected by the crustal magnetic field . i am grateful to d.g . yakovlev for discussions and also to v.a . urpin and the anonymous referee for useful critical remarks . this work was supported by a grant of the dynasty foundation and the international center for fundamental physics in moscow , by the russian foundation for basic research ( project no . 05 - 02 - 16245 ) and by the federal agency for science and innovations ( grant nsh 9879.2006.2 ) .

we study acoustic oscillations ( eigenfrequencies , velocity distributions , damping times ) of normal crusts of strange stars . these oscillations are very specific because of huge density jump at the interface between the normal crust and the strange matter core . the oscillation problem is shown to be self - similar . for a low ( but non - zero ) multipolarity @xmath0 the fundamental mode ( without radial nodes ) has a frequency @xmath1 hz and mostly horizontal oscillation velocity ; other pressure modes have frequencies @xmath2 khz and almost radial oscillation velocities . the latter modes are similar to radial oscillations ( have approximately the same frequencies and radial velocity profiles ) . the oscillation spectrum of strange stars with crust differs from the spectrum of neutron stars . if detected , acoustic oscillations would allow one to discriminate between strange stars with crust and neutron stars and constrain the mass and radius of the star . [ firstpage ] stars : neutron stars : oscillations .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Federal Support Payment Act''. SEC. 2. DECLARATIONS OF CONGRESS. (a) Right To Support.--The Congress hereby declares that every unemancipated child has a natural, moral, social, and Federal right to be supported by such child's parent or parents and that such right transcends the status of debt. (b) Effect of Exercise of Right To Travel.--The Congress further declares that while sound national policy requires that migration throughout the United States be unrestricted, experience has disclosed that in the exercise of the right of migration and travel many individuals leave behind them dependent and neglected children; and that although the courts of the State in which such children reside may have properly ordered an individual to meet his or her natural, moral, social, and Federal obligation to such children, once such individual has traveled to another State such individual has a practical sanctuary against jurisdiction of the original State of residence. (c) Instances of Departure Preceding Court Jurisdiction.--The Congress further declares that in other instances the departure preceded acquisition of jurisdiction over the individual by courts of the original State with like result. (d) Child Support Enforcement Amendments of 1984 Were Significant Steps.--In enacting the Child Support Enforcement Amendments of 1984 the Congress took significant steps to assist children in obtaining needed financial support from their parents regardless of their circumstances, but many of the evils outlined above remain. (e) Policy.--It is the policy of Congress in this Act to correct these evils-- (1) by requiring that orders of State courts directing individuals to meet their natural, moral, social, and Federal obligations to such children shall be enforced in the State courts in areas to which such individuals have migrated from the original jurisdiction within the United States; and (2) by giving State courts, in States to which such individuals have migrated, original jurisdiction in suits brought by citizens of other States to order such migrants to meet such obligations, to the end that such children will not suffer want or be made the objects of public welfare and thus become an unnecessary burden to the general public and be themselves thereby humiliated. SEC. 3. ENFORCEMENT OF STATE COURT ORDERS. (a) In General.--Part VI of title 28, United States Code, is amended by adding at the end thereof the following new chapter: ``CHAPTER 180.--ENFORCEMENT OF STATE COURT SUPPORT ORDERS ``Sec. ``3801. Definitions. ``3802. Registration of support orders. ``3803. Enforcement. ``3804. Notice to original court. ``Sec. 3801. Definitions ``As used in this chapter-- ``(1) the term `support order' means an order of a State court having jurisdiction over an individual, directing such individual to make payments periodically to (or for the support of) such individual's child (whether the issue of such individual's body, legitimate or illegitimate, or adopted); ``(2) the term `obligor', with respect to a support order, means an individual who is directed to make payments under the order; ``(3) the term `obligee' means any individual to whom the proceeds of a support order are payable for such individual, or for the use or benefit of another individual, or such other individual's guardian or guardian ad litem; ``(4) the term `original court', with respect to a support order, means the court in which the order was made; ``(5) the term `State' includes the territories and the District of Columbia; and ``(6) the term `registered', with respect to a support order, means registered under section 3102 of this title. ``Sec. 3802. Registration of support orders ``Any obligee of a support order may register the order in any court of any State in which an obligor of the order resides, if the court is located outside the State in which the order was made, and has jurisdiction to issue support orders. Registration shall be accomplished by filing with the clerk of the court a certified copy of the support order and of each order of the original court modifying the support order. ``Sec. 3803. Enforcement ``(a) Any court in which a support order is registered shall entertain contempt proceedings, in the same manner as if the order were an order of such court, against an obligor who fails to comply with the order within thirty days after being served notice that it has been registered. ``(b) No proceedings to enforce a support order shall be begun in any court under this section unless a copy of each order of the original court modifying the support order is registered under section 3102 of this title. ``(c) The cost of enforcement proceedings under this section shall be taxed against the party against whom the issues are resolved. The obligor shall be required to pay a reasonable attorney fee to the obligee if the court finds the proceedings were necessary to compel the obligor to comply with the support order. ``Sec. 3804. Notice to original court ``When, in any court, any support order is registered under section 3102 of this title or any proceedings are taken under section 3103 of this title to enforce a support order, written notice of such action under the seal of such court shall be sent to the original court.''. (b) Clerical Amendment.--The table of chapters for part VI of title 28, United States Code, is amended by adding at the end thereof the following new item: ``180. Enforcement of State Court Support Orders............ 3801''. SEC. 4. STATE COURT JURISDICTION. Section 1332 of title 28, United States Code, is amended by adding at the end the following new subsection: ``(e) State courts shall have original jurisdiction of civil actions brought by a citizen of another State to order a citizen of the State in which the court is located to make payments periodically to (or for the support of) such citizen's child (whether the issue of such citizen's body, legitimate or illegitimate, or adopted) if under the law of such State a State court is authorized to make such an order, as an incident to a divorce proceeding or otherwise.''.

Federal Support Payment Act - Amends the Federal judicial code to: (1) provide for the registration and enforcement of child support orders in States outside the State in which the order was made; (2) require notice of such registration and enforcement to be provided to the original court; and (3) grant State courts original jurisdiction of civil actions brought by a citizen of another State to order a citizen of the State in which the court is located to make payments periodically to (or for the support of) such citizen's child if under the law of such State a State court is authorized to make such an order.

during the past decade study of nonlinear behavior of magnetic crystals has been attracted large attention , specially it accompany with the progress in some other fields such as development of theory of nonlinear differential equation , achieving new laboratory results and also potential applications in other branches of science and technology [ 1 , 2 ] . particles with spin @xmath0 are more interesting among the other nano particles [ 3 , 4 ] . this is because of existing of complexity in their behavior due to their multipole dynamic spin excitations . in such systems , the number of necessary parameters for complete description of macroscopic properties increases up to 4s , that s stands for magnitude of system spin . also it worthwhile , the process of achieving classical spin equations and dynamic multipoles is based on coherent states that are obtained in @xmath1 group[5 ] . we consider unitary anisotropic hamiltonian as form of : @xmath2 which , @xmath3 are spin operators in lattice @xmath4 , and @xmath5 is anisotropy coefficient . this is hamiltonian of one dimensional ferromagnetic spin chain observed in compositions like @xmath6 [ 6 ] . in this paper the goal is to obtain classical equation for stated hamiltonian and finding the answer of spin wave for small linear excitations upper than the ground state . coherent states issued nearest approximation to classical state i.e. pseudo classical , because they minimize uncertainty principles . for this reason , in section 2 , coherent states for spin @xmath7 developed that are the same as coherent states in su(3 ) group . to obtain classical hamiltonian , we need average values of spin operator ; so in section 3 , these values and classical hamiltonian equation are derived . in section 4 , hamiltonian equation computed in previous section is substituted in classical equations of motion resulted from using feynman path integral on coherent states , and then we acquire spin wave equations and dispersion equations of dipole and quadupole branches for small linear excitation above the ground state , and finally we calculate soliton answers of linearized equations . coherent states are special quantum states that their dynamic is very similar to behavior of their classical system . the kind of coherent state that is used in a problem depends on symmetry of existent operators . with considering existent symmetry in operators of hamiltonian ( 1 ) , coherent states in su(3 ) group is used for accurate description and considering all multipole excitations . in this group , ground state considered as @xmath8 and its single - site coherent state is written as : @xmath9 is wigner function for spin @xmath7 and two angles @xmath10 and @xmath11 determine alignment of classical spin vector . angle @xmath12 determines direction of quadruple torque around the spin vector . parameter g specifies change of length of average value of quadruple torque and also of magnitude of spin vector . lagrangian can be obtained by use of feynman path integral for declared coherent states as:[8 ] @xmath13 where @xmath14 and h is classical energy of system obtained by averaging hamiltonian ( 1 ) on coherent states ( 2 ) . two other terms appear when acquiring lagrangian of spin system . the first is kinetic term that has berry phase characteristics issued from quantum interference of instanton paths and has important role in quantum phenomenons such as spin tunneling and the second is boundary term that depends on boundary values of path . both of term have no role in classical dynamic of spin excitations and so are not considered here . average spin values in su(3 ) group written as:[9 ] @xmath15 by averaging hamiltonian ( 1 ) and using ( 4 ) , the continuous limit of classical hamiltonian obtained as:[4 ] @xmath16 to obtain classical equation of motion , the above classical hamiltonian is substituted in motion equations resulted from lagrangian equation : @xmath17 these equations completely describe nonlinear dynamics of hamiltonian of problem up to quadrupole excitation . solutions of these equations are magnetic solitons . these equations result landau - lifshitz equation if quadrupole excitations ignored @xmath18 . so these equations are more general in comparison with landau - lifshitz and have more degree of freedom . it s noteworthy that solution of these equations has different range of solitons . for small linear excitation from ground stste , classical equations of motion change to : @xmath19 to obtain dispersion equations , functions @xmath20 and g are considered as plane waves and their substitution in linearized equations result in dispersion equation for spin wave near the ground state : @xmath21\end{aligned}\ ] ] from the above equation , it is obvious that both dipole and quadruple branches of unitary hamiltonian are dispersive in presence of linear excitations . to compute soliton answers of equations ( 7 ) , we define variable @xmath22 such as @xmath23 . in this case above equations convert to below nonlinear equations . @xmath24 the first equation is third order differential equation . so change of dipole moment in hamiltonian ( 1 ) is not of the form of soliton . solution of this equation has the following forms : @xmath25\end{aligned}\ ] ] the second equation is nonlinear klein - gordon equation and shows change of average value of quadruple excitation that its solution is of the form of hylomorphic solitons . these solitons are like q - ball solitons . the reason of this name is because of they cause matter have appropriate form . also these solitons are of the kind of non topologic ones because their boundary values in ground and infinity are the same from the topological point of view . if rewrite nonlinear klein - gordon equation ( 9 ) as : @xmath26 where @xmath27 numerical solution of ( 11 ) is plotted in figure ( 1 ) . in this computation we consider @xmath28 and @xmath29 . analytical solution of above nonlinear klein - gordon equation is the following form : @xmath30\end{aligned}\ ] ] where c is constant . in this paper , we study semi - classic theory for spin systems with spin @xmath31 that contain anisotropic exchange terms . it is shown that for anisotropic ferromagnet , value of average quadruple torque is not constant ( @xmath32 ) and its dynamic contains rotational term around classical spin vector ( @xmath33 ) and another dynamics that relates to change of length of quadruple torque . there are no such excitations in regular magnets and their dynamics is achieved by use of average value of heisenberg spin hamiltonian . also it is shown that soliton solutions are of the kind of non topologic hilomorphic solitons for quadruple excitations . o. abdulloev , kh . muminov , accounting of quadrupole dynamics of magnets with spin , proceedings of tajikistan academy of sciences , n.1 , 1994 , p.p . 28 - 30 ( in russian ) . v. g. makhankov , m. a. granados , and a. v. makhankov , `` generalized coherent states and spin @xmath34 systems , '' journal of physics a , vol . 29 , no . 12 , 2005

we discuss system with non - isotropic non - heisenberg hamiltonian with nearest neighbor exchange within a mean field approximation process . we drive equations describing non - heisenberg non - isotropic model using coherent states in real parameters and then obtain dispersion equations of spin wave of dipole and quadrupole branches for a small linear excitation from the ground state . in final , soliton solution for quadrupole branches for these linear equations obtained .

open pyeloplasty remains the gold standard for correcting ureteropelvic junction obstruction with a success rate between 90% to 98% . although endopyelotomy and retrograde dilation are alternative methods of managing ureteropelvic junction obstruction in children , the success of these 2 procedures is inferior to that reported for conventional dismembered pyeloplasty . laparoscopic pyeloplasty is rapidly becoming an acceptable procedure for ureteropelvic junction obstruction ( upjo ) in the pediatric population . the advent of smaller instrumentation and more experience with intracorporeal suturing allows this well - accepted procedure in adults to be implemented in the pediatric population . four children between 7 months to 8 years of age ( mean , 3.14 years ) underwent transperitoneal laparoscopic pyeloplasty for a upjo in a pelvic kidney . all patients except the 7-month - old patient presented with antenatal diagnosed hydronephrosis , which worsened and was associated with parenchymal thinning of the pelvic kidney . preoperatively , all patients had ultrasounds and diuretic radionuclide imaging ( dri ) evaluations consistent with upjo . all patients underwent cystoscopic evaluation with retrograde ureteropyelogram ( rgp ) and stent placement before laparoscopic positioning ( figure 1 ) . the transperitoneal laparoscopic approach previously described in the literature was implemented but slightly modified for the pelvic kidney . one was placed lateral to the contralateral rectus in the midclavicular line at the level of the umbilicus ; another at the umbilicus to hold a 30-degree 3-mm laparoscope ; and the remaining one near the midaxillary line lateral to the ipsilateral rectus 3 cm medial and cephalad from the anterior superior iliac spine ( figure 2 ) . three patients had a lower pole - crossing vessel , and 1 patient had a stenotic proximal segment . all reap - proximations were performed with 6 0 polyglactic acid sutures in an interrupted fashion . twelve sutures were placed at the upj with or without renal pelvis tapering , which was performed with a running 6 0 polyglactic acid suture . all pyeloplasties were performed with a double pigtailed ureteral stent placed during cystoscopic evaluation at the onset of the procedure . outcome measures included operative time , length of hospital stay , postoperative symptomatology , and resolution of obstruction by symptoms and ultrasonography , or dri , or both . all the patients were followed with ultrasonography 2 months and then every 6 months after the procedure . average operative time was 2.1 hours ( range , 1.5 to 2.8 ) . mean hospital stay was 2.15 days ( range , 1 to 7 ) . mean time to return to normal activity was 2 weeks ( range , 0.5 to 6 ) . after surgical repair , all 3 patients ( 100% ) were completely pain free at a mean follow - up of 12 months . all patients were evaluated 2 months postoperatively for an ultrasonographic evaluation revealing mild to moderate hydronephrosis . at a mean ultrasonographic follow - up of 11 months ( range , 6 to 20 ) , all 4 patients had resolution of the hydronephrosis . current published data support at this time that it is not recommended in children younger than 6 months . generally , the indications for laparoscopic pyeloplasty are identical to those of the open surgical approach , including failed previous retrograde or antegrade endopyelotomy . we were able to mobilize the ureter sufficiently that a culp - deweerd spiral , scardino - prince vertical flap , or a dismembered tubularized renal pelvic wall flap described by gill et al were not necessary . however , though the cohort is small , we feel that the same principles used in orthotopic laparoscopic pyeloplasty are easily recapitulated for the pelvic kidney . even with a small number of patients , our results seem to show that laparoscopic pyeloplasty is an option for treating upjo in pelvic kidneys . we feel that the transperitoneal laparoscopic approach is feasible in this specific , complex , pediatric population .

background : laparoscopic pyeloplasty is rapidly becoming an acceptable procedure for ureteropelvic junction obstruction in the pediatric population . we present our experience with transperitoneal laparoscopic pyeloplasty for ureteropelvic junction obstruction in pelvic kidneys in pediatric patients.methods:a transperitoneal laparoscopic approach was used for performing a pyeloplasty in 4 patients , 7 months to 8 years of age ( mean age , 3.14 ) , with ureteropelvic junction obstruction in a pelvic kidney.results:average operative time was 2.1 hours ( range , 1.5 to 2.8 ) . mean hospital stay was 2.15 days ( range , 1 to 7 ) . no intraoperative complications were noted.conclusions:transperitoneal laparoscopic pyeloplasty for pelvic kidneys is feasible in the pediatric population , and preliminary results appear to offer the same outcome as that seen in orthotopic kidneys .

the study of light elements , li and be and b , has progressed impressively in the last years , both in the theoretical and observational aspects ( see e.g. the proceedings edited by crane 1995 ) . on the observational side , observations of li in large , well defined samples , are becoming available , ( brown et al . 1989 , pasquini et al . 1994 , randich et al . 1996 ) , as well as new detailed observations in open clusters of different ages , either young ( soderblom et al . 1993 ) or as old as the sun ( balachandran 1995 ) . for the study of the oldest population of the galaxy , a large effort has been performed to analyze very metal poor stars in the field ( see i.e. spite 1995 for a review ) , and the first data on globular clusters have become available , for the old , metal poor gc s ngc6397 ( molaro and pasquini 1994 , pasquini and molaro 1996 ) and m92 ( deliyannis et al . 1995 ) . on the theoretical side several models have been developed which include new important features . standard models have been built with a more realistic treatment of the mixing in the convection zone ( dantona and mazzitelli 1994 ) , or with improved opacities ( swenson 1995 ) . non standard models were also improved and they include mechanisms previously neglected or only partially treated , like rotational mixing ( pinsonneault et al . 1992 , zahn 1994 ) , meridional circulation ( michaud and charbonneau 1991 ) , diffusion and mass losses ( swenson 1995 , vauclair and charbonnel 1995 ) . the homogeneity of stars in g.c . and the knowledge of their overall characteristics offer a powerful tool to address several topics concerning li abundance . by studying , for instance , the dependence of li abundance on stellar mass in a given gc , a detailed comparison with theoretical models can be performed , allowing to disentangle between the different mechanisms operating in the stellar interiors . by studying the li abundance in clusters spanning a large range of ages it would be possible to obtain precious information about the galactic evolution of lithium ( hobbs and pilachowski 1988 ) and its primordial fraction ( trimble 1991 ) . one interesting target among the near gc is certainly 47tuc ( = ngc104 = c0021 - 723 ) . the cluster is well studied ; with an age of at least 13@xmath4 0.5 gyr it belongs to the _ old _ generation of g.c . although its metallicity is more than 30 times higher than other coeval clusters ( hesser et al . observations of li in 47tuc and their comparison with the observations in ngc 6397 and m92 are therefore particularly suitable for the study of the lithium behavior with respect to stellar metallicity at a given age . the observations were obtained between october 11 and october 14 , 1994 using the emmi spectrograph ( giraud 1995 ) at the nasmyth focus of the 3.5 m ntt telescope . emmi was used in echelle mode , with grism 6 as crossdisperser providing a spectral coverage of 2000 . with a tectronix 2040@xmath82048 ccd and the f/5 long camera the scale is 0.067 / pixel in the li region . due to variable metereological conditions and to rather poor seeing , a slit aperture of 1.5 arcsec was mostly used , which gives a resolving power of @xmath2 18000 . the slit height , fixed at 10 arcsec , gives enough ( 35 ) pixels perpendicular to the dispersion direction to allow a good background - sky subtraction . the ccd was binned by two along the resolution , in order to minimize the contribution of the ccd read out noise . the ccd was also read in ` superslow ' mode which gave a ron of about 4e@xmath9/pixel . we were able to observe a total of 5 stars in 47tuc , from v=12.2 down to v=17.35 . observations are summarized in table 1 . the data were reduced using midas ( banse et al . 1988 ) facilities . special care was taken in the reduction of these low s / n data , in order to precisely subtract the background ( interorder+sky ) contribution and to take into account the presence of high energy particles events . to check the accuracy of the data the reduction was carried out using different procedures . the final spectra are presented in figure 1 . after rebinning to equal ( 0.12 ) wavelength step , the spectra were coadded with the proper weight ; note that no major spectrograph shifts were recorded during the whole run . the continuum was traced measuring the intensity of the spectra in several windows in selected regions surrounding the li line . in the case of very metal poor stars , this procedure can be easily applied because of the featureless appearence of the spectra . at the metallicity of 47tuc ( [ fe / h ] = -0.7 ) , however , the selection of the windows must be done carefully , due to the presence of metallic lines in the spectrum . the continuum regions were therefore selected from the inspection of high resolution , high s / n spectra ( pasquini et al . 1994 ) . equivalent widths were measured with simple integration . the fwhm of the li and ca i ( 6717 ) lines was of @xmath2 0.34 , in perfect agreement with what was expected from the instrument resolution . in estimating the errors on measured equivalent widths , we have assumed a conservative approach , in view of the uncertainties which influence the accuracy of the data : @xmath10ew = rms*res*w@xmath11 , where rms is the inverse s / n ratio as measured in the continuum windows close to the li line , res the measured resolution and w the number of resolution elements on which the integration has been carried out . to these uncertainties a value up to @xmath2 6 m should be added due to the possible uncertainties in positioning the continuuum ( cayrel 1988 ) . equivalent widths and s / n ratio are given in table 3 . at a distance of @xmath2 4.5 kpc , 47tuc is one of the best studied globular clusters . it is located at high galactic latitude and the reddening is rather low . in the literature reddening estimates range from e(b - v)=0.00 of cannon ( 1974 ) up to values of 0.08 ( menzies 1973 ) . however , best evidence is for intermediate values : crawford and snowden ( 1975 ) derived e(b - v)[email protected] ; hesser and philip ( 1976 ) obtained e(b - v)[email protected] and lee ( 1977 ) obtained e(b - v)[email protected] . in the following we will adopt e(b - v)= 0.04 as suggested by hesser et al . ( 1987 ) , but an error of 0.02 is possible here , and this is rather important in deriving the absolute value for li in the cluster . after a controversial discrepancy between the spectroscopic and photometric results , the last estimates of metallicity converge between the [ fe / h][email protected] , derived photometrically by hesser et al . ( 1987 ) and the [ fe / h][email protected] derived spectroscopically by d odorico et al . ( 1985 ) . in the following , a value of [ fe / h]= -0.7 will be adopted , but note that the uncertainties in metallicity have no significative influence in the determination of the li abundances . the observed stars are listed in table 1 . finding charts were provided by briley et al . ( 1994 ) , together with stellar colours and magnitudes , which are summarized in table 2 . with a visual magnitude around v@xmath2 17.35 and rather blue colors , 3 stars lie at the bright blue edge of the turnoff , indicating that they are in the upper part of the main sequence . to determine the stellar effective temperature , we have adopted the temperature scale of alonso et al . ( 1996b ) , based on the irfm ( see alonso et al . 1996a ) , to be able to compare the 47tuc abundances directly with the most recent determination of the li _ plateau _ ( bonifacio and molaro 1996 ) which is based on the alonso et al . ( 1996a ) effective temperatures . we note that the effective temperature used are in a very good agreement ( within 50 k ) with those obtained by using the briley et al . ( 1994 ) scale and with the vandenberg and bell ( 1985 ) scale used for ngc6397 by pasquini and molaro ( 1996 ) . for star l2734 , the effective temperature was derived from buser and kurucz ( 1992 ) , because none of the over mentioned scales is suitable for such a cool , evolved object . the uncertainty of this determination is somewhat higher than the one for the turnoff stars , but we note that the effective temperature adopted is not critical for this cool star . 0.2 cm 0.2 cm .summary of the observations : in column 1 the star names are given , the b suffix corresponds to stars from briley et al . 1994 , the l suffix for stars from lee ( 1977 ) ) [ cols= " > , > , > " , ] the t@xmath3 vs. m@xmath13 diagram for the observed stars is given in figure2 . in table 3 temperatures , equivalent widths and li abundances for the stars observed in 47tuc are given . the errors in the li abundances include only uncertainties coming from the equivalent widths measurements but an other comparable source of uncertainty comes from the error in the stellar t@xmath3 determination . considering the uncertainty ( @xmath4 0.02 ) in the reddening and possible systematic effects in the temperature scale adopted , an uncertainty in t@xmath3 of @xmath4 100 k is assumed , which would correspond to @xmath40.075 dex in [ li ] . other sources of uncertainty in the li determination come from the errors in the adopted gravity and microturbulence , and their contribution is only of 0.02 dex , much lower than the equivalent width and effective temperature terms . therefore the li abundance on the plateau of 47tuc is : [ li]= 2.37@xmath4 0.15 the [ li ] abundance in 47tuc is consistent with the _ plateau _ level of [ li]= 2.19 @xmath4 0.016 ( bonifacio and molaro ( 1996 ) ) at 1.2 @xmath14 level , but the li level measured in 47tuc is possibly slightly higher than the _ plateau_. this would imply a moderate li production for 47tuc , which is not surprising considering the higher metallicity of 47tuc . observations exist for the globular clusters ngc 6397 ( molaro and pasquini 1994 ; pasquini and molaro 1996 ) and m92 ( deliyannis et al 1995 ) , which have [ fe / h]=-2 and -2.25 respectively . the mean value for the abundances so far observed in stars close to the turnoff ( ignoring upper limits ) are [ li]=2.3 and 2.13 for ngc6397 and m92 , respectively . these values are , within the errors , consistent with the plateau abundance and slightly lower than in 47tuc . in figure 2 the stars observed in 47tuc ( triangles ) are overimposed with those observed in ngc 6397 ( squares ) , after scaling the stellar apparent luminosities according to the respective cluster distances and reddening ( alcaino et al . 1987 , hesser et al . 1987 ) , and the li abundances are given . in the same figure the observations of m92 from deliyannis et al . ( 1995 ) ( hexagons ) are included . for m92 a distance module of 14.75 and a reddening of e(b - v)=0.03 have been assumed . the effective temperatures of the stars in m92 and ngc6397 have been computed using the ( alonso et al . 1996 ) scale adopted for 47tuc . the li abundances for m92 were recomputed from deliyannis et al . ( 1995 ) li equivalent widths using the same atmospheric models adopted in this work and for ngc 6397 . the clusters are therefore in the same effective temperature reference scale and also the abundances are derived with the same atmospheric models . measurements errors are affecting the diagram of figure 2 in a complex way . on the top of known uncertainties , those from the ( b - v ) photometry will change slightly the stellar effective temperature , not only giving different li abundances , but also moving the stars in the diagram . the overall similarity in the li abundance among 47tuc , the other globular clusters and the _ plateau _ is remarkable , confirming that essentially the same li abundance is observed over three orders of magnitude variation in the metallicity . if , as suggested by boesgaard ( 1991 ) primordial li was an order of magnitude higher and the li observed in these clusters has been depleted by diffusion , winds , rotational mixing or other mechanism , then our observations require these mechanisms to be highly metallicity independent in the range -3.5 @xmath15[fe / h]@xmath15 - 0.7 . the same mechanism has instead to be strongly metallicity dependent at higher metallicity in order to reproduce the smooth increase of the li abundance envelope observed in the li - fe diagram of field stars ( rebolo et al . 1988 , see also next section ) . on the other hand , if these stars are essentially undepleted , the difference can be easily accomodated by a modest galactic li production , with most of the galactic li production occurring later on . several field stars with measured li abundance exist having metallicities similar to those of 47tuc . in figures 3a , b observations collected from several authors are plotted . the compilation includes all the field stars observed in li with a metallicity between -0.4 and -1 , bracketing the metallicity of 47tuc , with effective temperatures higher than 5500 k and estimated gravities @xmath163.5 , to avoid object which may have undergone depletion or dilution . it is known that at these metallicities a real spread in li abundances exists among field stars ( rebolo et al . the spread is present at temperatures far from those of the ` lithium dip ' or from those where convective induced depletion occurs . the spread is also unlikely an evolutionary effect , because the stars are quite firmly classified as genuine dwarfs . this spread has been interpreted in terms of different degrees of depletion and/or in terms of an age spread in the sample . one could expect that older stars are on average the more depleted ones . thus , it is remarkable that none of the field stars , which are on average younger than 47tuc , have abundances significatively higher than those observed in 47tuc . only hd 14221 ( balachandran 1990 ) with a metallicity of -0.4 and [ li]=2.9 is definitively higher , but , due to its high metallicity , this object can not be taken as a safe counterexample . the upper values of the observed [ li ] both in field stars _ and _ 47tuc at @xmath2 2.4 indicate that the [ li ] vs. fe abundance curve given by the upper envelope of figures 3a , b is basically independent of age , weakening the interpretation that an age - dependent depletion mechanism is in force ( boesgaard 1991 ) . these upper values are easily understood if no depletion has affected these stars . this in turn would suggest that we are just observing the increase of the galactic li enrichment . it would imply that only a very marginal increase in li abundance has occurred in the galaxy from the primordial value up to metallicities of @xmath2 -0.5 . in addition , since among field stars several are expected to be younger than 47tuc , this may also suggest that li enrichment depends more on metallicity rather than on age . we have to remember , however , that in old pop i stars some age - independent mechanism is acting , which increases the scatter of [ li ] abundances with respect to the metal poor objects ( pasquini et al . 1994 ) , and this mechanism has not yet been satisfactorily identified . according to the be measurements in metal poor stars and the expected li / be yields , the observed enhancement can be explained by high energy cosmic ray production , without the need of invoking other mechanisms . in fact , according to molaro et al ( 1996 ) , at [ fe / h]@xmath1 - 0.8 , be is [ be]=0.94 and the corresponding inferred li by the same spallation processes is [ li]=1.9 , when only @xmath17li isotope is considered . this value added to a primordial value of [ li]=2.20 gives [ li]=2.38 , which is precisely what it is observed in 47tuc . since an abundance up to [ li]@xmath23.1 is observed in the 4 gyrs old , solar metallicity cluster m67 ( pallavicini et al . 1996 ) , this interpretation would imply an increase of li abundance by 0.7 dex in the time ( and metallicity ) interval between 47tuc and m67 . for the third turnoff star ( b6 ) only an upper limit could be obtained . if the presence of li abundance scatter among 47tuc stars will be confirmed , this would indicate that the scatter observed in field stars at the 47tuc metallicities is not due to age or chemical composition differences , but rather to an extra mechanism capable of overdepleting li . it should be noticed that single stars in each cluster present li abundances which are as high as @xmath22.4 . in presence of a real dispersion of the li abundances in the clusters stars , only these high values would be close to the initial one . the presence of a spread in li abundances for similar stars belonging to m92 has been claimed by deliyannis et al . ( 1995 ) and successive observations ( boesgaard et al . 1996 ) confirmed that a statistically significative difference in the measured li equivalent widths exists . the three m92 stars considered are subgiants , and they have an effective temperature around 5750 k , that is very close to the point where subgiant dilution begins to be present ( pilachowski et al . 1993 ) . these stars are just 100 k hotter than star c4044 in ngc6397 , where the signs of dilution are evident ( cfr . figure 2 ) . photometric uncertainties may play an important role . an uncertainty in the ( b - v ) colours of 0.02 , as given by stetson and harris ( 1988 ) for two of the stars observed , corresponds to a difference in temperature of almost 100 k. this error is not only relevant for the derived abundances ( @xmath4 0.07 ) , but it may also shift the stars into the temperature regime where dilution is observed . a lower reddening , still allowed by the photometric observations , would result into lower effective temperatures , also moving the stars closer to the dilution zone . in addition , boesgaard et al . ( 1996 ) observed for the li - rich subgiant also different mg lines , and this could indicate that other intrinsic differences exist among the m92 stars . in 47tuc the comparison between star b6 with stars b5 and b7 may also suggest the presence of a scatter . for this case the stars have a temperature too hot to expect that depletion or dilution are effective , but with the s / n ratio of our observations the possible difference can not be considered as definitive . it is worth noticing that stars b5 and b7 have the same li and they are respectively cn rich and cn poor according to briley et al . ( 1994 ) ; therefore cn inhomogeneities among main sequence stars of 47tuc may not be related to the dispersion of li . the independence of the li abundance of nitrogen abundance had already been found by spite and spite ( 1986 ) by studying a sample of nitrogen rich field stars , and our result confirms spite s conclusion that nitrogen enhancement is not produced by deep mixing . pending more accurate observations , we can only conclude at the moment that the spread among similar stars of the same cluster has to be confirmed . very low li abundances are derived for the evolved stars in 47tuc and ngc6397 . this conclusion is not affected by the considered uncertainties . as pointed out by pilachowski et al . ( 1993 ) and pasquini and molaro ( 1996 ) , all present theories predict a levelling of the li abundance at [ li]@xmath21.1 for evolved stars with temperature below @xmath2 5100 k ( swenson 1995 ) , while observations in field and ngc6397 subgiants show a dramatic drop . our tight upper limits on b1 and l2734 in 47tuc confirm these previous studies , indicating that some other mechanism should be present , in addition to dilution , to produce an extra li depletion when stars are ascending the rgb . in this work we have presented and analyzed the first li observations in 5 turnoff and evolved stars of the old , metal rich globular cluster 47tuc . pushing the ntt telescope to its limits we have obtained high resolution observations for three v@xmath2 17.4 stars located in the spite _ plateau_. \1 ) the li abundance derived in two of the turnoff stars and from their composite spectrum is 2.37 @xmath4 0.15 . this value is slightly higher than the 2.20 found in the pop ii stars suggesting at most a mild increase in the li abundance . spallated li as deduced from the observed [ be ] can account for such an increase . \2 ) this finding , together with the fact that no field star in the metallicity range -1 to -0.4 show li levels substantially higher than the 47tuc turnoff stars , pose strong requirements on the possible models of li depletion in the stellar interior . proposed models have to account for an almost constant li level which extends from the most metal poor stars known up to metallicity -0.7 . \3 ) for the third turnoff star only an upper limit could be obtained . if the presence of li abundance scatter among 47tuc stars were confirmed , this would indicate that the scatter observed in field stars with similar metallicities is not due to age or chemical composition differences , but rather to an extra mechanism capable of overdepleting li . alcaino , g. , buonanno , r. , caloi , v. , castellani , v. , corsi , c.e . , iannicola , g. , liller , w. 1987 aj 94 , 917 . alonso , a. , arribas , s. , martinez - roger , c. 1996 a&as 117 , 227 alonso , a. , arribas , s. , martinez - roger , c. 1996 a&a 313 , 873 balachandran , s. 1990 apj 354 , 310 . balachandran , s. 1995 apj 446 , 203 . banse , k. , grosbol , p. , ponz , d. et al 1988 ` the midas image processing system ' in ` instrumentation for ground base astronomy : present and future ' , robinson , l.b . ed . ( springer ) boesgaard , a.m. 1996 in ` formation of the galactic halo .... inside and out ' , h. morrison and a. sarajedini eds . 92 boesgaard , a.m. 1991 apj 370 , l95 . bonifacio , p. molaro , p. 1996 mnras in press . briley , m.m . , hesser , j.e . , bell , r.a . 1991 apj 373 , 482 . briley , m.m . , hesser , j.e . , bell , r.a . , bolte , m. , smith , g.h . 1994 aj 108 , 2183 . brown , j.a . , sneden , c. , lambert , d.l . , dutchover , e. jr . 1989 apjs 71 , 293 . buser , r. , kurucz , r.l . 1992 a&a 264 , 557 . cayrel , r. 1988 , in ` iau symp . 132 , the impact of very high s / n spectroscopy on stellar physics ' , g. cayrel de strobel and m. spite eds . ( kluwer ) cannon r. d. 1974 mnras 167 551 . crane , p. 1995 ` the light element abundance ' ( springer ) . crawford , d.l . , snowden , m.s . 1975 pasp 87 , 561 . dantona , f. , and mazzitelli , i. 1994 apjs 90 , 467 . deliyannis , c.p . , boesgaard , a.m. , king , j.r . 1995 apj 452 , l13 . d odorico , s. , gratton , r.g . , ponz , d. 1985 a&a 142 , 232 . edvardsson b. , andersen , j. , gustafsson , b. , lambert , d.l . , nissen , p.e . , tomkin , j. 1993 a&a 275 , 101 giraud , e. 1995 ` the eso multi - mode instrument and the superb seeing imager ' , eso operating manual . hesser , j.e . , harris , w.e . 1987 pasp 99 , 739 . hesser , j.e . , philip a. g. d. 1976 pasp 88 89 . hobbs , l.m . , pilachowski 1988 apj 334 , 745 . kurucz , r. l. 1993 cd - rom no 11 , 13 , 18 . lee s. w. 1977 a&as 27 , 381 mayor , m. , imbert , m. et al . 1984 a&a 134 , 118 . menzies j. 1973 mnras 163 , 323 michaud g. , charbonneau p. 1991 space sci . rev 57,1 . molaro , p. , pasquini , l. 1994 a&a 281 , l77 . molaro , p. , f. primas , bonifacio , p. 1995 a&a 295 , l47 . pallavicini , r. , pasquini , l. , randich , s. 1996 a&a in preparation . pasquini , l. , liu , q. , pallavicini , r. 1994 a&a 287 , 191 . pasquini , l. , molaro , p. 1996 a&a 307 , 761 . pinsonneault , m.h . , deliyannis , c. p. , & demarque , p. 1992 apjs 78 , 179 . pilachowski , c.a . , sneden , c. , booth , j. 1993 apj 407 , 699 . randich , s. , gratton , r. , pallavicini , r. , pasquini , l. 1996 a&a in preparation . r. , molaro p. , beckman , j. e. , 1988 a&a 192 , 192 soderblom , d. r. et al 1993 aj 106 , 1059 spite , f. , spite , m. 1986 , a&a 163 , 140 spite , f. 1995 in ` the light element abundance ' , p. crane ed . , 239 ( springer ) swenson , f.j . 1995 apj 438 , l87 trimble , v. 1991 a&ar 3 , 1 vandenberg , d.a . , bell , r.a . 1985 apjs 58 , 561 vauclair , s. , charbonnel , c. 1995 a&a 295 , 715 zahn , j.p . 1994 a&a 288 , 829 .

we present high resolution observations ( fwhm=15 km s@xmath0 ) of the li region in 5 stars belonging to the old ( @xmath114 gyrs ) , metal rich ( [ fe / h]@xmath1 - 0.7 ) globular cluster 47tuc . at the eso ntt telescope we obtained emmi spectra for three [email protected] magnitude stars located at the turnoff with t@xmath3 on the spite _ plateau_. in two of the turnoff stars the lithium line is clearly detected and the mean lithium content [ li ] = 2.37@xmath4 [email protected] is derived . this value is slightly higher than the spite _ plateau _ at [ li]=2.19@xmath5 for field halo stars obtained with the same t@xmath3 scale by bonifacio and molaro ( 1996 ) . for the third turnoff star only an upper limit could be derived : [ li]@xmath6 2.19 . this upper limit may suggest the presence of some dispersion on the plateau stars of 47tuc as it is observed in field stars of similar metallicity . when compared with field dwarfs of [ fe / h ] @xmath1 -0.7 the li content of 47tuc turnoff stars is among the highest observed . considering the extreme age of 47tuc this suggests that no significant depletion affected these stars and it implies a mild li galactic enrichment between the epoch of pop ii formation and the formation of 47tuc stars with metallicities up to @xmath7 . spallation reactions , as deduced from be observations , can account for such an increase . the remaining two stars are evolved , and only upper limits could be placed at [ li ] @xmath60.7 and @xmath6 - 0.7 . these very low values imply some extra depletion mechanism in addition to dilution as it is observed in evolved field stars by pilachowki et al ( 1993 ) and in ngc6397 by pasquini and molaro ( 1996 ) .

World Sci-Tech Washington: To put it mildly, this is one gem of a gem. Scientists using two different age-determining techniques have shown that a tiny zircon crystal found on a sheep ranch in Western Australia is the oldest known piece of our planet, dating to 4.4 billion years ago. The timeline of the history of Earth, which places the formation of the Jack Hills zircon and a "cool early Earth" at 4.4 billion years. Photo: University of Wisconsin Writing in the journal Nature Geoscience on Sunday, the researchers said the discovery indicates that Earth's crust formed relatively soon after the planet formed and that the little gem was a remnant of it. Advertisement John Valley, a University of Wisconsin geoscience professor who led the research, said the findings suggest that the early Earth was not as harsh a place as many scientists have thought. To determine the age of the zircon fragment, the scientists first used a widely accepted dating technique based on determining the radioactive decay of uranium to lead in a mineral sample. But because some scientists hypothesised that this technique might give a false date due to possible movement of lead atoms within the crystal over time, the researchers turned to a second sophisticated method to verify the finding. They used a technique known as atom-probe tomography that was able to identify individual atoms of lead in the crystal and determine their mass, and confirmed that the zircon was indeed 4.4 billion years old. To put that age in perspective, the Earth itself formed 4.5 billion years ago as a ball of molten rock, meaning that its crust formed relatively soon thereafter, 100 million years later. The age of the crystal also means that the crust appeared just 160 million years after the very formation of the solar system. The finding supports the notion of a "cool early Earth" where temperatures were low enough to sustain oceans, and perhaps life, earlier than previously thought, Professor Valley said. This period of Earth history is known as the Hadean eon, named for ancient Greek god of the underworld Hades because of hellish conditions including meteorite bombardment and an initially molten surface. "One of the things that we're really interested in is: when did the Earth first become habitable for life? When did it cool off enough that life might have emerged?" Professor Valley said. The discovery that the zircon crystal, and thereby the formation of the crust, dates from 4.4 billion years ago suggests that the planet was perhaps capable of sustaining microbial life 4.3 billion years ago, Valley said. "We have no evidence that life existed then. We have no evidence that it didn't. But there is no reason why life could not have existed on Earth 4.3 billion years ago," he added. The oldest fossil records of life are stromatolites produced by an archaic form of bacteria from about 3.4 billion years ago. The zircon was extracted in 2001 from a rock outcrop in Australia's Jack Hills region, about 800 kilometres north of Perth. For a rock of such importance, it is rather small. It measures only about 200 by 400 microns, about twice the diameter of a human hair. "Zircons can be large and very pretty. But the ones we work on are small and not especially attractive except to a geologist," Professor Valley said. "If you held it in the palm of your hand, if you have good eyesight you could see it without a magnifying glass." Reuters ||||| Ever heard this life advice? When solving a big problem seems impossible, break it into smaller steps. Well, scientists just took one of geology's biggest controversies and shrunk it down to atomic size. By zapping single atoms of lead in a tiny zircon crystal from Australia, researchers have confirmed the crystal is the oldest rock fragment ever found on Earth — 4.375 billion years old, plus or minus 6 million years. "We've proved that the chemical record inside these zircons is trustworthy," said John Valley, lead study author and a geochemist at the University of Wisconsin, Madison. The findings were published today (Feb. 23) in the journal Nature Geoscience. Timeline showing major events in Earth history. Credit: Andrée Valley, University of Wisconsin Confirmation of the zircon age holds enormous implications for models of early Earth. Trace elements in the oldest zircons from Australia's Jack Hills range suggest they came from water-rich, granite-like rocks such as granodiorite or tonalite, other studies have reported. That means Earth cooled quickly enough for surface water and continental-type rocks just 100 million years after the moon impact, the massive collision that formed the Earth-moon system. [How Was The Moon Formed?] "The zircons show us the earliest Earth was more like the Earth we know today," Valley said. "It wasn't an inhospitable place." Dubious history Zircons are one of the toughest minerals on the planet. The ancient Australian crystals date back to just 165 million years after Earth formed, and have survived tumbling trips down rivers, burial deep in the crust, heating, squeezing and a tectonic ride back to the surface. The Australian zircons, from the Jack Hills, aren't the oldest rocks on Earth — those are in Canada — but about 3 billion years ago, the minerals eroded out some of Earth's first continental crust and became part of a riverbed. Geologists have carefully sorted out more than 100,000 microscopic Jack Hills zircons that date back to Earth's early epochs, from 3 billion to nearly 4.4 billion years ago. (The planet is 4.54 billion years old.) The crystals contain microscopic inclusions, such as gas bubbles, that provide a unique window into conditions on Earth as life arose and the first continents formed. Jack Hills, Australia, where rocks were found to contain the oldest known minerals on Earth, a 4.4 billion-year-old zircon. Credit: John Valley, University of Wisconsin Just three of the very oldest zircons have been found, ones that date back to almost 4.4 billion years ago. Their extreme age always makes the dates suspect, because of possible radiation damage. The radiation damage means the zircons could have been contaminated during their long lifetime. Zircons hold minute amounts of two naturally occurring uranium isotopes — isotopes are atoms of the same element with different numbers of neutrons. Uranium radioactively decays to lead at a steady rate. Counting the number of lead isotopes is how scientists date the crystals. But as the uranium kicks out lead atoms, the radioactive decay releases alpha particles, which can damage the crystals, creating defects. These defects mean fluids and outside elements can infiltrate the crystals, casting doubt on any conclusions about early Earth based on the zircons. More important, uranium and lead can move around within a crystal, or even escape or enter the zircon. This mobility can throw off the lead isotope count used to calculate the zircon ages, and is the source of the decades-long controversy over the Jack Hills zircons' Methuselah lifespan. "If there's a process by where lead can move from one part of the crystal to another place, then the place where lead is concentrated will have an older apparent age and the place from where it moves will have a younger apparent age," Valley said. Atom by atom Valley and his co-authors hope to end the debate by showing that even though one of the oldest Jack Hills zircons suffered radiation damage, the lead atoms stayed in place. The researchers painstakingly counted individual lead atoms within the oldest-known zircon with a recently developed technique called atom-probe tomography. Inside the zircon, lead atoms clustered together in damage zones just a few nanometers wide. Imagine cliques of teens during high school lunch — like teenagers, no lead atoms had left their zones. "We've demonstrated this zircon is a closed geochemical system, and we've never been able to do that before," Valley said. "There's no question that many zircons do suffer radiation damage, but I think relative to these zircons, this should settle it once and for all," Valley told Live Science's Our Amazing Planet. Cathodoluminescence image of a 400-μm zircon and the 3-D map made by atom-probe tomography of a group of ~10-nm clusters of radiogenic atoms of lead. Credit: John Valley, University of Wisconsin The key finding, that lead atoms stick close to home inside this primeval zircon, means age estimates based on uranium-lead dating techniques are accurate, the researchers report. The lead hasn't wiggled around enough to throw off the ages. A typical age measurement, made with a machine called an ion probe, zaps zircon segments that are thousands of times larger than the damage clusters. "This careful piece of work should settle the debate because it shows that indeed there is some mobility of lead, which was hypothesized to result in dates that were too old, but the scale of mobility is nanometers," said Samuel Bowring, a geochemist at MIT, who was not involved in the study. "Even the smallest volumes analyzed with the ion probe average out the heterogeneities," or variations within the zircon. The new atom-probe technique, while extremely laborious, can also be used to address questions of reliability at other sites where extremely old rocks have been found, the researchers said. [Have There Always Been Continents?] "Good zircons are forever, and what this does is help us separate the wheat from the chaff in a way we could never do before," Valley said. Email Becky Oskin or follow her @beckyoskin. Follow us @OAPlanet, Facebook and Google+. Original article at Live Science's Our Amazing Planet.

– When scientists claimed more than a decade ago that tiny crystals in Australia were 4.4 billion years old, they faced skepticism. The Earth itself, after all, is 4.5 billion years old, the Sydney Morning Herald notes. "Nothing in science goes without being questioned," geochemist John Valley tells NPR. Now, however, his team has proven the crystals' age is correct—in other words, they're the oldest Earth-formed materials ever found. Researchers dated the crystals, which need magnification to be seen, by investigating how much of the uranium within them had turned into lead. But that standard dating method wasn't enough to convince some fellow scientists. Doubters pointed out that as time went by, lead atoms could have shifted around inside the crystal, potentially resulting in inaccurate readings. So the experts turned to a process called atom-probe tomography, which allowed them to map out specific atoms, NPR reports. The study showed that, in fact, the atoms hadn't moved much. Now, "we've proved that the chemical record inside these zircons is trustworthy," Valley tells LiveScience. The findings indicate that the Earth may have been able to host life earlier than had been believed: "there is no reason why life could not have existed on Earth 4.3 billion years ago," Valley says.

SECTION 1. SHORT TITLE. This title may be cited as the ``Gila River Indian Community-- Phelps Dodge Corporation Water Rights Settlement Act of 1999'' and is herein referred to as ``this Act''. SEC. 2. CONSTITUTIONAL AUTHORITY. The Constitutional authority upon which this Act rests is the power of Congress to regulate commerce with foreign nations and among the Several States and with the Indian tribes, as set forth in section 8 of Article I of the United States Constitution. SEC. 3. PURPOSE. It is the purpose of this Act-- (1) to ratify, approve and confirm the Settlement Agreement among the Gila River Indian Community, Phelps Dodge Corporation, and the United States of America; (2) to authorize and direct the Secretary of the interior to execute and perform his duties under the Settlement Agreement and this Act; and (3) to authorize and direct the Secretary to perform certain actions which will assist in achieving a settlement of the water rights claims of certain Indian tribes in the Little Colorado River Basin in Arizona. SEC. 4. DEFINITIONS. As used in this Act, the following terms have the following meaning: (1) ``Allottees'' shall mean the owners of beneficial interests in allotted land within the Gila River Indian Reservation. (2) ``Blue Ridge Reservoir'' means that Reservoir in Navajo County, Arizona, owned by Phelps Dodge, as more fully described in the Settlement Agreement. (3) ``CAP'' shall mean the Central Arizona Project, a reclamation project constructed by the United States pursuant to the Colorado River Basin Project Act of September 30, 1968, 82 Stat. 885, as amended. (4) ``CAWCD'' shall mean the Central Arizona Water Conservation District, a political subdivision of the State of Arizona, which has executed a contract to repay to the United States the reimbursable costs of the CAP. (5) ``Community'' shall mean the Gila River Indian Community, an Indian community organized under section 16 of the Indian Reorganization Act of June 18, 1934, 48 Stat. 987, duly recognized by the Secretary, and its members. (6) ``Community's CAP Contract'' shall mean that contract between the Gila River Indian Community and the United States, dated October 22, 1992, providing for the delivery to the Gila River Indian Community of up to 173,100 acre-feet per annum of CAP water. (7) ``Globe Equity No. 59'' shall mean the decree entered June 29, 1935, in that action styled as The United States of America v. Gila Valley Irrigation District, et al., Globe Equity No. 59 in the District Court of the United States in and for the District of Arizona, as amended and supplemented. (8) ``Hopi tribe'' shall mean the federally recognized Indian tribe of that name. (9) ``Navajo Nation'' shall mean the federally recognized Indian tribe of that name. (10) ``Phelps Dodge'' shall mean Phelps Dodge Corporation, a New York corporation, its subsidiaries, affiliates, predecessors, successors and assigns. (11) ``Pueblo of Zuni'' shall mean the federally recognized Indian tribe of that name. (12) ``Reservation'' shall mean the Gila River Indian Reservation, as it existed on the Initial Effective Date of the Settlement Agreement, as shown on the map attached to the Settlement Agreement as exhibit ``B'' thereto. (13) ``San Juan Southern Paiute Tribe'' shall mean the federally recognized Indian tribe of that name. (14) ``Secretary'' shall mean the Secretary of the Interior or his lawful designee. (15) ``Settlement Agreement'' shall mean that agreement dated as of May 4, 1998, among Phelps Dodge, the Community and the United States. (16) ``SRP'' shall mean the Salt River Project Agricultural Improvement and Power District, a political subdivision of the State of Arizona, and the Salt River Valley Water Users' Association, an Arizona corporation. (17) ``United States'' shall mean the United States of America, in its capacity as trustee for the Community and of the Reservation; as trustee for the Allottees and of allotted lands on the Reservation; and, with respect to section 5.2 of the Settlement Agreement, in all other capacities required in order to execute the agreements and other instruments and to take the actions referred to in section 5.2 of the Settlement Agreement, including acting for the part of Defense Plant Corporation. SEC. 5. APPROVAL OF SETTLEMENT AGREEMENT. The Settlement Agreement is ratified, approved and confirmed. The Secretary shall execute the Settlement Agreement within sixty days of the enactment of this Act and shall perform all of the Secretary's duties thereunder as provided herein and in the Settlement Agreement. SEC. 6. TRANSFER OF RESERVOIRS. The Secretary shall take all actions specified in section 5.0 of the Settlement Agreement necessary on the Secretary's part to obtain title to Blue Ridge Reservoir from Phelps Dodge. The title to Blue Ridge Reservoir, once acquired by the Secretary, shall be held by the Secretary in trust for the benefit of the Navajo Nation. In connection with the Secretary's performance of his obligations under section 5.0 of the Settlement Agreement, the Navajo Nation, the Hopi Tribe, the San Juan Southern Paiute Tribe, the Pueblo of Zuni, and the United States, on behalf of each of them, are authorized to execute waivers of claims against Phelps Dodge and agreements not to object to certain uses of water by Phelps Dodge in substantially the form of exhibits ``E'' and ``J'' to the Settlement Agreement, which waivers and agreements are hereby ratified, approved and confirmed. The Navajo Nation, and the United States on behalf of the Navajo Nation, is further authorized to enter into an agreement with the Arizona Game & Fish Department confirming a minimum pool of water in Blue Ridge Reservoir and for other purposes in substantially the form of exhibits ``G'' and ``I'' to the Settlement Agreement, which agreements are hereby ratified, approved and confirmed. SEC. 7. REALLOCATION OF CAP WATER. Simultaneously with the transfer of Blue Ridge Reservoir to the United States as provided for in section 6 of this Act, the Secretary shall: (i) reallocate to the Community 12,000 acre-feet of the CAP water available to the Secretary pursuant to section 406(b) of title IV of Public Law 101-628, 104 Stat. 4483; (ii) amend the Community's CAP Contract to include the CAP water reallocated to the Community pursuant to this section; and, (iii) amend the Community's CAP Contract to extend the term thereof to 100 years, plus such additional term as may result from the exercise of the option provided for in, or other extension of, the Lease referred to in section 8 of this Act. (1) All water service capital charges and other capital charges of any nature associated with the CAP water reallocated to the Community pursuant to this Act shall be non-reimbursable to the United States by the Community. (2) All water service capital charges and other capital charges of any nature associated with 10,000 acre-feet of that CAP water currently available to the Community under the Community's CAP Contract which shares a priority with 510,000 acre-feet of non-Indian municipal and industrial CAP water shall be non-reimbursable to the United States by the Community. (3) For purposes of determining the allocation and repayment of costs of the CAP as provided in article 9.3 of Contract Number 14-0906-09W-09245, amendment No. 1, between the United States and CAWCD dated December 1, 1988, and any amendment or revision thereof, all of the water service capital charges and other capital charges of any nature associated with the water described in subsections 7(a) and 7(b) of this Act shall be non-reimbursable and shall be excluded from CAWCD's repayment obligation. (4) The United States shall either-- (A) not charge operation, maintenance, and replacement (OM&R) charges to the Community on the first 8,000 acre-feet of CAP water made available to the Community pursuant to this Act, and shall itself pay any such charges as are associated with such 8,000 acre-feet of CAP water; or (B) charge the Community only that portion of the OM&R charges associated with electrical energy pumping for the entire 12,000 acre-feet of CAP water made available to the Community pursuant to this Act, and shall itself pay other OM&R charges associated with such 12,000 acre-feet of CAP water. (5) In the event the CAP water made available to the Community pursuant to this Act is leased to Phelps Dodge as provided for in section 8 of this Act, the charges by the United States to Phelps Dodge for such water when delivered under the Lease shall be as provided in subsections (d)(1) or (d)(2) of this section 6. (6) In the event the exchange provided for in section 8 of this Act is not approved, the Secretary shall reallocate to Phelps Dodge 8,000 acre-feet of the CAP water referred to in subsection 6(b) hereof, shall amend the Community's CAP contract to reflect such reallocation, and shall enter into a contract with Phelps Dodge for permanent service for the delivery of such water to Phelps Dodge through the works of the CAP. The CAP water shall be free of all capital charges as provided in subsections 7(b) and 7(c) of this Act. The United States shall charge Phelps Dodge OM&R charges for such water only as provided in either subsections 7(d)(1) or 7(d)(2) hereof and shall itself pay such portions of the OM&R charges as are not paid by Phelps Dodge. (7) The provisions of section 226 of Public Law 97-293 (96 Stat. 1273, 43 U.S.C. 485h(f)) shall not apply to actions taken by the Secretary pursuant to sections 7, 8, or 9 of this Act. SEC. 8. CAP WATER LEASE. The Lease referred to in section 7.0 of the Settlement Agreement and attached thereto as exhibit ``M'' is hereby ratified, approved and confirmed. Notwithstanding the preceding sentence, the Lease shall not be effective as to the United States, and the Secretary shall not execute the Lease, until all environmental compliance associated with the Secretary's execution of the Lease has been completed and the exchange referred to in section 9 of this Act has been approved as provided in that section. In the event the Lease becomes effective, the Secretary and the Community may renew or extend the Lease at the end of the initial term, or any extended term of the Lease provided for in the initial Lease, upon such terms as the Community, the Secretary and Phelps Dodge may agree, provided that any such renewal or extension shall not exceed 100 years in term. Subject to the completion of environmental compliance, CAP water made available pursuant to the Lease may be used in the manner and at the locations provided for therein, including exchange for use in any county in Arizona outside the CAWCD service area. SEC. 9. EXCHANGE AGREEMENT. The Secretary and the Community are authorized to enter into an exchange agreement with Phelps Dodge pursuant to which the CAP water leased to Phelps Dodge by the Community under the Lease authorized under section 8 of this Act is delivered by Phelps Dodge to the Community in return for the right to divert water from the Gila River upstream of the Reservation. The term of any such exchange agreement, if approved as required by this section, shall be for 100 years, plus any additional term occasioned by the exercise of the option contained in the Lease or other extension authorized in the Lease or this Act. The Secretary shall commence negotiations with respect to the exchange agreement forthwith upon the enactment of this Act and shall process all environmental compliance associated with the exchange agreement and the Lease in an expeditious manner. The Secretary shall not execute the exchange agreement until all such environmental compliance has been finally concluded as provided in the Settlement Agreement and any necessary order approving the exchange, or any aspect of the exchange, has been obtained from the United States District Court in Globe Equity No. 59 and the order is final and subject to no further appeal. SEC. 10. APPROVAL OF WAIVERS. The waivers set forth in section 9.0 of the Settlement Agreement shall be effective, and shall be binding upon, the Community, and the United States, on behalf of the Community and the Allottees, from and after the date either of the conditions set forth in section 4(c) of the Settlement Agreement occurs. The United States is authorized and directed to execute the Settlement Agreement on behalf of the Allottees in its capacity as trustee for the Allottees and of allotted lands on the Reservation, and the Settlement Agreement shall be binding upon the Allottees. SEC. 11. MISCELLANEOUS. (a) Execution of the Settlement Agreement by the Secretary as required by this Act, and the Secretary's performance of the actions necessary to acquire title to Blue Ridge Reservoir for the benefit of the Navajo Nation pursuant to section 5.0 of the Settlement Agreement shall not constitute major Federal actions under the National Environmental Policy Act (42 U.S.C. 4321 et seq.). The Secretary shall carry out all environmental compliance required by sections 8 and 9 of this Act. Nothing in this Act shall be construed as exempting the United States from carrying out environmental compliance associated with the use of water from Blue Ridge Reservoir by the United States for the benefit of the Navajo Nation in the Little Colorado River Basin in Arizona. (b) The Navajo Nation, and the United States on behalf of the Navajo Nation, are authorized to enter into an agreement with the Town of Payson, Arizona, and the unincorporated communities of Pine and Strawberry, Arizona (``the Towns'') or any one of them, to subordinate water rights held in Blue Ridge Reservoir by the United States for the benefit of the Navajo Nation to rights to the use of not to exceed a cumulative total of 3,000 acre-feet per annum of water in Blue Ridge Reservoir acquired by the Towns pursuant to the law of the State of Arizona. (c) The Navajo Nation, and the United States on behalf of the Navajo Nation, are authorized to enter into an agreement with Phelps Dodge to subordinate water rights held in Blue Ridge Reservoir by the United States on behalf of the Navajo Nation to water rights acquired by Phelps Dodge in Blue Ridge Reservoir subsequent to the date of the enactment of this Act pursuant to the law of the State of Arizona for use on land owned by Phelps Dodge around Blue Ridge Reservoir identified in the Settlement Agreement. The term of any such agreement and the consideration to be paid therefor shall be as agreed to among the Navajo Nation and Phelps Dodge. (d) With regard to the environmental compliance required for the actions contemplated in sections 8 and 9 of this Act, the Bureau of Reclamation shall be designated as the lead agency, and shall coordinate and cooperate with the other affected Federal agencies as required under applicable Federal environmental laws. (e) The Secretary and the Community are authorized to execute any amendments of the Settlement Agreement and to perform any action required by any amendments to the Settlement Agreement which may be mutually agreed upon by the parties. (f) Except for the waivers authorized by section 6 of this Act, nothing in this Act or the Settlement Agreement shall be construed to quantify or otherwise affect the water rights, claims or entitlement to water of any Arizona tribe, band or community or of any claimant in the Gila River Adjudication, other than the Community, the United States on behalf of the Community and the Allottees, and Phelps Dodge. (g) Any party to the Settlement Agreement, and to the Lease and the exchange agreement referred to in sections 8 and 9 of this Act, respectively, if the same are approved, may bring an action or actions exclusively in the United States District Court for the District of Arizona for the interpretation and enforcement of this Act, the Settlement Agreement, the Lease and the exchange agreement, naming the United States and the Community as parties, and in any such action or actions, any claim by the United States or the Community to sovereign immunity from suit is hereby waived.

Gila River Indian Community-Phelps Dodge Corporation Water Rights Settlement Act of 1999 - Ratifies, approves, and confirms the May 4, 1998, settlement agreement among Phelps Dodge Corporation, the Gila River Indian Community, and the United States (agreement). Directs the Secretary of the Interior or his lawful designee (Secretary) to execute, and perform all of the Secretary's duties under, the agreement. (Sec. 6) Directs that: (1) the Secretary take all actions specified in the agreement necessary on the Secretary's part to obtain title to Blue Ridge Reservoir from Phelps Dodge; and (2) title to the Reservoir be held by the Secretary in trust for the benefit of the Navajo Nation. (Sec. 7) Directs the Secretary, simultaneously with the transfer of the Reservoir to the United States, to: (1) reallocate to the Community 12,000 acre-feet of Central Arizona Project (CAP) water; (2) amend the Community's CAP Contract to include the reallocated water; and (3) extend the Community's CAP Contract to 100 years, plus such additional term as may result from the exercise of the option provided for in, or other extension of, the lease referred to in the agreement. Sets forth provisions regarding nonreimbursability of water service and other capital charges and operation, maintenance, and replacement charges to the Community. (Sec. 8) Ratifies, approves, and confirms a lease referred to in the agreement. Makes such lease ineffective as to the United States and directs the Secretary not to execute it, until environmental compliance has been completed and the exchange has been approved. Allows the Secretary and the Community to renew or extend the lease at the end of the initial or any extended term as the Community, the Secretary, and Phelps Dodge may agree, with a limitation. (Sec. 9) Authorizes the Secretary and the Community to enter into an exchange agreement under which CAP water leased to Phelps Dodge by the Community is delivered by Phelps Dodge to the Community in return for the right to divert water from the Gila River upstream of the Gila River Indian Reservation. Sets the term of any such exchange agreement at 100 years, plus any additional term occasioned by the exercise of the option contained in the lease or other authorized extension. Directs the Secretary to commence negotiations regarding the exchange agreement and to process all associated environmental compliance expeditiously. Prohibits the Secretary from executing the exchange agreement until: (1) all such environmental compliance has been finally concluded; (2) any necessary order approving the exchange, or any aspect of the exchange, has been obtained from the U.S. district court; and (3) the order is final and subject to no further appeal. (Sec. 10) Makes specified waivers of the agreement effective, and binding upon the Community and the United States, on behalf of the Community and the owners of beneficial interests in allotted land within the Reservation (allottees), after the date certain conditions set forth in the agreement occur. Directs the United States to execute the agreement on behalf of the allottees in its capacity as trustee of allotted lands on the Reservation. Makes the agreement binding upon the allottees. (Sec. 11) Authorizes the Navajo Nation, and the United States on its behalf, to enter into an agreement with: (1) the town of Payson, Arizona, or the unincorporated communities of Pine and Strawberry, Arizona (the towns), to subordinate water rights held in the Reservoir by the United States for the benefit of the Navajo Nation to rights to the use of up to 3,000 acre-feet per annum of water in the Reservoir acquired by the towns under Arizona law; and (2) Phelps Dodge to subordinate water rights held in the Reservoir by the United States on behalf of the Navajo Nation to water rights acquired by Phelps Dodge in the Reservoir subsequent to this Act's enactment under Arizona law for use on land owned by Phelps Dodge around the Reservoir identified in the agreement. Designates the Bureau of Reclamation as the lead agency with regard to environmental compliance. Authorizes any party to the agreement, and to the lease and exchange agreement, if approved, to bring suit in the U.S. district court for the district of Arizona for the interpretation and enforcement of this Act, the agreement, the lease, and exchange agreement and waives claims by the United States or the Community to sovereign immunity.

the increased abundance of particles containing strange quarks in the spectrum of emitted hadrons , especially hyperons , was proposed by hagedorn and rafelski @xcite as a signal for the formation of quark matter in relativistic heavy ion collisions . soon afterwards , the enhanced pair production of strange quarks required for the saturation of strange quark phase space was predicted to occur as an effect of quark and gluon deconfinement @xcite . the predicted enhancement has been observed in many experiments ( see , in particular : @xcite ) . the parameter @xmath2 , describing the degree of saturation of the phase space of strange hadrons , has been determined by thermal chemical fits to the abundances of hadrons emitted in collisions between two @xmath3au nuclei at center - of - mass energies of 200 gev / nucleon at the relativistic heavy ion collider ( rhic ) . values for this parameter obtained in such fits range from @xmath4 @xcite to @xmath5 @xcite . it is important to understand how the dynamics of deconfinement and chiral symmetry affects the prediction of production of the strange quarks and therefore its enhancement . the recently developed three - flavor pnjl model @xcite has made such a study possible . in the present work we explore the effect of the temperature dependence of the polyakov loops and chiral condensates on the strange quark production . our article is structured as follows . after stating the basic equations of the pnjl model , including the thermal quark and antiquark distribution functions , we obtain an explicit fit for the temperature dependence of the effective action of the polyakov loop in mean - field theory . we confirm that this action satisfies the scaling of the thermal averages of the polyakov loop in different color representations by their casimir operator . we then calculate the temperature dependence of the thermal average of the adjoint polyakov loop , the thermal distribution function of transverse gluons and the contribution of transverse gluons to the thermodynamic potential . finally , we calculate the temperature dependence of the pair - production rate of strange quarks using the polyakov loop - suppressed quark and gluon distribution functions . with the aid of the pnjl model , we identify the temperature where the gluonic contribution to the production rate becomes dominant . the cross - over of the contributions from light quarks and gluons is a novel phenomenon which does not exist in the traditional approach to strange quark - pair production based on perturbation theory @xcite . the phase transformations of qcd matter due to deconfinement and chiral symmetry restoration have been combined in one theoretical framework , which is the nambu - jona - lasinio model with the polyakov loop ( pnjl model ) @xcite . the polyakov loop in color - su(3 ) representation @xmath6 is defined as @xmath7 where @xmath8 denotes that the exponential is path - ordered , @xmath9 denotes the temperature and @xmath10 is the temporal component of the @xmath11 gauge field in representation @xmath6 . in particular , @xmath12 and @xmath13 denote the polyakov loops in the fundamental and adjoint representations , respectively . the traces of the polyakov loops are defined as @xmath14 where @xmath15 and @xmath16 denote the color traces in the fundamental and adjoint representation , respectively . note that the dependence of @xmath17 , @xmath18 , @xmath19 and @xmath20 on the spatial coordinate @xmath21 is suppressed in ( [ eq : p - loop - def])-([eq : ell_8-def ] ) . with the above definitions , the lagrangian of the three flavor pnjl model is @xcite @xmath22 \nonumber \\ & & + g_d \left [ { \det \bar { \psi } \left ( { 1 - \gamma _ 5 } \right)\psi + h.c . } \right ] , \label{eq : pnjl - lagr}\end{aligned}\ ] ] where @xmath23 is the gauge - covariant derivative , @xmath24 is the effective potential for the polyakov loop and the three - flavor current quark mass matrix @xmath25 . in the limit of isospin symmetry , @xmath26 . in the mean - field approximation , the chiral condensates and the thermal averages of the polyakov loops are the order parameters of the phase transition @xcite . note that , in the mean - field approximation , the thermal average of the polyakov loop is independent of the spatial coordinate @xmath21 . to encode the features of the temperature dependence of the effective potential @xmath27 , the nonperturbative contribution to the gluon thermodynamic potential per unit volume is assumed to be of the following form @xcite : @xmath28 \right\ } , \label{eq : omega_g_np}\end{aligned}\ ] ] where @xmath29 and @xmath30 are the thermal averages of the polyakov loops in ( [ eq : ell_3-def ] ) . standard values for the parameters in ( [ eq : pnjl - lagr ] ) and ( [ eq : omega_g_np ] ) are @xmath31 gev , @xmath32 , @xmath33 , @xmath34 and @xmath35 gev @xcite . moreover , it is straightforward to obtain the quark partition function from the quark lagrangian , yielding the quark grand canonical thermodynamic potential per unit volume @xcite : @xmath36 \right . \nonumber\\ & & \left . \left.+ \tr_f \ln \left [ 1 + l_3^{\dagger } \exp\left ( { { - ( e_f(\mathbf{k } ) + \mu _ f ) \over t } } \right ) \right ] \right\ } \right\rangle \nonumber\\ & & -6\sum\limits_{f = u , d , s } \int \frac{d^3k}{(2\pi)^3 } e_f(\mathbf{k } ) \theta \left(\lambda ^2 - |\mathrm { \bf k}|^2 \right ) , \label{eq : grand - q}\end{aligned}\ ] ] where @xmath37 are the single - particle energies , and @xmath38 and @xmath39 are the constituent mass and chemical potential of the quark with flavor @xmath40 . the constituent quark masses are related to the current masses and the chiral condensates by @xmath41 where @xmath42 and @xmath43 . furthermore , in the mean - field approximation , the quark condensate contribution to the thermodynamic potential per unit volume is @xcite @xmath44 in the present article , the parameters are chosen as follows : @xmath45 gev , @xmath46 gev . the vacuum quark condensates are @xmath47 and @xmath48 @xcite . in the mean - field approximation , one easily derives the temperature dependence of the chiral condensates @xmath49 and @xmath50 as well as the thermal averages of the polyakov loops in the fundamental representation , i.e. @xmath51 and @xmath52 @xcite . furthermore , it is straightforward to derive from ( [ eq : grand - q ] ) the color - averaged distribution functions for @xmath53 and @xmath54 @xcite : @xmath55 where we introduced the abbreviations @xmath56 $ ] and chose an isospin - independent chemical potential for the light quarks : @xmath57 . equations ( [ eq : quark - dist ] ) and ( [ eq : antiquark - dist ] ) are obtained by assuming the weiss mean - field approximation @xcite . in [ sec : appendix ] , we discuss several polyakov - loop averaging procedures for evaluating the quark thermodynamic potential and thereby comparing the quark distribution functions derived from these different averaging procedures . in the following , we will consider the choice @xmath58 gev . these distribution functions are to be used in the study of the strange quark pair - production rates due to the process @xmath59 . in order to describe the process @xmath60 , we also need to calculate the adjoint polyakov loop and study how it affects the gluon distribution function . starting from the yang - mills lagrangian @xmath61 , it straightforward to write down the gluon partition function for the transverse gluons , and obtaining the perturbative contribution to the gluon thermodynamic potential per unit volume @xcite , @xmath62 \right\rangle \nonumber \\ & & + 8\int { \frac{d^3k}{(2\pi ) ^3}\left| { \mathrm { \bf k } } \right|\theta \left ( { \lambda ^2 - | \mathrm { \bf k } } |^2 \right)}. \label{eq : omega_g_p1}\end{aligned}\ ] ] because @xmath63 is assumed to be independent of the spatial coordinate @xmath64 in the mean - field approximation , the polyakov loop in the fundamental representation can be gauge rotated to diagonal form , @xmath65 , with @xmath66 . therefore , @xmath67 . \label{eq : ell_3-mfa}\end{aligned}\ ] ] in the same gauge , @xmath13 can be expressed in terms of the eigenvalues of @xmath12 @xcite : @xmath68 where @xmath69 . thus , @xmath70 inserting ( [ eq : l_8 ] ) into ( [ eq : omega_g_p1 ] ) and after some algebraic transformations , the color - averaged gluon distribution function is obtained as @xmath71 where @xmath72.\ ] ] the remaining task is to evaluate @xmath73 . in order to do so , we need to specify the full distribution of eigenvalues of the polyakov loop , i. e. the distribution of phases @xmath74 . the thermal average of any function of the eigenvalues of the polyakov loop , @xmath75 , is defined as @xmath76 where @xmath77 is the su(3 ) haar measure , the weight function @xmath78 denotes the distribution of eigenvalues of the polyakov loop . the haar measure for the su(3 ) symmetry group is given by @xmath79 . since @xmath80 , the integration in ( [ eq : expectation ] ) only goes over @xmath81 and @xmath82 . a suitable choice of the weight function is a crucial step in evaluating @xmath83 . we follow gocksch and ogilvie @xcite and gupta _ et al . _ @xcite in choosing a weight function of the form @xmath84 where @xmath85 and @xmath86 is a fit parameter depending on temperature . the particular form ( [ eq : weight ] ) is suggested by the strong coupling expansion of the gauge theory . we note that @xmath87 $ ] and @xmath88 have a corresponding structure expressed in terms of the eigenvalues of the fundamental polyakov loops , as can be seen from assuming @xmath89 to be in the form of ( 5 ) with @xmath90 and @xmath91 replaced by @xmath92 and @xmath93 respectively . starting from ( [ eq : weight ] ) and inserting the known values of @xmath29 into ( [ eq : expectation ] ) , the temperature dependence of @xmath94 can be solved numerically , as shown in figure [ fig : beta3 ] . we now have obtained an explicit expression for @xmath95 at each temperature . we note that the temperature corresponding to the minimum of @xmath96 in figure [ fig : beta3 ] coincides with the critical temperature of the deconfinement phase transition in the mean - field approximation . in their investigation of the gluonic contribution to the thermodynamic potential of the pnjl model , megias _ et al . _ @xcite used a weight function of similar form as ( [ eq : weight ] ) , but did not make the mean - field approximation . they determined the parameter @xmath96 from the empirical relation between string tension and the deconfinement temperature of the pure gauge theory . here , we have determined @xmath96 by imposing a self - consistency condition on the expectation value of the fundamental polyakov loop . with the weight function ( [ eq : weight ] ) , equation ( [ eq : expectation ] ) allows us to evaluate the thermal average of the adjoint polyakov loop @xmath97 and thus the gluon distribution function @xmath98 . the temperature dependence of the quark condensates and the thermal averages of the polyakov loop @xmath29 , @xmath99 were first calculated in @xcite , as well as the temperature dependence of @xmath97 are shown in figure [ fig : order_parameters ] . furthermore , the temperature dependence of the constituent masses of quarks are obtained from ( [ eq : mq ] ) and ( [ eq : ms ] ) , as shown in figure [ fig : masses ] . to verify the validity of @xmath97 obtained by this procedure , we check its consistency with the casimir scaling of the thermal averages of the polyakov loop observed in lattice qcd @xcite . casimir scaling refers to a relation , valid for all temperatures , between the thermal averages of the polyakov loop in different representations @xmath6 of color - su(3 ) of the form @xmath100 where @xmath101 and @xmath102 denotes the eigenvalue of the quadratic casimir operator in representation @xmath6 . for the adjoint representation , @xmath103 and thus @xmath104 . figure [ fig : casimir_scaling ] shows our results for @xmath105 , together with @xmath106 , as function of @xmath29 . as can be seen , the values of @xmath97 and @xmath107 show a good agreement with casimir scaling ( [ eq : casimir ] ) for temperatures @xmath9 ranging from @xmath108 gev to @xmath109 gev . by numerically evaluating @xmath73 for each power @xmath110 and as a function of temperature @xmath9 , the gluon distribution function can now be obtained from ( [ eq : gluon - dist ] ) . the ratios @xmath111 and @xmath112 are plotted in figure [ fig : distributions ] , where @xmath113 and @xmath114 are the free fermi - dirac and bose - einstein distributions , respectively , with the constituent quark mass @xmath115 in ( [ eq : mq ] ) and @xmath116 gev . when @xmath9 is near @xmath117 , gluon is more strongly suppressed than quarks in spite of the additional effect of chiral symmetry breaking on the constituent quark mass @xmath115 . furthermore , we evaluate the quark , antiquark , net quark and gluon number densities by @xmath118 , \label{eq : n_q - q2}\\ n_g = 2 ( n_c^2 - 1)\int \frac{d^3k}{(2\pi)^3 } f_g(k ) , \label{eq : n_g}\end{aligned}\ ] ] where the momentum integration is taken without imposing any cutoff . the number of flavors in ( [ eq : n_q])-([eq : n_q - q2 ] ) is 2 because we are evaluating the quark , antiquark , or net quark number densities for flavor @xmath119 and @xmath120 . figure [ fig : number_density](a ) shows the temperature dependence of the ( scaled ) quark , antiquark , net quark and gluon number densities , @xmath121 , @xmath122 , @xmath123 and @xmath124 , respectively . in figure [ fig : number_density](a ) , @xmath123 possesses similar features as that in the two - flavor pnjl model @xcite . moreover , @xmath124 is non - vanishing at low temperature due to the existence of the color - singlet gluon states . on the other hand , assuming zero quark chemical potentials for all three flavors , @xmath125 , we evaluate @xmath121 , @xmath124 and the ( scaled ) strange quark number density @xmath126 as functions of the temperature , as shown in figure [ fig : number_density](b ) . we note that at @xmath127 the quark densities have reached almost 90% of their asymptotic values ; whereas the gluon density is still less than 2/3 of its asymptotic value ( @xmath128 ) . the quark and gluon number densities reach 99% and 92% of their asymptotic values respectively at @xmath129 . with @xmath98 , we can now calculate the contribution of the thermal ( transverse ) gluons to the thermodynamic pressure : @xmath130 the ( scaled ) pressure @xmath131 is plotted as a function of the temperature in figure [ fig : potentials ] . because the thermal average of the adjoint polyakov loop @xmath132 for @xmath133 , @xmath131 approaches the asymptotic behavior predicted by the stefan - boltzmann value , @xmath134 when @xmath133 . figure [ fig : potentials ] confirms that the gluon pressure reaches @xmath135 of the stefan - boltzmann value at @xmath136 mev . with the expressions for @xmath137 , @xmath138 and @xmath139 , the strange quark pair - production rate for both @xmath140 and @xmath141 can be derived in the pnjl model . the strange quark pair - production rate per unit volume is given by @xmath142 where @xmath143 where @xmath144 . the cross sections are explicitly given by @xmath145 \right . \nonumber\\ & & \left . - \left ( { \frac{7}{8 } + \frac{31m_s^2 } { 8s } } \right)\left ( { 1 - \frac{4m_s^2 } { s } } \right)^{1 / 2 } \right\}. \label{eq : sigma - g}\end{aligned}\ ] ] setting @xmath146 and @xmath147 , we can simplify ( [ eq : a - q-1 ] ) and ( [ eq : a - g-1 ] ) as follows : @xmath148 f_q \left ( { k_1 } \right)f_{\bar { q } } \left ( { k_2 } \right ) , \label{eq : a - q-2 } \\ a_g & = & \frac{4}{\pi ^4}\int_{4m_s^2 } ^\infty ds \ , s \ ; \bar { \sigma } _ { gg \to s\bar { s } } \left ( s \right)\int_0^\infty dk_1 dk_2 \ , \theta \left ( { 4k_1 k_2 - s } \right)f_g \left ( { k_1 } \right)f_g \left({k_2 } \right ) . \label{eq : a - g-2}\end{aligned}\ ] ] by substituting equations ( [ eq : quark - dist ] ) , ( [ eq : antiquark - dist ] ) , ( [ eq : gluon - dist ] ) , ( [ eq : sigma - q ] ) and ( [ eq : sigma - g ] ) into equations ( [ eq : a - q-2 ] ) and ( [ eq : a - g-2 ] ) , the numerical values of the production rates are obtained as functions of the temperature . figure [ fig : rates ] shows the temperature dependence of the strange quark pair - production rates in the pnjl model , compared with those obtained for free quarks . one notices a number of qualitative differences between the rates calculated in the the pnjl model and those calculated in free perturbation theory . first , the rates are suppressed for all values of the temperature . this is , in part , due to the suppression of the thermal quark- and gluon excitations by the polyakov loop and , in another part , due to the fact that the effective strange quark mass remains larger than the current quark mass even at temperatures moderately above @xmath117 , as shown in figure [ fig : masses ] . we also note that the curves for the polyakov loop - suppressed gluon induced production rate @xmath149 drops below the quark induced production rate @xmath150 below @xmath151 mev , reflecting the stronger suppression of gluons at low temperature caused by the casimir scaling of the thermal average of the adjoint polyakov loop . we have studied the effects of deconfinement and chiral symmetry breaking on the rates of strange quark pair production in the framework of the pnjl model . as proposed in @xcite , the strange quark pair - production rate is enhanced in the deconfined phase for the free quarks and the production rate for @xmath152 is dominant at all temperatures . in the pnjl model , the enhanced production of strange quarks is also obtained , but the production rates for @xmath153 and @xmath152 cross over at @xmath154mev . the production rate for @xmath153 is dominant when @xmath155 , while that for @xmath152 is dominant when @xmath156 . besides , when @xmath157 , the production rates for @xmath153 and @xmath152 are both very small in the pnjl model because quark and gluon quasiparticles are strongly suppressed below @xmath117 . in this temperature region , strangeness production is dominated by hadronic reactions , which were investigated by rehberg _ _ in the njl model @xcite . in figure [ fig : rates ] , the coupling @xmath158 scales out when we compare the quark and gluon contributions to the production rate . we note that , approaching @xmath117 , one needs to take into account the interactions originated from the appearance of collective modes due to the onset of the spontaneous breaking of chiral symmetry , rendering our treatment incomplete in the transition region . however , our goal was to study at what temperature above @xmath117 the gluonic contribution to the production rate becomes dominant . we found that this temperature is around @xmath159 mev within the framework of the pnjl model . because this threshold is well beyond the temperature range in which the chiral phase transition occurs , as can be seen from figure [ fig : order_parameters ] , our neglect of the contribution from collective ( hadronic ) modes appears justified . a by - product of our investigation is the demonstration that the thermal average in ( [ eq : expectation ] ) satisfies casimir scaling ( [ eq : casimir ] ) of the fundmental and adjoint polyakov loops . this gives confidence that the weight function ( [ eq : weight ] ) can be used to obtain the temperature dependence of any quantity that involves the eigenvalues of the polyakov loop . for example , the temperature dependence of @xmath98 requires the evaluation of the averages @xmath160 . in turn , @xmath98 makes it possible to compute the contribution of the thermal ( transverse ) gluons to the pressure as a function of the temperature . this makes it unnecessary to include this contribution explicitly in the effective potential for the polyakov loop , as sometimes done in the literatures @xcite . in our study , the phase transformations of qcd , including deconfinement and chiral symmetry breaking , are incorporated into the evaluation of the thermal strange quark pair - production rate . using the same techniques , the effects of the polyakov loop on other signatures of quark - gluon plasma can be explored in the future . this work was supported in part by the u. s. department of energy under grant de - fg02 - 05er41367 . we thank kenji fukushima for several enlightening discussions about the pnjl model . we thank inga kouznetsova for helpful advice and johann rafelski for comments on the draft of this manuscript . one of us ( bm ) acknowledges the hospitality and support of the yukawa institute for theoretical physics in kyoto during the workshop program entitled _ new frontiers in qcd 2008 _ , which motivated this work . in this section , we discuss several polyakov - loop averaging procedures for the grand canonical thermodynamic potential in the quark sector and study their implications for the quark and antiquark distribution functions . this study can be easily extended to the polyakov - loop averaging procedures in the gluon thermodynamic potential , which are not explicitly formulated here . the quark grand canonical thermodynamic potential per unit volume is defined in terms of the quark grand partition function , @xmath161 where @xmath162 denotes the volume of the system . in the mean - field approximation , the quark grand partition function is associated with a set of quantum numbers , @xmath163 , where @xmath164 , @xmath165 , @xmath40 , @xmath166 and @xmath167 denotes momentum , spin , flavor , color and particle / antiparticle quantum number respectively . the average in ( [ eq : full_average ] ) is taken over the eigenvalues of the polyakov loop , as shown explicitly in ( [ eq : expectation ] ) . instead of the full average used in ( [ eq : full_average ] ) , an approximate averaging method used more frequently in the pnjl model is the quenched average : @xmath168 where @xmath169 denotes the single - particle partition function for each quantum number and the determinant runs over all quantum numbers @xmath170 . various further approximations can be applied to ( [ eq : quenched_average ] ) , which entail distinct averaging procedures . in the following texts , we discuss the differences among several polyakov - loop averaging procedures for the quark thermodynamic potential and clarify their effects on the quark and antiquark distribution functions . define the following subsets of @xmath170 : @xmath171 , @xmath172 and @xmath173 . starting from ( [ eq : quenched_average ] ) , we have the following ( approximate ) averaging procedures : @xmath174 where @xmath175 denotes the color determinant . equation ( [ eq : average-1 ] ) is the weiss mean - field approximation , which is frequently used in the literatures of the pnjl model @xcite . we note that ( [ eq : average-1 ] ) and ( [ eq : average-2 ] ) take the polyakov - loop average for quarks and antiquarks separately . this implies that , in the limit @xmath176 , only states with baryon quantum ( quark - triplet ) numbers contribute , but not states with meson quantum numbers ( quark - antiquark pairs ) . we further note that ( [ eq : average-1 ] ) and ( [ eq : average-3 ] ) replace the quenched average over the polyakov loop configuration by the unquenched average . we compare @xmath177 with @xmath178 in [ sec : comparison-1 ] and @xmath177 with @xmath179 in [ sec : comparison-2 ] . respectively , by deriving the quark distribution functions from equations ( [ eq : average-1])-([eq : average-3 ] ) . by the averaging procedure in ( [ eq : average-1 ] ) , the quark thermodynamic potential per unit volume in ( [ eq : grand - q ] ) is simplified to be @xmath180 \right . \nonumber\\ & & \left . + \ln \left [ 1 + 3\langle { \bar \ell _ 3 } \rangle \lambda_{- } + 3\langle { \ell _ 3 } \rangle \lambda_{-}^2 + \lambda_{-}^3 \right ] \right\ } \nonumber\\ & & -6\sum\limits_{f = u , d , s } \int \frac{d^3k}{(2\pi)^3 } e_f(\mathbf{k } ) \theta \left(\lambda ^2 - |\mathrm { \bf k}|^2 \right ) , \label{eq : grand - q-2}\end{aligned}\ ] ] where @xmath181 $ ] . the quark and antiquark distribution functions , ( [ eq : quark - dist ] ) and ( [ eq : antiquark - dist ] ) , are easily obtained from ( [ eq : grand - q-2 ] ) . on the other hand , if we start from ( [ eq : grand - q ] ) and use the averaging procedure defined in ( [ eq : average-2 ] ) , the quark and antiquark distribution functions are alternatively obtained : @xmath182 where @xmath92 and @xmath93 are expressed in ( [ eq : ell_3-mfa ] ) . by the definition of the thermal average ( [ eq : expectation ] ) and the weight function ( [ eq : weight ] ) , we can evaluate ( [ eq : quark - dist-2 ] ) and ( [ eq : antiquark - dist-2 ] ) explicitly . without losing generality , in this section we assume a vanishing @xmath119 and @xmath120 quark chemical potential , i.e. @xmath183 , which implies the simplification @xmath184 . figure [ fig : distr - comparison](a ) shows the comparison of the ratio @xmath185 obtained from ( [ eq : quark - dist ] ) with the ratio @xmath186 from ( [ eq : quark - dist-2 ] ) . the figure shows that the two ratios agree well for all temperatures , especially in the high momentum region , which is most relevant for the thermal strange quark pair - production rate . the gluon distribution function in ( [ eq : gluon - dist ] ) is derived from the gluon thermodynamic potential obtained by the averaging procedure analogous to ( [ eq : average-2 ] ) . on the other hand , if using the averaging procedure analogous to ( [ eq : average-1 ] ) instead , we obtain the gluon distribution function under the weiss mean - field approximation , namely @xmath187 assuming @xmath188 figure [ fig : distr - comparison](b ) shows the comparison of the ratio @xmath189 obtained from ( [ eq : gluon - dist-2 ] ) with that from ( [ eq : gluon - dist ] ) . they agree well in the high momentum region but deviate in the low momentum region . by the polyakov - loop averaging procedure ( [ eq : average-3 ] ) , we evaluate alternative quark and antiquark distribution functions , which , unsurprisingly , incorporate the probabilities of color - singlet quark - antiquark states . the quark distribution function derived from the averaging procedure ( [ eq : average-3 ] ) is @xmath190\nonumber\\ & & \times \left [ 1 + e^{\frac{-6e_q(k)}{t } } + \langle \tr_f l_3 \rangle e^{\frac{-(5e_q(k)-\mu)}{t } } + \langle \tr_f l_3^\dag \rangle e^{\frac{-(5e_q(k)+\mu)}{t } } \right.\nonumber\\ & & \left . + \langle \tr_f l_3 \tr_f l_3^\dag \rangle e^{\frac{-4e_q(k)}{t } } + \langle \tr_f l_3^\dag \rangle e^{\frac{-(4e_q(k)-2 \mu)}{t } } \right . \nonumber\\ & & \left . + \langle \tr_f l_3 \rangle e^{\frac{-(4e_q(k)+2 \mu)}{t } } + ( 2 \langle \tr_f l_3 \rangle + \langle \tr_f ( l_3^\dag)^2 \rangle ) e^{\frac{-(3e_q(k)- \mu)}{t } } \right.\nonumber\\ & & \left . + ( 2 \langle \tr_f l_3^\dag \rangle + \langle \tr_f l_3 ^ 2 \rangle ) e^{\frac{-(3e_q(k)+ \mu)}{t } } \right . \nonumber\\ & & \left . + \langle \tr_f l_3 \tr_f l_3^\dag \rangle e^{\frac{-2e_q(k)}{t } } + e^{\frac{-3(e_q(k)-\mu)}{t } } + e^{\frac{-3 ( e_q(k ) + \mu)}{t } } \right.\nonumber\\ & & \left . + \langle \tr_f l_3^\dag \rangle e^{\frac{-2 ( e_q(k)-\mu)}{t } } + \langle \tr_f l_3 \rangle e^{\frac{-2 ( e_q(k)+\mu)}{t } } \right . \nonumber\\ & & \left . + \langle \tr_f l_3 \rangle e^{\frac{- ( e_q(k)-\mu)}{t } } + \langle \tr_f l_3^\dag \rangle e^{\frac{- ( e_q(k)+\mu)}{t } } \right]^{-1 } , \label{eq : quark - dist-3}\end{aligned}\ ] ] where @xmath191 and @xmath192 . moreover , the antiquark distribution function @xmath193 can be obtained from ( [ eq : quark - dist-3 ] ) by interchanging @xmath194 and @xmath195 and replacing @xmath196 by @xmath197 . equation ( [ eq : quark - dist-3 ] ) contains a sum over the probabilities of all states of @xmath198 quarks and @xmath199 antiquarks , where @xmath200 . as noted before , ( [ eq : quark - dist-3 ] ) incorporates the contribution of color - singlet quark - antiquark states , which are not contained in the expression ( [ eq : quark - dist ] ) . figure [ fig : quark - full ] shows the comparison of the ratio @xmath201 obtained from ( [ eq : quark - dist-3 ] ) with @xmath185 obtained from ( [ eq : quark - dist ] ) , again for @xmath202 . the figure shows that the two ratios agree well for all temperatures , especially in the high momentum region . we also note that , when @xmath9 is near @xmath117 or @xmath157 , @xmath203 in ( [ eq : quark - dist-3 ] ) is slightly larger than @xmath204 of ( [ eq : quark - dist ] ) in the low momentum region . this difference can be traced back to the contribution of the color - singlet quark - antiquark states . in conclusion , because both @xmath205 and @xmath203 are in good numerical agreement with @xmath204 , we are justified to use ( [ eq : quark - dist ] ) and ( [ eq : antiquark - dist ] ) in the evaluation of the strange quark pair - production rate , as done in the main part of this article . 10 r. hagedorn and j. rafelski , phys . b * 97 * , 136 ( 1980 ) . j. rafelski and b. mller , phys . lett . * 48 * , 1066 ( 1982 ) [ erratum - ibid . * 56 * , 2334 ( 1986 ) ] . t. s. bir , b. lukacs , j. zimanyi and h. w. barz , nucl . phys . a * 386 * , 617 ( 1982 ) . p. koch , b. mller and j. rafelski , phys . rept . * 142 * , 167 ( 1986 ) . t. matsui , b. svetitsky and l. d. mclerran , phys . d * 34 * , 783 ( 1986 ) [ erratum - ibid . d * 37 * , 844 ( 1988 ) ] . e. andersen _ et al . _ [ wa97 collaboration ] , phys . b * 449 * , 401 ( 1999 ) . b. i. abelev _ et al . _ [ star collaboration ] , phys . c * 77 * , 044908 ( 2008 ) . m. kaneta and n. xu , arxiv : nucl - 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we study the temperature dependence of the adjoint polyakov loop and its implication for the momentum spectrum of gluons in the mean - field approximation . this allows us to calculate the contribution of the thermal ( transverse ) gluons to the thermodynamic pressure . as an application , we evaluate the rates for the strange quark pair - production processes @xmath0 and @xmath1 as functions of temperature including thermal effects on quark deconfinement and chiral symmetry breaking .

eplerenone , pregn-4-ene-7 , 21-dicarboxylic acid , 9 , 11-epoxy-17-hydroxy-3-oxo , -lactone , methyl ester ( 7 , 11 , 17 ) , is an aldosterone antagonist used as an adjunct in the management of chronic heart failure . it is similar to the diuretic spironolactone , though it may be more specific for the mineralocorticoid receptor . eplerenone is used alone or in combination with other medications to treat high blood pressure . it works by blocking the action of aldosterone , a natural substance in the body that raises blood pressure . eplerenone ( other names include sc-66110 , cgp-30083 , and epoxymexrenone ) is the first agent to block the mineralocorticoid receptor with a high degree of selectivity and is under development for human therapeutic use in the 4 treatment of hypertension and heart failure post myocardial infarction [ 15 ] . a few chromatographic methods have appeared in the literature for the quantification of eplerenone in using spe - lc - ms / ms for eplerenone and its hydrolyzed metabolite in human urine and development and validation of a liquid chromatography - tandem mass spectrometric assay for eplerenone and its hydrolyzed metabolite in human plasma . stability - indicating uplc method for analysis of eplerenone in a bulk drug and pharmaceutical dosage form . to the best of our knowledge , no stability - indicating lc method for the quantitative estimation of eplerenone in bulk drug substance samples in the presence of degradation products along with its potential impurities has been reported . the purpose of the present research work is to develop a single stability - indicating lc method for the determination of eplerenone and its related impurities and to establish the degradation pathway for eplerenone along with its four potential impurities . the developed lc method is validated with respect to specificity , lod , loq , linearity , precision , accuracy , and robustness . accordingly the aim of the present study is to establish degradation pathway of eplerenone through stress studies under a variety of ich - recommended test conditions [ 8 , 9 ] . samples of eplerenone and its related impurities are received from hetero labs limited a research foundation of the firm hetero drugs ltd , hyderabad , india ( figure 1 ) . all impurities and the eplerenone standard are of > 99% purity and as follows : eplerenone ( 99.1% ) , imp-1 ( 99.5% ) , imp-2 ( 95.6% ) , imp-3 ( 99.7% ) , and imp-4 ( 99.5% ) . in addition , hplc grade acetonitrile and methanol are purchased from merck ( darmstadt , germany ) . analytical reagent grade sodium dihydrogen phosphate monohydrate , phosphoric acid , and acetic acid are purchased from merck . highly pure water was prepared with the millipore milli - q plus water purification system . the lc system used for method development , forced degradation studies , and method validation consisted of a waters 2695 binary pump with an autosampler and a 2996 photodiode array detector ( pda ) . the output signal is monitored and processed using empower software on a pentium computer ( digital equipment co. ) . photostability studies are carried out in a photo stability chamber ( atlas suntest cps+ ) . thermal stability studies are carried out in a dry hot air oven ( cintex precision hot air oven ) . a waters symmetry c18 150 mm 4.6 mm , 5 m column is used with a mobile phase containing a gradient of solvents a and b. the buffer is composed of 0.1 m ammonium acetate , with its ph adjusted to 3.0 with orthophosphoric acid . solvents a and b consisted of buffer and acetonitrile in ratios of 800 : 200 ( v / v ) and 300 : 700 ( v / v ) , respectively . the flow rate of the mobile phase is 1.0 ml / min with a gradient program of 0/10 , 10/50 , 20/50 , 25/10 , and 30/10 ( time ( min)/%b ) . the column temperature is maintained at 30c and the detection wavelength is set at 240 nm . the injection volume is 20 l . the diluent consisted of buffer and acetonitrile in a ratio of 60 : 40 ( v / v ) ( table 1 ) . the lc - ms system ( agilent 2010 ev series liquid chromatography system triple quadrapole mass spectrometer ) was used for the identification of unknown compounds formed during forced degradation . a lichrospher rp 18e 250 4.6 mm , 5 m column was used as the stationary phase . buffer is 0.01 m ammonium acetate and 0.1% triethylamine , ph adjusted to 7.4 using phosphoric acid . the injection volume is 20 l . the analysis was performed in positive and negative electrospray ionization modes . the capillary and cone voltages were 4.5 kv and 5 v , respectively . the source and dissolvation temperatures were 250c and 200c , respectively , and the dissolvation gas flow is 1.2 ml min ( figure 3 ) . a stock solution of eplerenone ( 5.0 mg / ml ) was prepared by dissolving the appropriate amount of eplerenone solid in the diluent . working solutions of 0.15% are prepared from the stock solution for the determinations and assays of related substances , respectively . a stock solution of impurities ( mixture of imp-1 , imp-2 , imp-3 , and imp-4 ) at 1.0 mg / ml is also prepared in the diluent . the drug substance powder equivalent to 100 mg of sample is transferred into a 100-ml volumetric flask , and 70 ml of diluent is added . the flask is attached to a rotary shaker and shaken for 10 min to disperse the powder completely . the mixture is sonicated for 10 min and then diluted to the appropriate volume with diluent to make a solution containing 1.0 mg / ml . the solution is then filtered through a 0.45 nylon 66 membrane filter . specificity is the ability of the method to measure the analyte response in the presence of its potential impurities . [ 10 , 11 ] the specificity of the developed rplc method for eplerenone is determined in the presence of its related impurities ( namely , imp-1 , imp-2 , imp-3 , and imp-4 ) and degradation products . forced degradation studies are also performed on eplerenone to provide an indication of the stability - indicating property and specificity of the proposed method . the stress conditions employed for the degradation study included light ( carried out as per ich q1b ) , heat ( 100c ) , acid hydrolysis ( 1 m hcl ) , base hydrolysis ( 0.5 m naoh ) and oxidation ( 15% h2o2 ) . for heat and light studies , the samples were exposed for 168 hrs , whereas the samples are treated for 2 h for acid , base hydrolysis , and for oxidation . the peak purity of the eplerenone stressed samples is also checked by using a waters 2996 photo diode array detector ( pda ) . the purity angle is within the purity threshold limit in all of the stressed samples , demonstrating the homogeneity of the analyte peak . the contents of impurities were calculated for the stress samples against a qualified reference standard . the mass balance ( % assay + % of impurities + % of degradation products ) is calculated for all of the samples ( table 2 ) . the precision of the related substance method is investigated by injecting six individual preparations of ( 5 g / ml ) eplerenone spiked with 0.05% each of imp-1 , imp-2 , imp-3 , and imp-4 . the % rsd of the areas of imp-1 , imp-2 , imp-3 , and imp-4 is calculated . the intermediate precision of the method is evaluated using a different analyst and instrument located within the same laboratory . the precision of the assay method is evaluated by carrying out six independent assays of a test sample of eplerenone against a qualified reference standard . the lod and loq for imp-1 , imp-2 , imp-3 , and imp-4 are estimated at a signal - to - noise ratio of 3 : 1 and 10 : 1 , respectively , by injecting a series of dilute solutions with known concentrations . the precision study is also carried out at the loq level by injecting six individual preparations of imp-1 , imp-2 , imp-3 and imp-4 and calculated the % rsd of the areas . linearity test solutions for the assay method are prepared from a stock solution at six concentration levels from 50 to 150% of the analyte concentration ( 50 , 75 , 100 , 125 , and 150 ) . linearity test solutions for the related substance method are prepared by diluting the impurity stock solution ( 2.5 ) to the required concentrations . the solutions are prepared at eight concentration levels from the loq to 150% ( loq , 0.075% , 0.12% , 0.15% , 0.18% , and 0.225% ) . the slope and y - intercept of the calibration curve are reported ( table 3 ) ( figure 4 ) . linearity test solutions for the related substance method were prepared by diluting the impurity stock solution ( 2.5 ) to the required concentrations . the solutions are prepared at six concentration levels from the loq to 150% ( loq , 0.075% , 0.12% , 0.15% , 0.18% , and 0.225% ) . the slope and y - intercept of the calibration curve are reported ( table 3 ) . accuracy of the assay method is evaluated in triplicate at three concentration levels 50 , 100 , and 150 , and the percentage recoveries are also calculated . eplerenone did not show the presence of imp-2 imp-4 , but contained 0.03% of imp-1 , 0.06% of imp-3 . standard addition and recovery experiments are conducted to determine the accuracy of the related substance method for the quantification of all four impurities ( imp-1 , imp-2 , imp-3 , and imp-4 ) in the drug substance . the study was carried out in triplicate at 0.075% , 0.15% , and 0.225% of the analyte concentration ( 5.0 g / ml ) . the percentage of recoveries for imp-1 , imp-2 , imp-3 , and imp-4 is calculated ( table 4 ) . to determine the robustness of the developed method , the experimental conditions are altered and the resolution between eplerenone and imp-1 , imp-2 , imp-3 , and imp-4 is evaluated . the flow rate of the mobile phase is 1.0 ml / min . to study the effect of the flow rate on the resolution , the flow rate is changed by 0.2 units ( to 0.8 and 1.2 ml / min ) . the effect of ph on the resolution of the impurities is studied by varying the ph by 0.2 units ( buffer ph of 4.3 and 4.7 ) . the effect of the column temperature on the resolution is studied at 25c and 35c instead of 30c . in all these varied conditions , the components of the mobile phase remained constant , as outlined in section 2.3 . the solution stability of eplerenone in the assay method is carried out by leaving both the sample and reference standard solutions in tightly capped volumetric flasks at room temperature for 48 h. the same sample solutions are assayed for in 6 h intervals over the study period . the mobile phase stability was also examined by assaying the freshly prepared sample solutions against freshly prepared reference standard solutions for 6 h intervals up to 48 h. the prepared mobile phase remained constant during the study period ( figure 2 ) . the % rsd of the eplerenone assay is calculated for the mobile phase and solution stability experiments . the solution stability of eplerenone and its impurities in the related substance method is carried out by leaving a spiked sample solution in a tightly capped volumetric flask at room temperature for 48 h. the content of imp-1 , imp-2 , imp-3 , and imp-4 is determined at 6 h intervals up to the study period . the mobile phase stability is also investigated for 48 h by injecting the freshly prepared sample solutions for every 6 h interval . the content of imp-1 , imp-2 , imp-3 , and imp-4 is determined in the test solutions . the main objective of the chromatographic method is to separate imp-1 , imp-2 , imp-3 , imp-4 , eplerenone , and the generated degradation products from the analyte peak during stress studies . impurities and degradation products are coeluted by using different stationary phases , such as c8 , cyano , and phenyl , with various mobile phases with buffers , such as phosphate , sulphate and acetate with different ph values ( 25 ) , and organic modifiers , including acetonitrile and methanol , in the mobile phase . 0.1 m ammonium acetate buffer with a ph value of 2.4 and methanol ( 50 : 50 , v / v ) at a flow rate of 1.2 ml / min is chosen for the initial trail with a 100 mm 4.6 mm i d column and 1.8 m particle size c18 stationary phase . when an impurity - spiked solution is injected , the resolution between the impurities and analyte is poor . imp-1 and imp-3 are almost co - eluted with the analyte . to improve the resolution between the impurities and analyte , acetonitrile is replaced with methanol in the mobile phase and flow rate the resolution between the impurities and analyte was slightly improved but one of the impurities is not eluted even after 40 min of run time . to optimize the resolution between the impurities and the retention time of the impurities , trails are carried out with different mobile phase ratios using buffer and acetonitrile ( buffer : acetonitrile : 90 : 10 , 80 : 20 , 70 : 30 v / v ) . isocratic trials are not successful in achieving a favorable resolution between impurity and analyte peaks and the elution of the process impurities . therefore , a gradient method is selected using buffer and acetonitrile in a ratio of 80 : 20 , 30 : 70(v / v ) as mobile phase a and water and acetonitrile in a ratio of 30 : 70 ( v / v ) as mobile phase b. different gradient programs were investigated and satisfactory results are obtained when a gradient program of 0/10 , 10/50 , 20/50 , 25/10 , and 30/10 ( time ( min)/%b ) is used . degradation was not observed in eplerenone stressed samples subjected to light and heat . significant degradation of the drug substance and product is detected under acid and base hydrolysis , leading to the formation of one major unknown degradation product at 0.31 rrt ( figure 2 ) . peak purity test results derived from the pda detector confirmed that the eplerenone peak and the degraded peaks are homogeneous and pure in all of the analyzed stress samples . degradation studies are carried out for the stress samples ( at 100 g / ml ) against a qualified reference standard of eplerenone ( figure 2 ) . the assay of eplerenone is unaffected by the presence of imp-1 , imp-2 , imp-3 , imp-4 , and its degradation products , confirming the stability - indicating power of the developed method . an lcms study was carried to determine the m / z value of the major degradation product formed under acid and base hydrolysis using an agilent 2010 ev series liquid chromatography system coupled with triple quadrapole mass spectrometer . buffer is 0.01 m ammonium acetate and 0.1% triethylamine , ph adjusted to 7.4 using phosphoric acid . the m / z value obtained for the degradation product resolving at 0.31 and 0.86 rrt in esi - positive mode was 451(m+1 ) . the impurity was isolated using preparative lc - ms . based on the mass number the identified degradant is methyl hydrogen 9 , 11 dihydroxy , 17--hydroxy-3-oxopregn 7--carbonate , 21--carboxylic acid with molecular weight of 451.10 ( figure 1 ) . the % rsd of eplerenone during the method precision study is within 3.0% and the % rsd values of the area of imp-1 , imp-2 , imp-3 , and imp-4 in the related substance method precision study are within 10.0% . the % rsd of the results obtained in the intermediate precision study was within 3.0% and the % rsd of the areas of imp-1 , imp-2 , imp-3 , and imp-4 were well within 5% , revealing the high precision of the method ( table 3 ) . the limits of detection and quantification of eplerenone , imp-1 , imp-2 , imp-3 , and imp-4 for a 20-l injection volume are given in table 3 . the precision at the loq concentration for imp-1 , imp-2 , imp-3 , and imp-4 , is below 10.0% . the linear calibration plot for the method is obtained over the tested calibration range ( 50%150% level ) and the obtained correlation coefficient is greater than 0.999 . the linear calibration plot for the related substance method is determined over the calibration range ( loq to 0.225% with respect to analyte concentration ) for imp-1 , imp-2 , imp-3 , and imp-4 , a correlation coefficient of greater than 0.999 is obtained . the linearity was checked for the related substance method over the same concentration range for three consecutive days . the % rsd values of the slope and y - intercept of the calibration curves are within 15.0% . these results showed an excellent correlation between the peak areas and concentrations of imp-1 , imp-2 , imp-3 , and imp-4 ( table 3 ) . the percentage recovery of eplerenone impurities in the drug substances , that is , imp-1 , imp-2 , imp-3 , and imp-4 , ranged from 94.99 to 105.45 , from 96.29 to 101.33 , 96.45 to 105.26 , and from 95.77 to 105.88 , respectively . the uplc chromatograms of spiked samples at the 0.15% level of all four impurities in the eplerenone drug substance sample are shown in figure 2 . in all of the deliberately varied chromatographic conditions carried out as described in section 2.7.5 ( flow rate , ph , and column temperature ) , the resolution between the closely eluting impurities , namely , imp-3 and imp4 , is greater than 5.0 , illustrating the robustness of the method . the variability of eplerenone and the impurities area response is within 2% and within 3% , respectively . the % rsd of assaying eplerenone during the solution stability and mobile phase stability experiments is within 1% . no significant changes are observed in the content of imp-1 , imp-2 , imp-3 , and imp-4 during the solution stability and mobile phase stability experiments when performed using the related substances method . the results of the solution and mobile phase stability experiments confirm that the sample solutions and mobile phase used during the related substance determinations are stable up to 48 h. mobile phase is proved to be stable up to five days . the gradient uplc method developed and used for stress studies also fit for quantitative , related substance and assay determination of eplerenone . the behavior of eplerenone under various stress conditions is studied , and the hydrolysis ( base ) degradant is identified as methyl hydrogen 9 , 11 dihydroxy , 17--hydroxy-3-oxopregn 7--carbonate , 21--carboxylic acid by lcms and presented . all the degradation products and process impurities are well separated from the drug substance which demonstrates the stability - indicating power of the rp - lc analytical method .

degradation pathway for eplerenone is established as per ich recommendations by validated and stability - indicating reverse phase liquid chromatographic method . eplerenone is subjected to stress conditions of acid , base , oxidation , and thermal and photolysis . significant degradation is observed in acid and base stress conditions . four impurities are studied and the major degradant ( rrt about 0.31 ) was identified by lc - ms and spectral analysis . the stress samples are assayed against a qualified reference standard and the mass balance is found close to 99.5% . efficient chromatographic separation is achieved on a waters symmetry c18 stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 240 nm at a flow rate of 1.0 ml min1 . in the developed lc method the resolution between eplerenone and four potential impurities ( imp-1 , imp-2 , imp-3 , and imp-4 ) is found to be greater than 4.0 . regression analysis shows an r value ( correlation coefficient ) of greater than 0.999 for eplerenone and four potential impurities . this method is capable to detect the impurities of eplerenone at a level of 0.020% with respect to test concentration of 1.0 mg ml1 for a 20 l injection volume . the developed uplc method is validated with respect to specificity , linearity and range , accuracy , precision , and robustness for impurities and assay determination .

in spite of all our recent progress in the understanding of physics at the electroweak scale , the source of dark matter ( dm ) and the origin of the matter - antimatter asymmetry @xcite ( bau ) still remain unclear . it is today well understood that the solution to either of these problems requires physics beyond the standard model ( sm ) . on the one hand if the standard model baryon number violating interactions @xcite cease to be in equilibrium in the bubbles of the broken phase , the matter - antimatter asymmetry may be generated at the electroweak phase transition via the mechanism of electroweak baryogenesis @xcite . for such a mechanism to be realized in nature a strongly first order electroweak phase transition is required . however the phase transition in the standard model for values of the higgs mass consistent with the lep bounds is a crossover @xcite and hence any baryon asymmetry generated at the weak scale would be erased . moreover , the sources of cp - violation are insufficient to generate a baryon number consistent with the one observed in nature @xcite . electroweak baryogenesis remains nevertheless as an attractive possibility in models of physics beyond the standard model at the weak scale . it has been shown that the minimal supersymmetric standard model ( mssm ) is consistent with this mechanism provided one of the superpartners of the top quark is lighter than the top quark and the higgs boson is lighter than @xmath1120 gev @xcite@xcite . this mechanism also demands the presence of charginos and neutralinos at the weak scale , which provide the necessary cp - violating sources @xcite@xcite and also a natural dark matter candidate . electroweak baryogenesis may also be realized in the next - to minimal supersymmetric extension of the standard model ( nmssm ) where some of the mssm constraints can be relaxed . in particular there are modifications to the tree - level effective potential @xcite that may ensure a strongly first order phase transition @xcite@xcite without a light stop . on the other hand the standard model does not provide any natural source for the observed dark matter . neutrinos are too light to give any sizeable contribution and there is no evidence of the possible existence of sufficient jupiter - like , baryonic objects . moreover , recent wmap measurements @xcite-@xcite exclude the presence of a significant baryonic contribution to the observed dark matter density . the natural candidates for the source of dark matter are new , neutral , stable , weakly interacting particles with masses of the order of the weak scale . these particles lead naturally to a relic density of the order of the critical density and appear in many models beyond the standard model . in particular they are present in models of softly broken supersymmetry at the tev scale . the lightest supersymmetric particle in these models tends to be neutral and its stability is ensured by a parity symmetry , @xmath2 , which also ensures the proton stability . acceptable values of the dark matter density and a successful realization of the mechanism of electroweak baryogenesis may be simultaneously obtained in minimal supersymmetric models , in certain phenomenologically interesting regions of the parameter space @xcite , @xcite . in the previous models , as well as in all successfully considered scenarios , the strengthening of the phase transition proceeds from the existence of new , extra scalars in the theory , while the cp - violating and dark matter sources proceed from new fermion fields . the common lore from all previous works was that the presence of extra bosons was a necessary requirement to induce a strong enough first order electroweak phase transition . in fact it is currently understood that bosons coupled to the higgs field @xmath3 with coupling @xmath4 favor a first order phase transition : they create a cubic term in the higgs effective potential @xmath5 either at the tree level , as in the nmssm , or by its contribution to the one - loop thermal effective potential @xmath6 . on the other hand fermions do not give rise to any cubic term in the high temperature expansion in powers of @xmath7 of the thermal integrals and hence they were neither believed to give rise to a barrier between the symmetric @xmath8 and broken @xmath9 phases nor to trigger a first order phase transition . in this paper we will prove that while the latter statement remains true for weakly coupled fermions @xmath10 it is not for strongly coupled ( but still perturbative ) ones @xmath11 that can indeed induce a strongly first order phase transition consistent with electroweak baryogenesis . in this work we shall first show that in standard model extensions with extra fermions strongly coupled to the higgs field the first order phase transition may be sufficiently strengthened in order to avoid erasure of the baryon asymmetry in the broken phase . we shall analyze in detail a simple model , which can be considered as a particular realization of split supersymmetry @xcite , where the standard supersymmetric relations between the yukawa and gauge couplings are not fulfilled . we shall stress , however , that in such a model , the physical vacuum becomes unstable and therefore the strength of the electroweak phase transition may not be properly defined without an ultraviolet ( uv ) completion of this model , that includes the presence of heavier , stabilizing fields . an example of such fields may be provided by softly broken supersymmetry , although other extensions are possible . we shall show that this low - energy effective theory , with higgsinos and gauginos strongly coupled to the higgs , may arise from a soft supersymmetry breaking model , based on a gauge extension of the standard model gauge group , with new ( asymptotically free ) gauge interactions that become strong at the tev scale , and are responsible for the strong yukawa couplings of higgsinos and gauginos to the sm higgs field . this gauge extension of the mssm provides a uv completion of the model analyzed in this paper and allows for large higgs masses . the article is organized as follows . in section [ phase ] we present the general ideas leading to the strengthening of the phase transition in the presence of strongly coupled fermions , and the need for the presence of stabilizing fields . in section [ higgsinos ] the phase transition for the standard model extension containing higgsinos , winos and binos strongly coupled to the higgs field is worked out in detail . we show that a strong enough first order phase transition can be accommodated even with a heavy higgs , @xmath0 gev . in section [ cp ] the cp - violating currents induced by the charginos that lead to the observed baryon asymmetry of the universe for natural values of cp - violating phases are presented . we show that in order to reproduce the wmap results on the bau the cp - violating phases must be @xmath12 if all squarks are heavy enough to be decoupled from the thermal bath . otherwise if some light squark ( e.g. the right - handed stop ) remains in the spectrum , the cp - violating phases can be as small as a few times @xmath13 . in section [ edm ] the two - loop contributions to the electron electric dipole moment from the charginos and neutralinos in our model ( in the absence of light squarks ) are evaluated , assuming that all relevant cp - violating effects are associated with the new fermions . for the values of the parameters satisfying all other requirements the generated electric dipole moment is below the present experimental bound , although the model may be tested in the future if experimental bounds improve by a few orders of magnitude . in section [ dark ] we discuss the dark matter constraints in our scenario , whereas compatibility of the strongly coupled fermions with electroweak precision measurements is considered in section [ precision ] . a natural region in the space of parameters is found where all requirements are fulfilled . a discussion on a possible uv completion of the model is presented in section [ strongc ] . finally we reserve section [ conclusions ] for our conclusions . the finite temperature effective potential of the higgs field @xmath3 is , by definition , the free - energy associated with @xmath3 . the one - loop , finite temperature contribution to the free - energy density is given by @xmath14 where @xmath15 is the number of degrees of freedom ( d.o.f . ) of the particle , @xmath16 is the higgs - dependent particle mass , and @xmath17 where @xmath18 [ @xmath19 stands for the contribution from bosons [ fermions ] . in this section we will consider for simplicity masses of the form @xmath20 , where @xmath4 is the yukawa coupling and @xmath21 is a constant mass parameter as it will be the case in the model considered in section [ higgsinos ] . ] . for large masses ( @xmath22 ) the functions @xmath23 are exponentially small , which means that heavy species are decoupled from the thermal plasma . for small masses ( @xmath24 ) @xmath23 can be expanded in a power series of @xmath25 . this is the case of the minimal standard model . in fact adding this expansion to the zero - temperature effective potential in the sm one obtains the well known expression for the free - energy density @xmath26 where the first term comes from the entropy density contribution of relativistic particles , with @xmath27 the number of effectively light species in the plasma @xcite ( @xmath28 for the sm ) , and the second term is the field dependent effective potential @xmath29 in the sm the parameters of eq . ( [ veff ] ) are well known and given by @xcite @xmath30 where the vacuum expectation value of the higgs at zero temperature is normalized to @xmath31 gev . a free energy of the form of the sm one , eq . ( [ feffsm ] ) , leads to a first order phase transition at a critical temperature given by @xmath32 the value of the higgs field at the minimum of the potential is @xmath33 , \label{fim}\ ] ] and the order parameter at the critical temperature is given by @xmath34 . notice that the parameter @xmath35 is very small because only the ( transverse ) gauge bosons contribute to it and , as a consequence , @xmath36 is much smaller than @xmath37 ( unless @xmath38 ) and the phase transition is very weakly first - order the transition becomes second order in the one - loop approximation . ] . moreover , for physical values of the higgs mass , the small value of @xmath39 causes perturbation theory to break down and only non - perturbative calculations become reliable . to overcome this problem sm extensions containing extra bosons strongly coupled to the higgs sector have been considered in the literature @xcite . in general these bosons would contribute to the parameter @xmath35 and would strengthen the first order phase transition . in this paper we will prove that a similar effect is produced by fermions strongly coupled to the higgs sector , even if in the high temperature regime they do not contribute to the cubic term in the effective potential . in general we will consider particle species that contribute to the one - loop effective potential as in eq . ( [ bucle ] ) , not light enough for the validity of the power expansion of @xmath40 but not necessarily so heavy as to consider them to be decoupled in the typical range of temperatures of the electroweak phase transition . the @xmath3-dependent part of the free energy density would then be given by @xmath41 /2\pi ^{2},\ ] ] where the first term is given by eq . ( [ feffsm ] ) , the last one is the finite temperature contribution of the new , heavy particles , @xmath42 is the zero temperature contribution , and the plus and minus signs in front of @xmath42 correspond to bosons and fermions , respectively . the zero - temperature one - loop effective potential @xmath43 is given by @xmath44 where @xmath45 is a polynomial in @xmath3 that contains quadratic and quartic terms with coefficients that depend on the renormalization conditions @xcite . by imposing the renormalization conditions already used in the sm , eq . ( [ veff ] ) , in particular that the tree - level values of the minimum and higgs mass are not shifted by radiative corrections , i.e. @xmath46 we obtain @xmath47 with @xmath48 where we are using the notation : @xmath49 , @xmath50 , and so on . for the case where the @xmath3 dependence of the mass eigenvalue is @xmath51 the potential ( [ vimi ] ) has the familiar expression @xmath52 .\ ] ] let us first stress that , unless the higgs is heavy , strongly coupled fermions may create a problem of vacuum stability at scales close to the electroweak scale . this can be easily understood from the fact that the tree - level quartic coupling , defined as the coefficient of the quartic term in the effective potential , is given by @xmath53 and the radiative corrections are proportional to the fourth power of the yukawa coupling , @xmath4 , and to the number of degrees of freedom . as we shall demonstrate , a relevant effect may only be obtained for a value of the number of degrees of freedom times @xmath54 larger than @xmath55 . for such values vacuum stability occurs at scales of the order of tev and therefore the presence of new , stabilizing fields is necessary in order to define a consistent low - energy effective theory . an efficient way of stabilizing the potential in the presence of strongly coupled fermions is to assume the presence of heavy bosonic degrees of freedom with similar couplings and number of degrees of freedom . for simplicity , let us here assume that the fermions have a dispersion relation @xmath56 , and a number of degrees of freedom @xmath57 , and there are bosonic , stabilizing fields with a dispersion relation @xmath58 with equal number of degrees of freedom . then , taking into account only the radiative corrections associated with these heavy fields , the maximum value of @xmath59 consistent with vacuum stability may be obtained from the condition of a positive quartic coupling at scales much larger than @xmath60 , and it is given by @xmath61 observe that for heavy higgs bosons and/or weakly coupled fermions @xmath59 becomes much larger than the weak scale . if , however , @xmath4 takes large values and @xmath62 becomes light then @xmath59 approaches @xmath63 and the effect of stabilizing fields is to cancel the zero temperature contribution of fermions plus giving additional finite temperature contributions . in order to get an understanding of the effects to be expected by the presence of these new particles , let us first consider a fermion particle with a mass , @xmath64 , much larger than @xmath37 for @xmath65 . if this effect is obtained for large values of the yukawa coupling , then the sum of the effects of the fermions and the stabilizing fields at zero temperature is small and , in this extreme case that maximizes the contribution of fermions ( and that of the stabilizing fields ) to the phase transition , we can ignore the zero temperature contributions . then , in the symmetric phase the species is light and contributes to @xmath27 , but in the broken - symmetry phase it is heavy and approximately decouples from the thermal plasma . usually such a decoupling species would transfer its entropy to the thermal bath , causing a temperature rise . during a phase transition we would naively expect that the effect of such a reheating is to _ delay _ the appearance of the true vacuum , to decrease the critical temperature and subsequently to increase the value of @xmath39 . more quantitatively , at constant @xmath27 the critical temperature is given by the condition @xmath66 , corresponding to degenerate minima of @xmath67 ] . as we will show below , this condition changes if the number of light degrees of freedom is different in the two phases , @xmath68 . in our example , the decoupling particle has a mass @xmath69 , and its contribution to the free - energy density in the broken phase vanishes , while in the symmetric phase is equal to @xmath70 , where @xmath71 is its number of degrees of freedom . the condition of degenerate minima of @xmath72 , eq . ( [ freeen ] ) , then gives @xcite @xmath73 this condition is attained at a lower critical temperature , @xmath74 . moreover we have that @xmath75 and the phase transition is more strongly first - order . it was already noticed in ref . @xcite that @xmath76 in the context of the electroweak phase transition could be important for baryogenesis . we can now estimate @xmath77 by noticing that the value of the effective potential ( [ veff ] ) at the minimum @xmath78 can be written as @xmath79 where we have made the approximation @xmath80 . ( [ tcprima ] ) implies that @xmath81 for the order parameter to increase from @xmath82 to the value @xmath83 , necessary to preserve the baryon asymmetry @xcite , we need @xmath84 . so it seems that particles with few d.o.f . will produce an effect . conversely given @xmath85 , the bound on the higgs mass is relaxed from @xmath86 to @xmath87 notice that if the new value @xmath36 is @xmath88 , then the perturbative ( one - loop ) approach is fully justified even for small values of @xmath35 . it should be noticed that eqs . ( [ tcprima])([deltafi ] ) give only an estimate of @xmath89 and @xmath90 . in fact , the effective number of light d.o.f . varies continuously from @xmath27 to @xmath91 , as @xmath3 goes from @xmath92 to @xmath90 . therefore we have a function @xmath93 that contributes to @xmath94 , and the correct value of the vacuum expectation value ( vev ) is obtained by minimizing the complete free energy , eq . ( [ freeen ] ) . once the dependence of @xmath95 on @xmath3 is taken into account , we can not use analytical approximations and we need to resort to numerical calculations . observe that in the limit studied above fermions and bosons gave equally important contributions to the phase transition strength and the number of degrees of freedom is the sum of the one associated to the fermions and that of stabilizing fields . in the rest of this work we will consider bosons that are heavier than the fermions , and therefore lead to a smaller finite temperature contribution than in the example above . we will now consider adding a fermion particle with mass @xmath96 to the sm with a higgs mass @xmath97 gev , but we will retain the effects of the heavy particles in the broken phase . we consider only fermion species and their ( heavier ) stabilizing fields since , as explained above , the effect of bosons on the phase transition has been extensively studied in the literature @xcite , @xcite@xcite . in fig . [ fermiones ] we plot the number of degrees of freedom @xmath57 that give @xmath98 as a function of the mass parameter @xmath21 , for different values of the yukawa coupling @xmath4 . the invariant mass of the stabilizing fields has been set to their maximum value consistent with vacuum stability , eq . ( [ bosonstab ] ) . as anticipated , for @xmath99 , and for large values of the yukawa couplings , only a small number of degrees of freedom are necessary in order to obtain a strongly first order phase transition . [ ] [ tl]@xmath21 [ gev][][l]@xmath57 [ ] [ r]@xmath4 a minimal standard model extension ( i.e. the introduction of a single species ) is possible with bosons but not with fermions , since the sm higgs is an @xmath100 doublet . in order to construct an invariant yukawa lagrangian the simplest possibilities are , either doublet and singlet fermions ( as e.g. a generation of mirror leptons and/or quarks ) or doublet and triplet fermions ( as e.g. light higgsinos and gauginos ) remnant from ( split ) supersymmetry @xcite . in the next section we will consider the latter possibility . in this section we will consider the particular case of higgsinos ( @xmath101 ) , winos and binos ( @xmath102 ) coupled to the sm higgs doublet @xmath103 with the lagrangian @xmath104 where @xmath105 and the yukawa couplings @xmath106 and @xmath107 are arbitrary , @xmath108 , @xmath109 , @xmath110 , where @xmath57 and @xmath111 are the @xmath100 and @xmath112 gauge couplings respectively , and the higgs doublet is related to the mssm higgses by @xmath113 @xcite . the matching with the couplings of a possible uv completion of the model will be done in section [ strongc ] . for the moment we will just assume that there is such a uv completion and that it provides the necessary stabilizing fields as it was discussed in section 2 . ] . the chargino mass matrix is @xmath114 and the squared mass matrix has eigenvalues @xmath115 where @xmath116 , @xmath117 . the mass matrix for neutralinos is @xmath118 the eigenvalues of this matrix are cumbersome , so we consider the particular case @xmath119 , @xmath120 , and @xmath121 . the eigenvalues of the squared mass matrix are thus @xmath122 and @xmath123 in this case the chargino eigenvalues become very similar to those in eq . ( [ eigenn2 ] ) : in particular we have @xmath124 , @xmath125 , and @xmath126 in eq . ( [ eigenc ] ) . we can further simplify the problem by also setting @xmath127 , since in this case eqs . ( [ eigenc ] ) and ( [ eigenn2 ] ) become @xmath128 that corresponds to 6 degrees of freedom ( a dirac spinor and a majorana spinor ) with squared mass @xmath129 , 6 with squared mass @xmath130 , and 2 ( light ) majorana particles with masses @xmath21 and @xmath131 . a total of 16 fermionic degrees of freedom out of which only 12 are coupled to the sm higgs . clearly , for @xmath132 the majorana particle with mass @xmath131 is just a pure bino state of mass @xmath133 , which decouples from the other low - energy states and therefore plays no role in determining the strength of the electroweak phase transition . in the following , we shall concentrate on this particularly simple case . from eq . ( [ eigen ] ) it is clear that all the results in this case will be symmetric under @xmath134 . the simplest limiting case is when @xmath135 and @xmath136 . in this case the eigenvalues are degenerate , @xmath137 , with 12 degrees of freedom corresponding to 3 dirac spinors , and the situation is identical to the simple example illustrated in the previous section . one expects that other limits will be less favorable for the phase transition . for instance if we take @xmath138 ( i.e. @xmath139 ) , the eigenvalues are @xmath140 . this means that , unless @xmath141 , in the broken - symmetry phase half of the particles become heavier than in the symmetric phase but the other half become lighter . therefore , unless @xmath142 is also small , less degrees of freedom than in the case @xmath143 will contribute to this effect . in fig . [ transi ] we plot the free energy at different temperatures for a yukawa coupling @xmath144 , a higgs mass of 120 gev and @xmath145 gev . we can explicitly see from the figure shape that there is a first order phase transition with an order parameter @xmath146 . [ ] [ b]@xmath147[][t]@xmath148 [ ] [ r]@xmath149[][r]@xmath37 = 4.7 cm in fig . [ phimantideg ] we plot the ratio of the higgs vev to the temperature , evaluated at the critical temperature , as a function of the mass @xmath131 for the case @xmath150 and @xmath151 gev . as expected , the strength of the phase transition decreases with @xmath131 . this illustrates the fact that for large @xmath131 the particle is decoupled already in the symmetric phase , hence the vev @xmath90 has a smaller value , which corresponds in the @xmath152 limit , to that of the electroweak phase transition in the standard model . [ ] [ l]@xmath39[][b]@xmath131 [ gev ] in fig . [ hmu2 ] we plot the values of the yukawa coupling @xmath4 necessary to induce a strongly first order phase transition for the case @xmath153 and @xmath151 gev . it is clear from the plot that for such a small value of the higgs mass , a strengthening of the phase transition may only be achieved for @xmath154 . let us stress that this lower bound may be weakened by assuming slighly smaller values of @xmath59 . for instance , taking @xmath155 to be 0.9 times the maximum value allowed in eq . ( [ bosonstab ] ) is enough to ensure that values of @xmath156 and masses @xmath21 of order of 100 gev are allowed . [ ] [ l]@xmath39[][t]@xmath131 [ gev ] [ ] [ c]@xmath21 we are interested in a strong enough phase transition for baryogenesis , which means that the higgs vev must be large enough for sphaleron processes to be suppressed in the broken - symmetry phase ( in order to avoid the washout of the bau after the phase transition ) . in the case of fig . [ phimantideg ] this happens up to a value @xmath157 determined by the condition @xmath158 . observe that the top - quark , with 12 degrees of freedom ( similar to the chargino - neutralino system ) and a yukawa coupling @xmath159 in our normalization , is not able to generate such a strong first - order phase transition in the sm . it is well known that the value of the higgs mass plays a prominent role in the strength of the phase transition in the standard model and extensions thereof . up to now we have fixed it to a `` minimal '' value , @xmath160 gev . however our mechanism of strengthening the phase transition by using strongly coupled fermions , although certainly sensitive to the value of the higgs mass , permits to go to higher values . in fig . [ mhiggs ] we plot , for fixed values of the yukawa coupling , the values of @xmath131 that give @xmath98 as a function of the higgs mass . we can see that , as expected , there is an upper bound on the higgs mass that depends on the yukawa coupling @xmath161 . moreover the upper value of the higgs mass has an approximate linear behaviour as a function of the yukawa coupling @xmath4 as can be readily deduced from fig . [ mhiggs ] . imposing perturbativity of the theory at the low scale sets a generic upper limit on the yukawa coupling @xmath162 which from fig . [ mhiggs ] yields a corresponding upper limit on the higgs mass of @xmath163 gev . in general , for large values of @xmath4 , the requirement of perturbative consistency of the theory up to high energies may only be fulfilled by embedding this model into a more complete theory where couplings become asymptotically free ( see section [ strongc ] ) . for the particularly interesting uv completion proposed in section [ strongc ] the upper limit on the yukawa coupling is , as we will see , more restricted , @xmath164 , which translates into the stronger higgs mass upper bound @xmath165 gev for @xmath166 of order 100 gev . [ ] [ r]@xmath131 [ gev][][br]@xmath62 [ gev ] [ ] [ r]@xmath167[][r]@xmath144 [ ] [ r]@xmath168[][t]@xmath169 the model we have proposed contains higgsinos @xmath170 and electroweak gauginos @xmath171 , @xmath172 , coupled to the sm higgs through the lagrangian ( [ lagrangiano ] ) with yukawa couplings @xmath173 , @xmath174 and majorana masses @xmath175 . we have concentrated on the case @xmath176 , in which the bino state decouples from the other low energy states . similar results for the phase transition would be obtained in any model in which the bino would decouple from the low energy theory , for instance if @xmath177 and @xmath178 is much larger than the weak scale . although the bino is absent at low energies , there is still a state with mass approximately equal to @xmath179 that is a candidate for dark matter . this will be analyzed in section [ dark ] where we will show that a modest splitting between the yukawa couplings @xmath180 and @xmath181 will be necessary to accomodate the observed dm energy density , although a large separation is not permitted by electroweak precision measurements . in this way introducing a small splitting between @xmath181 and @xmath180 is not expected to modify substantially the previous results in this section . in fact in the approximation of neglecting terms of order @xmath182 in the diagonalization of the mass matrices one can prove that the mass eigenvalues still correspond to one majorana spinor with mass @xmath21 , two dirac spinors with squared masses given in eq . ( [ eigenc ] ) and two majorana spinors with squared masses , @xmath183 which of course coincides with the degenerate result of eq . ( [ eigen ] ) in the limit of @xmath184 . the result of eq . ( [ eigendelta ] ) also proves that the modification of the strength of the phase transition due to the non - degeneracy will be small at least in the validity region where eq . ( [ eigendelta ] ) holds . more explicitly , in fig . [ phideltah2 ] we show numerically the variation of the order parameter @xmath39 away of the degenerate point as a function of @xmath185 for @xmath186 and @xmath187 gev . we see that the phase transition is weakened by @xmath188 for @xmath189 . [ ] [ l]@xmath39[][br]@xmath190 up to this point we have discussed the electroweak phase transition in the absence of cp - violating phases . however for the baryogenesis mechanism to work we need a non - vanishing cp - violating phase in the parameters of the theory that will trigger baryon number generation . as in the mssm studies , we shall consider real yukawa couplings ( related to gauge couplings in the mssm ) and majorana gaugino masses , and a complex mass parameter @xmath191 . to conclude this section we would like to consider how the phase transition and in particular the order parameter @xmath39 vary with the phase @xmath192 . the result is presented in fig . [ fivarfi ] [ ] [ l]@xmath39[][b]@xmath192 ( rad ) [ ] [ c]@xmath193[][c]@xmath194 [ ] [ c]@xmath195[][c]@xmath196 [ ] [ c]@xmath197[][c]@xmath198 where we plot @xmath39 as a function of @xmath192 for @xmath199 gev and yukawa couplings @xmath186 , @xmath200 . the plot at @xmath201 is consistent with the corresponding results that can be read off from fig . [ phimantideg ] while the strength of the first order phase transition decreases by only a tiny amount for @xmath12 @xmath202 violating phases , i.e. for @xmath203 . the chargino sector in the model presented in section [ higgsinos ] has a similar structure to the chargino sector in the minimal supersymmetric standard model . the only difference is that the couplings @xmath204 and @xmath205 are replaced by arbitrary couplings @xmath181 and @xmath180 , respectively , as can be seen in the corresponding mass matrix ( [ masac ] ) . as in the mssm the cp - violating phase can have its origin , after field redefinitions , in the phase @xmath192 of the ( complex ) @xmath21-parameter . a general method for computing the effects of cp - violating mass terms on particle distributions was introduced in ref . @xcite leading to an efficient transport of cp - violating quantum numbers into the symmetric phase where weak sphalerons are active and can trigger electroweak baryogenesis for all bubble wall widths . the method was adapted to the mssm by a number of papers @xcite-@xcite where a set of coupled differential equations , that include the effect of diffusion , particle number changing reactions and cp violating terms , were solved to find various particle number densities diffused from the bubble wall , where cp - violation takes place , to the symmetric phase where sphalerons are active . these methods can be adapted to the present model by just considering the particular structure of the chargino mass matrix given by eq . ( [ masac ] ) . we will further make the simplifying assumption that all @xmath202 violation resides in the fermionic sector . otherwise there should be extra contributions to the @xmath202 violating currents from the bosonic ( stabilizing ) fields , although these contributions are expected to be suppressed with respect to the fermionic ones because the stabilizing fields are heavier than the fermions . so from this point of view our results will be mostly conservative . in particular we will follow the formalism of refs . @xcite where a method was developed to compute the cp - violating sources induced by the passage of a bubble wall in a system of fermions that interact in a way similar to the one described above , in an expansion of derivatives of the higgs fields . the method allows for the computation of the currents in a resummation to all orders of the higgs vacuum expectation value effects . it was found that there are two different cp - violating sources from the chargino sector which the total baryon asymmetry depends upon . the leading contribution is provided by @xmath206 that is proportional to the variation of the angle @xmath207 $ ] at the wall of the expanding bubble . the source ( [ source1 ] ) has a resonant behaviour for @xmath208 and it is the leading contribution in the mssm . however , the higgs sector of our model ( which contains just the sm higgs doublet ) can be considered as the @xmath209 limit of the mssm higgs sector ( where @xmath210 is the pseudoscalar mass ) in which case @xmath211 and the source ( [ source1 ] ) does not contribute to the diffusion equations . the second contribution to the baryon asymmetry is proportional to @xmath212 in the limit @xmath209 only the second term in ( [ source2 ] ) survives . moreover we will consider in this section @xmath213 ( i.e. @xmath214 ) as we will see in section [ precision ] . ] in which case the only remaining source is proportional to @xmath215 . this region is , as it was proven in ref . @xcite , very insensitive to the resonance region relating @xmath216 and @xmath179 and it provides a very natural region of parameters where electroweak baryogenesis can hold . although in the mssm such a region provided a very tiny amount of baryon asymmetry , in the present model all effects are enhanced by the strong yukawa couplings of the higgs to charginos as we will see in this section . in the mssm there is an additional suppression of the source , eq . ( [ source2 ] ) , due to the large values of @xmath217 necessary to fulfill the lep bounds on the lightest cp - even higgs boson mass @xcite , @xmath217 of order 10 . as stressed above in this model , instead , @xmath218 . following the formalism of refs . @xcite the solution of the diffusion equations , in the limit where the strong sphaleron ( @xmath219 ) and yukawa processes ( @xmath220 ) are fast enough , provide quark number density for third generation doublets @xmath221 and singlets @xmath222 as functions of the number density for the higgs doublet coupled to the top quark @xmath223 , as @xmath224 where @xmath225 are statistical factors @xcite @xmath226 that satisfy the condition @xmath227 ( @xmath228 ) for weyl fermions ( complex bosons ) . in turn the density @xmath229 is transverse to the bubble wall and we are neglecting the bubble curvature . ] is obtained from the diffusion equations as a function of the particle number changing rates , cp - violating sources and diffusion constants , as explained in ref . @xcite , yielding from eq . ( [ densi ] ) the quark number densities @xmath230 . in order to evaluate the baryon asymmetry generated in the broken phase @xmath231 we first need to compute the density of left - handed quarks and leptons , @xmath232 , in front of the bubble wall in the symmetric phase . these chiral densities bias weak sphalerons to produce a net baryon number . considering particle species that participate in fast particle number changing transitions , and neglecting all yukawa couplings except those corresponding to the top quark , only quark doublets do contribute to @xmath232 . then assuming that all quarks have nearly the same diffusion constant it turns out that @xcite @xmath233 and therefore from eq . ( [ densi ] ) @xmath234 it turns out that the baryon asymmetry can be written as @xcite @xmath235 where @xmath236 is the number of families , @xmath237 the bubble wall velocity and @xmath238 , where @xmath239 @xcite , is the weak sphaleron rate . for the model presented in this paper , where squarks and the non - sm higgs bosons are superheavy , @xmath240 gev ( @xmath241 , @xmath242 and @xmath243 ) , it turns out that the coefficient in eq . ( [ densidad ] ) is @xmath244 . this sm suppression was already pointed out by giudice and shaposhnikov @xcite and consequently the baryon asymmetry @xmath231 in our model is produced by sub - leading effects . assuming @xmath245 we can go beyond the approximation of eq . ( [ densi ] ) and work out corrections of @xmath246 . this was done in ref . @xcite leading to an @xmath247 correction to @xmath248 , @xmath249 , in our model as @xmath250 where @xmath251 is the quark diffusion constant and the strong sphaleron rate is given by @xmath252 , where @xmath253 is an order one parameter @xcite . when ( [ deltass ] ) is inserted into ( [ nb ] ) it produces the baryon asymmetry generated by the sub - leading @xmath247 effects . we have numerically checked that this correction is insufficient to generate the observed baryon asymmetry of the universe . another , more important , correction that can lead to a non - zero value of the baryon asymmetry to leading order in @xmath219 are yukawa and gauge radiative corrections to statistical coefficients @xmath225 ( or equivalently thermal masses ) @xcite . expanding eq . ( [ kf ] ) in a power series of @xmath254 we can write @xmath255 keeping only the strong gauge ( @xmath256 ) and top yukawa ( @xmath257 ) couplings one obtains in our model the statistical coefficients , @xmath258 with @xmath259 where @xmath260 is the top quark yukawa coupling and @xmath261 the strong gauge coupling . numerically , @xmath262 is more important than @xmath263 but since the strong correction to all quarks is universal it cancels in the contribution to the baryon asymmetry . in fact to linear order in @xmath264 one can write the density @xmath248 in eq . ( [ densidad ] ) as @xmath265 and the proportionality coefficient turns out to be @xmath266 . this is the reduction factor we get from such a sub - leading effect . the numerical calculation of the baryon - to - entropy ratio @xmath267 is presented in fig . [ ewbg2 ] ( lower solid line ) where we plot its ratio to the experimentally determined value @xmath268 @xcite as a function of the yukawa coupling @xmath4 and we have fixed the cp - violating phase @xmath269 . in fact the phase @xmath270 that would be required for fixing @xmath271 is given by the inverse value plotted in fig . [ ewbg2 ] . we have chosen the case @xmath272 , and small values of @xmath273 gev , where the phase transition is favoured , and typical values of the bubble width and velocity @xcite given by the friction of the plasma . calculating the exact value of @xmath274 is out of the scope of this paper . however , as noticed in ref . @xcite , the effect of the velocity variation on the bau is likely to be an @xmath12 one effect and should not modify the main conclusions of this paper . ] . since the computation of the baryon asymmetry has been performed by ignoring corrections of order one , the main conclusion one can extract from the results of fig . [ ewbg2 ] is that cp - violating phases such that @xmath270 is of order one are necessary to obtain a value of the baryon asymmetry consistent with the experimentally determined values , for any value of @xmath154 . the amount of generated baryon number density can be increased if some squark is light enough to be in equilibrium with the thermal bath during the phase transition , in which case the sm suppression is avoided . the typical case that was considered in previous studies is that of a light right - handed stop @xcite that corresponds to values of the supersymmetry breaking soft masses @xmath275 and @xmath276 . in that case the statistical coefficients are given by @xmath242 , @xmath277 , @xmath278 and @xmath243 and the coefficient @xmath279 in eq . ( [ densidad ] ) does not vanish to leading order in @xmath247 . in fact it is given by @xmath280 and this produces an enhancement factor of @xmath281 with respect to the case where all squarks are superheavy . this enhancement factor produces larger values of @xmath267 ( and so smaller phases are allowed ) as can be seen in fig . [ ewbg2 ] upper solid line . now fixing @xmath271 can be consistent with phases @xmath282 . notice finally that a similar enhancement would also appear if other squark species ( i.e. right - handed sbottom or left - handed doublet ) are light ; this effect is not particularly linked to the lightness of right - handed stops . as mentioned above , the upper solid line in fig . [ ewbg2 ] corresponds to the extreme case where there are no extra bosons in the low energy spectrum , or equivalently stop masses in the tev range or larger tev the stop contribution to @xmath283 is @xmath284 and @xmath285 , much smaller than the previously considered thermal effects . ] . of course there can be intermediate situations where the stop is heavy but still does not fully decouple from the thermal plasma . in this case it contributes to the statistical factor @xmath283 with some small value that can significantly contribute to the @xmath279-parameter and departure its value from zero . for instance if @xmath286 gev , its contribution to the statistical factor @xmath283 as given from ( [ kb ] ) is @xmath287 which produces in ( [ densidad ] ) a value @xmath288 and enhances the value of @xmath267 from its value with fully decoupled right - handed stops . the corresponding value of @xmath267 is plotted in fig . [ ewbg2 ] ( dashed line ) . we can see that the cp - violating phase for @xmath271 is now @xmath289 . a similar effect would be produced by other not - so - heavy third generation squarks . in the absence of light squarks , baryon number generation demands the presence of large phases in the chargino and neutralino sectors . in the previous section , we assumed gaugino masses and yukawa couplings to be real , and therefore the relevant phase is the one of the @xmath21 parameter . although one - loop corrections to the electron electric dipole moments are suppressed in the limit of heavy fermions , as has been stressed in ref . @xcite , two - loop contributions become relevant . in this section we will evaluate the two - loop contribution to the electron electric dipole moment from the fermion and higgs sector . in fig . [ edmfig ] we plot the chargino contribution to the electron electric dipole moment @xcite , for @xmath290 , with @xmath216 real and positive ( @xmath291 ) , maximal cp - violating phase , @xmath292 , @xmath293 , and for @xmath294 , @xmath295 gev ( solid line ) ; @xmath296 , @xmath151 gev ( dashed line ) ; and @xmath296 , @xmath297 gev ( dot - dashed line ) . we have verified that the results vary only slightly for non - vanishing values of @xmath298 , which , as we will show in sections [ dark ] and [ precision ] , are preferred by dark matter and precision electroweak constraints . [ ] [ c]@xmath299 as discussed above , for values of @xmath300 , the electroweak phase transition is weakly first order and the generated baryon asymmetry is not preserved . for slightly larger values , @xmath301 , small values of @xmath302 gev and higgs mass values smaller than 125 gev are demanded in order to make the phase transition strongly first order . the present electric dipole moment bound , @xmath303 @xcite does not put a bound on this model for these values of @xmath304 and @xmath179 . for larger values of @xmath304 and similar values of @xmath179 , fig . [ edmfig ] shows that the electron electric dipole moment contributions become smaller and in addition , as shown in fig . [ ewbg2 ] , smaller phases are demanded for the baryon number generation . therefore , the electric dipole moment bounds become even weaker in this case . however the anticipated improvement of a few orders of magnitude in this quantity @xcite will be sufficient to test this model even for values of @xmath296 , provided the values of @xmath179 are in the range necessary to obtain a good dark matter source and avoid the lep invisible constraints : for large values of @xmath178 , ( or for @xmath305 ) and small values of @xmath306 , the lightest neutralino mass is mainly a higgsino with mass approximately equal to @xmath179 . for @xmath307 , the chargino and the second lightest neutralino are heavier than 200 gev and therefore , the stronger experimental bound comes from the @xmath308 invisible width . surprisingly , for @xmath293 , the tree - level coupling of the lightest neutralino to the @xmath308 vanishes and therefore the invisible width bounds become very weak . however as we shall analyze in section [ dark ] , assuming thermal production of the lightest neutralino , an acceptable relic density may only be obtained for a small but non - vanishing coupling to the @xmath308 . quite generally , if the dark matter density is determined by the s - channel @xmath308-annihilation cross section of a neutralino , an acceptable relic density may only be obtained for values of the neutralino mass larger than 35 gev , what in this case implies @xmath309 gev @xcite . for such a range of values of @xmath179 , a bound on the electric dipole moment of about @xmath310 e cm will be enough to test this model for @xmath311 and @xmath312 , as required for baryogenesis in the absence of light squarks . one of the most attractive features of the model presented above is that the particles that lead to a strengthening of the electroweak phase transition are the same as the ones leading to a generation of the baryon number at the weak scale . it would be most important if the same particles would also provide a good dark matter candidate . as stated in the introduction stable , neutral , weakly interacting particles lead naturally to a dark matter relic density of the order of the one present in nature . as we will see , under the assumption of an @xmath313-parity symmetry , the lightest neutralino of the model presented above becomes a good dark matter candidate . let us work in the simplest case , in which the bino mass @xmath178 takes large values ( @xmath314 ) and mixes only weakly with the higgsino ( @xmath315 ) . in such a case , due to the strong yukawa couplings @xmath180 and @xmath181 , the charginos and two of the neutralinos acquire masses of about @xmath316 . the mass of the lightest neutralino is close to @xmath179 and the lightest neutralino is therefore an almost pure higgsino state . assuming that all squarks , stabilizing bosons and heavy higgses , if present , are considerably heavier than the lightest higgsino , the states which determine the neutralino annihilation cross section are the light sm - like higgs boson and the @xmath308-gauge boson . due to the small coupling of the sm higgs boson to quarks and leptons , the annihilation cross section via s - channel higgs boson production is very small , unless the neutralino mass is very close to @xmath317 , a quite unnatural possibility that we shall discard for the aim of this work . hence the annihilation cross section is governed by the coupling of the lightest neutralino to the @xmath308-gauge boson . the coupling of a neutralino state to the @xmath308-gauge boson is proportional to the difference of the square of the components @xmath318 of the neutralino into the two weak higgsino states @xmath319 , g_z ( |n_1|^2 - |n_2|^2 ) this difference vanishes for values of @xmath320 , and increases for increasing values of @xmath306 . considering small differences between the values of @xmath180 and @xmath181 , the lightest neutralino , with mass approximately equal to @xmath179 , is given by _ 2 + _ 1 and hence g_z . [ coupling ] the annihilation cross section is proportional to the square of @xmath321 and inversely proportional to the square of the difference between the lightest neutralino mass and the resonant mass value , @xmath322 . therefore , the smaller the coupling @xmath321 , the closer the modulus of the parameter @xmath21 should be to the resonant mass value . hence , in order to get a value of the relic density consistent with the one determined by wmap , there must be a correlation between the departure of @xmath179 from @xmath322 and the difference of the yukawa couplings of the two higgsinos to the wino and higgs field . the numerical estimates of the values of @xmath179 for a given value of @xmath304 have been obtained by computing the relic density , which is inversely proportional to the thermal average annihilation cross section , h^2 = ( _ x_f^dx g_*^1/2)^-1 , where @xmath323 , @xmath324 is the mass of the lightest neutralino particle and @xmath325 the temperature of the universe @xcite . the value of the variable @xmath326 at the freeze - out temperature , @xmath327 , is given by the solution to the eq . @xcite x_f = , where @xmath328 is the number of degrees of freedom of the neutralino , @xmath329 is the total number of relativistic degrees of freedom at temperature @xmath330 , and @xmath331 is the planck mass . the thermal average of the annihilation cross section may be computed by standard methods and , for a particle of mass @xmath324 , is given by @xcite = _ 4m_^2^ds wk_1(/t)/16 m_^4tk_2(m_/t ) , [ sigv ] where @xmath332 is the usual mandelstam parameter , @xmath333 and @xmath334 are modified bessel functions , and the quantity w is defined to be w = ( 2)^4^(4)(p_1+p_2-_fp_f)||^2 , where @xmath335 is the squared matrix element averaged over initial states , and summed over final states . in fig . [ relic ] we plot the required value of @xmath179 in order to obtain the central value of the relic density consistent with the recent experimental results @xmath336 @xcite as a function of @xmath306 . the average values of the yukawa couplings have been fixed to @xmath337 ( dashed lines ) and @xmath296 ( solid lines ) . lower and upper lines for each set of @xmath304 values correspond to two different values of the cp - violating phase , @xmath338 and @xmath339 respectively . larger values of @xmath340 lead to larger values of @xmath179 . we show the results only for small values of @xmath340 , since as we will discuss in the next section , large values of @xmath340 lead to unacceptably large corrections to the precision electroweak observables . a non - vanishing phase has only a significant impact on the relic density determination for values of @xmath341 and @xmath342 gev ( @xmath343 ) , for which the phase transition is no longer strongly first order and/or unacceptably large corrections to the precision electroweak data are generated . otherwise , the variation induced by the cp - violating phases is of the order of ( or smaller than ) the present experimental uncertainty in the relic density . indeed , a one sigma variation of the relic density results for values of @xmath344 gev ( 60 gev ) would be obtained by varying @xmath179 by about 3 gev ( 1.5 gev ) . it is important to compare the results shown in fig . [ relic ] with those in fig . [ mhiggs ] . for @xmath301 it follows from fig . [ mhiggs ] that in order to preserve a strongly first order phase transition one needs @xmath302 gev and a higgs mass smaller than 125 gev . as seen in fig . [ relic ] , such small values of @xmath179 are also consistent with dark matter constraints , provided that @xmath345 . as emphasized before , and as we will show in detail in section 7 , the requirement of consistency with the precision electroweak data further constraints the allowed parameter space . for @xmath296 , the constraints coming from the requirement of a sufficiently strong phase transition are much weaker . values of @xmath179 and of the higgs mass as large as 200 gev are consistent with this constraint . this is a much larger region of values of the parameter @xmath179 than the one consistent with dark matter constraints , for the small values of @xmath340 that are required by precision electroweak data ( see section 7 ) . therefore , also in this case the allowed region of parameters may only be determined once the analysis of the constraints coming from the consistency with precision electroweak data are evaluated . finally notice that , for a fixed value of @xmath346 in fig . [ relic ] , the region above ( below ) the line @xmath347 corresponds to @xmath348 ( @xmath349 ) . therefore while the region above the corresponding curve is excluded since it would predict too much dm density , the region below it is not excluded provided there is another candidate for dark matter in the theory . heavy fermions , with large couplings to the higgs field , may induce large corrections to the electroweak precision measurement parameters . extra contributions may come from the stabilizing fields , but in this section we shall assume that the uv completion of the model is such that they are small . a very trivial ( ad hoc ) way of achieving this is if the stabilizing fields are a set of scalar singlet fields strongly coupled to the higgs boson . for instance we can consider the case of @xmath350 scalar ( complex ) singlets giving a contribution to the scalar effective potential given by @xmath351 . this set of singlet fields contributes to the one - loop effective potential of the higgs field as @xmath352 bosonic degrees of freedom with a mass squared @xmath353 that corresponds to the typical case of stabilizing fields introduced in section [ phase ] and @xmath354 , are equal and/or that the corresponding yukawa couplings @xmath355 , as we have been assuming in section [ phase ] . it is easy to see that a necessary stabilization condition is provided by @xmath356 . ] . as it is obvious this system of stabilizing ( singlet ) fields would not contribute to the electroweak precision observables or to the cp - violating observables analysed in the previous sections . in the following , we will just concentrate on the contribution to the electroweak precision measurement parameters from the fermionic sector of the theory . it is well known that if the fermion masses proceed from the usual contraction of a left - handed fermion doublet and a right - handed fermion singlet with the higgs doublet , and if the mass difference of the fermion components of the doublet field is small , the contribution of heavy fermions to the @xmath357-parameter is about @xmath358 . on the other hand the contribution to the @xmath325-parameter would depend on the size of the mass difference between the up and down fermions . cancellation of anomalies requires the presence of at least two such new heavy fermion doublets and therefore the contribution to the @xmath357-parameter tends to be large , @xmath359 . in the case under analysis , however , the symmetry breaking masses proceed from the coupling of the higgsino doublets to the higgs field and an @xmath360-triplet of winos . contrary to the standard case of heavy fermions , the contribution to the @xmath357-parameter becomes small in this case . for a given value of the average yukawa coupling @xmath304 , the contribution to the @xmath325 parameter , instead , becomes sizeable for large values of @xmath306 , while the contribution to the parameter @xmath361 is an order of magnitude smaller than the contribution to @xmath325 . we shall work in the limit in which @xmath178 is large . thus the mixing of binos with the winos and higgsinos becomes small and therefore the binos decouple from the precision measurement analysis . for large values of the yukawa couplings , the lightest neutralino has a mass close to @xmath179 and a coupling to the @xmath308-gauge boson given by eq . ( [ coupling ] ) . as explained in section [ higgsinos ] , for @xmath293 there are two dirac charginos degenerate in mass with two majorana neutralinos and the @xmath325 parameter contribution vanishes . the mass difference between the neutralinos and charginos grows linearly with @xmath306 , as does the coupling of the lightest neutralino to the @xmath308-gauge boson , and the @xmath325 parameter grows quadratically with @xmath306 , as shown in fig . [ rho ] , for values of @xmath296 ( solid line ) and @xmath294 ( dashed line ) . moderate contributions to the @xmath325-parameter are not in conflict with electroweak precision measurements . even in the absence of any other physics at the weak scale the corrections to the @xmath325-parameter coming from the neutralino and chargino sector may be largely compensated by the negative contribution induced by the presence of a heavy higgs , which contributes to the @xmath357 and the @xmath325 parameters in a way proportional to the logarithm of its mass , @xmath362 where @xmath363 is a reference higgs mass value . the model under analysis falls therefore under the class of models which give a small contribution to the @xmath361 parameter and sizeable contributions to the @xmath325 parameter . although the new physics gives only negligible contribution to @xmath357 , a sizeable contribution to the @xmath357 parameter may also be induced by a heavy higgs boson . a fit to the precision electroweak data in this class of models has been done by the lep electroweak working group @xcite . for a reference higgs mass value of 150 gev , they find @xmath364 with an 85% correlation between the two parameters . taking this into account we show in fig . [ stu ] the 68% c.l . ( solid lines , hatched ellipses ) and 95% c.l . ( dashed lines ) region of allowed values of the new physics contribution to the @xmath357 and @xmath325 parameters for values of the higgs boson mass equal to 115 gev , 200 gev and 300 gev , respectively . observe that , since we are presenting a fit to the allowed new physics contribution to the @xmath357 and @xmath325 parameters , for each value of the higgs mass the origin of coordinates represents the sm value . from the results of figs . [ relic ] , [ rho ] and [ stu ] , we see that for a fixed value of the average yukawa coupling , @xmath304 , the requirement of an acceptable relic density and a good fit to the precision electroweak data implies an interesting correlation between values of @xmath306 , the parameter @xmath179 and the higgs mass . the value of the higgs mass is also bounded from above from the requirement of a successful generation of the baryon asymmetry . for instance , for @xmath296 , fig . [ mhiggs ] shows an upper bound on the higgs mass of about 200 gev and therefore from fig . [ stu ] it follows that a good fit to the electroweak data may only be obtained for values of the new physics contribution to the parameter @xmath365 ( if the new physics contributions to the parameter @xmath357 are small , as in the case under analysis ) . the upper bound on @xmath325 translates into an upper bound on @xmath306 . from fig . [ rho ] we get that @xmath366 0.18 , and from fig . [ relic ] this leads to an acceptable relic density only for @xmath367 gev . for @xmath301 the corrections to the precision electroweak parameters are slightly smaller than for @xmath296 . however , as emphasized before , from fig . [ mhiggs ] we see that consistency with a strong electroweak phase transition can only be obtained for a higgs mass value close to its present lower bound , @xmath368 gev , and small values of @xmath302 gev . from fig . [ stu ] , this implies that the new physis contribution to the parameter @xmath369 , and therefore from fig . [ rho ] one obtains that @xmath370 . interestingly enough , from fig . [ relic ] , we find that the same region of parameters is consistent with the dark matter relic density provided @xmath371 gev . observe that the allowed values of @xmath179 approximately coincide with the ones obtained for @xmath372 . in this work we have analyzed the properties of a model with light charginos and neutralinos which are strongly coupled to the sm higgs . such large values of the yukawa couplings do not arise in minimal supersymmetric extensions of the standard model , since these couplings are determined by supersymmetric relations to the weak couplings . it is therefore an important question to understand under which conditions such a low energy effective theory may be obtained . one possibility is to assume that , although the quantum numbers of the light particles are those of higgsinos and gauginos of supersymmetric theories , the theory is not related to any supersymmetric theory at high energies . a more interesting possibility would be to consider this theory as a particular realization of split supersymmetry @xcite , but where the particular relation between the yukawa couplings and the gauge couplings has been broken by supersymmetry breaking interactions . one of the problems with this alternative is the one of vacuum stability . in addition , due to the strong yukawa couplings , perturbative consistency is lost at scales much lower than the gut scale and therefore perturbative unification of the gauge couplings can not be achieved . in this section we shall show that this low energy effective theory may also arise in low energy supersymmetric models with extra , strongly coupled gauge sectors , if the scale of supersymmetry breaking is larger than the scale of spontaneous symmetry breakdown of the extended gauge sector to the standard model one . a supersymmetric extension provides the necessary stabilizing fields in a natural way . on the other hand in this extension the strong yukawa couplings are proportional to the strong gauge couplings , which become asymptotically free at high energies . this ultraviolet completion of the theory allows the preservation of perturbative consistency up to high energies and therefore the possibility of perturbative unification of gauge couplings . in order to illustrate this property let us consider the model analyzed in ref . the model is based on the low energy gauge group su(3)_c su(2)_1 su(2)_2 u(1)_y . [ gaugeg ] first and second generation left - handed quark and leptons transform in the fundamental representation of @xmath373 , i.e. @xmath374 of @xmath375 , while the third generation left - handed quark and leptons and the two mssm higgs bosons transform in the fundamental representation of @xmath376 , @xmath377 . the model also includes a bifundamental @xmath378 higgs field @xmath379 , as well as a singlet field @xmath357 . the scalar component of the bifundamental takes a vacuum expectation value @xmath380 , breaking @xmath381 . the gauge bosons w^ = [ wl ] remain massless after this symmetry breakdown and interact with an effective gauge coupling @xmath382 . this model can be made consistent with gauge coupling unification by embedding the group @xmath383 into the grand unified product group @xmath384 broken by bi - fundamental field @xmath385 diagonal vev s @xcite . in the model of ref . @xcite there are extra fields transforming under @xmath373 but not under @xmath376 . with this particle content the coupling @xmath386 of @xmath376 is asymptotically free , but @xmath387 of @xmath373 is not . we shall work under the assumption that the coupling @xmath386 becomes strong at the scale @xmath388 of spontaneous symmetry breaking of the symmetry @xmath389 , and therefore the winos of @xmath376 interact strongly with the higgs and higgsinos . for our analysis here , the relevant term in the superpotential is @xmath390 , and the relevant supersymmetry breaking terms in the gaugino - higgsino sector are the masses of the gauginos , @xmath391 , corresponding to the two groups @xmath392 . in the absence of supersymmetry breaking terms the superpartners of @xmath393 would become the low energy winos , interacting with higgsinos and higgs bosons with the weak coupling @xmath394 . in order to get a strongly interacting wino - higgsino - higgs sector at low energies we need to decouple the bifundamental higgsinos @xmath395 , as well as the weakly interacting wino @xmath396 from the weak scale theory . this may be achieved by choosing the supersymmetry breaking parameters @xmath391 and the higgsino mass parameter @xmath397 to verify _ 1 , m _ g_2 u , _ 2 g_2 u supersymmetry is therefore broken before the scale of breakdown of @xmath398 group to @xmath360 . the wino of @xmath373 is only weakly coupled with the bidoublet higgsinos and its large supersymmetry breaking mass ensures its decoupling from the low energy theory . for the parameters given above the low energy wino has a mass m_2 _ 2 - [ m2 ] and has a component on the strongly coupled wino of @xmath376 of order @xmath399 , with _ g_2 u / m_. the effective yukawa couplings between the low energy winos and the two higgsinos are therefore given by @xmath400 where we have assumed that the cp - odd higgs mass is larger than the weak scale , and therefore a single , sm - like , cp - even higgs boson remains in the low - energy theory . assuming @xmath401 we get that , in this realization of the low energy theory , the yukawa couplings @xmath402 . on the other hand , a very large supersymmetric mass @xmath397 would also demand to be compensated in a precise way by a similarly large supersymmetry breaking mass in order to get the proper @xmath403 breaking scale . lower values of @xmath397 would reduce the strongly coupled gaugino component of the low - energy wino state and would require a fine - tuning between the two terms in eq . ( [ m2 ] ) in order to obtain a small value of the effective low - enegy wino mass . therefore in this model , a moderate amount of fine - tuning is required to get consistency with phenomenological constraints and a strong electroweak phase transition . we can now ask if the strongly coupled gauge bosons may serve as the stabilizing bosonic fields defined in section [ phase ] . let us first stress that the particular extension of the mssm presented above leads to extra contributions to the precision electroweak observables . small values of these extra contributions may only be obtained for values of @xmath404 larger than a few tev @xcite . since @xmath404 acts as the bosonic mass @xmath59 defined in eq . ( [ bosonstab ] ) , these particles can only act as stabilizing fields if the higgs is heavier than the range consistent with a strongly first order phase transition . it would be interesting to investigate possible regions of parameter space in which cancelations between different contributions take place and consistency with data may be achieved for lighter gauge boson masses . otherwise , additional fields would be necessary to stabilize the higgs potential . a very simple possibility , that has already been pointed out in section [ precision ] is that the stabilizing fields are gauge singlets , harmless from the point of view of electroweak precision measurements . these singlets should couple strongly to the higgs sector , in order to stabilize the fermionic part of the zero - temperature effective potential , but should not contribute strongly to the higgs quartic coupling since in that case the phase transition would become weakly first order . a simple example of a model producing the required effect is given by a singlet superfield @xmath405 coupled to the higgs field doublets as well as to a set of @xmath350 singlet fields @xmath406 , with superpotential @xmath407 where all couplings and the masses @xmath408 and @xmath409 are positive . the absence of a coupling of the singlet fields @xmath406 to the higgs doublets as well as the appearence of only terms proportional to @xmath410 in the superpotential may be understood as a result of the invariance of the theory under a global @xmath411 symmetry . the supersymmetric masses of the singlet fields , @xmath408 and @xmath409 , are assumed to be much larger than the weak scale , suppressing the mixing of light singlet fermions with the standard gauginos and higgsinos . we shall also assume that there are supersymmetry breaking effects in the bosonic @xmath412-sector that prevent the possibility of integrating out the superfields @xmath412 from the weak - scale theory and allow the bosonic @xmath412-sector to be the stabilizing fields with mass given by ( [ bosonstab ] ) . such supersymmetry breaking effects should also ensure the preservation of the modifications to the low - energy higgs quartic coupling induced by the presence of the superfields @xmath412 in the theory . furthermore we will assume that the superfield @xmath405 can be integrated out supersymmetrically so that for scales below @xmath409 it gives rise to an effective superpotential as @xmath413 the above superpotential gives rise to a coupling in the tree - level potential between the @xmath357 sector and the higgs sector , @xmath414 to an @xmath103-quartic coupling as @xmath415 , where ~_2 ^ 22 , and to a self - interacting quartic coupling @xmath416 fields _ s ~ _ 1 ^ 2 . since we have concentrated in this work on the results obtained in the model with strongly interacting gauginos and higgsinos for small values of @xmath306 , the value of @xmath218 , and therefore @xmath417 . for @xmath418 and @xmath419 , one obtains values @xmath420 , necessary for the singlets @xmath406 to stabilize the one - loop higgs potential against the fermion contribution . on the other hand , for @xmath421 , as required to obtain a good description of the dark matter relic density and precision electroweak observables , the contribution to the quartic coupling is not too large . this has implications for the higgs boson mass . in fact , for values of @xmath218 , the d - term contribution to the higgs mass is small and the higgs mass may be raised above ( or around ) the mssm values , due to the tree - level contribution m_h^2 2v^2 + ( loop - effects ) + ( d - term ) . values of the higgs mass of order 115200 gev may be naturally obtained for @xmath422 0.10.3 , that appear in this model for values of @xmath409 of the order of the tev scale and values of @xmath423 somewhat larger than one . by choosing the appropriate value of @xmath350 and the values of the couplings @xmath424 , one can reach a situation similar to the one described in the previous sections . a detailed analysis of the parameter space in this particular model is outside the scope of the present paper . in this article we have shown that heavy fermions with strong couplings to the higgs fields may induce a strengthening of the electroweak phase transition and can also provide the proper cp - violating sources for the generation of baryogenesis . these heavy fermions , however , also induce for light higgs bosons an instability of the higgs potential at zero temperature and therefore require an ultraviolet completion of the theory to recover the consistency of the low - energy theory . in this work , we have assumed that the heavier , stabilizing fields have oposite statistics but similar couplings and number of degrees of freedom as the fermion fields . the above properties are then associated with the low energy theory consisting both of the heavy fermions and the heavier , stabilizing fields . we have illustrated this possibility by considering a model with tev scale higgsinos and gauginos that may lead to a sufficiently strong first order electroweak phase transition for values of the higgs mass as large as 300 gev . this is quite different from the results of the mssm , in which a light stop is necessary , and the higgs mass should be lower than @xmath1 120 gev to enhance the strength of the electroweak phase transition . also at variance with the case of the mssm is the fact that in this scenario the particles that induce a strong first order phase transition are the same ones responsible for the generation of the baryon asymmetry at the weak scale . this model preserves most of the properties of low energy supersymmetry , including a good dark matter candidate . beyond the problem of vacuum stability , however , the low - energy yukawa couplings deviate from the ones obtained in minimal supersymmetric extensions of the sm , and their strength spoils the perturbative consistency of the theory at scales of about a few tev . we have shown , however , that the model may be considered as the low energy effective description of a gauge extended supersymmetric standard model , in which the strength of the yukawa couplings is related to the gauge couplings of an extended asymptotically free gauge sector , that becomes strongly interacting at tev scales . this ultraviolet completion of the model solves the strong coupling problem and introduces new heavy particles that , due to their supersymmetric relations to the higgsinos and gauginos , tend to stabilize the higgs potential in a natural way . the stability of the potential , however , may only be achieved for values of the heavy particle masses smaller than about 1 tev . these relatively small values of the heavy gauge boson masses lead to large corrections to the precision electroweak observables , unless cancellations between different contributions occur . alternatively , we also have shown that the model can be completed with singlets that may stabilize the zero - temperature effective potential while providing higgs masses consistent with present experimental bounds and with the required strongly first order phase transition . finally , we have shown that this model may be tested by electron electric dipole moment experiments in the near future . we would like to thank p. batra , a. delgado , t. tait and d. morrissey for very helpful discussions . this work was supported in part by the rtn european programs hprn - ct-2000 - 00148 and hprn - ct-2000 - 00152 , and by cicyt , spain , under contracts fpa 2001 - 1806 and fpa 2002 - 00748 . work at anl is supported in part by the us doe , div . of hep , contract w-31 - 109-eng-38 . fermilab is operated by universities research association inc . under contract de - ac02 - 76ch02000 with the doe . sakharov , _ jetp lett . _ * 91b * ( 1967 ) 24 . g. t hooft , _ phys . _ * d14 * ( 1976 ) 3432 [ erratum-_ibid . _ * d18 * ( 1978 ) 2199 ] . manton , _ phys . rev . _ * d28 * ( 1983 ) 2019 ; f.r . klinkhamer and n.s . manton , _ phys . _ * d30 * ( 1984 ) 2212 . d. bodeker , _ phys . _ * b426 * ( 1998 ) 351 [ arxiv : hep - 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new fermions , strongly coupled to the standard model higgs boson , provide a well motivated extension of the standard model ( sm ) . in this work we show that , once new physics at heavier scales is added to stabilize the higgs potential , such an extension of the sm can strengthen the first order electroweak phase transition and make the electroweak baryogenesis mechanism feasible . we propose a sm extension with tev higgsinos , winos and binos that satisfy the following properties : * a ) * the electroweak phase transition is strong enough to avoid sphaleron erasure in the broken phase for values of the higgs mass @xmath0 gev ; * b ) * it provides large cp - violating currents that lead to the observed baryon asymmetry of the universe for natural values of the cp - violating phase ; * c ) * it also provides a natural dark matter candidate that can reproduce the observed dark matter density ; * d ) * it is consistent with electroweak precision measurements ; * e ) * it may arise from a softly broken supersymmetric theory with an extra ( asymptotically free ) gauge sector ; * f ) * it may be tested by electron electric dipole moment experiments in the near future .

the recent measurements of the local cosmic - ray electron and positron fluxes have stimulated a lot of interest in the cosmic - ray field . the sharp rise in the positron fraction detected by pamela @xcite seems a clear indication of the existence of a nearby positron source in addition to the secondary positron component due to the interaction of primary species with the interstellar medium along propagation . the very recent high - statistic measurement by fermi @xcite of the all - electron flux ( namely the flux of electrons plus positrons without charge discrimination ) , while not confirming previous hints of an anomalous peak by atic @xcite and ppb - bets @xcite , has found a spectral index sensibly harder than the one inferred from past extrapolations for the electron spectrum based on lower energy ( and less accurate ) data . such a picture leaves room for a substantial contribution from unconventional ( or previously disregarded ) lepton sources , and it is very tempting to consider the possibility that a large component of the positron and electron flux is provided by the pair annihilation of dark matter ( dm ) particles , possibly forming the dm halo of the milky way ( for early proposals in this direction see , e.g. , @xcite ; for reviews on indirect dm detection see , e.g. , @xcite ) . the latest fits of the data with such a component , see , e.g. , @xcite confirm that this picture is viable . two general features of the dm - induced source were well - known even from early analyses : i ) to match the level of the positron background , the local pair annihilation rate needs to be much larger than the one expected for thermal dm weakly interacting massive particles ( wimps ) , within standard assumptions for the universe thermal history and the local dm distribution ; ii ) having normalized the annihilation rate to the observed positron flux , there are very stringent bounds on the wimp model from measurements of the local antiproton flux , disfavouring annihilation modes giving rise to a hadronic yield , and favouring the leptonic channels . dm models fulfilling these requirements have been proposed recently , see , e.g. , @xcite . for what concerns the first requirement , they mainly focus on a mechanism to account for a mismatch between the thermally averaged annihilation cross section at the freeze - out in the early universe and a much larger annihilation cross section in the halo today . alternatively , one could invoke an enhancement in the positron signal based on the presence of a local population of dense dark matter substructures , with the pair annihilation rate being large because the average of the number density of dm pairs is much greater than one half of the square of the mean dm number density ( i.e. , in terms of the local dm halo density @xmath0 , @xmath1 ) . when considering an average effect within many realizations of the milky way substructure population as extrapolated from current @xmath2cdm numerical n - body simulations , the mean enhancements in the local cosmic - ray fluxes are typically very modest , possibly below a factor of few @xcite . large effects , at the level needed to account for pamela and fermi data , have been claimed instead in connection to a ( few ) single , very dense , nearby substructure(s ) @xcite ; the price to pay in this case is that one has to refer to a configuration with a very small realization probability according to the n - body simulations , or to rely on a subhalo picture which is less standard . both in discussing average effects from a full subhalo population and in tracing the effect of individual substructures , the approach of the recent papers and the vast majority of papers in the literature has been to ignore the fact that one is dealing with a system which is not static , and the emission and propagation of charged particles has been treated in the steady state limit . the distribution of substructures in the galaxy is not rotationally supported ; their typical velocity can be estimated from the total mass density profile of the milky way . assuming for simplicity spherical symmetry for the galaxy and an isothermal sphere for the subhalo phase - space distribution function , the velocity dispersion for such a distribution is simply equal to @xmath3 times the value of the circular velocity @xcite , i.e. , assuming 250 km s@xmath4 for the local rotational speed @xcite , about 300 km s@xmath4 . an object moving at such speed on an orbit perpendicular to the galactic plane has a time of crossing of the diffusive halo region for cosmic - rays , say a cylinder with a 4 kpc half - height , of about @xmath5 s. such value is comparable to the typical confinement time for cosmic rays as estimated in the simplified `` leaky - box '' propagation models , and to the energy loss timescale for electrons and positrons @xcite . this is clearly just a qualitative argument ( actually not even referring to the most appropriate quantities , see the discussion below ) to illustrate that the effect of proper motion of dm substructure can be relevant . indeed , we will show that there is the possibility that local antimatter measurements reflect a transient due to dm annihilations in a subhalo , rather than a source to be modeled in the steady state limit . the paper discusses the main features of the local antimatter fluxes resulting from individual dm substructures , taking proper motion into account . analytic solutions for the propagation equation , as appropriate for positrons and antiprotons / antideuterons , are presented taking into account the most relevant terms , referring to a simplified description of the diffusion region , the interstellar medium and radiation field ( these are the same kind of assumptions which are usually implemented for dm studies in the steady state limit , as well as , most often , to discuss electron / positron fluxes from astrophysical sources ) . we show results in a few benchmark configurations for the propagation parameters and for the orbit of the dm source . we introduce a few sample possible interpretations for the pamela and fermi positron / electron data , illustrating how sensitive one becomes to different assumptions . in particular , we show that , contrary to the picture extensively discussed in recent analyses , it is no longer true that one can extract from the data , in a unique way , model independent particle physics observables , such as the dm mass , the pair annihilation cross section and the annihilation channel . we also consider the gamma - ray signals associated to this scenario and compare with current limits as well as with the detection prospects in the upcoming future . the paper is organized as follows . in section [ sec : crprop ] , we present the description of the particle propagation in the galaxy . we discuss point - like dm substructures as sources of positrons and compare to pamela and fermi data in section [ sec : positronpoint ] and [ sec : positrondata ] , respectively . the contribution to the antiproton flux is presented in section [ sec : antiproton ] . in section [ sec : extra ] , we compute other detectable extra features of the electron / positron flux , such as the associated radiative emission and the dipole anisotropy of the spectrum . section [ sec : concl ] concludes . details on the solution of the transport equation for positrons and antiprotons are reported in the appendix . the random walk of charged cosmic - rays in the turbulent and regular component of the galactic magnetic fields is usually treated through an effective description . defining @xmath6 the number density per unit total particle momentum of a given particle species ( i.e. , @xmath7 is the number of particles in the momentum interval @xmath8 ) , the propagation equation can be casted in the general form ( see , e.g. @xcite ) : @xmath9 - \frac{n}{\tau_f } - \frac{n}{\tau_r}\ , . \label{eq : prop_n}\ ] ] here @xmath10 is the source term , including primary , spallation and decay contributions , @xmath11 is the spatial diffusion coefficient , @xmath12 is the convection velocity , diffusive reacceleration is described as diffusion in momentum space and is determined by the coefficient @xmath13 , @xmath14 is the momentum gain or loss rate , @xmath15 is the time scale for loss by fragmentation , and @xmath16 is the time scale for radioactive decay . the problem is usually solved for stationary sources and assuming @xmath6 has reached equilibrium ( i.e. setting the left - hand side of the equation to zero ) , through a fully numerical integration of the general model , see , e.g. , the galprop @xcite and the dragon @xcite packages , or implementing ( a chain of ) semi - analytic solutions valid within a set of simplifying assumptions , see , e.g. , @xcite . in our analysis we will follow the second route , implementing however solutions of the diffusion equations valid for positron or antiproton primary sources which are non - stationary . as commonly done , we will assume a spatially constant diffusion coefficient and introduce a spatial average for the positron / electron energy loss rate ; we will also neglect both convection and reacceleration , sketching the relative energy dependent effects through an appropriate choice of the momentum scaling of the spatial diffusion coefficient . this very simplified scheme , which is flexible enough to introduce many study cases without neglecting any of the physical effects we wish to discuss , can actually be sufficient for a fair description of some of the key observables in cosmic - ray physics . e.g. , ref . @xcite introduces , for the galprop numerical package , the case of a standard diffusive model with spatial diffusion coefficient of the form : d(p ) = d_0 ( ) ^ , with @xmath17 being the particle velocity in unit of the speed of light , @xmath18 being its rigidity , and with the following parameter choice : @xmath19 , @xmath20 , @xmath21 for @xmath22 and @xmath23 for @xmath24 ( having neglected @xmath13 , from now on we will simply label @xmath11 as @xmath25 ) . the diffusion region is treated as a cylinder extending from @xmath26 to @xmath27 in the vertical direction , with standard primary sources in a thin layer around @xmath28 , and up to @xmath29 in the radial direction ; in the example of ref . @xcite , @xmath30 kpc and @xmath31 kpc . parameters are tuned to reproduce observational constraints , and in particular the relative abundance of secondary to primary components . indeed , running the public available version of galprop within this setup , we find a fairly good fit to the boron over carbon ratio data ( reduced @xmath32 for @xmath33 gv , considering the b / c measurements at high energy by atic @xcite , cream @xcite , heao3 @xcite , and crn @xcite , and having assumed a spectral index for primary nuclei of 2.35 and 2.1 for , respectively @xmath34 gv and @xmath35 gv ) , and to the antiproton over proton ratio as recently measured by pamela . we label this parameter choice as `` model a '' , and take it as reference benchmark case . a comprehensive discussion of the dependence of our results on the propagation model is clearly beyond the scope of this paper ; the main trends we will present are essentially insensitive to slight readjustments in the parameter space . one of the most relevant parameters for our discussion is the vertical size of the propagation region @xmath36 . it is well known that the local measurements of secondary to primary ratios are mostly sensitive to @xmath37 rather than to each of the two parameters . the degeneracy would be broken by local measurements of the so - called `` radioactive clocks '' , namely unstable secondaries , such as @xmath38be as compared to @xmath39be . such data are however not very accurate at present . we consider two extreme setups : a thin halo model with @xmath40 kpc and a thick model with @xmath41 kpc ; @xmath42 is rescaled to , respectively , @xmath43 and @xmath44 in @xmath45 as we find simulating this model with galprop and refitting the b / c ratio ( reduced @xmath46 and @xmath47 ; the thin halo model is labeled as `` model b '' , while the thick one as `` model c '' ) . within these models the local primary proton and electron fluxes are reproduced as well ( for the electron injection spectrum we take a spectral index of 2.30 at high energy , i.e. above @xmath48 gev ) . the spectra obtained with galprop in our reference cases will be used to as background estimates in the next sections ; the local electron and positron flux are computed with the spatially - dependent energy loss terms following from the standard templates for the interstellar radiation field and the magnetic field profile as implemented in the code . when computing primary components from wimp annihilations we will introduce instead the simplification of a spatially - constant energy loss term , referring to an average value valid in the local neighborhood . in the energy loss configuration `` h '' , which we assume as standard reference , the synchrotron and inverse compton energy loss terms are driven , respectively , by an average magnetic field in the diffusion region which is about @xmath49 g , and a mean background starlight density @xmath50 @xcite , on top of the cosmic microwave background component . for comparison , we will also consider a template in which both quantities are sharply reduced , assuming @xmath51 g and @xmath52 ( we label this energy loss configuration by `` l '' ) . gev , 500 gev and 1 tev ) and as a function of the positron momentum @xmath53 as measured locally , the proper motion scale @xmath54 ( black dashed curves ) is compared to distance @xmath55 at which the positron green function is maximal ( thick solid curves ) and the range of values for which the green function is 10% of the maximum ( thin solid curves ) . the propagation model ah is assumed , see the text for more details . _ right panel : _ the same as for the left panel , but for @xmath56 gev and the six combinations of diffusion and energy loss models.,width=294 ] gev , 500 gev and 1 tev ) and as a function of the positron momentum @xmath53 as measured locally , the proper motion scale @xmath54 ( black dashed curves ) is compared to distance @xmath55 at which the positron green function is maximal ( thick solid curves ) and the range of values for which the green function is 10% of the maximum ( thin solid curves ) . the propagation model ah is assumed , see the text for more details . _ right panel : _ the same as for the left panel , but for @xmath56 gev and the six combinations of diffusion and energy loss models.,width=294 ] consider the limit of a point - like dark matter substructure , entering the diffusion region at the point @xmath57 at the time @xmath58 and moving along an orbit @xmath59 ( e.g. , @xmath60 if one can approximate such motion as a straight line trajectory with constant velocity @xmath61 ) , with dark matter made of wimp dark matter particles of mass @xmath62 , annihilating in pairs with annihilation rate @xmath63 and positron yield per annihilation @xmath64 . the positron dark matter source @xmath10 at the position @xmath65 , momentum @xmath66 and time @xmath67 , takes the form : q ( , t , p ) = ^3 , [ eq : pointsource ] where @xmath68 , the total dark matter annihilation rate in the source , contains all terms not depending on spatial coordinates , momentum and time : = ( v ) d_s ( v ) v_s . here @xmath69 is the dark matter density profile within the substructure , and the expression after the equivalence sign defines the annihilation volume @xmath70 , having normalized @xmath71 to the reference value @xmath72 gev @xmath73 . the positron number density per unit momentum is given by : n(r , p , t ) = _ t_i^t dt_0 _ p^p_max dp_0 g(r , t , p;_p(t_0),t_0,p_0 ) [ eq : epnsol ] the green function @xmath74 is given in appendix [ app : pos ] ; neglecting boundary conditions it is approximately in the form : g \{-^2 } [ eq : epgreensimply ] where we introduced the distance @xmath75 between the source and the observer at the time @xmath76 , the energy loss timescale @xmath77 , and diffusion length @xmath78 , defined through @xmath79 . looking at this expression , we can guess that including the time dependence in the propagation equation is relevant whenever the variation of @xmath80 within the time @xmath81 , say @xmath82 , is larger or comparable to @xmath78 . consider the high energy limit , in which the energy loss term scales like @xmath83 and the diffusion coefficient like @xmath84 , with @xmath85 ; the square of the ratio between @xmath54 and @xmath78 goes like : 5 10 ^ -2 [ eq : ratiodl ] where @xmath86 and @xmath87 are reference values for the diffusion coefficient and energy loss rate at 1 gev , respectively , @xmath45 and @xmath88 , @xmath89 the substructure velocity in units of @xmath90 , @xmath91 is the positron momentum in the equilibrium distribution in units of 100 gev , and @xmath92 the ratio between such momentum and the momentum of the positron at the source . being energy losses very effective at high energy , the time spent in the system before losing most of the energy by particles injected with very high momentum tends to be very small . the distance traveled by a dm subhalo in the same timescale is very small as well , and , in this case , proper motion can be safely neglected . an analogous picture occurs when considering cases with small difference between momentum at injection and momentum at equilibrium , and thus with short timescale associated to the electron / positron transport . one sees from eq . [ eq : ratiodl ] that @xmath93 for @xmath94 or large @xmath66 . on the other hand , we expect proper motion to be relevant at intermediate to low energies . this effect is illustrated also in fig . [ fig : epdiff ] : in the left panel , for a few values of the momentum at the source @xmath95 , we compute @xmath78 as a function of @xmath66 and , correspondingly , find the value of @xmath55 , namely , the distance from us along the direction perpendicular to the galactic plane at which the exact green function @xmath74 reaches its maximum ( thick solid lines ) . neglecting boundary conditions as in eq . ( [ eq : epgreensimply ] ) , we would simply find @xmath96 ; in the plot the scaling of @xmath55 with @xmath66 gets more rapid when the distance approaches the vertical boundary of the diffusion region at @xmath97 kpc ( the propagation model `` ah '' is assumed in the plot ) . also displayed are the range of distances within which the green function is larger than one tenth of its maximum and our estimate for @xmath54 , as defined above . in the right panel , we plot the same quantities for a single injected momentum ( @xmath98 gev ) , but looping over the three propagation models and the two energy loss configurations as specified in the previous section . in both panels , comparing @xmath55 and the 10% range to @xmath54 , one sees that there are large @xmath66 intervals over which proper motion effects are expected to be large . , and moving along a vertical orbit intersecting the galactic plane at a short distance from the observer . each curve refer to a different time of observation , with the distance @xmath80 of the source from the observer playing the role of time variable . this is useful since we can compare with the spectra one obtains for static sources placed at the same distances . the positron flux is multiplied by @xmath99 to match the approximate scaling in the static limit . _ right panel : _ for a give time of observation ( namely , fixing @xmath100 kpc ) , predictions for the flux within our benchmark setups for the propagation model.,width=294 ] , and moving along a vertical orbit intersecting the galactic plane at a short distance from the observer . each curve refer to a different time of observation , with the distance @xmath80 of the source from the observer playing the role of time variable . this is useful since we can compare with the spectra one obtains for static sources placed at the same distances . the positron flux is multiplied by @xmath99 to match the approximate scaling in the static limit . _ right panel : _ for a give time of observation ( namely , fixing @xmath100 kpc ) , predictions for the flux within our benchmark setups for the propagation model.,width=294 ] to discuss the contribution to the local positron flux @xmath101 from a single point source , we start considering the sample case of a source moving with constant velocity @xmath102 , on a trajectory which is perpendicular to the galactic plane , intersecting the plane at a small distance from the sun ( say 10 pc , the precise value has little relevance for the discussion ) . to emphasizes propagation effects , we refer to a dark matter model , of given mass and total annihilation rate , with prompt annihilation into @xmath103 pairs , i.e. with a monochromatic positron spectrum @xmath104 . in fig . [ fig : scal ] we fix @xmath105 gev and show the shape of the induced local positron fluxes in a few sample cases . in the left panel , each curve refers to a different time of observation , but rather than labeling them by time steps , we indicate the distance @xmath80 of the source from the observer , along the trajectory and at the time when the positron flux is measured ( dashed lines for an approaching source , solid line for a source which has passed nearby and now is moving away ; for reference , in the example we are considering , a shift of 1 kpc in @xmath80 corresponds to a time interval @xmath106 s , i.e. about an order of magnitude lower than the typical `` escape time '' for particles of these energies as extrapolated in simple `` leaky box '' propagation models ) . for comparison , we also show the case of static sources ( dotted lines ) , at a given distance from the sun . from the green function solution ( again sufficiently away from the boundaries of the propagation region ) we can guess that , in the static limit , the peak of the product @xmath107 scales like @xmath108 . this is indeed what we find in the plot , where the quantity @xmath109 has been normalized to 1 in arbitrary units for @xmath110 pc ; the figure shows also the departure from such scaling in case of a non - stationary source , with the result for approaching , static and departing sources essentially coinciding only in the limit of small distances and large energies . for moderate to large distances the height of the peaks increases ( decreases ) for a source which has passed by ( is approaching ) . the spectral shapes are also very different , with the sharp cutoffs at low energy enforced by the mismatch between the time interval from positron emission to detection and the energy loss timescale , which increases at lower energies . positron propagation is treated according to model `` ah '' as introduced above ; such model has @xmath30 kpc and hence an approaching source at @xmath111 kpc , along the vertical trajectory we are considering , has just entered the diffusion region and induces a local positron flux which is marginal compared to the flux from the same source after passing by and being on the other side of the trajectory at the same distance . even after the source has left the diffusion region there is still a population of positrons which has been left behind contributing to the local flux , especially at low energies : here a larger @xmath80 just reflects a longer time interval since the injection time and hence a more efficient degrading of the injected high energy positrons to small energies . in the right panel of fig . [ fig : scal ] , we take one of the cases plotted in the left panel , namely a source moving away from the observer and being at @xmath100 kpc at the time of observation , and show instead the dependence of the spectral shape and the normalization of the measured flux on the benchmark models chosen for propagation and energy losses . indeed the differences between the various cases are rather striking ; this gives a feeling for the fact that there are large uncertainties related to propagation in our problem , which are not resolved tuning the model , as we did , to local measurements of secondary to primary nuclei ratios . furthermore , there are potentially other relevant issues which we do not address in our simplified approach . e.g. , we expect some dependence of the results on how boundary conditions are treated in the diffusion model : we are adopting here the standard approach of a spatially constant diffusion coefficient and free escape ( i.e. the diffusion coefficient going to infinity ) as a sharp transition at the vertical boundaries ; this is the same approach followed , e.g. , in galprop . considering a less sharp transition between the two regimes , with , e.g. , an exponential vertical scaling of the diffusion coefficient as proposed by @xcite , we would obtain smoother cutoffs in the spectra of sources at large distances shown in the left panel of fig . [ fig : scal ] . a gradient in the energy loss term would also mildly affect the prediction for the local positron flux . , in the benchmark propagation model ah . the two values of @xmath80 refer to the distances which the source has from the observer at the time the flux is measured and after the source has passed in the vicinity of the observer ; the set of curves displayed refer to a few sample orbits for the source ( see the text for details).,width=294 ] , in the benchmark propagation model ah . the two values of @xmath80 refer to the distances which the source has from the observer at the time the flux is measured and after the source has passed in the vicinity of the observer ; the set of curves displayed refer to a few sample orbits for the source ( see the text for details).,width=294 ] fig . [ fig : scal2 ] considers the cases for a lighter and heavier wimp ( respectively , 100 gev and 1 tev ) and , referring again to the propagation model ah , discusses the dependence of the locally measured positron flux on the orbit of the source , having chosen two sample values of the present distance of the source from the observer ( 1 kpc and 3 kpc and source moving away from the observer ) . the thick solid lines correspond to the source moving along a vertical orbit intersecting the galactic plane at 10 pc from the observer ( i.e. , the same orbit as in fig . ) , while thin solid lines are obtained in a few cases in which this scale is varied up to 1 kpc for @xmath112 kpc , and to 2 kpc for @xmath113 kpc , or inclining the orbit from vertical to a 45@xmath114 incident angle ; as it can be seen , such cases are essentially equivalent and show that what is actually relevant for the result is how much time the source spend within a distance from the observer corresponding to diffusion length @xmath78 ( with @xmath78 depending on the emission and observation energies ) . such time is about the same for all solid lines , while it changes if the source speed is changed . the dashed and dotted lines refer to the same orbit as for the thick solid line but with a source speed which is , respectively , twice as large and half of it , namely 600 km s@xmath4 and 150 km s@xmath4 versus 300 km s@xmath4 . the dash - dotted lines refer instead to a circular orbit with velocity matching the observed circular velocity , i.e. about 250 km s@xmath4 . for comparison spectral shapes in the static limit are also displayed . the picture emphasizes further the fact that the encounter with a dark matter point - source determines a transient in the local positron flux , and that the static approximation is roughly valid only for nearby sources , for which the energy of the measured positrons is not significantly different from the energy at emission , or for very energetic positrons . we have focussed the discussion on dm sources with a monochromatic positron spectrum , still it can be very simply extended to dm sources with a generic positron emission spectrum ( which can be obviously thought as a superposition of line spectra for different masses and annihilation rates ) , along the same patterns regarding the dependence on distance and energy . as an application of the general discussion outlined in the previous section , and to introduce a focus on a specific case despite the many ingredients and parameters involved in the problem , we consider the possibility of a major contribution from a single non - static dm point - source to the local electron / positron spectrum as recently measured by pamela @xcite and fermi @xcite . final state of annihilation has been considered , as well as two sample values of the dm mass . the fit was performed assuming that the primary electron spectral index and normalization follows from the fermi data.,width=294 ] final state of annihilation has been considered , as well as two sample values of the dm mass . the fit was performed assuming that the primary electron spectral index and normalization follows from the fermi data.,width=294 ] for what concerns the background from ordinary astrophysical electrons and positrons , we will consider two possibilities . in the first scenario , the bulk of the `` all - electron '' spectrum measured by fermi is due to primary electrons emitted in supernova cosmic - ray sources ( with only a mild contamination , at the 10 - 20% level , from secondary electrons and positrons ) , and , hence , we can use this data - set to derive the electron spectral index at the sources . the second possibility is that the fermi measurement has actually found an extra electron and , possibly , positron source , comparable to standard contributions at about 100 gev or so , and dominating at high energy up to the cutoff found by hess at about 1 tev @xcite ; in this second scenario , we assume that the primary electron spectrum is softer and can be inferred from preliminary ( less accurate ) lower energy data on the electron - only spectrum presented by pamela @xcite , while the extra contribution is dominated by a single dm source . starting with the first background choice , we show in fig . [ fig : pamela1 ] ( left panel ) two examples of fits of the pamela positron fraction at high energy with a component due to dm annihilations in a subhalo . the fits have been obtained with sample values of the wimp mass and a given annihilation channel , respectively 500 gev and 1 tev and the monochromatic @xmath103 final state . we have also assumed that the source moves with constant velocity @xmath102 on the trajectory perpendicular to the galactic plane already introduced for fig . [ fig : scal ] . looping over the propagation models discussed in the previous sections , we have extracted the best - fit values for the source distance and the total annihilation rate in the source @xmath68 . for a given propagation model , the background is inferred normalizing the proton flux to the locally observed spectrum , making a prediction for the secondary electron and positron components using the galprop package , and deriving the primary electron spectral index and normalization from the fermi data . including then the dm component , the fit to the pamela , fermi and hess data ( the hess datasets are rescaled within systematic uncertainties to match the normalization from fermi ) is performed allowing for a 20% variation in the normalization of the secondary spectra ( reflecting various uncertainties on their modelling ) and on the primary electrons , as well as a slight tilt in the primary electron spectral index ; the fit disregards pamela datapoints below 10 gev , since the force - field method we are implementing to take into account solar modulation , with modulation parameter of 0.55 gv , is probably not sufficiently accurate , and a modulation which takes into account the charge sign should be implemented instead @xcite . for a given wimp mass , and for all propagation parameters except for the thin halo model ( model b ) , this procedure produces configurations with moderate to small @xmath115 . they are restricted in a rather narrow range of allowed distances ; however this range shifts with wimp mass , choice of the propagation model and the velocity of the source along the orbit . the parameters for the two sample models obtained from the fit and plotted in fig . [ fig : pamela1 ] are given in the first two rows of table [ tab : fit ] . .sample dm models [ cols="^,^,^,^,^,^,^,^,^ " , ] , and that the primary electron spectral index is slightly harder than the one you would infer from the fermi data.,width=294 ] , and that the primary electron spectral index is slightly harder than the one you would infer from the fermi data.,width=294 ] analogously , fig . [ fig : pamela1b ] shows two sample fits of the data in the case of a primary electron spectral index slightly softer , according to the picture mentioned at the beginning of this section . since we need to account for a positron / electron exotic contribution up to 1 - 2 tev , dm wimps needs to be rather heavy ( e.g. , we take 5 tev and 3 tev ) , while the choice of the annihilation channel is again not critical ( we chose to refer to the case of pair annihilation into the @xmath116 final state ) . the results from the fit are reported in the last two rows of table [ tab : fit ] . a few issues should be stressed looking at this table . first , for all the four selected models , the @xmath115 indicate fairly good fits , although not exceptionally good ( one should also take into account that , especially for fermi , errors in the data - set are correlated , while we have simply added in quadrature statistical and systematic errors ) ; our interest is , however , to show the feasibility of the framework , rather than playing with all possible uncertainties in the background and the signal to improve the fits further ( and indeed a slight readjustment of the background could lead to better fits in all cases ) . a second issue is that the values which we find for the total annihilation rate @xmath68 are very large for all models , as one sees converting them to the annihilation volume @xmath70 under the hypothesis that the annihilation cross section is of the order @xmath117 @xmath118 s@xmath4 ( this is , roughly speaking , the level needed for a thermal relic wimp to match the dm density in the universe in case of standard assumptions for the universe thermal history , and without invoking an enhancement in the cross section going from the freeze - out to the zero temperature limit , see , e.g. , @xcite ) . annihilation volumes of the order of @xmath119 kpc@xmath120 are much larger than typical values predicted for dm substructures in n - body simulations of hierarchical clustering for milky - way size dm halos , with a realization probability for a configuration containing these sources , supposing one can extrapolate from the results shown in ref . @xcite for static sources , below few in @xmath121 . on the other hand , in a different scenarios , such as the one in which the adiabatic formation of an intermediate mass black hole drives a sharp enhancement of the dark matter density inside the hosting substructure @xcite , the probability density of @xmath70 for these sources has a peak at about @xmath122 kpc@xmath120 and a tail extending to much larger values @xcite . there is also the possibility that the reference value @xmath117 @xmath118 s@xmath4 is a significant underestimate of the pair annihilation cross section , and in this case @xmath70 would be appropriately downscaled . having shown that it is not manifestly implausible to interpret current positron / electron data within the single dm substructure scenario , the examples chosen for figs . [ fig : pamela1 ] and [ fig : pamela1b ] question the standard methods applied to extract model - independent informations on the dm candidate : it is usually assumed that interpreting an excess as a dm signal gives an estimate of the dm particle mass when the energy threshold for the excess is detected , that the spectral shape of the excess determines the dominant annihilation channel , while the normalization is mainly an indicator of the level of the pair annihilation rate . here , instead , the threshold is just setting a lower limit to the dm particle mass , since the energy at which the exotic component dies out depends also on the distance of the dm point - source . regarding the shape of the spectrum , we have shown that this is a transient , keeping little memory of the spectrum at the source , and indeed , in the plot , the spectral shapes of the single source contribution and that from the smooth dm halo component are sensibly different in all examples . finally , the level of the induced flux depends mainly on the product @xmath123 , and it is difficult to give any solid estimate for the annihilation volume @xmath70 . derived from the pamela data on the positron ratio and fermi data on the all electron flux . a sample wimp model is considered ( @xmath105 gev and monochromatic @xmath124 final state ) , while we loop over propagation model configurations ( left panel ) and a few possibilities for the point source orbit ( right panel ) . results are compared to the level of @xmath68 required to match either the brightest unidentified egret source , the faintest source detected by egret and the level of the @xmath125-ray sensitivity for fermi.,width=294 ] derived from the pamela data on the positron ratio and fermi data on the all electron flux . a sample wimp model is considered ( @xmath105 gev and monochromatic @xmath124 final state ) , while we loop over propagation model configurations ( left panel ) and a few possibilities for the point source orbit ( right panel ) . results are compared to the level of @xmath68 required to match either the brightest unidentified egret source , the faintest source detected by egret and the level of the @xmath125-ray sensitivity for fermi.,width=294 ] in table [ tab : fit ] , we quote the prediction for the gamma - ray flux , integrated above 100 mev , induced by the dm point - source in the four selected models : in the first two cases , with only monochromatic @xmath126 as tree - level final state of annihilation , the flux is due to photons emitted as a final state radiation ( fsr ) , with the rate and photon energy distribution for the @xmath127 which are estimated in terms of the lowest order process @xmath128 and in the approximation for @xmath129 ( see , e.g. , @xcite and references therein ; an eventual model - dependent `` internal bremsstrahlung '' contribution @xcite is not included here ) . for the last two cases , the annihilation into @xmath130 gives rise to decay chains containing neutral pions , which in turn decay to two photons ; this process is accounted for by linking to the pythia montecarlo simulations as provided by the darksusy package @xcite . the level of the integrated gamma - ray fluxes , slightly above @xmath131 @xmath132 s@xmath4 , is much lower than the one for the brightest unidentified egret source , i.e. about @xmath133 @xmath132 s@xmath4 , or the level of the faintest source detected by egret , i.e. about @xmath134 @xmath132 s@xmath4 @xcite ( in a more detailed comparison one should consider also the fact that the energy spectra for the sources proposed here are sensibly softer than typical spectra for egret sources ) , but well within the sensitivity for the fermi lat instrument , about @xmath135 @xmath132 s@xmath4 considering intermediate to high latitudes and a 2 year data taking period @xcite ( again we are not taking into account spectral features , and also the fact that the sensitivity we quote for a dm signal was computed based on a gamma - ray background as extrapolated from egret gev measurements of the diffuse gamma - ray emission which are not being confirmed by fermi and will have to be sensibly lowered , see , e.g. , @xcite ) . this is a trend we see in general . derived from the pamela data on the positron ratio and fermi data on the all electron flux . the left panel is specular to the right panel of fig . , but for the @xmath136 final state . in the right panel the mass scale for the dm candidate is varied and a few sample values of the distance for a source moving away from the observed along a vertical orbit are considered . results are compared to the level of the @xmath68 required to match either the brightest unidentified egret source , the faintest source detected by egret and the level of the @xmath125-ray sensitivity for fermi.,width=294 ] derived from the pamela data on the positron ratio and fermi data on the all electron flux . the left panel is specular to the right panel of fig . , but for the @xmath136 final state . in the right panel the mass scale for the dm candidate is varied and a few sample values of the distance for a source moving away from the observed along a vertical orbit are considered . results are compared to the level of the @xmath68 required to match either the brightest unidentified egret source , the faintest source detected by egret and the level of the @xmath125-ray sensitivity for fermi.,width=294 ] in fig . [ fig : epluslimit1 ] , we compute the upper limit to the total annihilation rate @xmath68 from the pamela data on the positron ratio and from the fermi data on the `` all - electron '' flux ( limits are extracted separately for the two datasets , allowing for extra freedom in the background normalization and spectral index ; the most stringent one is displayed ) . these constraints are compared to the values of @xmath68 corresponding to an integrated @xmath125-ray luminosity at the level of the brightest unidentified egret source , of the faintest source detected by egret and of the fermi @xmath125-ray sensitivity . we have chosen a benchmark wimp model , with @xmath105 gev and annihilating into monochromatic @xmath124 . we display the results for : _ i ) _ the reference vertical orbit and different propagation models ( left panel , the displayed cases are the same as in fig . [ fig : scal ] , see the relative discussion in the text ; the values of @xmath80 refer to the distance of the point source from the observer at the time when the positron flux is measured , after the source has passed in the neighborhood of the observer ) ; _ ii ) _ the reference propagation model ah and a few possibilities for the point - source orbit ( right panel , the sample orbits are a subset of those considered in fig . [ fig : scal2 ] ; negative @xmath80 refers to an approaching source , positive @xmath80 to a source moving away from the observer ) . in the right panel of fig . [ fig : epluslimit1 ] , we also sketch the error that can be induced by estimating positron constraints assuming the stationary limit . dotted curves refer to static point - sources and show ( making the comparisons with the appropriate color coding ) that the bounds , except for nearby sources , are systematically overestimated for approaching sources and greatly underestimated for sources moving away from the observer . clearly , the gamma - ray luminosity of a point - source scales with @xmath137 . the scaling with distance , or better with time , of the local positron flux depends on many different ingredients which are hard to extract from observations . the picture , however , is intuitively clear : unless the dm point - source is extremely close to the observer inducing a very large gamma - ray flux ( at a level which can be already excluded by egret ) , it can generate a substantial contribution to the electron / positron flux measured by pamela and fermi , without being in conflict with present gamma - ray observations . in particular , we expect , for intermediate distances , the balance to lean towards the electron / positron side since there is a time interval during which electrons / positrons go through a diffusion transient while the gamma - ray intensity decreases as the inverse of time squared . when the diffusion transient is over and the local positron population becomes negligible , i.e. at large positive distances in the plot , the gamma - ray limit takes over again . on the other hand , if a substantial contribution to the positron flux measured by pamela is actually due to a dm point source , it is unlikely that such source will not be detected by fermi in @xmath125-rays . this does not necessarily mean that it will be identified as a dm source . indeed , fermi will measure spectra only up to about 300 gev and spectral features might not be easily identifiable , as well as the cross correlation with the positron flux is not anymore unambiguous , as we already stressed . these conclusions do not depend critically on the wimp model , as we show in fig . [ fig : epluslimit2 ] . in the left panel , we consider the same configurations of the right panel in fig . [ fig : epluslimit1 ] , but now for a wimp model annihilating into @xmath136 . in this case , the @xmath125-ray yield is enhanced ( being the @xmath138-decay channel open ) and the electron / positron yield is softer ; still , at intermediate distances , a picture inducing a sizable local flux of positrons is not in conflict with the egret observations , but again within the fermi @xmath125-ray sensitivity . in the right panel of fig . [ fig : epluslimit2 ] , we show the constraints on @xmath68 obtained considering a few values for the source distance ( still moving away from the observer on a vertical orbit with a velocity of 300 km s@xmath4 ) and varying the wimp mass . the interplay between electron / positron and gamma - ray observations is changing only slightly with mass , while it is again evident that the static approximation may be misleading . and for different values of the distance @xmath80 of the source at the time of observation . in the left panel , the source is getting closer to the observer . in the right panel , the source , after passing in the vicinity of the observer , is moving away . a wimp mass of 500 gev and pair annihilations into @xmath139 have been assumed , as well as the propagation model a. for comparison , spectral shapes for a static source at the corresponding distances and for pair annihilations in the smooth dm halo are also shown.,width=294 ] and for different values of the distance @xmath80 of the source at the time of observation . in the left panel , the source is getting closer to the observer . in the right panel , the source , after passing in the vicinity of the observer , is moving away . a wimp mass of 500 gev and pair annihilations into @xmath139 have been assumed , as well as the propagation model a. for comparison , spectral shapes for a static source at the corresponding distances and for pair annihilations in the smooth dm halo are also shown.,width=294 ] we focus now the discussion on the possibility that dark matter pair annihilations within a substructure give rise to an antiproton yield . this is possible if the final states of annihilation include weak gauge bosons or quarks , instead of leptons only , as we considered so far . analogously to the positron case , in the limit of a point - like dark matter substructure , the antiproton source function takes the form : q_|p ( , t , e ) = ^3 , [ eq : pointsourcepb ] where @xmath140 is the differential antiproton yield per annihilation and @xmath68 is the total dark matter annihilation rate in the source already introduced above . solving the propagation equation with this source function , we find the corresponding number density per unit energy : n(r , e , t ) = _ -^t dt_0 g(r , t , e;_p , t_0 ) , where the green function @xmath74 is given in appendix [ app : pbar ] . as for positron , it is instructive to consider its approximate form by neglecting boundary conditions ; assuming at first that also antiprotons annihilations in the gas disc along propagation play a minor role , @xmath74 goes like : g , [ eq : pbgreensimply ] where the diffusion length depends explicitly on time : @xmath141 . suppose for simplicity that the substructure is moving along a straight line trajectory with constant velocity @xmath61 , namely @xmath142 ; in this case @xmath74 can be rewritten in the form : g [ eq : pbgreensimply2 ] where we have introduced a `` static '' timescale @xmath143 , with @xmath144 being the distance between the point - source and the observer at the time of observation ( which would be , of course , the distance between the point - source and the observer at all times in the static limit ) , and a `` dynamical '' timescale @xmath145 , and we have defined @xmath146 as the cosine of the angle between the vectors @xmath61 and @xmath147 ( which is negative for a source approaching the observer and positive for those moving away ) . we recognize that @xmath148 and @xmath149 are the appropriate quantities to compare for a first guess on whether proper motion is relevant or not in estimating antiproton fluxes from point sources ; in particular , eq . ( [ eq : pbgreensimply2 ] ) can be integrated over time , giving : _ -^t dt_0 g . [ eq : pbgreensimply3 ] in the limit for @xmath150 , this expression correctly reduces to the green function of the three dimensional laplacian , while for @xmath151 we see that proper motion starts to become important . for typical values of the propagation parameters in the model , we find : = 1.5 , where @xmath152 is antiproton energy in units of 10 gev and @xmath153 is the source distance in units of 1 kpc . as for the positrons , we find the effect of proper motion to be negligible either in the limit of nearby sources or going to high energies , while we expect it to be significant in the other cases . actually , eq . ( [ eq : pbgreensimply ] ) and ( [ eq : pbgreensimply2 ] ) contain an oversimplification , since they were derived neglecting antiprotons annihilations during propagation , an effect which defines a third timescale that could also be relevant : depending on energy , the antiproton loss via annihilation can be much larger than the leakage from the boundaries of the diffusion region . when including this extra timescale , the expression for @xmath74 becomes less transparent ; we show instead results for a few sample cases obtained by implementing the exact green function . in fig . [ fig : pbscal1 ] , we plot the spectral shape for the local antiproton flux from a source moving along the reference trajectory , namely a path perpendicular to the galactic plane and intersecting it at a short distance from the observer , with the source moving at constant velocity @xmath102 . we have also chosen the propagation model a , and defined the dark matter model through a sample value for the wimp mass , @xmath105 gev , and assuming that the annihilation is dominantly into @xmath139 pairs . as in the previous plots , @xmath80 refers to the distance of the source from the observer at the time of observation and is used instead of a time variable to compare more easily to the static limit ( dotted curves in the plot ) . there is a evident transient at small and intermediate energies , soon after the source has entered the diffusion region ; the spectrum starts to fully match the static limit case only when the source arrives very close to the observer . moving away from the observer , the scaling with distance is less severe than in the static limit and a contribution to the local antiproton flux persists much later than the time at which the source has left the propagation region ( the vertical boundary is at @xmath30 kpc in model a ) . since high energy antiprotons diffuse more efficiently , at late times the spectral shape becomes steeper and starts again to differ sensibly from the shape of the component due to pair annihilations in the smooth dark matter halo ( dash - dotted line in the plot ) . note that the latter , contrary to the positron case , traces rather closely the shape of static point - sources . pc and to the scaling with distance of the companion induced gamma - ray flux , i.e. @xmath137 . @xmath139 annihilation channel is considered ( giving rise at the same time to antiprotons , positrons and photons ) and three sample values of the wimp mass @xmath62 . the antiproton and positron fluxes are plotted at the energies @xmath154 which are equal to @xmath155 ( left panel ) and @xmath156 ( right panel).,width=294 ] pc and to the scaling with distance of the companion induced gamma - ray flux , i.e. @xmath137 . @xmath139 annihilation channel is considered ( giving rise at the same time to antiprotons , positrons and photons ) and three sample values of the wimp mass @xmath62 . the antiproton and positron fluxes are plotted at the energies @xmath154 which are equal to @xmath155 ( left panel ) and @xmath156 ( right panel).,width=294 ] ( 200 gev and 1 tev ) and two sample energies @xmath154 ( equal to @xmath155 and @xmath156 ) , and assuming pair annihilations into @xmath139 . in the left panel , the results refer to the standard vertical trajectory and to our three benchmark propagation models a , b & c ( intermediate , thin - halo & thick - halo , see text for details ) . in the right panel , for the propagation model a , the color coding refers to different orbits , namely three vertical trajectories with velocities of the source changing from 300 to 600 or 150 km s@xmath4 , and a circular orbit in the galactic plane with velocity matching the local circular velocity 250 km s@xmath4 . , width=294 ] ( 200 gev and 1 tev ) and two sample energies @xmath154 ( equal to @xmath155 and @xmath156 ) , and assuming pair annihilations into @xmath139 . in the left panel , the results refer to the standard vertical trajectory and to our three benchmark propagation models a , b & c ( intermediate , thin - halo & thick - halo , see text for details ) . in the right panel , for the propagation model a , the color coding refers to different orbits , namely three vertical trajectories with velocities of the source changing from 300 to 600 or 150 km s@xmath4 , and a circular orbit in the galactic plane with velocity matching the local circular velocity 250 km s@xmath4 . , width=294 ] the @xmath139 annihilation channel is a copious source of positrons and gamma - rays ( mainly from the production and decay of pions ) . in fig . [ fig : pbscal2 ] , we compare the scaling with distance ( i.e. time ) of the locally measured antiproton and positron fluxes at an energy corresponding to a fraction of the wimp mass ( 1/5 and 1/50 , respectively , in the left and right panels ) for three sample values of @xmath62 . both antimatter fluxes are normalized to the scaling with distance of the induced gamma - ray emission , which goes simply like @xmath137 . the ratio between charged - particle fluxes to the gamma - ray flux increases rapidly around @xmath157 since the local number density of positrons and antiprotons decreases less severely when the distance from the source is smaller than the corresponding diffusion length . at negative @xmath80 , i.e. for a source approaching the observer , one can see again the transients due to the fact that the source has just entered the diffusion region ; these transients are essentially specular in the two cases . on the other hand , the contribution to the local antiproton population tends to survive much longer than for the positron component . when the source is moving away , the antiproton flux scales , at least at intermediate distances and except for very energetic antiprotons , like @xmath137 ; positrons have instead much sharper transients , due to the efficient energy loss term . [ fig : pbscal2 ] has been obtained for the reference propagation model ( ah , with the `` h '' labeling the energy loss configuration for positrons only ) and the reference trajectory . as for the positrons , we expect the results for the antiproton flux to depend on the choice of the propagation parameters and the orbit for the point source . this is illustrated in fig . [ fig : pbscal3 ] : in the left panel , we show the scaling of the locally measured antiproton flux with distance considering two sample wimp masses , two sample energies and the benchmark trajectory , while looping over the three reference propagation models . the main effect here is due to the increase in the diffusion coefficient going from model b to model a and then to model c , as well as to the boundary conditions , entering more critically for the thin - halo model b ( @xmath158 kpc ) ; note , however , that even for model b a sizable contribution to the local flux may be due to sources which are well outside the diffusion region and that would not be included in the static limit treatment . in the right panel of fig . [ fig : pbscal3 ] , we consider instead a few of the orbits that we have already introduced to discuss positron fluxes , with the pattern for source velocities which is analogous here ; note that in the circular orbit case the transient following a close encounter can be sufficiently long lasting for the induced antiproton population to persist up to the next close encounter ( what we plot is the `` equilibrium '' configuration after a couple of full orbits ) . finally , in fig . [ fig : pbscal4 ] , we summarize the picture by comparing , for a wimp model with @xmath139 annihilation channel , the constraints on the total annihilation rate which are set by the latest measurements by pamela of the antiproton to proton ratio @xcite , the electron / positron measurements by pamela and fermi , as well as searches for point @xmath125-ray sources by egret . projected limits for the fermi @xmath125-ray telescope are also shown . analogously to the case of the smooth dm halo component , we find for a dm substructure contribution that if wimp annihilates in a channel in which antiprotons are copiously emitted , the measured antiproton flux sets tighter constraints than electron / positron data , except possibly for extremely heavy dm candidates . this trend is reinforced going to larger distances . the information from egret is inconclusive , while fermi is going to cover most , if not all , the parameter space currently probed by antiproton or positron searches . the displayed results refer to a source moving along the reference vertical trajectory , approaching or moving away from the observer ; however , analogous conclusions hold for other configurations . the extension to other wimp annihilation channels also leads to similar results . derived from the pamela data on the antiproton fraction ( solid lines ) , pamela data on the positron ratio and fermi data on the all electron flux ( dash - dotted curves ) . the source is moving along the reference vertical trajectory and is approaching the observer ( left panel ) or moving away from the observer ( right panel ) . results are compared to the level of the @xmath68 required to match either the brightest unidentified egret source , the faintest source detected by egret and the level of the @xmath125-ray sensitivity for fermi.,width=294 ] derived from the pamela data on the antiproton fraction ( solid lines ) , pamela data on the positron ratio and fermi data on the all electron flux ( dash - dotted curves ) . the source is moving along the reference vertical trajectory and is approaching the observer ( left panel ) or moving away from the observer ( right panel ) . results are compared to the level of the @xmath68 required to match either the brightest unidentified egret source , the faintest source detected by egret and the level of the @xmath125-ray sensitivity for fermi.,width=294 ] radiative emissions are unavoidably associated to electron / positron yields ; in particular , the inverse compton ( ic ) radiation component due to the interaction of high energy electrons on optical starlight is peaked in the range between tens to hundreds of gev and may be sizable for the intense dark - matter lepton emitters we have been considering . the ic photon emissivity is obtained by folding , at any given point within the diffusion region , the ic emission power with the electron / positron number density , see , e.g. , @xcite : j_ic(,,t)=2^m__m_ede p_ic(,e , ) n(,e , t ) , [ eqjic ] where the ic power is given by : p_ic(,e , ) = chd ( , ) ( , , e ) v [ eqpic ] where @xmath159 is the energy of the target photons , @xmath160 is their differential energy spectrum and @xmath161 is the klein nishina cross section . the spatial dependence and spectrum of the number density of starlight photons can be computed from photometric maps of the galaxy ; we will adopt the model implemented in the public release of the galprop numerical package @xcite . on the other hand , the analytic solution introduced in section [ sec : positronpoint ] for computing the electron / positron number density @xmath6 was obtained assuming a spatially constant electron / positron energy loss term , and , hence , also a mean value for the background starlight density , rather than its value as a function of the spatial coordinates . this should not be regarded as a severe inconsistency , since the ic on starlight is just one of the effects contributing to the energy loss term , which main uncertainty is related to synchrotron emission on background magnetic fields . having computed the ic emissivity field as in eq . [ eqjic ] , the relative @xmath125-ray flux for a local observer is obtained simply by summing contributions along the line of sight . -ray spectra for a dm point - source composed by 500 gev wimps annihilating into monochromatic electrons and positrons , and moving along the reference vertical trajectory . the solid lines refer to the ic emissivity and are computed for three different directions of observation labeled by the latitude @xmath162 ( the longitude is @xmath163 ) ; dashed lines refer to the fsr component in the direction of the source , while dotted lines show the galactic @xmath125-ray background . the dm signals are computed for three sample distances of the source , assuming that , for each distance , the normalization of the total annihilation rate in the source is the maximum allowed by current pamela and fermi electron / positron data , see the limits derived in fig . . ] an example is given in fig . [ fig : ic ] , where we refer again to the model introduced at the beginning of the discussion , namely a point source composed by 500 gev wimps annihilating into monochromatic electrons and positrons and moving on a vertical orbit intersecting the galactic plane at a short distance from the observer , see figs . [ fig : scal ] and [ fig : epluslimit1 ] . the propagation scenario considered is the ah model ( recall that in this model the vertical scale height of the diffusion region is 4 kpc ) and the time variable is again replaced by the distance from the observer . having assumed a velocity of the point source of 300 km s@xmath4 , we consider three sample cases , i.e. @xmath164 kpc with the source that has passed close to the observer and is now moving away . the induced ic flux ( solid lines ) is shown for three different directions of observation , all at the longitude @xmath163 ( i.e. opposite to the galactic center ) , with latitude @xmath165 ( the direction towards the point source in our example ) , @xmath166 or @xmath167 . we plot also the background level corresponding to the emission from galactic cosmic - rays ( dotted lines ) computed with galprop , and the dm - induced @xmath125-ray component due to fsr at the source ( which is obviously present only in the direction of the dm substructure ) . the normalization of the total annihilation rate , or of the annihilation volume , has been chosen by saturating the current limits from pamela or fermi , see the results in fig . [ fig : epluslimit1 ] . this explains the relative strength of the fsr components . one can see that the ic flux in the direction of the source can be as large as the fsr contribution ( for @xmath168 ) or even larger ( for @xmath111 kpc ) . most notably , the spatial size of the ic emission is significant , inducing a signal larger than the background even tens of degrees away from the source . consider , however , that the case displayed here is the most favorable , since the source is located in the portion of the sky with the faintest galactic background , and we have not included the uncertain extragalactic component . for @xmath169 kpc , i.e. for the source outside the diffusion region , the ic term drops dramatically . this is due to the fact that there is no fresh source of high energy electrons and positrons , and the ones injected along the transit of the source through the diffusion region have rather rapidly degraded their energy . therefore , there is no efficient high energy source to up - scatter starlight photons to @xmath125-ray frequency . the trend is probably exaggerated by the fact that we are assuming a sharp boundary for the propagation region , while a smoother boundary condition would be certainly more physical and would probably lead to a smoother transition between the cases , @xmath111 kpc to the @xmath169 kpc . from the sample case discussed , we can infer that it is rather likely that if the local positron flux receives a sizable contribution from a single point - source , the induced ic flux is a relevant target for the fermi @xmath125-ray telescope . a more thorough discussion about this point is delayed to an upcoming dedicated analysis . as pointed out by recent analyses ( see e.g. , @xcite ) , a single nearby point - like source ( e.g. , a pulsar ) , being the dominant local positron source at high energy , induce an anisotropy which could be at a detectable level . in this section , we reconsider this possibility in the context of dm substructure . we take into account proper motion effects , which are not relevant for bursting - like sources as pulsars . we assume the dominant contribution to the anisotropy to be given by the dipole term . in order to detect an anisotropy along a certain direction at a good confidence level , the required number of events has to be very large . therefore , although the anisotropy in the positron spectrum would be higher than in the total electron plus positron spectrum , we refer to the latter , being the detection prospects for fermi much more promising than for pamela . if the anisotropy is dominated by the dipole term , the intensity at a given point as a function of the direction of observation has only one maximum . the degree of dipole anisotropy can be defined by the quantity @xmath170 , where @xmath171 and @xmath172 are the maximum and minimum @xmath173 intensity with respect to direction . expanding the intensity in spherical harmonics up to the dipole term , we have : @xmath174 , where @xmath175 is the angle with respect to the direction of maximal anisotropy , @xmath176 , and @xmath177 and @xmath178 are angle - independent coefficients . note that contrary to the case of a stationary point - source ( with homogeneous and isotropic propagation parameters ) , the @xmath179-dependent terms of the dipole are not null . although the direction of maximal anisotropy ( chosen , e.g. , as the @xmath180-axis ) is , in general , unknown , we can define the particle flux @xmath181 along such direction by integrating over all the possible directions the projection over @xmath180 of the intensity , i.e. , @xmath182 , and by estimating it as @xmath183 . the latter is obtained in the diffusion approximation @xcite , but it is valid at first order ( i.e. , for small anisotropies ) also when including energy losses . moreover , we assume the anisotropies in directions orthogonal to @xmath180 to be subdominant ( i.e. , @xmath184 ) . by equating the two expressions for @xmath181 , one gets @xcite : = = , [ eq : anis ] where @xmath185 denotes the contribution to the @xmath173 number density induced by a dm substructure , @xmath186 is the contribution from cosmic - rays , and @xmath187 . neglecting boundary conditions , @xmath188 is given by the gradient of eq . [ eq : epnsol ] : |n_dm(r , p , t)| = ^1/2 , [ eq : anis2 ] with @xmath95 obtained from @xmath189 and @xmath190 for @xmath191 , respectively . . ] we plot in fig . [ fig : anis ] , the degree of dipole anisotropy for the benchmark dm scenarios in table [ tab : fit ] . comparing models 3 and 4 , describing sources at analogous distance and with analogous local spectrum , one can note that , as intuitive , an approaching source would induce a higher anisotropy than a moving - away source ( both on a straight - line trajectory ) . on the other hand , for sources at moderate distance the mismatch is quite small and the picture is similar to the stationary case . the degree of anisotropy is strongly and inversely correlated to the diffusion length ( see eq . [ eq : anis2 ] ) . although the benchmark dm models 1 and 2 induce a very similar local spectrum ( see fig . [ fig : pamela1 ] ) and describe substructures moving away from us on a vertical trajectory at the same velocity , in the second case the electrons and positrons undergo a greater diffusion before reaching us , and the anisotropy is suppressed with respect to the first case . note that the maximum of the curves in fig . [ fig : anis ] occur at larger energy than the peaks in figs . [ fig : pamela1 ] and [ fig : pamela1b ] , being the diffusion and the related wash - out of anisotropies less effective at high energy . the degree of dipole anisotropy for the benchmark models in fig . [ fig : anis ] can be observable by fermi in few years of data taking . on the other hand , the predictions for the anisotropy associated to a dm substructure suffer of many theoretical uncertainties , as in the case of the spectrum , and , depending on the trajectory , the degree of anisotropy can be suppressed or slightly enhanced with respect to an analogous ( i.e. , at analogous distance from the observer ) stationary point - like case . we have discussed the contribution to the local antimatter fluxes due to individual wimp dm substructures , accounting for the substructure proper motion . we have derived analytic solutions to the propagation equation as appropriate for a time - dependent positron and antiproton primary sources , identifying the relevant quantities to discriminate whether proper motion effects are relevant or not . we found that , for both positrons and antiprotons , the static limit is a fair approximation only in the case of high energy particles and nearby sources , while it fails in all other situations . the discussion has involved a few benchmark dm candidates and and a few sample orbits for the substructure . as an application of the general discussion , we focused first on wimps annihilating into leptons only , and we derived sample fits of the pamela positron excess and fermi all - electron data . the fits have been obtained starting from some arbitrary values of the wimp mass , demonstrating that , for a single non - static dm point - source , it is no longer true that one can extract from the data , in a unique way , as extensively done in recent analyses , model independent particle physics observables , such as the dm mass , the annihilation yield and the pair annihilation cross section . indeed , the threshold of the local electron / positron spectrum can not be used as a sure indicator of the dm particle mass , being possibly set by the distance of the dm substructure . the relation between the shapes of the injection spectrum and of the propagated spectrum is not straightforward for a non - static dm substructure , which behaves as a transient source . moreover , the annihilation rate depends on the product of the pair annihilation cross section times the unknown annihilation volume of the substructure , rather than on @xmath192 only . the pamela positron excess can be explained in such a scenario , provided that a large annihilation rate in the substructure is considered . this requires either a large annihilation volume ( much larger than typical values predicted for dm substructures in n - body simulations , but viable for scenarios accounting for the adiabatic formation of an intermediate mass black hole in the substructure ) and/or a pair annihilation cross section significantly enhanced with respect to the reference thermal value . we have then used pamela and fermi electron / positron data to derive , under different configurations , limits to the total annihilation rate in the dm source . these limits have been compared to the bounds extracted from the @xmath125-ray luminosities associated to the same dm models . the general trend is that the @xmath125-ray signal induced by a dm point - source , giving a sizable contribution to the local positron flux , is below the level of the brightest unidentified egret sources , but well above the fermi @xmath125-ray telescope sensitivity . we have also discussed wimp models giving raise to an antiproton yield through pair annihilations in the substructure , as in the case with @xmath193 as final state of annihilation . analogously to the electron / positron case , single dm sources inducing a significant contribution to the local antiproton flux can be detected by fermi in @xmath125-rays ( on the other hand , as for the smooth dm halo component , a positron / electron flux at the level of pamela and fermi data can be hardly obtained in such wimp models without violating antiproton limits ) . finally , we sketched two further features in connection to positron / electron emission from a dm point - 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[ eq : prop_n ] which is valid for a generic non - stationary primary source of electrons and positrons in a disc - like galaxy and with the following simplifying assumptions : we consider a model with diffusion coefficient and energy loss term that are a function of momentum only , while they are assumed to be spatially constant within the cylindrical propagation volume ; we impose free escape at the vertical boundary of the diffusion region ( i.e. that the equilibrium number density vanishes at @xmath194 ) and neglect the radial boundary ( i.e. in the limit of radial size of the diffusion region @xmath29 being much larger than @xmath36 ) . reacceleration and convection are also neglected . in cartesian coordinates eq . ( [ eq : prop_n ] ) becomes : = q(r , p , t ) + d(p ) n - p ( n ) [ eq : eplus_point ] the solution described here is a generalization of the one derived in ref @xcite to the case of diffusion coefficient @xmath25 and momentum gain / loss term @xmath195 which are generic function of the particle momentum @xmath66 ; the notation we use is hence analogous to that of @xcite . we start by introducing @xmath196 , and solve the equation for @xmath197 rather than for @xmath6 , using the green function method and neglecting at first the vertical boundary condition : - + g - g p = ( r - r_0 ) ( t - t_0 ) ( p - p_0 ) . [ eq : eplus_green1 ] going to the fourier transforms in the variables @xmath198 and @xmath67 , we find : |g = e^ikr_0+it_0 ( p - p_0 ) . [ eq : eplus_green2 ] the solution of this equation is easily derived replacing the electron / positron momentum @xmath66 with a double change of variables : = -_p^p_max ^2 = 4 _ _ 0^d d ( ) = - 4 _ p^p_0 d , and considering first the case @xmath199 . the physically relevant solution vanishes for @xmath200 since we will not include energy gain effects , but only energy losses ( i.e. , the term @xmath201 in the equations above is negative ) ; we find : |g = |g_0 e^ , where we defined @xmath202 and the constant @xmath203 is obtained integrating eq . ( [ eq : eplus_green2 ] ) around @xmath204 : - . |^p_0+_p_0- = |g_0 = e^ikr_0+it_0 . taking now the inverse fourier transform , we find the green function : g_free ( r , t , p;_0,t_0,p_0)= ( ( t - t_0)- ) , where it is now manifest to recognize @xmath78 as a diffusion length scale and @xmath81 as an energy loss timescale ; the subscript `` free '' was added to the green function since we have not included the vertical boundary condition yet . this is implemented with the image charge method , i.e. having defined @xmath205 , and having factorized the green function as @xmath206 , @xmath207 is given by : g_zb - ti ( r , p;_0,p_0)= _ n=-^+ ( -1)^n ; [ eq : epgzbti ] it is easy to verify that @xmath208 . the density per unit energy is then : n(r , p , t ) = -_-^+dx_0 _ -^+dy_0 _ -h_h^+h_h dz_0 _ -^t dt_0 _ p^p_max dp_0 g_zb(r , t , p;_0,t_0,p_0 ) q(_0 , t_0,p_0 ) . in case the source @xmath10 is point - like , such as the point - like dark matter substructure in eq . ( [ eq : pointsource ] ) , entering the diffusion region at the time @xmath58 , the density per unit energy becomes the expression in eq . ( [ eq : epnsol ] ) , or equivalently takes the form ( which is the one we use for numerical calculations ) : n(r , p , t ) = _ t_i ^t dt_0 | the numerical inversion of the relation @xmath209 . finally , we just remark that in case of a stationary diffuse electron / positron source , @xmath210 reduces to the familiar expression derived in the literature @xcite ( again generalized to @xmath25 and @xmath195 which are arbitrary functions of @xmath66 ) : n(r , p ) = -_-^+dx_0 _ -^+dy_0 _ -h_h^+h_h dz_0 _ p^p_max dp_0 g_zb - ti ( r , p;_0,p_0 ) q(_0,p_0 ) , i.e. for a stationary axisymmetric source ( i.e. for @xmath211 with @xmath212 the radial variable in a cylindrically symmetric system ) : n(r , p ) = _ p^p_max _ 0^r_h dr_0 _ 0 ( ) _ -h_h^+h_h dz_0 _ n=-^+ q(r_0,z_0,p_0 ) , where we introduced the function @xmath213 , with @xmath214 the modified bessel function of first kind . analogously to the positron case , we sketch here a solution to eq . [ eq : prop_n ] which can be applied to a generic non - stationary primary source of antiprotons . we assume again that the propagation region is a cylinder and that the diffusion coefficient is spatially constant within it ; we impose free escape as vertical boundary condition , while neglecting the boundaries in the radial direction . we still do not include reacceleration and convection , as well as energy losses give a negligible effect for antiprotons . we include instead the antiproton absorption effect , assuming it is mainly due to a thin gas disk , with gas target density constant in space and localized at @xmath28 . in cartesian coordinates eq . ( [ eq : prop_n ] ) becomes : = q(r , e , t ) + d(e ) n- p(e ) ( z ) n [ eq : pbar_point ] with the term accounting for @xmath215 losses due to collisions with the interstellar medium being @xmath216 , where @xmath217 is half of the gas disc height , and the gas disk is assumed to be made of hydrogen with constant density @xmath218 . the solution sketched here is analogous to the one presented in ref . @xcite in a different context . it is derived through the green function method , neglecting at first the vertical boundary condition : d(e ) ( + + ) - p(e ) ( z ) g - g t = - ( r - r_0 ) ( t - t_0 ) [ eq : pbar_green1 ] the following steps are to take the fourier transforms in the @xmath219 and @xmath220 directions , i.e. @xmath221 : d(e ) - d(e ) k^2 |g - p(e ) ( z ) |g - |g t = - e^ik_xx_0+ik_yy_0 ( z - z_0 ) ( t - t_0 ) [ eq : pbar_green2 ] with @xmath222 , and to make a laplace transformation in the @xmath67 variable , i.e. @xmath223 : d - ( d k^2 + s ) - p(e ) ( z ) = - e^ik_xx_0+ik_yy_0-st_0 ( z - z_0 ) [ eq : pbar_green3 ] away from @xmath28 and @xmath224 , the equation takes the form : - ^2 = 0 with @xmath225 ; the three solutions in the three distinct regions ( i.e. the region between @xmath226 and @xmath227 , and those below and above it , setting the appropriate boundary conditions at @xmath228 ) are matched to find @xmath229 imposing its continuity and that ( as one derives integrating eq . ( [ eq : pbar_green3 ] ) around @xmath224 and @xmath28 ) : d .|^z_0+_z_0- + e^ik_xx_0+ik_yy_0-st_0 = 0 d .|^0+_0- - p(e ) ( z=0 ) = 0 . one finds @xmath230 , where @xmath231}{p / d+2\omega } \frac{\left| sign(z)-sign(z_0)\right|}{2 } \nonumber \\ & & + \left\{\frac{\exp\left[-\omega\left|\left| z \right|-\left| z_0 \right|\right|\right]}{2\omega } -\frac{p / d\;\exp\left[-\omega\left(\left| z \right|+\left| z_0 \right|\right)\right ] } { 2\omega\,(p / d+2\omega ) } \right\ } \frac{\left| sign(z)+sign(z_0)\right|}{2}\ , . \label{eq : prop_f2}\end{aligned}\ ] ] this expression can be inverted analytically to recover @xmath74 . one can take first the inverse laplace transform and find : |g = e^ik_xx_0+ik_yy_0-(k_x^2+k_y^2 ) _ p^2/4 g(z , t;z_0,t_0 ) with : g(z , t;z_0,t_0 ) - ( + ) , where we defined : @xmath141 and @xmath232 . finally , taking the inverse fourier transform we find the green function : g_free ( r , t;_0,t_0)= g(z , t;z_0,t_0 ) where the subscript `` free '' was added since we did not include the vertical boundary condition yet . as for the positron case , this is implemented with the image charge method , i.e. having defined @xmath205 , the green function is : g_zb ( r , t;_0,t_0)= _ n=-^+ ( -1)^n g(z_n , t;z_0,t_0 ) . note that the expression we found is analogous to eq . [ eq : epgzbti ] for positrons ; actually switching off antiproton annihilations ( i.e. setting @xmath233 ) the two expressions are formally identical , except that the definition of diffusion length here is different from the diffusion length introduced for positrons , with time appearing explicitly in @xmath234 for antiprotons rather then implicitly through the momentum loss as in the @xmath78 for positrons . the density per unit energy is then : n(r , e , t ) = _ -^+dx_0 _ -^+dy_0 _ -h_h^+h_h dz_0 _ -^t dt_0 g_zb(r , t , e;_0,t_0 ) q(_0 , t_0,e ) .

the local antimatter fluxes induced by an individual dark matter ( dm ) substructure can be significantly dependent on the proper motion of the source . we derive analytic solutions to the propagation equation for time - dependent positron and antiproton primary sources , finding that the static limit is a fair approximation only for very high energy particles and nearby sources . we discuss weakly interacting massive particle ( wimp ) models fitting the pamela positron excess and the fermi all - electron data . we show that , for a single non - static dm point - source , one can not extract from the data , in a unique way , model independent particle physics observables , such as the wimp mass , the pair annihilation cross section , and the annihilation yield . the gamma - ray emission associated to wimp models inducing a significant local flux of positrons or antiprotons is found to be compatible with egret measurements , but it can be definitely singled out with the fermi - lat telescope .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Transition-to-Success Mentoring Act''. SEC. 2. TRANSITION-TO-SUCCESS MENTORING PROGRAM. (a) Authorization of Appropriations.--Section 1803 of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6553) is amended to read as follows: ``There are authorized to be appropriated to carry out this part $50,000,000 for fiscal year 2012 and such sums as may be necessary for each succeeding fiscal year.''. (b) Transition-to-Success Mentoring Program.--Part H of title I of such Act (20 U.S.C. 6551 et seq.) is amended by adding at the end the following: ``Subpart 3--Transition-to-Success Mentoring Program ``SEC. 1831. TRANSITION-TO-SUCCESS MENTORING PROGRAM. ``(a) In General.--From the amounts appropriated to carry out this section, the Secretary shall award grants to eligible entities to establish, expand, or support school-based mentoring programs to assist eligible students with the transition from middle school to high school. ``(b) Application.--To receive a grant under this section, an eligible entity shall submit an application to the Secretary at such time, in such manner, and containing such information as the Secretary may require. ``(c) Uses of Funds.-- ``(1) Required uses of funds.--An eligible entity that receives a grant under this section shall use the grant funds to establish a mentoring program, or expand or support an existing mentoring program, in all middle schools served by the entity, under which each eligible student enrolled in such schools is assigned to a success coach who-- ``(A) creates a plan for success for the student that-- ``(i) is reviewed with the student and teachers and parents of the student; ``(ii) includes, for each academic year, the student's academic, personal, and career exploration goals, and a strategy on how to accomplish such goals; and ``(iii) identifies the student's strengths, weaknesses, and academic progress; ``(B) enters into a signed, written agreement with the parents of the student that describes how the parents should assist the student in carrying out the plan for success; ``(C) meets with the student at least once per month to-- ``(i) assist the student in achieving the goals under the plan for success; ``(ii) identify the student's academic areas of weaknesses, provide the student with the tools necessary to develop the student's potential for academic excellence, and ensure the student's successful transition from middle school to high school; and ``(iii) in the case of a student with behavioral issues, assist the student in behavior management techniques; ``(D) at least quarterly, meets with the student and the parents, teachers, or counselors of the student to-- ``(i) evaluate the student's progress in achieving the goals under the plan for the current academic year; and ``(ii) revise or establish new goals for the next academic year; and ``(E) serves as the student's advocate between the teachers and parents of the student to ensure that the teachers and parents understand the student's plan. ``(2) Authorized uses of funds.--An eligible entity that receives a grant under this section may use such funds to-- ``(A) develop and carry out a training program for success coaches; and ``(B) cover the cost of any materials used by success coaches under the mentoring program. ``(d) Grant Duration.--A grant under this section shall be awarded for a period of 5 years. ``(e) Reporting Requirements.-- ``(1) Eligible entities.--An eligible entity receiving a grant under this section shall submit to the Secretary, at the end of each academic year during the grant period, a report that includes-- ``(A) the number of students who participated in the school-based mentoring program that was funded in whole or in part with the grant funds under this section; ``(B) data on the academic achievement of such students; ``(C) the number of contact hours between such students and their success coaches; and ``(D) any other information that the Secretary may require to evaluate the success of the school-based mentoring program. ``(2) Secretary.-- ``(A) Interim report.--At the end of the third fiscal year for which funds are made available to carry out this section, the Secretary shall submit to Congress an interim report on the success of the school-based mentoring programs funded under this section that includes the information received under paragraph (1). ``(B) Final report.--At the end of the fifth fiscal year for which funds are made available to carry out this section, the Secretary shall submit to Congress a final report on the success of the school-based mentoring programs funded under this section that includes the information received under paragraph (1). ``(f) Definitions.--In this section: ``(1) At-risk student.--The term `at-risk student' means a student who has been identified as a student who has below a 2.0 grade point average or the equivalent and who may-- ``(A) be at-risk of academic failure; ``(B) be dropping out of school; ``(C) have a drug or alcohol problem; ``(D) be pregnant or a parent; ``(E) have come into contact with the juvenile justice system in the past; ``(F) have limited English proficiency; ``(G) be a gang member; ``(H) have dropped out of school in the past; or ``(I) have a high absenteeism rate at school. ``(2) Eligible entity.--The term `eligible entity' means-- ``(A) a local educational agency that-- ``(i) receives, or is eligible to receive, funds under part A of title I; or ``(ii) is a high-need local educational agency; or ``(B) a partnership between a local educational agency described in subparagraph (A) and a nonprofit, community-based organization. ``(3) Eligible student.--The term `eligible student' means a student who-- ``(A) is enrolled in a middle school served by an eligible entity; and ``(B) is an at-risk student. ``(4) High-need local educational agency.--The term `high- need local educational agency' has the meaning given to the term in section 2102(3)(A). ``(5) Middle school.--The term `middle school' means a nonprofit institutional day or residential school, including a public charter school, that provides middle school education, as determined under State law, except that the term does not include any education below grade 6 or beyond grade 9. ``(6) School-based mentoring.--The term `school-based mentoring' refers to mentoring activities that-- ``(A) are closely coordinated with a school by involving teachers, counselors, and other school staff who may identify and refer students for mentoring services; and ``(B) assist at-risk students in improving academic achievement, reducing disciplinary referrals, and increasing positive regard for school. ``(7) Success coach.--The term `success coach' means an individual who-- ``(A) is-- ``(i) an employee of a local educational agency in which a mentoring program receiving support under this section is being carried out; or ``(ii) a volunteer from a nonprofit, community-based organization that provides volunteers for mentoring programs in secondary schools; and ``(B) prior to becoming a success coach-- ``(i) received training and support in mentoring from an eligible entity; and ``(ii) underwent a screening by an eligible entity that included-- ``(I) appropriate job reference checks; ``(II) child and domestic abuse record checks; and ``(III) criminal background checks.''.

Transition-to-Success Mentoring Act - Amends title I of the Elementary and Secondary Education Act of 1965 (ESEA) to reauthorize appropriations under part H (School Dropout Prevention). Establishes a transition-to-success mentoring program under part H of the ESEA requiring the Secretary of Education to award five-year grants to local educational agencies (LEAs) or partnerships between LEAs and community-based nonprofit organizations to establish, expand, or support school-based mentoring programs to assist at-risk students in transitioning from middle to high school. Requires grantees to assign to each at-risk student in his or her middle school a success coach who: (1) creates a plan of success for the student; (2) enters into an agreement with the student's parents regarding their role in implementing such plan; (3) meets with the student at least once a month to assess and assist the student's progress; (4) meets at least quarterly with the student and the student's parents, teachers, or counselors to evaluate the student's progress and revise or establish new goals for the next academic year; and (5) serves as the student's advocate between the student's parents and teachers. Authorizes the use of grant funds to train success coaches and cover the cost of any materials they use under the mentoring program.

the majority of the total baryonic matter in the local ( @xmath17 ) universe is predicted to be concentrated in highly ionized gas . structures that are already virialized contain warm ( @xmath18 k ) or hot ( 10@xmath19 k ) gas [ the dense interstellar medium ( ism ) of galaxies , and the intracluster medium ( icm ) of clusters of galaxies ] . the greater amount of baryonic matter is predicted to lie in , as yet unvirialized , matter in the form of a tenuous warm - hot intergalactic medium ( whim , hellsten et al . , 1998 ) . the detection and study of these components is needed for the proper understanding of large and small scale structures in the universe . however , while x - ray emission from the virialized density peaks of the icm and ism has been detected and intensively studied in x - rays , the predicted highly ionized gas in the whim has been poorly studied so far , due to instrumental limitations . the low density of the whim leads to low emissivity , so that studies of the whim in emission are a formidable challenge . however , absorption depends only on the total column density of the medium , not on density , and background light sources in the form of quasars ( aldcroft et al . , 1994 ) and gamma - ray bursts ( fiore et al . 2000 ) are readily available . a few high ionization transitions , notably ovi @xmath201031.93 , lie in the uv , but the most prominent ions ( cvi , ovii , oviii , neix ) have their strongest transitions in the soft x - ray band ( 10 - 40 ) for a wide range of temperatures ( @xmath21 k , nicastro et al . , 1999 ) , which should give rise to an `` x - ray forest '' of absorption lines ( e.g. perna & loeb , 1998 , fang & canizares , 2000 ) . the advent of high resolution ( @xmath221000 ) soft x - ray spectroscopy with _ _ and xmm-_newton _ allows sensitive studies of the whim possible . interstellar ovi was first detected in the uv with the _ copernicus _ satellite ( jenkins , 1978a , 1978b , and york , 1977 ) , but only recently has data from the _ far ultraviolet spectroscopic explorer _ ( fuse ) satellite shown the presence of extragalactic ovi intervening absorpion ( e.g. tripp et al . , 2001 , sembach et al . , 2000 ) . in this paper we present the first x - ray detection of highly ionized absorption along the line of sight towards the blazar pks 2155 - 304 , with the _ chandra _ hrcs - letg ( _ high resolution camera spectrometer_-_low energy transmission grating _ : brinkman et al . , 2000 ) . we argue that the physical and dynamical conditions implied by these lines require an extragalactic , low density , origin . hence these lines are the first detection of the x - ray forest . the bright z=0.116 blazar pks 2155 - 304 ( falomo , pesce , & treves , 1993 ) is a calibration source for both the high energy and low energy resolution gratings of _ chandra _ , and has been observed several times with all the possible grating - detector configurations . the longest of these observation lasted @xmath23 ks , for a total net good - time exposure of 62.7 ks , and was performed with the hrcs - letg configuration on 1999 december 25 . in the public _ data archive we found two more hrcs - letg observations of this source , performed on 2000 may 31 , and 2001 april 6 , with net exposures of 25.8 ks and 26.6 ks respectively . we retrieved the primary and secondary data products ( fabbiano et al . , 2001 , in prep . ) of these three _ chandra _ hrcs - letg observations of pks 2155 - 304 , and reprocessed their event files with the _ ciao _ ( elvis et al . , 2001 , in prep . ) software ( v. 2.1.3 ) using the most up - to - date calibration files as of 2001 august ( caldb v. 6.2 ) to extract source and background spectra and corresponding 1st - order anciliary response files ( arfs ) and redistribution matrices ( rmfs ) according to the on - line data analysis `` threads '' provided by the _ chandra x - ray center _ ( cxc ) . during the long 1999 december observation the source was at the particularly high flux level of 21 mcrab , with a 0.3 - 6 kev flux of @xmath24 erg s@xmath8 @xmath25 . in both the subsequent hrcs - letg observations , instead , the flux level of pks 2155 - 304 was more normal at about 6 mcrab in the 0.3 - 6 kev band . however , despite the large change in flux , the spectral shape of the underlying 0.3 - 6 kev continuum did not change significantly between or during the three observations ( using simple power law continuum models , we measured variations in the spectral slope to be less than @xmath26 at 90 % confidence level ) . to increase the signal to noise ratio of our data , we then coadded the three hrcs - letg spectra and averaged the corresponding arfs , weighting them by the respective exposure times . the result ( figure 1a ) is one of the highest quality _ chandra _ grating spectra so far for an extragalactic source , with some 600 counts , or a signal to noise ratio of about 25 , per resolution element ( r@xmath27 , fwhm @xmath28 660 km s@xmath8 at 20 ) in the continuum , over the entire 10 - 25 wavelength ( @xmath29 kev ) range . to ensure a self - consistent analysis , and because of the @xmath30 times higher spectral resolution provided , we also retrieved the fuse ( moos et al . , 2000 ) data of pks 2155 - 304 from the fuse public archive , extracted the fluxed spectrum , and analyzed the wavelength range around ovi ( 1027 - 1035 ) and oi ( 1037 - 1040 ) to obtain independent estimates of the positions , widths and equivalent widths of the local ovi@xmath31 and oi@xmath32(@xmath33 ) components , recently discovered and published by savage et al . ( 2000 ) and sembach et al . the fuse observation was taken with the lwrs aperture ( @xmath34 ) with a total exposure time of 38.6 ks , and covers the entire 980 - 1180 range . we used data from the lif mirror and the a1 detector segment , which have optimal efficiency in the waveband around the ovi line . the data were calibrated and cleaned following the procedures presented in the fuse data analysis cookbook ( v. 1.0 , sankrit et al . , 2001 ) . the resolution of the final data is @xmath35 km s@xmath8 . we performed simultaneous spectral fitting of both the fluxed fuse data and the responses - folded _ chandra _ hrcs - letg data , using the _ sherpa _ ( siemiginowska et al . , 2001 , in prep . ) package for spectral fitting in _ ciao_. in the following two sections we summarize our results . for sources of a few mcrab the inherent order confusion problem of the _ chandra _ hrcs - letg ( brinkman et al . , 2000 ) is important only at @xmath36 . furthermore , narrow features , such as absorption lines , are not in any case seriously affected . so we limited our spectral analysis to the shorter wavelengths of 11 - 24 ( @xmath29 kev ) range , allowing us to use only the 1st - order rmfs and arfs , to fit our spectra . errors throughout the paper are quoted at a 90 % confidence level , for 1 interesting parameter . to model the 11 - 24 portions of the continuum of pks 2155 - 304 , we used a power law attenuated by an equivalent hydrogen column density of @xmath37 @xmath25 neutral gas to account for the measured galactic absorption from cold gas along the line of sight to this source ( dickey & lockman , 1990 ) , the local damped ly@xmath38 absorption line in the hst - stis spectrum of pks 2155 - 304 can not provide a better estimate of the galactic column of neutral h along this line of sight . ] . the model used for the neutral absorber includes only photoelectric edges by neutral elements , and so does not account for resonant absorption lines from the same elements . we obtained a statistically acceptable fit with a power law photon index of @xmath39 , consistent previous results ( e.g. kataoka et al . , 2000 ) . the residuals to this fit clearly show ( at a significance level greater than 8 @xmath3 ) two strong and unresolved ( see 3.1 ) features in absorption ( fig . 1b , d ) , at wavelengths consistent with the ovii@xmath4 and the neix@xmath4 resonant lines at zero velocity , plus a third intense oi@xmath40 resonant absorption line from gaseous oi ( fig . negative residuals are also present at the energy of the instrumental resonant molecular oi absorption line ( fig . the residuals around the expected oviii@xmath4 and the ovii@xmath9 rest - frame wavelengths also show absorption features at a lower ( @xmath41 ) significance level ( fig . 1e , see 3.1 ) . we added six negative gaussians to our continuum model , and refitted the data , leaving the positions and the total flux of all the gaussians free to vary independently , but linking all the widths ( in units of km s@xmath8 ) of the high ionization resonance lines from o and ne . the best fitting line parameters values are listed in table 1 , along with the derived ion column densities for all the atomic transitions . we also include in table 1 2@xmath3 upper limits on the equivalent widths of the two lines of nex@xmath4 and neix@xmath9 , which we derived by adding two more gaussians to our model , freezing their positions to the rest - frame wavelengths of these transitions and calculating the errors on the lines normalizations . .*best fitting uv and x - ray absorption line parameters * [ cols="^,^,^,^,^,^,^ " , ] @xmath42 absorption line ew are formally negative ; here we drop the sign . @xmath43 frozen . @xmath44 krause , 1994 . the strong solid - state instrumental oi line at @xmath45 (fig . 1a , c ) , is only partly accounted for by the current effective area model ( fig . 1c , dashed curve ; see also table 1 ) and is easily separated by the hrcs - letg from the gas phase oi@xmath40 resonant transition at @xmath46 ( krause , 2001 ) , which is also clearly visible in our data ( fig . 1c ) , and will be object of study of a forthcoming paper . here we stress only how the intervening galactic cold absorber is clearly distinguished from the highly ionized intervening medium seen through the he - like and h - like resonant lines from o and ne ( table 1 ; see also 3.1 for differences in the dynamics ) . we also used _ sherpa _ to fit the 1027 - 1035 portion of the fuse spectrum of pks 2155 - 304 around the strongest line of the ovi@xmath47 doublet , at @xmath48 . residuals after a fit with a power law continuum model , show resolved ovi@xmath47 absorption in these data , with at least two components present ( figure 2 ) . we added two negative gaussians to our best fit continuum model . the fit shows that one line is relatively narrow ( fwhm @xmath12 km s@xmath8 ) and slightly redshifted ( @xmath49 km s@xmath8 in the rest frame ) , and the other is broader ( fwhm @xmath14 km s@xmath8 ) and blueshifted ( @xmath15 km s@xmath8 ; see table 1 ) . these values are consistent with those reported by savage et al . ( 2000 ) and sembach et al . ( 2000 ) . * we looked for ly@xmath38 absorption associated with these two components , but verified that they both would fall well within the voigt wings of the damped ly@xmath38 due to cold absorption in our own galaxy , and are so not visible . * the fuse spectrum of pks 2155 - 304 also shows the presence of strong oi@xmath50(@xmath33 ) absorption ( see figure 1 in sembach et al . , 2000 ) . for this line we measure @xmath51 ( @xmath52 km s@xmath8 ) and fwhm of @xmath53 km s@xmath8 , much narrower than the width of either of the ovi@xmath50 components . to intercompare the dynamics of the gas producing the detected absorption lines , figure 3 shows their residuals , in velocity space , from the fuse and _ chandra _ spectra to their best fitting continuum models . zero velocities in this diagram correspond to the rest frame wavelengths of the detected transitions ( verner et al . , 1996 , krause , 1994 ) . the spectral resolution of the hrcs - letg ( r@xmath27 , fwhm @xmath28 660 km s@xmath8 at 20 ) does not resolve the high ionization x - ray absorption lines ( see table 1 ) . the spectral resolution of the fuse spectrometer ( @xmath54 , fwhm @xmath28 20 km s@xmath8 at @xmath55 ) is more than one order of magnitude larger than that of the _ chandra _ hrcs - letg , and is sufficient to resolve the ovi@xmath56 absorption into at least two components ( figure 3a ; table 1 ) . the total width of the ovi@xmath47 complex in the fuse spectrum is fwhm=264@xmath57 km s@xmath8 , fully consistent with the upper limit on the width of the high ionization x - ray lines ( table 1 ) . we also note that both position and width of the oi@xmath32(@xmath33 ) absorption line in the fuse spectrum , are clearly different from widths and positions of each of the two ovi components in the same spectrum ( fig . 3a , f ) , but again fully consistent with width and position of the oi@xmath58 line in the _ chandra _ spectrum ( fig . 3f , c , table 1 ) . we then conclude that : ( a ) the high ionization lines , both in the uv and x - rays are likely to be produced by gas with similar dynamical properties , and broad range of dispersion velocities ( from the uv profile ) , while ( b ) the low ionization atomic oi lines ( both in fuse and _ chandra _ ) are produced by a slow - moving cloud of cold gas , with relatively low internal dispersion velocity , and so differs dramatically in both physical and dynamical properties from the high ionization gas . in the following we discuss only the highly ionized component . absorption lines equivalent widths ( ews ) , and their ratios , can in principle provide invaluable information on the physical state of the gas , and allow one to distinguish between quite different scenarios . however these diagnostics can only be applied to unsaturated lines . fortunately the uv ovi@xmath47 lines are clearly not saturated , since the ratio between the ews of the doublet ( @xmath59 and @xmath60 ) , is fully consistent with the oscillator strengths ( oss ) ratio of 2 ( savage et al . , 2000 ) . for the x - ray lines of ovii , oviii and neix , in principle , one could compare the ews of the corresponding k@xmath38 and k@xmath61 lines . however , the errors on the ews of the k@xmath61 lines from these ions are too large . an alternative approach uses the curve of growth ( cog ; e.g. spitzer , 1978 ) , computed for a given doppler parameter , to see whether each line falls on the linear branch of the cog . we ran our model for resonant absorption ( nicastro , fiore and matt , 1999 ) to produce cogs for the ovi@xmath31 , the ovii@xmath4 , the oviii@xmath4 doublet , and the neix@xmath4 . we assume a doppler parameter of b=200 km s@xmath8 , since this is the observed @xmath3 of the ovi@xmath47 complex . the cogs are plotted in figure 4 , along with the maximum possible measured ews ( best fit + 2@xmath3 ) of each line ( ews are plotted in absolute value ) . for the ovi@xmath31 complex we considered the total ew from the two best fit gaussians . all the lines ews fall well within the linear branches of their cogs . hence the lines are not saturated , and the resulting column densities , listed in table 1 , should be reliable . . the fuse and _ chandra _ spectra of pks 2155 - 304 contain absorption features from local intervening ionized gas that span a broad ionization interval , from neutral ( oi ) , through mildly ionized ( ovi , ovii ) , to highly ionized ( ovii , oviii and neix ) . the neutral and the ionized components have very different dynamical and physical properties and so must belong to two different , spatially separated , systems . the profile of the ovi complex in the fuse spectrum suggests that the ionized component is also made up of at least two different absorbers : one slow - moving , with relatively low internal dispersion velocity and possibly associated with a cloud in the galactic disk , and one moving towards us with a velocity of about 150 km s@xmath8 ( @xmath62 km s@xmath8 transforming from the heliocentric to the galactic standard of rest frame ) and with a similar internal dispersion velocity and possibly associated either with an ionized high velocity cloud in the galactic halo , or with a whim filament . in the next sections we demonstrate that neither pure collisional ionization nor pure photoionization models can account for the presence of strong ovii and neix absorption with the observed intensity of the ovi lines , unless the three absorbers ( one x - ray and the two uv ) are associated with three different galactic clouds with drastically different equilibrium conditions ( with temperatures differing by an order of magnitude ) , and so locations . alternatively we show that if there is one highly tenuous absorber , then the photoionization contribution by the diffuse x - ray background becomes important and can change the internal ion abundance distribution to account for all the uv and x - ray observational constraints in a single absorbing medium . these solutions however , imply path lengths of the order of several mpc , and so definitively locate the uv - x - ray absorber in the intergalactic medium ( igm ) , beyond our galaxy on a scale of the local group , or somewhat bigger . for the photoionization contribution by the diffuse , extragalactic x - ray background , we adopt an euv to @xmath63-ray spectral energy distribution [ i.e. the specific flux @xmath64 given by a broken power law with an exponential high energy cutoff ( i.e. @xmath65 e^{-(e / e_f)}$ ] , with @xmath66 for @xmath67 , @xmath68 for @xmath69 , @xmath70 , @xmath71 , @xmath72 kev , and @xmath73 kev ; we also adopt a low energy cutoff at energies lower than the hydrogen ionization threshold @xmath74 ) . we assume a normalization of 10 ph s@xmath8 @xmath25 kev@xmath8 sr@xmath8 , at 1 kev ( parmar et al . , 1999 , boldt , 1987 , and fabian & barcons , 1992 ) . following the hellsten et al . ( 1998 ) parameterization for the redshift evolution of the x - ray background , we can write the ratio between the diffuse background ionizing photons density and the electron density of a filaments at redshift z ( i.e. , the ionization parameter u ) as : @xmath75 n_e^{-1 } \int_{\nu_{hi}}^{+\infty } d\nu 4 \pi ( f_{bkg}(\nu ) / h\nu ) \simeq 1.4 \times 10^{-7 } n_e^{-1 } ( 1 + z)^3 = 0.7 \delta^{-1 } ( \omega_b h^2 / 0.02)^{-1},\ ] ] where @xmath76 is the frequency of the h ionization threshold . in eq . [ uxrb ] we defined the local igm overdensity compared with the mean density of the universe , @xmath77 , as @xmath78 , where @xmath79 @xmath80 ( hellsten et al . , 1998 ) . hence , for typical overdensities of @xmath81 ( hellsten et al . , 1998 , dav et al . , 2000 ) , we expect , at any redshift , @xmath82 , for @xmath83 ( walker et al . , 1991 ; h = 0.5 ) . given the flat x - ray spectrum of the x - ray background , xrb photoionization greatly modifies the ionic distribution of a purely collisionally ionized gas at temperatures lower than logt @xmath84 , for electron densities of @xmath85 @xmath80 ( @xmath86 ) . photoionization is not important at typical ism densities of @xmath87 to 1 @xmath80 ( e.g. spitzer , 1990 ; but see 4.5 for alternative ionizing sources ) . we ran cloudy ( vs. 90.04 , ferland , 1997 ) to build models for temperatures ( in k ) from logt = @xmath88 and densities @xmath89 @xmath80 . figure 5 shows the ratios between the predicted ionic abundances of ovii / ovi ( black curves ) , oviii / ovi ( green curves ) , oviii / ovii ( red curves ) and neix / ovii ( blue curves ) . solid curves are for @xmath90 @xmath80 , while long - dashed curves correspond to @xmath91 @xmath80 ( i.e. @xmath92 ) . the thick sections of the lines delimit the 2@xmath3 allowed intervals given the measured relative ion column densities derived from the corresponding ews ( see table 1 ) , using the formula - valid only when the lines are not saturated - @xmath93 ( nicastro , fiore , & matt , 1999 ) , where @xmath94 is the relative abundance of the element x , compared to h , and @xmath95 is the relative density of the ion @xmath96 of the element @xmath97 . figure 5 uses the total measured ew for the ovi@xmath47 complex ( i.e. narrow and broad components combined ) . according to the above formula , the ratio between equivalent widths of two lines from two different ions of the same element , then , depends only on the ratio of the corresponding equivalent widths . instead , for ions from different elements , the relative ion densities are proportional to the inverse of their relative metallicity ( i.e. @xmath98 ) . for the neix / ovii ratio ( blue lines ) we show allowed regions for a solar ne / o ratio ( magenta , dotted line , delimited by perpendicular tickmarks ) and for 2.5 times solar ( [ ne / o]@xmath99 , grevesse & anders , 1989 , grevesse & noels , 1993 . blue , dashed line ) . this values are discussed in 4.3 . let us consider first the galactic `` high - density '' solutions , for which the gas is in pure collisional ionization equilibrium . the ratio of ovii@xmath4 to the entire ovi@xmath56 uv complex ( thick solid black curve ) sets a quite stringent upper limit of logt @xmath100 ( t in k ) on the allowed temperature of the ovi - ovii absorber , if both the lines are produced by the same material . however , the oviii and neix ions are clearly too highly populated to be consistent with the intensities of the ovi and ovii lines , requiring logt@xmath101 , and so no common solution exists for all the lines . we find that this is true for any @xmath102 @xmath80 . let us now consider the extreme extragalactic `` low - density '' ( @xmath91@xmath80 ) solution ( fig . 5 , thick long - dashed curves ) where photoionization by the diffuse xrb overionizes the medium . these conditions allow the oxygen ovi , ovii , and oviii ions to have a common temperature ( shaded region in fig . 5 ) for the relatively low temperature range @xmath103 logt @xmath104 . a consistent solution for even the oxygen lines , requires the absorber to be highly tenuous ( @xmath105 @xmath80 ) . a solar ne / o ratio ( magenta , dotted intervals ) is not consistent with these conditions , but a ne / o ratio of @xmath106 times solar ( blue , dashed interval ) provides consistency for all the ions ( see 4.7 ) . increasing the ne / o metallicity ratio decreases the neix / ovii relative density ratio estimated from the corresponding measured ew ratio - see 4.2 - and so lets the thick intervals in figure 5 shift toward the left on the theoretical @xmath107 curve , down to the region where a common solution for all the ions can be found . for a given temperature , we can derive the equivalent h column density of this gas . assuming ne / o = 2.5 and logt = 5.45 gives @xmath108_{\odot}^{-1}$ ] @xmath25 . this translates , for a constant electron density of @xmath109 @xmath80 , to a linear size of the absorbing cloud of gas of @xmath110_{\odot}^{-1}$ ] mpc , consistent with a filament with an overdensity of @xmath111 located in the intergalactic medium near to our galaxy . for o abundances of 0.3 @xmath112 ( as found in clusters of galaxies , sarazin , 1988 ) the size would increase to @xmath113 mpc ( @xmath16 % of the distance to pks 2155 - 304 , and @xmath114 % of the distance to the first group of galaxies close to our line of sight to the blazar : penton stocke , & shull , 2000 ) . the above discussion is based on the hypothesis that both the broad and narrow components of the ovi absorption complex are produced by a single , structured , absorber that is also producing the x - ray absorption . here we explore alternative multi - component solutions . let us suppose that only one of the two ovi@xmath47 absorption lines in the uv spectrum , is associated with the x - ray absorber . the broader ovi line contributes about 1/3 to the total observed equivalent width from the ovi system , while the remaining 2/3 are provided by the narrower line ( see tab . 1 ) . based on the strengths of the ovi@xmath47 lines and on the above discussion , it is then natural to associate the broader uv component with the x - ray absorber . in this case the narrow and more intense ovi component would be produced by a galactic cloud of moderately ionized gas in collisional equilibrium . this `` narrow '' line gas must have a temperature of logt@xmath115 if the size of the cloud is not to exceed 1 kpc , the size of a big halo cloud ( e.g. spitzer , 1990 ) , given the measured ew and assuming a maximum galactic ism density of @xmath116 @xmath80 . the upper limit on the temperature , instead is set by the observed ew(ovi@xmath117/ew(ovii@xmath4 ) ratio , and this gives logt@xmath118 . the second absorber should instead produce the broader and weaker ovi line , and all the x - ray lines . we tested this hypothesis by building a diagram similar to that in fig . 5 , but considering a variable fraction ( from 0 to 1 ) of the ew of the broad ovi@xmath47 line ( figure 6 ) . we find that equilibrium , high density solutions exist only if a fraction of 5 to 25 % ( at 2@xmath3 ) of the broad ovi line is produced by the same gas producing the x - ray absorption . these solutions are limited to a range of temperatures around logt=6.4 , whose width depends on the relative [ ne / o ] abundance : @xmath119 for [ ne / o]@xmath120 ( dashed regions in fig . 6 ) . for logt = 6.4 and [ ne / o]@xmath121 , we find @xmath122_{\odot}^{-1}$ ] , and so a linear size of @xmath123_{\odot}^{-1}$ ] pc , for @xmath90 @xmath80 . since only 25 % of the broad ovi@xmath47 can come from x - ray absorbing gas , a third _ ad hoc _ galactic absorber similar in dynamical properties to the absorber imprinting the broad ovi@xmath47 line , but with temperature differing by at least an order of magnitude from the temperature of the uv - x - ray absorber , is required to explain the remaining broad ovi absorption . alternatively , a highly structured and , again , _ ad hoc _ multi - temperature plasma , with at least two zones separated by a sharp front , and with the same kinematics , would be needed to account for all the observed uv and x - ray lines . we can broaden the range of allowed temperature and increase the fraction of ovi absorption produced by the x - ray absorber , by allowing both the ne / o ratio to be supersolar , and the gas density to be lower than @xmath124 @xmath80 . however this converges to the extragalactic solution ( 5.2 ) . we find that an acceptable solution with a minimum size is obtained for logt = 5.7 , @xmath125 ( i.e. @xmath126 ) , and ne / o = 2 , which gives @xmath127_{0.3\times\odot}^{-1}$ ] @xmath80 and @xmath128_{0.3\times\odot}^{-1}$ ] mpc . as we have demonstrated ( 4.1 , 4.3 ) x - ray photoionization is needed to modify the ion relative abundance distribution from the pure collisionally ionized case ( with logt = 5.3 - 5.7 ) , to allow for the simultaneous presence of ovi , ovii and oviii , and also neix . in order for the photoionization contribution to play a significant role , the ionization parameter has to be of the order of @xmath129 ( 4.1 ) . since the ionization parameter . @xmath130 , is simply the ratio between the number density of ionizing photons and the electron density of the gas , @xmath130 increases as either the electron density in the gas decreases ( as in the igm case ) or the distance between the source of ionizing photons and the gas cloud decreases . so high values of u might also be reached in gas with typical ism densities ( i.e. @xmath131 @xmath80 ) illuminated by other , discrete and locally much brighter hard x - ray sources than the xrb . in this section we explore this second possibility . based on the needed value of @xmath129 we can put constraints on the brightness of the ionizing source as seen by us , and on the angular separation between the source and the gas cloud . let us consider an intervening cloud of gas located at a distance @xmath132 from us , along a given line of sight , and an ionizing source , located at a distance @xmath133 from us . let @xmath134 be the distance between the ionizing source and the gas cloud . we can write : ( a ) @xmath135 ; ( b ) @xmath136 ; and ( c ) @xmath137 . in the above equations , @xmath138 is the source luminosity , and @xmath139 and @xmath140 are the source fluxes as seen by us and the gas cloud respectively . these two fluxes are related to each other through the source - gas angular separation @xmath141 : @xmath142 . the ionization parameter u at the illuminated face of the cloud can then be written as a function of the source flux as seen by us : @xmath143 , where @xmath144 is the total flux of ionizing photons ( @xmath145 ) . to maximize the contribution from hard x - ray ionizing photons we use as the ionizing continuum a cutoff power law with @xmath146 from the h ionization threshold up to 100 kev , and @xmath147 from 100 kev up to infinity . this gives a total flux of ionizing photons of @xmath148 ph s@xmath8 ( where @xmath149 is the observed flux between 2 and 10 kev , and we assumed @xmath150 ) . our value @xmath129 then gives : @xmath151 . for @xmath152 arcmin and gas densities in the ism range @xmath153 @xmath80 , then , the 2 - 10 kev observed flux must be as large as @xmath154 erg s@xmath8 @xmath25 ( @xmath155 crab ) , to efficiently ionize the gas . for a 30 times smaller separation , this fluxes reduce to @xmath156 erg s@xmath8 @xmath25 ( @xmath157 crab ) . no such source is currently seen . for halo distances of 30 kpc the implied 2 - 10 kev luminosities are @xmath158 erg s@xmath8 ( @xmath159 pc ) , far too large for any known stellar - size galactic source , and @xmath160 erg s@xmath8 ( @xmath161 pc ) , just about the maximum observed luminosity for the most luminous known ultra - luminous - x - ray sources ( ulxs ) or beamed microquasars . for the much closer distances of galactic disk objects , say , 10 pc , these luminosities reduce to more normal values for x - ray binaries ( i.e. @xmath162 erg s@xmath8 , and @xmath163 erg s@xmath8 ) but the physical separations between the source and the gas cloud become very small : @xmath164 pc and @xmath165 pc respectively . so , either very luminous sources , or very close source - to - gas systems are needed to efficently ionize a tenuous gas cloud in our galaxy to the observed degree . we searched the rosat - wgacat ( white , giommi , & angelini , 1994 ) for bright x - ray sources in a 30 arcmin radius cylinder , centered on the line of sight to pks 2155 - 304 . we found 33 unidentified sources plus an f0 star with rosat - pspc count rates between 0.0019 and 0.024 ct s@xmath8 , and angular distances from the line of sight from @xmath166 to @xmath167 arcmin . the closest of these sources to the pks 2155 - 304 line of sight has a count rate of 0.0073 ( source a : 1wga j2158.8 - 3011 ) , while the brightest ( 0.025 ct s@xmath8 ) is at a distance of 15.1 arcmin ( source b : 1wga j2158.2 - 3000 ) . we used pimms to convert these count rates , into flux . to maximize the possible contribution at energies e@xmath168 kev , we assumed a hard x - ray continuum ( a powerlaw with @xmath146 ) heavily absorbed by a column of @xmath169 @xmath25 intrinsic neutral gas . this gave 2 - 10 kev fluxes of @xmath170 erg s@xmath8 @xmath25 ( @xmath171 crab ) , for source a , and @xmath172 erg s@xmath8 @xmath25 ( @xmath173 crab ) for source b , at least ( i.e. using @xmath174 @xmath80 ) 4 and 5 orders of magnitude , respectively , lower than the values required to photoionize the gas at these angular separations . let us consider a microquasar highly beamed into the direction of the gas cloud , and whose line of sight to us is somewhat perpendicular to the beam direction . the probability for a microquasar to be beamed in the direction of the gas cloud , and located within a 20 - 130 pc radius sphere from the gas cloud , depends on the distribution of the parent poulation , that , for microquasars , is largely unknown . we can compute here the minimum beaming factor needed , in the above optimal geometrical configuration , for source a or b to efficiently ionize a cloud of gas along the line os sight to pks 2155 - 304 . the luminosity amplification due to beaming , in the direction of the jet , is given by : @xmath175 . the observed luminosity along a perpendicular direction is insted de - boosted by the factor : @xmath176 ( urry & shafer , 1984 ) . in the above equations , @xmath177 is the source intrinsic luminosity , @xmath63 is the lorentzian factor , and @xmath178 ( urry & shafer , 1984 ) . solving for the intrinsic luminosity , and using as maximum value for the beamed luminosity of a microquasar @xmath179 erg s@xmath8 and the observed value of @xmath180 erg s@xmath8 ( for source b , at 30 kpc ) , we obtain a minimum relativistic factor of @xmath181 , to compare with the estimated upper limit of @xmath182 for the microquasar grs 1915 + 105 ( mirabel & rodriguez , 1999 ) . any deviation from the above ideal geometry , would give a much larger lorentz factor . low density gas has long recombination times . a source may thus have been much more luminous in the past and ionized the gas then , from which the gas has not yet recovered . let us first suppose that the most luminous x - ray source we are currently seeing in the rosat archive is a binary system that went through a ulx phase ( king et al . , 2001 ) in the past ( from the calculation in 4.5.1 , for source a and b we need l(outburst)/l(now)@xmath183 , respectively ) . the recombination time for the ovii - oviii ions , in gas with electron density of @xmath90 @xmath80 is of about @xmath184 years ( nicastro et al . , 1999 ) . typical ulx phases are thought to last for @xmath185 years , and in our galaxy the total estimated rate of ulxs is of 1 every @xmath186 years ( king et al . , 2001 ) . so , allowing for a maximum delay of @xmath187 years , we may expect n = 2 ulxs in all the galaxy over a period of @xmath188 years . assuming , for the halo , a 30 kpc radius sphere , this gives a ulx density , over the same period , of n = @xmath189 kpc@xmath190 . so , the maximum number of ulxs expected over a period @xmath191 in a random @xmath192 pc radius sphere in our galaxy ( the physical distances between sources a and b and the line of sight to pks 2155 - 304 , if both sources are put at 30 kpc from us , in the outskirts of the galactic halo ) is of @xmath193 , making prior ionization by a powerful transient source highly unlikely , albeit with _ a posteriori _ statistics . a final possibility is that in the past the center of our galaxy went through an agn phase , producing far higher luminosities and photoionizing any low - density ( @xmath194 @xmath80 ) clouds in the galactic halo . at these densities we have @xmath195 years . let us then suppose that less than @xmath196 years ago the @xmath197 @xmath198 black hole in the center of our galaxy ( chakrabarty & saha , 2001 ) was emitting at its eddington luminosity of @xmath199 erg s@xmath8 . assuming a typical spectral energy distribution ( sed ) for agn ( mathews & ferland , 1987 ) this would produce an ionization parameter of @xmath200 at the surface of @xmath174 @xmath25 halo clouds located at a distance d from the central agn . to produce the observed line ratios , the photoionization contribution must be such that @xmath201 at the illuminated face of such a cloud of gas . this gives a distance for the gas cloud of @xmath202 kpc , consistent with the outermost size of the galactic halo . this solution requires that all halo clouds would show uv and x - ray absorption with similar physical properties as those observed in pks 2155 - 304 . using the much lower luminosities estimated by asca for the central agn in our galaxy about @xmath203 years ago ( i.e. @xmath204 erg s@xmath8 , koyama et al . , 1996 ) , gives distances of 1 - 5 kpc , well within the galaxy s halo , and therefore not consistent with the the galactic coordinates of pks 2155 - 304 ( given our distance of about 10 kpc from the galactic center ) . from our analysis of the combined uv and x - ray data , we conclude that the x - ray absorption and at least the broad ovi@xmath47 are likely to be produced in tenuous extragalactic medium , with @xmath205 @xmath80 . from the position of the ovi@xmath206 and assuming that the feature lies within a few mpc from our galaxy , the gas is falling toward our galaxy with a bulk velocity of @xmath207 km s@xmath8 ( in the galactic standard of rest frame ) . the feature has a dispersion velocity ( @xmath208 km s@xmath8 ) comparable with the bulk velocity , and a temperature of logt@xmath209 . the implied overdensity is @xmath126 and the total linear size of the feature along our line of sight is about @xmath210_{0.3\odot}^{-1}$ ] mpc . the ne / o abundance can be reduced to solar if we allow for inhomogeneities in the flow , since inhomogeneities increase the upper limits on both the temperature and the density , and so also decrease the lower limit on the linear size of the feature ( from 3 @xmath211_{0.3\times\odot}^{-1}$ ] mpc to @xmath212_{0.3\times\odot}^{-1}$ ] kpc ) . such inhomogeneities may arise near our galaxy halo , where the gas may mix with denser medium , cooling and producing part of the observed ovi@xmath206 absorption . the above overdensities and linear sizes are consistent with those predicted for the whim by hydrodynamical simulations for the formation of structure in the local universe ( e.g. hellsten , 1998 ) , and in particular in our local group ( kravtsov , klypin , and hoffman , 2001 ) . according to these simulations , the local igm is concentrated in filaments with overdensities of @xmath213 connecting already virialized structured ( galaxies and clusters of galaxies ) , that were shock - heated during the collapse of the density perturbations . the average sizes of these perturbations are of the order of 30 - 50 mpc in the local universe , but the total extent of the density peaks are usually not larger than a few mpc . the velocities of the matter in these filaments , should be of the order of the proper motions of the virialized structures that they connect , @xmath214 km s@xmath8 . we note that these velocities are of the same order as those observed on the blue side of the structured and complex ovi@xmath47 profile in the uv spectrum of pks 2155 - 304 . we also note that both the dynamics of this gas ( as derived from the ovi line ) and its physical state are very similar to those found ( using uv absorption lines only ) for the intervening ionized absorber along the line of sight to the quasar h 1821 + 643 ( tripp et al . , 2001 ) : internal dispersion velocities of the order of @xmath215 km s@xmath8 ( fwhm of the broad ly@xmath38 line ) , temperature in the range @xmath216 logt @xmath217 ( assuming pure collisional ionization ) , and pathlength of about 3 mpc ( using @xmath218 km s@xmath8 mpc@xmath8 ) . we predict that the planned high resolution and high quality x - ray spectra of this object , should then show ovii@xmath4 absorption with an intensity similar to that found here . in virtually all the cases discussed , the ne / o ratio in the absorber along the line of sight towards pks 2155 - 304 is required to be higher than solar . there are various ways to reconcile with this problem : ( 1 ) type ii supernovae give rise to ne / o ratios much higher than type i supernovae , compared to si ( tsuro et al . , 1997 and references there in ) ; ( 2 ) o can be depleted on to dust grains , but noble gas like ne would not . if superwinds from galaxies are responsible for the enrichment of the igm , then in order to produce high gaseous ne / o ratios compared to solar , they must be able to produce a considerable amount of dust before leaving the high density galaxy environment . ( 3 ) in the modeling above , we have assumed a simple parameterization of ionizing background . the true shape of the background is clearly more complex , and a harder background would result in a large ne / o ratio . any or all of these factors might be playing a role in the observed value of [ ne / o ] . it is important to notice that dust can easily survive at the kinetic temperatures ( i.e. @xmath219 k ) and densities ( i.e. @xmath220 @xmath80 ) of such a warm igm filament . in such regime , the sputtering lifetime is inversely proportional to the gas density , and largely independent from the dust grain composition and gas temperature ( draine & salpeter , 1979a , b ) . the survival time of a small interstellar grain of size @xmath221 @xmath222 m will be larger than @xmath223 yr in the igm filament , and even larger for grains of larger size . we estimated the reddening expected along the line of sight to pks 2155 - 304 , based on ( a ) the observed equivalent h column density , ( b ) the typical size of a silicate dust grain , and ( c ) a typical ism gas / dust ratio . in this condition the estimated e(b - v ) is of about @xmath224 mag , fully consistent with the observations ( schlegel et al . , 1998 ) . finally we note that [ ne / o ] overabundances of @xmath225 , compared to solar , have already been observed in several astrophysical environments ( e.g. paerels et al . , 2001 , brinkman et al . , 2001 ) , strongly suggesting that the non - o - depleted values of this quantity , measured in stelar atmospheres , are not representative of the average gaseous [ ne / o ] ratio in the universe . in this paper we report the first discovery of the `` x - ray forest '' of absorption lines produced by highly ionized intergalactic medium . high significance x - ray absorption lines of ovii , oviii and neix are detected along the line of sight to the bright blazar pks 2155 - 304 , and are associated with a known ovi uv absorber . we demonstrate that the dynamical properties of the x - ray and the uv absorber are fully consistent with each other , and that a reasonable common and self - consistent physical solution can be found only if photoionization and collisional ionization both contribute to the ionization of the absorbing gas . this requires electron densities of about @xmath226 @xmath80 for the diffuse x - ray background to be significant . this low denisty requires a linear size , along the line of sight , of the order of @xmath227_{0.3\times\odot}^{-1}$ ] mpc . this clearly locates the absorber outside our galaxy in intergalactic space . we demonstrate that both the dynamical and physical properties of such an absorber are remarkably consistent with those predicted for the low redshift warm phase of the igm as predicted by hydrodynamical simulations for the formation of structures in the universe . finally we find that solutions with a ne / o ratio of about 2.5 times solar are favored , suggesting type - ii supernova enrichment , or the presence of dust in the igm . aldcroft , t. , elvis , m. , mcdowell , j. , & fiore , f. , 1994 , apj , 437 , 584 + arav , n. , brotherton , m.s . , becker , r.h . , gregg , m.d . , white , r.l . , price , t. , hack , w. , 2001 , apj , 546 , 140 + boldt , e. , 1987 , iau symp . , 124 , observational cosmology , ed . a. hewitt , g. burbidge , & li zhi fang ( dordrecht : reidel ) , 611 . + brinkman , a.c . , et al . , 2000 , apj , 530 , l111b + brinkman , a.c . , et al . , 2001 , a&a , 365 , l324 + dickey , j.m . & lockman , f.j . , 1990 , ara&a , 28 , 215 + draine , b.t . , & salpeter , e.e . , 1979a , apj , 231 , 77 + draine , b.t . , & salpeter , e.e . , 1979b , apj , 231 , 438 + ebisawa , k. , maeda , y. , kaneda , h. & yamauchi , s. , 2001 , to appear in science , astro - 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we present the first x - ray detection of resonant absorption from warm / hot local gas either in our galaxy , or in the intergalactic space surrounding our galaxy , along the line of sight toward the blazar pks 2155 - 304 . the _ chandra _ hrcs - letg spectrum of this z=0.116 source clearly shows , at @xmath0 level , unresolved ( fwhm @xmath1 km @xmath2 at a 2@xmath3 confidence level ) ovii@xmath4 and neix@xmath4 resonant absorption lines at @xmath5 and @xmath6 ( i.e. @xmath7 km s@xmath8 in the rest frame , from the ovii@xmath4 line ) . oviii@xmath4 and ovii@xmath9 from the same system are also detected at a lower significance level ( i.e. @xmath10 ) , while upper limits are set on oviii@xmath9 , nex@xmath4 and neix@xmath9 . the fuse spectrum of this source shows complex ovi@xmath11 absorption at the same redshift as the x - ray system , made by at least two components : one relatively narrow ( fwhm @xmath12 km s@xmath8 ) and slightly redshifted ( @xmath13 km s@xmath8 ) , and one broader ( fwhm @xmath14 km s@xmath8 ) and blueshifted ( @xmath15 km s@xmath8 ) . we demonstrate that the physical states of the uv and x - ray absorbers are hard to reconcile with a single , purely collisionally ionized , equilibrium plasma . we propose , instead , that the x - ray and , at least the broader and blueshifted uv absorber are produced in a low density intergalactic plasma , collapsing towards our galaxy , consistent with the predictions of a warm - hot intergalactic medium ( whim ) from numerical simulations . we find that any reasonable solution requires overabundance of ne compared to o by a factor of @xmath16 , with respect to the solar value . we propose several scenarios to account for this observation .

since the year 1974 , when bound @xmath4 states ( charmonium ) were discovered , they have been thoroughly studied experimentally and theoretically , contributing to better knowledge of the standard model parameters . generally , the theoretical description of charmonium decays requires the knowledge of the perturbative effects in @xmath4 annihilation , and non - perturbative corrections to the charmonium wave function . however , ratios of decay rates into different final states are only sensitive to perturbative qcd contributions . in the present paper we focus on the subset of two - loop perturbative corrections to the ground - state paracharmonium decays @xmath5 and @xmath6 . abelian @xmath7 corrections to both decays are related to the one - loop correction to parapositronium decay by a trivial replacement of coupling constants @xcite . non - abelian one - loop contributions were presented in @xcite . @xmath8 corrections to @xmath5 were discussed in @xcite , but those results did not include light - by - light scattering type contributions . then we calculate these diagrams which form a gauge - independent subset . multiloop corrections in the perturbation theory can be calculated by the asymptotic expansion @xcite . but at the present stage , it is impossible to calculate the two - loop diagrams considered in this paper by the ordinary asymptotic expansions because of the complexity of the diagrams . in order to calculate them we adopt the method of the large mass expansion ( lme ) @xcite . we introduce an artificial large mass m for the internal charm quarks and execute the asymptotic expansion with the mass scale of the external charm quarks @xmath9 ( soft scale ) and the mass scale of the internal charm quarks m ( hard scale ) . when the loop momenta of the internal charm quarks are factorized into the soft scale , we can expand the propagators of the charm quarks by the ratio @xmath10 . the expansions of the propagators reduce the original diagrams to the simpler ones which we can calculate . after that we obtain the results in a series of @xmath10 and identify the artificial mass m with the original one @xmath9 . the present paper is organized as follow . in sec . [ sec2 ] , we review the example of parapositronium decay @xmath11 to demonstrate the method of lme and obtain two - loop qed results . in sec . [ sec3 ] , we adapt the results in the p - ps decay to the paracharmonium decays @xmath12 and @xmath1 , and obtain the two - loop qcd corrections by counting the color factors . in sec . [ sec4 ] , we have a summary . [ [ tree - level - decay - rate ] ] tree - level decay rate + + + + + + + + + + + + + + + + + + + + + two diagrams in fig . [ fig1 ] contribute to the tree level decay . , width=226 ] if we artificially set the mass of the internal propagator @xmath13 ( with electron mass ) , the total @xmath14-annihilation cross section and the p - ps decay rate are calculated in the low momentum limit as @xmath15 where @xmath16 is the electron velocity , @xmath17 , and @xmath18 . here the value of the positronium wave function at the origin is @xmath19 with @xmath20 . making @xmath21 , we obtain the well known p - ps decay rate at the tree level . the same result can be obtained using the optical theorem : @xmath22 , \label{2opti}\end{aligned}\ ] ] where two diagrams @xmath23 and @xmath24 are shown in fig . [ fig2 ] . and @xmath24 are shown . [ fig2],width=264 ] however , we here expand the wick rotated propagator by a large mass m before the loop integral as @xmath25 . the right hand side of eq . ( [ 2opti ] ) is calculated as @xmath26 = \pi \alpha_{e}^{2 } \bigl(8 r^4 -16 r^6 + \cdots \bigr ) , \label{1tg}\end{aligned}\ ] ] which coincides with the first terms in the expansion of eq . ( [ tot2 ] ) . we introduce the gauge parameter in the photon propagator to check the gauge symmetry . in general the introduction of the artificial mass m breaks the gauge symmetry , namely , the ward - takahashi identity . however , when both of electron and positron rest , the gauge symmetry is restored and the result in eq . ( [ 1tg ] ) does not depend on gauge parameter . [ [ two - loop - correction ] ] two - loop correction + + + + + + + + + + + + + + + + + + + we proceed to two - loop contributions involving light - by - light scattering diagrams . we calculate the corrections @xmath27 to the leading order cross section @xmath28 through the optical theorem : @xmath29 , \label{imm}\end{aligned}\ ] ] where the three - loop diagrams @xmath30 , @xmath31 , and @xmath32 are shown in fig . [ fig4 ] . and @xmath32 are shown.[fig4 ] , width=529 ] here the internal fermion loop is considered massless , while the case of electron in the internal loop has been considered in @xcite . the sum of imaginary parts of these diagrams is gauge - independent . for divergences , we employ the dimensional regularization with @xmath33 . the diagrams with inverse orientation of the fermion loop exist and their contributions are same . assigning the artificial large mass to the two internal electron propagators , we now have to consider several possibilities for the loop momentum scales . in the case of diagram @xmath30 , for example , we take @xmath34 and @xmath35 as the three independent loop momenta and the following four regions exist : 1 . @xmath36 , 2 . @xmath37 , 3 . @xmath38 , and 4 . @xmath39 . to calculate the hardest three - loop integrals in region 1 ( all soft momenta ) , we use the mincer package @xcite and the factorized integrals are calculated in form @xcite using well - known formulae . although each of @xmath40 $ ] and @xmath41 $ ] has the divergences of @xmath42 and depends on gauge parameter , the sum is free from divergences and gauge parameter . we can obtain it up to the first eight terms : @xmath43 \cdot \frac{\pi}{\alpha^{4 } } & = & + r^4 ( -0.394 + 4 \log r ) + r^6 ( 0.121 -8 \log r ) \nonumber \\ & + & r^8 ( 0.113 + 12.3 \log r ) + r^{10 } ( -0.316 -16.9 \log r ) \nonumber \\ & + & r^{12 } ( 0.481 + 21.7 \log r ) + r^{14 } ( -0.618 -26.7 \log r ) \nonumber \\ & + & r^{16 } ( 0.734 + 31.9 \log r ) + r^{18 } ( -0.834 - 37.3 \log r ) . \label{2resm12}\end{aligned}\ ] ] here and hereafter only three digits in the coefficients are shown . $ ] can be calculated up to the first six terms : @xmath45 \cdot \frac{\pi}{\alpha^{4 } } = & + & r^4 ( -0.313 + 8 \log r ) + r^6 ( -0.706 -16 \log r ) \nonumber \\ & + & r^8 ( 1.40 + 25.0 \log r ) + r^{10 } ( -1.93 -34.8 \log r ) \nonumber \\ & + & r^{12 } ( 2.31 + 45.2 \log r ) + r^{14 } ( -2.62 - 56.1\log r ) . \label{2resm3 } \end{aligned}\ ] ] @xmath46 $ ] is gauge invariant in itself and has no divergence . the series in eqs . ( [ 2resm12 ] ) and ( [ 2resm3 ] ) apparently do not converge at @xmath47 . however , we can choose an expansion parameter @xmath48 instead of @xmath49 such that these series converge . the comparison between eqs . ( [ tot2 ] ) and ( [ 1tg ] ) suggests an appropriate substitution , @xmath50 the change of the variable reconstructs the series in eq . ( [ 2resm12 ] ) into the following series of z , @xmath51 \cdot \frac{\pi}{\alpha^{4 } } = + z^2 ( -0.445 + 0.5 \log z ) + z^3 ( 0.166 ) \nonumber \\ & & + z^4 ( 0.0108 + 0.0111 \log z ) + z^{5 } ( -0.000899 + 0.00740 \log z ) \nonumber \\ & & + z^{6 } ( -0.00156 + 0.00462 \log z ) + z^{7 } ( -0.00110 + 0.00297 \log z ) \nonumber \\ & & + z^{8 } ( -0.000690 + 0.00198 \log z ) + z^{9 } ( -0.000421 + 0.00137 \log z ) , \label{2zm12 } \end{aligned}\ ] ] which are good convergent series . the series in eq . ( [ 2resm3 ] ) are also converted to good convergent series of @xmath48 . since the obtained series are limited in the first several terms , we should estimate the errors with the remaining infinite series . we rewrite the series in eq . ( [ 2zm12 ] ) as @xmath52 and estimate the errors as @xmath53 . here we can conservatively set @xmath54 because of the ratio @xmath55 . we can obtain the result , @xmath43 \cdot \frac{\pi}{\alpha^{4 } } & = & \biggl(\sum_{i=2}^{9}c_{i } + \frac{tc_{9}}{2(1-t ) } \biggr ) \pm \frac{t|c_{9}|}{2(1-t ) } \\ & = & -0.2726 \pm 0.00034 \ ( \equiv d_{12 } ) , \label{2rese12}\end{aligned}\ ] ] where we write this result as @xmath56 for the latter references . in the same way , we can obtain the results , @xmath45 \cdot \frac{\pi}{\alpha^{4 } } & = & -0.4692 \pm 0.0029 \ ( \equiv d_{3 } ) . \label{2rese3 } \\ \mbox{im } \bigl[\mbox{m}_{1 } + \mbox{m}_{2}+\mbox{m}_{3 } \bigr ] \cdot \frac{\pi}{\alpha^{4 } } & = & -0.7419 \pm 0.0033 \ ( \equiv d_{tot } ) . \label{2totres}\end{aligned}\ ] ] we check that the results in eqs . ( [ 2rese12 ] ) and ( [ 2rese3 ] ) are supported by the results of two summation methods , hlder summation and shanks transformation . [ [ paracharmonium - decays - to - photons ] ] paracharmonium decays to photons + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + the decay rate is given in the analogous form to eq . ( [ 2decay ] ) as @xmath57 where @xmath58 is the charmonium wave function . the tree - level decay rate is @xmath59 with the charm mass @xmath9 , the electric charge of the charm quark @xmath60 , and @xmath61 . we here use the color singlet wave function for @xmath62 , @xmath63 and @xmath64 are the color indices . two - loop qcd corrections have the three diagrams corresponding to @xmath30 , @xmath31 and @xmath32 in fig . [ fig4 ] . diagram @xmath65 corresponding to @xmath30 is shown in the left in fig . [ fig8 ] , where @xmath66 is the generators of qcd . in fig . [ fig4 ] for the decay @xmath12 ( @xmath67 ) is shown in the left ( right ) . [ fig8 ] , width=377 ] we restrict the quarks running in the fermion loop to the up , down , and strange quarks which can be regarded as massless . we can obtain @xmath68 $ ] , counting the extra factors relative to @xmath69 $ ] , as @xmath70 } { \mbox{im } \bigl[\mbox{m}_{1}(e^{-}e^{+ } \rightarrow e^{-}e^{+})\bigr ] } = \biggl(\frac{\alpha_{s}}{\alpha_{e}}\biggr)^{2 } ( q_{c})^{2 } [ ( q_{u})^{2}+(q_{d})^{2}+(q_{s})^{2 } ] \cdot \mbox{t}_{r}^{2}(n_{c}^{2}-1 ) , \label{3ext}\end{aligned}\ ] ] where @xmath71 is the strong coupling constant and @xmath72 . the extracted factors in eq . ( [ 3ext ] ) are common to the diagram where the orientation of the fermion loop is reversed in fig . [ fig8 ] and they are also common to the other two diagrams corresponding to @xmath31 and @xmath32 in fig . [ fig4 ] . then , using eqs . ( [ imm ] ) , ( [ 3etad ] ) and ( [ 3ext ] ) with @xmath73 and @xmath74 , we obtain the decay rate including the two - loop corrections as @xmath75 . \label{3degg}\end{aligned}\ ] ] [ [ paracharmonium - decays - to - gluons ] ] paracharmonium decays to gluons + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + the decay rate is obtained by the formula analogous to eq . ( [ 3etad ] ) . the tree - level decay rate is @xmath76 with @xmath77 . three diagrams which correspond to three in fig . [ fig4 ] contribute to the two - loop qcd corrections . diagram @xmath65 is the right one in fig . [ fig8 ] . using the wave function in eq . ( [ singlet ] ) , we obtain the common extra factors for @xmath78 as @xmath79 = \mbox{im } \bigl[\mbox{m}_{1,2}(e^{-}e^{+ } \rightarrow e^{-}e^{+ } ) \bigr ] \cdot \mbox{t}_{r}^{2 } c_{f}^{2 } n_{q } , \label{3ex12}\end{aligned}\ ] ] where @xmath80 is the number of the light quarks . the color factor for @xmath32 is different from one for @xmath30 and @xmath31 , as @xmath81 with @xmath82 . thus , we obtain the decay rate as @xmath83 . \label{3dggres}\end{aligned}\ ] ] it should be noted that if we average the colors of the charm and anti - charm quarks in this calculation , the divergences are not cancelled because the color factors for @xmath30 and @xmath31 are different as @xmath84 \mbox{tr}[t^{a}t^{d}t^{c}t^{b } ] \not= \mbox{tr}[t^{a}t^{b}t^{c}t^{d } ] \mbox{tr}[t^{a}t^{d}t^{b}t^{c}]$ ] . the qcd bare lagrangian has the gluon four - point interaction , unlike qed , and the gluon four - point function has divergences proportional to the interaction term in the bare lagrangian . however , the requirement that @xmath62 is color singlet state in eq . ( [ singlet ] ) reduces the color factors for @xmath30 and @xmath31 from the different ones to the common ones in eq . ( [ 3ex12 ] ) and eliminates the potential divergences in the two - loop qcd corrections . [ [ numerical - values - of - corrections ] ] numerical values of corrections + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + + we first estimate the corrections in @xmath12 as @xmath85 \label{3epp } \\ & = & \gamma_{0}(\eta_{c } \rightarrow \gamma \gamma ) \bigl[1+(-0.439)+ ( -0.0125 + 0.017 \cdot \delta_{\gamma}^{others } ) \bigr ] . \label{3epp2}\end{aligned}\ ] ] here we use the values of the one - loop corrections @xmath86 @xcite and the two - loop corrections are written as @xmath87 from eq . ( [ 3degg ] ) . @xmath88 denotes the other two - loop corrections . we also use the coupling constant at the scale of the charm quark mass , @xmath89 @xcite . we find that the obtained two - loop corrections account for @xmath90 of the tree - level decay rate , neglecting the uncertainty of @xmath91 in eq . ( [ 2totres ] ) due to its smallness . we next estimate the corrections in @xmath1 in the same way : @xmath92 . \label{3gg}\end{aligned}\ ] ] where in the analogue to eq . ( [ 3epp ] ) , the one - loop correction is @xmath93 @xcite . the two - loop correction is @xmath94 from eq . ( [ 3dggres ] ) . the obtained corrections account for @xmath95 of the tree level . the ratio of the decay rates in eq . ( [ 3epp2 ] ) to one in eq . ( [ 3gg ] ) is free from the ambiguity of the wave function @xmath96 . to compare the ratio to the experimental value , we need the other corrections @xmath97 and @xmath98 , which we leave for future work . we calculate the two - loop qcd corrections to the decay modes @xmath0 and @xmath1 involving light - by - light scattering diagrams with light quark loops by the method of lme . the obtained series in lme are transformed into ones with good convergence properties by a change of the expansion parameter . the obtained corrections to the decay @xmath12 account for @xmath2 of the tree - level and the corrections to @xmath1 account for @xmath3 . the artificially introduced large mass does not break the gauge symmetry in the kinematic case of both initial particles at rest because the results are independent of the gauge parameter . regarding the divergences of the two - loop qcd corrections to @xmath1 in the present paper , the nature that the observed hadron , @xmath62 in this case , is color singlet state , eliminates the potential divergences .

we calculate the two - loop qcd corrections to paracharmonium decays @xmath0 and @xmath1 involving light - by - light scattering diagrams with light quark loops . artificial large mass expansion and convergence improvement techniques are used to evaluate these corrections . the obtained corrections to the decays @xmath0 and @xmath1 account for @xmath2 and @xmath3 of the leading order contribution , respectively .

Lou Brooks If there’s one thing I learned in graduate school, it’s that the poet Philip Larkin was right. (“They fuck you up, your mum and dad, / They may not mean to, but they do.”) At the time, I was a new mom with an infant son, and I’d decided to go back to school for a degree in clinical psychology. With baby on the brain and term papers to write, I couldn’t ignore the barrage of research showing how easy it is to screw up your kids. Of course, everyone knows that growing up with “Mommy Dearest” produces a very different child from one raised by, say, a loving PTA president who has milk and homemade cookies waiting after school. But in that space between Joan Crawford and June Cleaver, where most of us fall, it seemed like a lot could go wrong in the kid-raising department. As a parent, I wanted to do things right. But what did “right” mean? One look in Barnes & Noble’s parenting section and I was dizzy: child-centered, collaborative, or RIE? Brazelton, Spock, or Sears? The good news, at least according to Donald Winnicott, the influential English pediatrician and child psychiatrist, was that you didn’t have to be a perfect mother to raise a well-adjusted kid. You just had to be, to use the term Winnicott coined, a “good-enough mother.” I was also relieved to learn that we’d moved beyond the concept of the “schizophrenogenic mother,” who’s solely responsible for making her kid crazy. (The modern literature acknowledges that genetics—not to mention fathers—play a role in determining mental health.) Still, in everything we studied—from John Bowlby’s “attachment theory” to Harry Harlow’s monkeys, who clung desperately to cloth dummies when separated from their mothers—the research was clear: fail to “mirror” your children, or miss their “cues,” or lavish too little affection on them, and a few decades later, if they had the funds and a referral, they would likely end up in one of our psychotherapy offices, on the couch next to a box of tissues, recounting the time Mom did this and Dad didn’t do that, for 50 minutes weekly, sometimes for years. Our main job as psychotherapists, in fact, was to “re-parent” our patients, to provide a “corrective emotional experience” in which they would unconsciously transfer their early feelings of injury onto us, so we could offer a different response, a more attuned and empathic one than they got in childhood. At least, that was the theory. Then I started seeing patients. My first several patients were what you might call textbook. As they shared their histories, I had no trouble making connections between their grievances and their upbringings. But soon I met a patient I’ll call Lizzie. Imagine a bright, attractive 20-something woman with strong friendships, a close family, and a deep sense of emptiness. She had come in, she told me, because she was “just not happy.” And what was so upsetting, she continued, was that she felt she had nothing to be unhappy about. She reported that she had “awesome” parents, two fabulous siblings, supportive friends, an excellent education, a cool job, good health, and a nice apartment. She had no family history of depression or anxiety. So why did she have trouble sleeping at night? Why was she so indecisive, afraid of making a mistake, unable to trust her instincts and stick to her choices? Why did she feel “less amazing” than her parents had always told her she was? Why did she feel “like there’s this hole inside” her? Why did she describe herself as feeling “adrift”? I was stumped. Where was the distracted father? The critical mother? Where were the abandoning, devaluing, or chaotic caregivers in her life? As I tried to make sense of this, something surprising began happening: I started getting more patients like her. Sitting on my couch were other adults in their 20s or early 30s who reported that they, too, suffered from depression and anxiety, had difficulty choosing or committing to a satisfying career path, struggled with relationships, and just generally felt a sense of emptiness or lack of purpose—yet they had little to quibble with about Mom or Dad. Instead, these patients talked about how much they “adored” their parents. Many called their parents their “best friends in the whole world,” and they’d say things like “My parents are always there for me.” Sometimes these same parents would even be funding their psychotherapy (not to mention their rent and car insurance), which left my patients feeling both guilty and utterly confused. After all, their biggest complaint was that they had nothing to complain about! At first, I’ll admit, I was skeptical of their reports. Childhoods generally aren’t perfect—and if theirs had been, why would these people feel so lost and unsure of themselves? It went against everything I’d learned in my training. But after working with these patients over time, I came to believe that no florid denial or distortion was going on. They truly did seem to have caring and loving parents, parents who gave them the freedom to “find themselves” and the encouragement to do anything they wanted in life. Parents who had driven carpools, and helped with homework each night, and intervened when there was a bully at school or a birthday invitation not received, and had gotten them tutors when they struggled in math, and music lessons when they expressed an interest in guitar (but let them quit when they lost that interest), and talked through their feelings when they broke the rules, instead of punishing them (“logical consequences” always stood in for punishment). In short, these were parents who had always been “attuned,” as we therapists like to say, and had made sure to guide my patients through any and all trials and tribulations of childhood. As an overwhelmed parent myself, I’d sit in session and secretly wonder how these fabulous parents had done it all. Until, one day, another question occurred to me: Was it possible these parents had done too much? Here I was, seeing the flesh-and-blood results of the kind of parenting that my peers and I were trying to practice with our own kids, precisely so that they wouldn’t end up on a therapist’s couch one day. We were running ourselves ragged in a herculean effort to do right by our kids—yet what seemed like grown-up versions of them were sitting in our offices, saying they felt empty, confused, and anxious. Back in graduate school, the clinical focus had always been on how the lack of parental attunement affects the child. It never occurred to any of us to ask, what if the parents are too attuned? What happens to those kids? ||||| Lou Brooks If there’s one thing I learned in graduate school, it’s that the poet Philip Larkin was right. (“They fuck you up, your mum and dad, / They may not mean to, but they do.”) At the time, I was a new mom with an infant son, and I’d decided to go back to school for a degree in clinical psychology. With baby on the brain and term papers to write, I couldn’t ignore the barrage of research showing how easy it is to screw up your kids. Of course, everyone knows that growing up with “Mommy Dearest” produces a very different child from one raised by, say, a loving PTA president who has milk and homemade cookies waiting after school. But in that space between Joan Crawford and June Cleaver, where most of us fall, it seemed like a lot could go wrong in the kid-raising department. As a parent, I wanted to do things right. But what did “right” mean? One look in Barnes & Noble’s parenting section and I was dizzy: child-centered, collaborative, or RIE? Brazelton, Spock, or Sears? The good news, at least according to Donald Winnicott, the influential English pediatrician and child psychiatrist, was that you didn’t have to be a perfect mother to raise a well-adjusted kid. You just had to be, to use the term Winnicott coined, a “good-enough mother.” I was also relieved to learn that we’d moved beyond the concept of the “schizophrenogenic mother,” who’s solely responsible for making her kid crazy. (The modern literature acknowledges that genetics—not to mention fathers—play a role in determining mental health.) Still, in everything we studied—from John Bowlby’s “attachment theory” to Harry Harlow’s monkeys, who clung desperately to cloth dummies when separated from their mothers—the research was clear: fail to “mirror” your children, or miss their “cues,” or lavish too little affection on them, and a few decades later, if they had the funds and a referral, they would likely end up in one of our psychotherapy offices, on the couch next to a box of tissues, recounting the time Mom did this and Dad didn’t do that, for 50 minutes weekly, sometimes for years. Our main job as psychotherapists, in fact, was to “re-parent” our patients, to provide a “corrective emotional experience” in which they would unconsciously transfer their early feelings of injury onto us, so we could offer a different response, a more attuned and empathic one than they got in childhood. At least, that was the theory. Then I started seeing patients. My first several patients were what you might call textbook. As they shared their histories, I had no trouble making connections between their grievances and their upbringings. But soon I met a patient I’ll call Lizzie. Imagine a bright, attractive 20-something woman with strong friendships, a close family, and a deep sense of emptiness. She had come in, she told me, because she was “just not happy.” And what was so upsetting, she continued, was that she felt she had nothing to be unhappy about. She reported that she had “awesome” parents, two fabulous siblings, supportive friends, an excellent education, a cool job, good health, and a nice apartment. She had no family history of depression or anxiety. So why did she have trouble sleeping at night? Why was she so indecisive, afraid of making a mistake, unable to trust her instincts and stick to her choices? Why did she feel “less amazing” than her parents had always told her she was? Why did she feel “like there’s this hole inside” her? Why did she describe herself as feeling “adrift”? I was stumped. Where was the distracted father? The critical mother? Where were the abandoning, devaluing, or chaotic caregivers in her life? As I tried to make sense of this, something surprising began happening: I started getting more patients like her. Sitting on my couch were other adults in their 20s or early 30s who reported that they, too, suffered from depression and anxiety, had difficulty choosing or committing to a satisfying career path, struggled with relationships, and just generally felt a sense of emptiness or lack of purpose—yet they had little to quibble with about Mom or Dad. Instead, these patients talked about how much they “adored” their parents. Many called their parents their “best friends in the whole world,” and they’d say things like “My parents are always there for me.” Sometimes these same parents would even be funding their psychotherapy (not to mention their rent and car insurance), which left my patients feeling both guilty and utterly confused. After all, their biggest complaint was that they had nothing to complain about! At first, I’ll admit, I was skeptical of their reports. Childhoods generally aren’t perfect—and if theirs had been, why would these people feel so lost and unsure of themselves? It went against everything I’d learned in my training. But after working with these patients over time, I came to believe that no florid denial or distortion was going on. They truly did seem to have caring and loving parents, parents who gave them the freedom to “find themselves” and the encouragement to do anything they wanted in life. Parents who had driven carpools, and helped with homework each night, and intervened when there was a bully at school or a birthday invitation not received, and had gotten them tutors when they struggled in math, and music lessons when they expressed an interest in guitar (but let them quit when they lost that interest), and talked through their feelings when they broke the rules, instead of punishing them (“logical consequences” always stood in for punishment). In short, these were parents who had always been “attuned,” as we therapists like to say, and had made sure to guide my patients through any and all trials and tribulations of childhood. As an overwhelmed parent myself, I’d sit in session and secretly wonder how these fabulous parents had done it all. Until, one day, another question occurred to me: Was it possible these parents had done too much? Here I was, seeing the flesh-and-blood results of the kind of parenting that my peers and I were trying to practice with our own kids, precisely so that they wouldn’t end up on a therapist’s couch one day. We were running ourselves ragged in a herculean effort to do right by our kids—yet what seemed like grown-up versions of them were sitting in our offices, saying they felt empty, confused, and anxious. Back in graduate school, the clinical focus had always been on how the lack of parental attunement affects the child. It never occurred to any of us to ask, what if the parents are too attuned? What happens to those kids?

– Working as a therapist upended everything Lori Gottlieb thought she had learned about parenting, she writes in an Atlantic piece certain to stir a Tiger Mom-sized controversy. Gottlieb found many depressed, anxious patients on her couch—who instead of recounting their horrible childhoods, waxed poetic about their loving parents who cared about nothing more than their happiness. Modern parents, she realizes, may be creating unhappy adults by caring so much about their children's happiness that they insulate them from discomfort and criticism, leaving them unable to handle the setbacks of adult life. Much like the immune system needs to be exposed to pathogens, "kids also need exposure to discomfort, failure, and struggle," a child psychologist tells Gottlieb. "I know parents who call up the school to complain if their kid doesn’t get to be in the school play or make the cut for the baseball team." Parents may be mistaking their own emotional needs for their children's, creating a generation of narcissists as a result, Gottlieb writes. "By trying so hard to provide the perfectly happy childhood, we’re just making it harder for our kids to actually grow up," she writes. "Maybe we parents are the ones who have some growing up to do—and some letting go." Click to read Gottlieb's entire piece.

one of the most promising outcomes of the study of gravitational lensing is the potential to determine the hubble constant , h@xmath1 , independent of the standard distance ladder ( refsdal 1964 ) . the light travel times for the lensed images are not equal due to the geometrical path length difference caused by the gravitational potential of the lens . this results in a time delay between the lensed images that can be measured by monitoring the images over a period of time . thus , given a measurement of time delay and a knowledge of the gravitational potential of the lens , one can estimate h@xmath1 . at present , the accuracy of h@xmath1 values determined by this method is limited mainly by our knowledge of the mass distribution in the distant lensing galaxy . so far , time - delay measurements are available for seven lensed systems . for the twin quasar 0957 + 561 the measured values at both radio and optical wavelengths are in agreement and have been confirmed by observing variability in the image b after it was recorded in the image a ( schild & thomson 1997 , kundi et al . 1997b , haarsma et al . 1999 ) . while for this system a reliable measurement of the time delay has been achieved , translation into an estimate of the hubble constant turns out to be not straightforward ( narasimha , 1999 ) . for the systems pg 1115 + 080 ( schechter et al . 1997 ) , b1608 + 656 ( fassnacht et al . 1999 ) , pks 1830 - 211 ( lovell et al . 1998 ) , b1600 + 434 ( koopmans et al . 2000 ) the measured delays are less accurate , mainly because it is not easy to extract the intrinsic variability and determine its phase lag between the images . the system b0218 + 357 has good time delay measurements ( biggs et al . 1999 ) and the redshift combination of the lens and source are favourable for a possible determination of h@xmath1 , but the lens models continue to be ill - constrained . however , these systems together cover various combinations of the distance to the source and lens as well as the distance from the lens to the source ; hence an estimate of the distance scale from time - delays in all these systems together would be an important step to determine the hubble constant and the large scale geometry of the universe . the lens system b1422 + 231 is particularly interesting in this respect , as the redshift of the source , z@xmath2 , ( patnaik et al . 1992 ) is very large compared to the redshift of the lens , z@xmath3 , ( kundi et al . 1997a , tonry 1998 ) and consequently , the time - delay is a more direct measure of the distance to the lens . b1422 + 231 is a quadruple system which has been observed at various wavebands ( patnaik et al . 1992 ; lawrence et al . 1992 ; remy et al . 1993 ; yee & ellingson 1994 ; bechtold & yee 1995 ; akujor et al . 1996 ; yee & bechtold 1996 ; impey et al . 1996 ) . several models have been presented to explain the lens system ( hogg & blandford 1994 , narasimha & patnaik , 1994 , kormann , schneider & bartlemann 1994 , mao & schneider 1998 ) . detailed radio maps at sub - milliarcsecond resolution are available for the images ( patnaik et al . 1999 ) and the mapping of the resolved structures of the images can be used for construction of the lens models . optical spectra of the images have been taken with high sensitivity ( impey et al . 1996 ) and the emission line profiles of strong lines like ly@xmath4 have been used by narasimha & srianand ( 1999 ) to constrain the lens models . thus , it is clear that a measurement of the time - delay for this system will be useful for the calibration of the cosmic distance scale , even though the source is not highly variable . the vla monitoring campaign of the gravitational lens b1422 + 231 was carried out at two frequencies , 8.4 and 15 ghz between 1994 march 03 to september 16 . we used two 50 mhz - wide if bands at each frequency . we used 3c286 ( j1331 + 3030 ) to calibrate the flux density scale , oq208 ( j1407 + 2827 ) as the phase calibrator , and 3c287 ( j1330 + 2509 ) as a control source since it is not expected to be a variable source . the other reason for selecting this source is that it is close to the declination of our target source to ensure proper calibration of gain as a function of elevation . the observations were carried out for about 30 min on each day , the integration time for the target source was 5 min at each frequency and the rest of the time was used for observing the calibration and control sources . accurate calibration is of vital importance in this kind of monitoring observations . the observations of the two calibrators ensure that any variations in them must be due to calibration errors and hence these variations can , at least partially , be removed from the light curve of the lensed images . we chose two different frequencies in order to have confidence in the measurements of time delay as it is independent of frequency , though the variability of quasars does depend on the frequency in the sense that they tend to be more variable at higher frequencies . in the present case , we chose 8.4 and 15 ghz for the following reasons . in the a configuration of the vla the resolutions are about 0.2 and 0.13 arcsec at 8.4 and 15 ghz respectively , which allows clean separation of the images . in the b configuration , however , the two brighter images , a and b , are blended together at 8.4 ghz since the resolution is three times poorer , while there is no such difficulty at 15 ghz . we can sample the light curve over the periods of a and b configurations of the vla at 15 ghz but only during the a configuration at 8.4 ghz . the data were calibrated and imaged using the aips software package of national radio astronomy observatory . assumed flux densities of 3c286 were 5.145 jy and 5.124 jy at the centre frequencies of the two if bands which are 8.4149 ghz and 8.4649 ghz respectively , and 3.449 jy and 3.457 jy at 14.9649 ghz and 14.9149 ghz respectively . since 3c286 is partially resolved at these frequencies , we followed the standard procedure in using the shortest baselines to set the scale of flux density . we assumed that both oq208 and 3c287 are unresolved sources and used them to determine the gain solutions . we then used the aips program getjy to determine the flux densities of these two sources which are bootstrapped from 3c286 . the source 3c287 is , in fact , partially resolved in the a - array ( its flux density changes from 1.4 jy at short spacings to 0.9 jy at the longest spacing at 15ghz ) . we could have mapped the source to determine its flux density . however , the assumption that it is a point source affects its flux density measurement by only 0.5% ( our method gets less flux density ) . thus the assumption that 3c287 behaves as a point source is justified . moreover , we avoid introducing errors as a result of the mapping process . the vla configuration was changed from a to b during our monitoring campaign . in fact , the data presented for 8.4 ghz was only for the duration of the a - array . we do not see any effects of the change of the array configuration in the light curves of the calibrators at 15ghz , giving confidence in the calibration method followed . we used the gain solutions for the phase calibrator , oq208 , to interpolate the amplitude and phase corrections for the target source . the observations were scheduled in intervals of between 2 and 11 days . the measured flux densities are presented in tables 1 and 2 for 8.4 and 15 ghz respectively . at 15 ghz we had 51 epochs covering both a and b configurations of the vla . at 8.4 ghz we had only 18 epochs since its span was limited to the a configuration . [ cols= " < , < , < , < , < , < , < , < , < , < , < , < , < " , ] @xmath5 after eliminating two days when the reference star exhibited considerable fluctuation . + @xmath6 the smoothed cubic spline did not converge and hence we can not get a time delay for the total flux . + for the system pg1115 + 080 , again , our results are broadly in agreement with schechter et al . ( 1997 ) . however , a few comments are worth mentioning . first , the time delay between images b and c are generally stable against analysis technique or some amount of noise in the data . but the time delay between the merging image a and the other two are sensitive to the method adopted as well as the noise in the reference star . second , for the whole data , our time delay between images b and c is slightly smaller than the value given by schechter et al . but if we drop two days on which the fluctuation in the magnitude of the reference star was comparable to the amplitude of variability of the quasar , the time delay becomes 24.4 days , which is exactly in between the values derived by schechter et al . and barkana ( 1997 ) . third , our value for the time delay between images a and b range from 6 to 11 days , depending on using or dropping the data for the two days . the corresponding value for the time delay between images c and a vary between 14 and 13 days . consequently , our time delay ratio between ca and ab are always consistent with the lens models ; the small ratio supports a compact lens and higher value for the hubble constant while the larger ratio favours an extended lens and smaller hubble constant . we have monitored b1422 + 231 with the vla at two different frequencies . the light curves were sampled at intervals of 2 to 10 days only because we did not have a good idea of the amplitude of intrinsic variability and were interested in the image d in view of its importance for cosmological distance calibration . consequently , we are unable to get very accurate value for the time delay between images . but we are able to determine the time delay between the bright images using the 15 ghz observations , obtaining 1.5 , 7.6 and 8.2 days for ab , ca and cb time delays respectively . more extensive monitoring at significantly higher signal to noise ratio is necessary to determine the time delay between the weak image d and the other images . we would like to thank j. schmid - burgk and k.m . menten for critical comments and the comments of an anonymous referee which resulted in improving the presentation of the paper . we have made use of information available at the castle web - site ( http://cfa-www.harvard.edu/glensdata/ ) for gravitational lenses maintained by c.s . kochanek , e.e . falco , c. impey , j. lehr , b. mcleod and h .- w . we are grateful to nrao for their support in carrying out these observations . the national radio astronomy observatory is a facility of the national science foundation operated under cooperative agreement by associated universities , inc . dn acknowledges support from indo - french centre for the promotion of advanced research , through contract 1410 - 2 . akujor , c.e . , patnaik , a.r . , smoker , j.v . , garrington , s.t . , 1996 , in kochanek , c.s , hewitt , j.n . , eds , proceedings of the 173rd symposium of the iau ` astrophysical applications of gravitational lensing ' , kluwer academic publishers , dordrecht , p335 + barkana , r. , 1997 , apj , 489 , 21 + bechtold , j. , yee , h.k.c . , 1995 , aj , 110 , 1984 + biggs , a.d . , browne , i.w.a . , helbig , p. , koopmans , l.v.e . , wilkinson , p.n . , perley , r.a . , 1999 , mnras , 304 , 349 + fassnacht , c.d . , pearson , t.j . , readhead , a.c.s . , browne , i.w.a . , koopmans , l.v.e . , myers , s.t . , wilkinson , p.n . , 1999 , apj , 527 , 498 + haarsma , d.b . , hewitt , j.n . , lehr , j. , burke , b.f . , 1999 , apj , 510 , 64 + hogg , d.w . , blandford , r.d . , 1994 , mnras , 268 , 889 + impey , c.d . , foltz , c.b . , petry , c.e . , browne , i.w.a . , patnaik , a.r . , 1996 , apj , 462 , l53 + koopmans , l.v.e . , de bruyn , a.g . , xanthopolous , e. , fassnacht , c.d . , 2000 , aa , in press + kormann , r. , schneider , p. , bartlemann , m. , 1994 , a&a , 286 , 357 + kundi , t. , hogg , d.w . , blandford , r.d . , cohen , j.g . , lubin , l.m . , larkin , j.e . , 1997a , aj , 114 , 2276 + kundi , t. , turner , e.l . , colley , w.n . , gott , iii , r . , rhoads , j.e . , wang , y. , bergeron , l.e . , gloria , k.a . , long , d.c . , malhotra , s. , wambsganss , j. , 1997b , apj , 482 , 75 + lawrence , c.r . , neugebauer , g. , weir , n. , matthews , k. , patnaik , a.r . , 1992 , mnras , 259 , 5p + lovell , j. , jauncey , d.l . , reynolds , j.e . , wieringa , m.h . , king , e.a . , tzioumis , a.k . , mcculloch , p.m. , edwards , p.g . , 1998 , apj , 508 , l51 + mao , s. , schneider , p. , 1998 , mnras , 295 , 587 + nair , s. , 1994 , ph.d . thesis , bombay university , unpublished + nair , s. narasimha , d. , rao , a.p . , 1993 , apj , 407 , 46 + narasimha , d. , 1999 , pramana , 53 , 921 + narasimha , d. , 2000 , in rencontres de moriond , les arcs , eds . y. mellier , j .- kneib & m. moniez + narasimha , d. , patnaik , a.r . , 1994 , in surdej , j. , fraipont - 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we present the radio light curves of lensed images of the gravitational lens b1422 + 231 . the observations have been carried out using the vla at 8.4 and 15 ghz over a period of 197 days . we describe a method to estimate the time delay from the observed light curves . using this method , our cross - correlation analysis shows that the time delay between images b and a is [email protected] , between a and c is [email protected] , between b and c is [email protected] . when applied to other lensed systems with measured time delays our new method gives comparable results . gravitational lensing - quasar b1422 + 231 - time delay

human african trypanosomiasis ( hat ) or african sleeping sickness is a serious life threatening disease . around 60 million people in 36 african countries are currently in constant threat of infection . although the reported number of cases has dropped over recent years , the actual number of unreported cases is estimated to be around 7000080000 . hat is caused by infection with trypanosoma brucei , a vector - borne parasite , which is transmitted by the bite of tsetse flies . the symptoms of the disease occur in two main stages . in the first stage , known as the hemolymphatic phase , the parasites multiply in blood , subcutaneous tissues , and lymph , causing headaches , fever , itching , joint pains , and swelling of lymph nodes . in the second stage , or neurological phase , this phase entails confusion , change of behavior , reduced coordination , sensory disturbances , disturbance of sleep cycle , and finally death . most available drugs for hat display severe toxic side effects , require long periods of administration , and/or are expensive due to the logistics to reach rural african areas . further , resistance to all in use drugs has been observed in the laboratory and/or in the field , resulting in an urgent requirement for better , safer , and inexpensive therapeutic alternatives to the current treatments . genetic knockdown studies have identified several proteins that are essential for the survival of the parasite , including members of the protein kinase ( pk ) family . in trypanosoma brucei pks are essential in many fundamental cellular processes , e.g. , proliferation , differentiation , and cell cycle control , and can therefore be considered as potential drug targets for the treatment of hat . in the t. brucei genome there are two kinases that are highly homologous to human glycogen synthase kinase 3 ( hsgsk3 ) : tbgsk3 short and tbgsk3 long . rna interference ( rnai ) knockdown of tbgsk3 has shown that tbgsk3 short is critical for cell growth , with a role in the control of mitosis and/or cytokinesis . the ability to selectively inhibit tbgsk3 over the off - target hsgsk3 is highly desirable because mouse knockout studies revealed that the disruption of the murine gsk3 gene causes embryonic lethality ; consequently , nonselective inhibitors are not applicable for use in infants and women of child bearing age . from a homology perspective , tbgsk3 is not only very closely related to hsgsk3 but also to other human pks such as cyclin dependent kinase 1 ( hscdk1 ) and cyclin dependent kinase 2 ( hscdk2).hscdk2 and hscdk1 are essential for g1/g2 progression and s / m - phase entry of the cell cycle . off - target inhibition of these human kinases will therefore result in cell cycle arrest and reduction of cellular proliferation and as such potentially lead to severe side effects . over the past decade , various groups and pharmaceutical companies have identified multiple series of hsgsk3 inhibitors . recently , astex therapeutics and researchers at the university of osaka have developed a series of aminopyrazoles that are potent inhibitors of hsgsk3. co - crystal structures of this series with hsgsk3 are not available to date ; however , complex structures with the closely related hscdk2 have been determined . in all structures , the pyrazole scaffold forms two hydrogen bonds to the hinge region of hscdk2 ( figure 1 ) . further , the nh group of the 3-position amide forms an additional hydrogen - bond interaction to the backbone of leu83 . a water - mediated hydrogen bond from the amide carbonyl oxygen atom to the backbone the r residues ( figure 2 ) access the gatekeeper region between the gatekeeper residue phe80 and the catalytic asp145 ( figure 1 ) . the r substituents occupy the hydrophobic pocket ii , formed by the backbone of the linker region , leu83 , phe82 , and side chains of ile10 , asp86 , and leu134 . finally , an intramolecular hydrogen bond between the r - nh and r - carbonyl group is present . the similarity of hscdk2 , hsgsk3 , and tbgsk3 indicates that aminopyrazoles will also bind into the atp - binding site of the latter enzyme . co - crystal structure ( 2vu3 ) of at7519 ( carbon atoms in gray ) bound to cdk2 . key : red sphere , water molecule ; black dashed lines , protein ligand and water ligand hydrogen bonds ; yellow stick , hydrogen atom .. generic binding mode of the r and r substituted aminopyrazole scaffold ( carbon atoms in gray ) . herein , we describe the design , synthesis , and biological evaluation of aminopyrazole inhibitors which bind to tbgsk3 short . the inhibitors were also tested against the closely related off - targets hsgsk3 and hscdk2 and evaluated against a panel of mammalian protein kinases . the most potent compound has nanomolar affinity for tbgsk3 short , is selective over hsgsk3 and hscdk2 , and clean in the kinase panel . by using computer - aided molecular modeling enzyme affinity correlated with inhibition of t. b. brucei proliferation , albeit a 100-fold offset in potency , was found . in light of these results , the aminopyrazole derivatives developed by astex therapeutics and yumiko uno et al . for inhibition of hscdk2 and hsgsk3 enzymes were chosen as a starting point for the investigation of tbgsk3 short inhibitors . aminopyrazoles analogues were generated by substituting at either r or r position ( figure 2 ) using two synthetic routes ( scheme 1a , b ) . reagents and conditions used in routes a and b : ( a ) trans-4-methoxycyclohexylamine , edc , hobt , dmf , rt ; ( b ) 10% pd / c , h2 , dmf , rt ; ( c ) rcooh , edc , hobt , dipea , rt ; ( d ) socl2 , meoh , 0c , rt ; ( e ) 10% pd / c , h2 , etoh , rt ; ( f ) 2,6-dimethoxybenzoylchloride , et3n , dioxane , rt ; ( g ) naoh , dioxane , h2o , rt ; ( h ) r2nh2 , polystyrene - bound carbodiimide , hobt , acetonitrile , mw , 100 c . a structural model of tbgsk3 was built to assess the differences in the binding sites of tbgsk3 short , hsgsk3 , and hscdk2 and to guide ligand design . an overlay of 42 hsgsk3 crystal structures showed that there is low flexibility in the atp binding site . only the regions including phe67 and arg141 showed some mobility . arg141 also spans a number of distinct conformations , including examples where it occupies space in the binding site ( 1j1b , 1j1c , 1o9u , 2o5k ) and therefore could influence docking results . however , to allow for ligands of a significant size , we have used examples with arg141 pointing out of the binding site . therefore , two homology models for tbgsk3 were generated representing both states of phe67 . as we were mainly interested in aminopyrazoles with less extended r groups , the crystal structure with phe67 pointing toward the hinge ( with structure 1r0e as a representative ) the selection of 1r0e instead of other members of this group ( with phe67 pointing toward the hinge ) was arbitrary . for this analysis , all residues that are located within 6 of the ligand bound to the template structure ( 1r0e ) were considered . the binding pockets of tbgsk3 and hsgsk3 differ by nine amino acid residues ( table 1 , figure 3a ) . of the amino acid side chains that point toward the ligand , the most significant differences are the replacement of tyr134 in hsgsk3 with phe103 , leu132 with met101 , gln72 with leu36 , and tyr140 with his109 . in total 16 out of 26 amino acids were found to be different ( table 1 , figure 3b ) , the most important of these differences being the replacement of lys20 in cdk2 with leu36 , phe80 with met101 , his84 with pro105 , lys89 with arg110 , and ala144 with cys170 . interestingly , most of the amino acid differences occurred in the hydrophobic pocket ii and the gatekeeper region . therefore , we decided to direct the optimization of the lead scaffold toward suitable interactions with amino acids which are located in these subpockets of the atp binding site . amino acids of hgsk3 or hscdk2 which differ in tbgsk3 short are shown in boldface . superposition of the binding sites of the homology model of tbgsk3 short ( blue carbon atoms ) with ( a ) the hsgsk3 crystal structure ( pdb code 1r0e ) and the solvent accessible surface of tbgsk3 short is shown in light blue . only residues that differ between the binding pockets are shown . the synthesis of r and r substituted aminopyrazole derivatives started from 4-nitro - pyrazole-3-carboxylic acid 1 and is described by two different routes ( scheme 1 ) based on previous work from wyatt et al . in route reduction of the subsequent intermediate 2 by hydrogenation in the presence of palladium on carbon generated amino pyrazole 3 . the conversion to compounds 4a z was accomplished by coupling of 3 with a suitable selection of carboxylic acids . in route b , after esterification of the carboxyl group of 1 , the nitro group of intermediate 5 was reduced to afford amine 6 . treatment of 6 with 2,6-dimethoxybenzoyl chloride under standard conditions , followed by base hydrolysis of the ester , provided acid 8 . in the final step , 8 was coupled with appropriate amines in a microwave reaction using polystyrene - bound carbodiimide to yield final compounds 9a x . twenty - six r substituted aminopyrazole analogues ( table 2 ) were made according to the synthetic route shown in scheme 1a . a range of r groups varying in size and polarity was chosen to probe whether the differences in the gate keeper region between tbgsk3 , hsgsk3 , and hscdk2 could be exploited to derive selective and potent tbgsk3 inhibitors ( figure 3 ) . concentration required to inhibit the growth of t. b. brucei in culture by 50% over 72 h. concentration required to inhibit the growth of mrc5 cells in culture by 50% over 72 h. all compounds showed good potency against tbgsk3 ( < 1 m ) . an unsubstituted phenyl ring ( 4f ) provided on average a 20-fold improvement of inhibition potency relative to saturated six - membered ring systems ( 4a and 4b ) and benzyl groups ( 4c , 4d , and 4e ) . in general , a variety of different aryl and heteroaryl rings ( 4g4y compared to 4a and 4b ) in the r position led to significantly improved potency against tbgsk3 . additionally , a wide variety of substituents were tolerated on the phenyl ring . in general , ortho - substituted phenyl rings gave the best improvement in activity compared to the unsubstituted phenyl group ( 4j , 4k , 4 m , and 4n ) . the methoxyphenyl moieties in 4j , 4 m , and 4n , which had tbgsk3 ic50 values of 4 , 2 , and 3 nm , respectively , were the most favorable substituents . interestingly , this was also the most selective compound for hscdk2 ( > 1000-fold ) . to rationalize the observed selectivity , all analogues were docked into the binding sites of tbgsk3 , hsgsk3 , and hscdk2 and their poses were visually analyzed . for most compounds , a binding mode similar to that observed for at7519 in hscdk2 ( figure 1 ) was predicted in tbgsk3 , hsgsk3 , and hscdk2 . one important difference between hscdk2 , tbgsk3 , and hsgsk3 is the gatekeeper residue ( table 1 , figure 3a , b ) . while hsgsk3 and tbgsk3 enzymes have leu or met , respectively , in this position , in hscdk2 phe is present . as a consequence , the gatekeeper region of hscdk2 ( located between phe80 and asp145 ) is more restricted compared to the other two enzymes . this resulted in a higher energy , out of plane conformation of the amide group of 4f when binding into this pocket ( figure 4 ) , while a low energy conformation was found when binding into t. brucei and human gsk3 ( not shown ) . further , without induced fit adaptations , the bulky r - substituents such as the 2,6-dimethoxybenzamide group of 4 m , the 2,4,6-trimethoxybenzamide groups 4n , and the phenylaminobenzamide groups of 4k and 4l can only be accommodated by the gatekeeper region of tbgsk3 and hsgsk3 but not the narrower hscdk2 gatekeeper region . these observations might explain the reduced binding affinity of 4f for hscdk2 compared to hsgsk3 . of note , this explanation is further supported by the report by wyatt et al . , which found that the aryl groups which are located in the same position need to twist in order to provide potent cdk2 activity docking results suggested that the phenyl ring of compound 4f needs to be significantly twisted out of plane by approximately 60 compared to the amide in order to fit into the gatekeeper region .. all r substituted compounds were tested for their ability to inhibit the proliferation of bloodstream form ( bsf ) t. b. brucei in culture . as an initial indication of potential toxicity , compounds 4a4z were additionally tested against proliferating human fetal lung fibroblast cells ( mrc5 cell line ) . four compounds ( 4 g , 4j , 4 m , and 4y ) had ec50 values < 1 m and a further 11 compounds had ec50 values <3 m against bsf t. b. brucei ( table 2 ) . the ec50 values correlated well with enzyme activity ( r = 0.73 , figure 5 ) . however , a 100-fold drop from enzyme to cellular activity was observed . selectivity over the mrc5 cells was achieved with compounds 4 m ( 60-fold ) , 4s ( > 19-fold ) , 4x ( 12-fold ) , and 4n ( > 9-fold ) , however , the majority of compounds showed a poor selectivity over mrc5 cells . correlation between the inhibition of recombinant tbgsk3 and bloodstream form t. b. brucei proliferation by r substituted aminopyrazole derivatives ( 4a z ) . as 4 m was the most potent inhibitor of tbgsk3 and proliferation of t. b. brucei cells , we retained the 2,6-dimethoxybenzamide group at position r for optimization of the r substituent . r substituted aminopyrazole analogues ( 9a9x ) were made according to the synthetic route shown in scheme 1b to explore the structural requirements for improvement of antiparasitic activity and selectivity over the closely related human kinases . the majority of variations led to potent tbgsk3 inhibitors , indicating that chemical diversity at this position was well tolerated ( table 3 ) . one of the sar trends observed was that six - membered saturated rings ( 9c ) and seven - membered saturated rings ( 9d ) were favored over their three- and four - membered equivalents ( 9a and 9b ) . further , it was noted that the replacement of the cyclohexane of 9c with a phenyl ring or 4-pyridine , to give 9k or 9l , gave a 6-fold decrease in potency against tbgsk3 . the 2-pyridine analogue ( 9 m ) , on the other hand , was much less active ( 50-fold ) against tbgsk3 . homologation of aromatic ( 9 g ) and saturated six - membered ( 9j ) rings by one carbon atom produced inhibitors with 1 nm activity for tbgsk3 . for aliphatic side chain derivatives 9r9w , the pentanyl and 1-isopropoxypropanyl analogues had ic50 values of 1 nm . the impact of replacing the amide group ( 3-position ) with carboxylic acid and ester groups was investigated with compounds 8 and 7 . compound 8 containing a carboxylate group in the 4-position showed a dramatic loss in activity ( ic50 > 50 m ) . the ester group of compound 7 on the other hand was better tolerated ( ic50 0.5 m ) . interestingly , compared with 4a4z , a majority of r substituted analogues ( 9a9x ) showed selectivity over hscdk2 and hsgsk3. these are the most selective tbgsk3 inhibitors described to date . concentration required to inhibit the growth of t. b. brucei in culture by 50% over 72 h. concentration required to inhibit the growth of mrc5 cells in culture by 50% over 72 h. the predicted binding mode of 9 g in tbgsk3 offers an explanation for the observed selectivity ( figure 6 ) . in the highest scoring docking pose , the core scaffold adopts a similar binding mode as observed for at7519 in hscdk2 ( figure 1 ) . in addition , the docking results suggested that the hydrophobic pocket ii of tbgsk3 was occupied by the n - benzylamide group of 9 g in such a way that its phenyl moiety formed t - shaped edge - to - face interactions with the side chain of phe103 and hydrophobic interactions with leu36 and ala26 . in hgsk3 , phe103 is replaced with a tyr ( table 1 , figure 3a ) , resulting in steric clash and electrostatic repulsion toward the benzyl moiety of 9 g . further , leu36 is substituted with gln72 in hgsk3 and lys20 in hscdk2 , diminishing hydrophobic interactions between the benzyl moiety of 9 g and these residues . overall , these changes together with differences in the gatekeeper region of hscdk2 ( see above ) are likely to be responsible for the high selectivity of 9 g for tbgsk3 over hgsk3 and hscdk2 . similar observations regarding the r group placement and selectivity were also made for compound 9h supporting this model . proposed binding mode of 9 g in the homology model of tbgsk3 ( blue carbon atoms ) overlaid on the hsgsk3 crystal structure ( pink carbon atoms ) . both ligand and protein are represented as sticks and color coded by atom types . ligand carbon atoms are shown in gray , protein carbon atoms of tbgsk3 are shown in blue , and hsgsk3 carbon atoms in salmon . hydrogen bonds and hydrophobic interactions are shown as black dotted lines , with interaction distances in angstroms . tbgsk3 amino acids which are involved in hydrophobic interactions with the benzyl group are marked in bold . the gold sphere represents the center of the phenyl ring .. the r substituted compounds were tested against bsf t. b. brucei and mrc5 cells . as for the r - substituted analogues , a good correlation between the ec50 and ic50 values and a 100-fold drop in activity between the biochemical and cell assay was observed ( figure 7 ) . compound 9c had an ec50 for t. b. brucei of 4 m ( table 3 ) . limited selectivity ( > 7-fold ) over mrc5 cells was achieved with compounds 9c , 9d , 9 g , 9s , and 9 t . it was found that the compounds showed selective inhibition of tbgsk3 over hsgsk3 ( > 20-fold ) and hscdk2 ( > 1200-fold ) . correlation between the inhibition of recombinant tbgsk3 and bloodstream from t. b. brucei proliferation using r substituted aminopyrazole derivatives ( 9a x ) . pk inhibitors frequently inhibit multiple kinases , often leading to off - target toxic effects . to assess the selectivity of the aminopyrazole inhibitors , remaining activity at 10 m concentration was measured for compounds 4f , 4 m , and 4y against a panel of 80 human pks and for compound 9 g against 124 human pks . compounds 4 m and 9 g were found to be highly specific ( table 4 ) . compound 4 m inhibited only two pks , namely gsk3 and cdk2 , at more than 80% . 9 g showed activity against three pks : gsk3 , mapkap - k2 , and mink1 at more than 80% . compound 4f was found to inhibit seven pks and compound 4y 15 pks by greater than 80% at 10 m . numbers represent average percentage of activity compared to the control at 10 m . in this table , only kinases with activity values < 20% are shown ( for full table see supporting information ) . in this work , we exploited the knowledge of the previously described aminopyrazoles inhibitors of hscdk2 and hsgsk3 to identify selective inhibitors of the tbgsk3 short isoform . this kinase has been shown using genetic manipulation studies to be essential for the survival of the t. b. brucei parasite . however , we wanted to confirm if antiparasitic activity could be gained using selective , small molecule inhibitors of tbgsk3 . the ability to selectively inhibit tbgsk3 over hsgsk3 and hscdk2 is essential to avoid potential side effects . therefore , more than 50 aminopyrazole derivatives were synthesized and screened against tbgsk3 , hsgsk3 , hscdk2 , and proliferating t. b. brucei and human cells in culture . the results ( table 2 and table 3 ) showed that almost all compounds were highly potent tbgsk3 inhibitors . the activity could be rationalized using the homology models and subsequent molecular docking studies ( figure 4 and figure 6 ) . the aminopyrazole derivatives make three h - bond interactions with the kinase hinge region , driving much of the potency of the compounds against the three kinases studied . selectivity could be derived from substitution at both r and r positions . from a homology perspective , hscdk2 is the most closely related kinase to hsgsk3. although , the enzymes only share approximately 33% amino acid identity , their atp binding pockets are highly conserved , resulting in the majority of known hscdk2 inhibitors also potently inhibiting hsgsk3. the results demonstrated that the required profile could be achieved , with several compounds with high affinity ( < 18 nm ) for tbgsk3 showing high selectivity ( > 500-fold ) over hscdk2 . docking studies provided a number of important insights into the binding modes and the selectivity profile of aminopyrazole derivatives . first , the docking results suggested that if the phenyl ring of compound 4f is planar with the amide group at r position it can not bind into the truncated gate keeper region of hscdk2 , defined by phe80 in hscdk2 , compared to met101 in tbgsk3 . to fit into this region of hscdk2 , the phenyl ring needs to significantly twist out of plane of the amide , with a torsion angle of approximately 60 , resulting in reduced binding affinity ( figure 4 ) . to stabilize this twist , di - ortho - substituents on the r phenyl group are required to cause a steric / electronic clash with the carbonyl of the amide bond . however , this region of the pocket in hscdk2 is narrow ( in a plane perpendicular to the hinge backbone and the pyrazole core ) , only allowing small ortho - substituents ( such as in compound 9 g ) on the phenyl group . in contrast , the wider gatekeeper regions of hgsk3 and tbgsk3 can tolerate large substituents such as the ortho - dimethoxy groups of compound 4 m or 4n and the ortho - phenylaminobenzamide groups of 4k or 4l . second , the highest increase in selectivity ( > 10000-fold ) over hscdk2 was achieved by accessing the hydrophobic pocket ii . exploitation of hydrophobic interactions in these two pockets not only reliably increased ligand - binding affinity but also impacted on the selectivity profile of these compounds . on the basis of the biological results of compound 9 g and structural modeling studies , we have shown that selectivity over hsgsk3 can be achieved by exploiting the phe103tyr , leu36gln , and ala26ile active site differences in the hydrophobic pocket ii of tbgsk3 enzyme ( figure 6 ) . taken together , the region between the gate keeper residue and the catalytic aspartate of the dfg loop , together with the hydrophobic pocket ii , are the key areas to exploit to achieve high selectivity over hscdk2 . the tbgsk3 short enzyme ic50 values correlated well with the t. b. brucei antiproliferative ec50 activities of the described substituted aminopyrazole inhibitors ( figures 5 and 7 ) , indicating that the compounds act on target . however , a 100-fold drop in cell activity was observed , compared to that in the tbgsk3 assay ( 1 m ) . the calculated physical properties ( mw < 473 ; log p 0.43.6 ; psa < 130 ) of the series of compounds suggest this loss of activity was not driven by lack of cellular penetration . in addition , the compound series was observed to be highly chemically stable under the range of synthetic conditions used during the chemistry campaign , suggesting that chemical degradation was not responsible for the loss of activity in the proliferation assay . although metabolism by the parasite can not be ruled out , the high degree of correlation between enzyme inhibition and antiparasitic activity suggests this is not the case , as it would be not expected that all compounds be metabolized to a constant extent . therefore , the drop of activity was probably due to the high atp concentration ( millimolar range ) in the cell compared to the kinase assay conditions . furthermore , chemical proteomic profiling conducted in parasite cell extracts confirmed that compound 4 m binds the endogenous tbgsk3 short with nanomolar affinity and very few other kinase targets with much lower affinity in the micromolar range . in this study , we have developed a series of substituted aminopyrazole amides as tbgsk3 short inhibitors starting from a compound series initially designed by astex therapeutics to inhibit hscdk2 and hsgsk3. sar investigation and optimization successfully provided 18 low nanomolar ( ic50 < 10 nm ) inhibitors of tbgsk3 with high selectivity ( > 10000-fold ) over hscdk2 . with compound 9 g , we have shown that good ( 330-fold ) selectivity over hsgsk3 can be achieved by targeting the hydrophobic pocket ii . in addition , 9 g proved to be highly selective against a panel of 124 human pks , showing > 90% inhibition at 10 m against only one pk , hsgsk3. molecular modeling has also shown that despite overall conservation in sequence and conformation between the three pks ( hsgsk3 , hscdk2 , and tbgsk3 ) , the binding pockets have distinct features that determine their specificity for particular compounds . further , we have shown that enzymatic inhibition correlates well with cell efficacy over a wide range of concentrations and a representative member of this series binds the endogenous tbgsk3 with nanomolar potency , indicating that compounds definitely act on target . however , a general 100-fold drop in activity between target and cellular activities resulted at best in compounds with low micromolar antiparasitic activity . taken together , this data suggests that specific atp competitive hinge binders of tbgsk3 short require low picomolar potency to obtain nanomolar antiproliferative activity against t. brucei . first , non - atp competitive approaches to inhibition of tbgsk3 , through irreversible hinge binders or allosteric inhibitors , could be pursued . however , these approaches have potential downsides , through the introduction of a reactive functionality or an increased chance of resistance causing mutations , respectively . second , a polypharmacology approach through the inhibition of a number of essential t. brucei kinases in addition to tbgsk3 could be investigated , although obtaining selectivity over human kinases would be more problematical . however , the aminopyrazole compounds ( 4a4z and 9a9x ) reported here represent an excellent start for chemistry optimization of selective tbgsk3 short inhibitors and an outstanding probe for studying the physiological functions of tbgsk3 short in t. brucei parasites . subsequently , modeler 9.2 was used to build homology models of tbgsk3 short , whereas the hsgsk3 crystal structure ( pdb code 1r0e ) served as template . modeler was run with default settings , and only the highest - scoring structure was used for further analysis and modeling . flexx 2.0.1 ( biosolveit gmbh ) was used to dock ligands flexible into protein binding sites . the active sites were defined as the areas within 7 of the co - crystallized ligands of hscdk2 ( pdb code 2vu3 ) and hsgsk3 ( pdb code 1r0e ) or the equivalent residues in the homology model of tbgsk3 . in all three structures , protonation states of amino acids and the orientations of the protons of hydroxyl and amine groups of active - site residues a highly conserved water molecule ( h2o 82 in 1r0e or h2o 2134 in 2vu3 ) was kept in all three protein structures used for docking . docking was carried out using default settings , and only the highest scoring binding modes were visually analyzed . all figures of protein binding sites were prepared using pymol . for compound potency determinations , compounds were solubilized in dmso at a top concentration of 3 mm and serially diluted to achieve 10-point titration of final assay concentrations from 30 m to 0.3 nm with a final dmso concentration of 1% ( v / v ) . the reaction mixtures contained 1 m biotinylated gsp2 substrate , 1 m atp , 3.7 kbq / well [ -33p]-atp and 2.5 nm tbgsk3 in the tbgsk3 kinase assay buffer . gsk3 inhibitors were screened for selectivity assessment also against hsgsk3. for hsgsk3 assay , the reaction mixes contained 1 m biotinylated gsp2 substrate , 2 m atp , 7.4 kbq / well [ -33p]-atp and 15 nm hsgsk3 in the tbgsk3 kinase assay buffer ( 25 mm tris - hcl , ph 7.5 , 10 mm mgcl2 , 5 mm dtt , 0.02% chaps , 2 u / ml heparin ) . for hscdk2/cyclin a assay , the reaction mixtures contained 1 mm cdk5 biotinylated peptide substrate ( biotin - c6-pktpkkakkl ) , 1 m atp , 7.4 kbq / well [ -p]-atp and 2 nm hscdk2/cyclin a in the kinase assay buffer ( 50 mm tris - hcl , ph 7.5 , 10 mm mgcl2 , 2 mm dtt , 100 mm nacl , 0.2 mm egta , 0.02% ( v / v ) brij35 ) . the statistical significance of the compound potency ( ic50 ) was based on the performance of standard molecules which have been tested to a high replication . in the case of tbgsk3 short assay the average pic50 value was 8.26 with a sd ( standard deviation ) of 0.23 . the minimum significant ratio ( msr ) of 0.4 was evaluated considering the following formula : where sd is the standard deviation and n the number of replicate values routinely used for the assay ( 2 in our case ) . this implies that a difference of > 0.4 in pic50 can be considered statistically significant for this assay . in the case of hsgsk3 assay , the standard compound gw8510 was tested 47 times across 5 independent runs , with an average pic50 value of 8.10 and a sd of 0.21 . this implies that a difference of > 0.3 in pic50 can be considered statistically significant for this assay . for the hscdk2 assay , the analysis was performed using two different standards ( gw8510 and staurosporine ) tested respectively five times in a single run and 19 times in 2 independent runs . this implies that a difference of > 0.3 in pic50 can be considered statistically significant for this assay . selected compounds were screened against a panel of mammalian kinases routinely run by the division of signal transduction therapy ( dstt ) at the university of dundee in duplicate at 10 m . enzymes included in the panel and assay conditions are reported in the literature . all biochemical assays are run below the km for the atp for each enzyme , allowing comparison of inhibition across the panel . measurement of inhibition of the proliferation of mrc5 ( human lung fibroblast ) cells and t. b. brucei bloodstream stage cells was performed using a modification of the cell viability assay previously described . compounds ( 50 m to 0.5 nm ) were incubated with 2 10 cells / well in 0.2 ml of the appropriate culture medium ( mem with 10% fetal bovine serum for mrc5 cells ) in clear 96-well plates . plates were incubated at 37 c in the presence of 5% co2 for 69 h. resazurin was then added to a final concentration of 50 m , and plates were incubated as above for a further 4 h before being read on a biotek flx800 fluorescent plate reader . h and c nmr spectra were recorded on either a bruker avance dpx 300 or 500 mhz spectrometer . chemical shifts ( ) are expressed in parts per million ( ppm ) and coupling constants ( j ) are in hertz ( hz ) . signal splitting patterns are described as singlet ( s ) , broad singlet ( br s ) , doublet ( d ) , triplet ( t ) , quartet ( q ) , quintuplet ( quin ) , sextuplet ( sex ) , septet ( sept ) , multiplet ( m ) , or combinations thereof . lcms ( liquid chromatography mass spectrometry ) analyses were performed with either an agilent hplc 1100 series connected to a bruker daltonics microtof or an agilent technologies 1200 series hplc connected to an agilent technologies 6130 quadrupole lcms , and both instruments were connected to an agilent diode array detector . lcms chromatographic separations were conducted with a phenomenex gemini c18 column , 50 mm 3.0 mm , 5 m particle size ; mobile phase / acetonitrile + 0.1% hcooh 80:20 to 5:95 over 3.5 min , and then held for 1.5 min ; flow rate 0.5 ml min . high resolution electrospray measurements ( hrms ) were performed with a bruker daltonics microtof mass spectrometer . thin layer chromatography ( tlc ) was carried out on merck silica gel 60 f254 plates using uv light and/or kmno4 for visualization . when applicable , all glassware was oven - dried overnight and all reactions were carried out under dry and inert conditions ( argon atmosphere ) . all in this work synthesized compounds had a measured purity of greater than 95% ( measured on analytical hplc - ms system ) . m data are given below to substantiate the purity and integrity of the compounds . h nmr , c nmr , and hrms experiments were also used to confirm compound identity and purity . a mixture of 4-nitro-3-pyrazolecarboxylic acid ( 1 ) ( 2.33 g , 14.8 mmol ) , trans-4-methoxy - cyclohexylamine ( 2.39 g , 18.5 mmol ) , edc ( 3.55 g , 18.5 mmol ) , and hobt ( 2.50 g , 18.5 mmol ) in dmf ( 75 ml ) was stirred at ambient temperature for 16 h. the mixture was reduced in vacuo and partitioned between saturated aqueous sodium bicarbonate and etoac . the organic layer was washed ( water , brine ) , dried ( mgso4 ) , and reduced in vacuo to give a yellow oil , which was purified by column chromatography , eluting 0100% etoac in petroleum ether to give 2 . h nmr ( dmso - d6 dmso - d6 ) ( ppm ) 14.02 ( s , 1h ) , 8.73 ( s , 1h ) , 8.57 ( d , j = 7.81 hz , 1h ) , 3.74 ( m , 1h ) , 3.24 ( s , 3h ) , 3.11 ( m , 1h ) , 1.95 ( dd , j = 55.8 , 10.9 hz , 4h ) , 1.27 ( m , 4h ) . c nmr ( dmso - d6 ) ( ppm ) 159.04 , 141.49 , 132.17 , 131.44 , 77.40 , 55.01 , 47.58 , 29.67 , 29.30 . lrms ( es ) : a solution of 2 ( 1.13 g , 4.2 mmol ) in dmf ( 100 ml ) was treated with 10% palladium on carbon then shaken under hydrogen at room temperature and atmospheric pressure for 5 h. the reaction mixture was diluted with etoac , filtered through celite , washing with further etoac , and the filtrate reduced in vacuo to give crude 3 as brown oil . yield : 982 mg , 98% . h nmr ( cd3od ) ( ppm ) 7.23 ( s , 1h ) , 3.84 ( m , 1h ) , 3.37 ( s , 3h ) , 3.23 ( m , 1h ) , 2.07 ( dd , j = 45.8 , 11.2 hz , 4h ) , 1.38 ( m , 4h ) . c nmr ( meod - d4 ) ( ppm ) 165.58 , 134.15 , 133.13 , 118.22 , 79.72 , 56.15 , 48.58 , 31.37 . lrms ( es ) : m / z 239 [ m + h ] . a mixture of benzoic acid ( 0.051 g , 0.42 mmol ) , 3 ( 0.1 g , 0.42 mmol ) , edc ( 0.096 g , 0.5 mmol ) , and hobt ( 0.068 g , 0.5 mmol ) in dmf ( 10 ml ) was stirred at ambient temperature for 16 h. the mixture was reduced in vacuo and partitioned between saturated aqueous sodium bicarbonate and etoac . the organic layer was washed ( water , brine ) , dried ( mgso4 ) , and reduced in vacuo to give a creamy solid 4f , which was purified by column chromatography . evaporation of the appropriate fraction yielded the desired compound as an amorphous solid . h nmr ( cdcl3 ) ( ppm ) 10.65 ( s , 1h ) , 8.52 ( s , 1h ) , 8.01 ( d , j = 7.2 hz , 2h ) , 7.57 ( t , j = 7.2 hz , 1h ) , 7.51 ( m , 2h ) , 6.86 ( d , j = 8.3 hz , 1h ) , 4.01 ( m , 1h ) , 3.39 ( s , 3h ) , 3.22 ( m , 1h ) , 2.16 ( m , 4h ) , 1.42 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 164.36 , 163.21 , 133.54 , 133.28 , 132.03 , 128.83 , 127.24 , 123.74 , 120.82 , 78.13 , 55.91 , 47.48 , 30.69 , 30.11 . hrms ( es ) : calcd for c18h23n4o3 [ m + h ] 343.1765 , found 343.1751 . h nmr ( cdcl3 ) ( ppm ) 9.86 ( s , 1h ) , 8.35 ( s , 1h ) , 6.83 ( d , j = 8.3 hz , 1h ) , 3.95 ( m , 1h ) , 3.39 ( s , 3h ) , 3.21 ( m , 1h ) , 2.44 ( m , 1h ) , 2.22 ( m , 2h ) , 2.11 ( m , 6h ) , 1.94 ( m , 2h ) , 1.81 ( m , 2h ) , 1.40 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 171.61 , 163.21 , 133.28 , 123.22 , 122.55 ( t , j = 239.4 hz ) , 120.71 , 78.07 , 55.91 , 47.50 , 42.74 , 32.85 ( t , j = 23.5 hz ) , 30.35 , 25.73 . hrms ( es ) : calcd for c18h27f2n4o3 [ m + h ] 385.2046 , found 385.2036 . h nmr ( cdcl3 ) ( ppm ) 9.86 ( s , 1h ) , 8.34 ( s , 1h ) , 6.81 ( d , j = 8.1 hz , 1h ) , 4.07 ( m , 2h ) , 3.95 ( m , 1h ) , 3.47 ( m , 2h ) , 3.39 ( s , 3h ) , 3.20 ( m , 1h ) , 2.59 ( m , 1h ) , 2.13 ( d , j = 11.0 hz , 4h ) , 1.91 ( m , 4h ) , 1.40 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 171.97 , 163.30 , 133.22 , 123.23 , 120.71 , 78.12 , 67.26 , 55.92 , 47.50 , 42.20 , 30.64 , 30.12 , 29.10 . lrms ( es ) : m / z 351 [ m + h ] . hrms ( es ) : calcd for c17h27n4o4 [ m + h ] 351.2027 , found 351.2011 . h nmr ( cd3od ) ( ppm ) 8.20 ( s , 1h ) , 7.38 ( t , 7.7 hz , 1h ) , 7.347.26 ( m , 1h ) , 7.187.05 ( m , 2h ) , 3.83 ( m , 1h ) , 3.80 ( s , 2h ) , 3.33 ( s , 3h ) , 3.16 ( m , 1h ) , 2.06 ( br d , j = 11.5 hz , 2h ) , 1.97 ( br d , j = 12.0 hz , 2h ) , 1.34 ( m , 4h ) . c nmr ( cd3od ) ( ppm ) 169.57 , 164.14 ( d , j = 159.5 hz ) , 134.23 , 132.98 , 130.64 ( d , j = 10.9 hz ) , 125.75 , 123.77 , 123.20 ( d , j = 18.2 hz ) , 121.96 , 116.48 ( d , j = 21.7 hz ) , 79.69 , 56.14 , 48.68 , 37.61 , 31.41 , 31.27 . hrms ( es ) : calcd for c19h24fn4o3 [ m + h ] 375.1827 , found 375.1817 . h nmr ( dmso - d6 ) ( ppm ) 13.13 ( s , 1h ) , 9.76 ( s , 1h ) , 8.15 ( s , 1h ) , 8.00 ( d , j = 8.3 hz , 1h ) , 7.317.23 ( m , 2h ) , 7.02 ( d , j = 8.0 hz , 1h ) , 6.93 ( t , j = 7.4 hz , 1h ) , 3.82 ( s , 3h ) , 3.793.70 ( m , 1h ) , 3.24 ( s , 3h ) , 3.07 ( m , 1h ) , 2.01 ( d , j = 11.4 hz , 2h ) , 1.79 ( d , j = 11.4 hz , 2h ) , 1.45 ( m , 2h ) , 1.21 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 167.30 , 162.43 , 157.02 , 132.38 , 130.90 , 128.59 , 123.21 , 122.30 , 120.44 , 119.70 , 110.88 , 77.70 , 55.41 , 55.04 , 46.70 , 38.17 , 30.26 , 29.73 . lrms(es ) : m / z 387 [ m + h ] . hrms ( es ) : calcd for c20h27n4o4 [ m + h ] 387.2027 , found 387.2028 . h nmr ( dmso - d6 ) ( ppm ) 13.18 ( br s , 1h ) , 9.86 ( s , 1h ) , 8.14 ( s , 1h ) , 8.05 ( d , j = 7.9 hz , 1h ) , 7.51 ( d , j = 8.2 hz , 2h ) , 7.36 ( t , j = 8.2 hz , 1h ) , 4.10 ( s , 2h ) , 3.76 ( m , 1h ) , 3.24 ( s , 3h ) , 3.08 ( s , 1h ) , 2.01 ( m , 2h ) , 1.81 ( m , 2h ) , 1.45 ( m , 2h ) , 1.19 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 170.16 , 162.31 , 135.49 , 131.62 , 129.68 , 128.30 , 128.10 , 122.23 , 122.09 , 77.68 , 55.04 , 46.77 , 38.23 , 30.25 , 29.74 . hrms ( es ) : calcd for c19h23cl2n4o3 [ m + h ] 425.1142 , found 425.1147 . h nmr ( cdcl3 ) ( ppm ) 10.89 ( d , j = 12.2 hz , 1h ) , 8.45 ( s , 1h ) , 8.07 ( m , 1h ) , 7.44 ( m , 1h ) , 7.22 ( m , 1h ) , 7.13 ( m , 1h ) , 6.73 ( d , j = 8.3 hz , 1h ) , 3.96 ( m , 1h ) , 3.29 ( s , 3h ) , 3.11 ( m , 1h ) , 2.05 ( m , 4h ) , 1.31 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 162.80 , 160.84 ( d , j = 246.9 hz ) , 160.53 , 133.81 ( d , j = 10.9 hz ) , 131.77 , 124.79 , 123.19 , 121.42 , 120.65 ( d , j = 10.7 hz ) , 116.46 ( d , j = 21.8 hz ) , 78.19 , 55.88 , 47.27 , 30.75 , 30.14 . lrms ( es ) : m / z 361 [ m + h ] . hrms ( es ) : calcd for c18h22fn4o3 [ m + h ] 361.1670 , found 361.1645 . h nmr ( dmso - d6 ) ( ppm ) 13.40 ( s , 1h ) , 10.22 ( s , 1h ) , 8.32 ( s , 1h ) , 8.29 ( d , j = 8.6 hz , 1h ) , 7.907.88 ( m , 1h ) , 7.847.81 ( m , 1h ) , 7.787.75 ( m , 2h ) , 3.72 ( m , 1h ) , 3.23 ( s , 3h ) , 3.06 ( m , 1h ) , 2.00 ( br d , j = 12.5 hz , 2h ) , 1.76 ( br d , j = 12.5 hz , 2h ) , 1.45 ( m , 2h ) , 1.14 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 163.34 , 162.73 , 135.06 , 133.01 , 132.78 , 130.73 , 128.39 , 126.63 ( d , j = 5.2 hz ) 126.04 ( d , j = 29.1 hz ) , 123.57 ( d , j = 276.3 hz ) , 122.06 , 120.30 , 77.66 , 55.06 , 46.97 , 30.28 , 29.67 . lrms ( es ) : m / z 411 [ m + h ] . hrms ( es ) : calcd for c19h22f3n4o3 [ m + h ] 411.1639 , found 411.1621 . h nmr ( cdcl3 ) ( ppm ) 10.04 ( s , 1h ) , 8.39 ( s , 1h ) , 7.53 ( d , j = 7.6 hz , 1h ) , 7.39 ( t , j = 7.6 hz , 1h ) , 7.30 ( d , 7.7 hz , 1h ) , 7.25 ( t , j = 7.5 hz , 1h ) , 6.87 ( d , j = 8.3 hz , 1h ) , 3.92 ( m , 1h ) , 3.36 ( s , 3h ) , 3.16 ( m , 1h ) , 2.90 ( q , j = 7.6 hz , 2h ) , 2.08 ( br d , j = 10.0 hz , 4h ) , 1.35 ( m , 4h ) , 1.26 ( t , j = 7.6 hz , 3h ) . c nmr ( cdcl3 ) ( ppm ) 167.60 , 163.29 , 142.86 , 134.89 , 133.19 , 130.65 , 129.69 , 127.15 , 126.11 , 123.25 , 120.94 , 78.18 , 55.86 , 74.45 , 30.58 , 30.12 , 26.44 , 15.84 . hrms ( es ) : calcd for c20h27n4o3 [ m + h ] 371.2078 , found 371.2078 . h nmr : ( dmso - d6 ) ( ppm ) 13.25 ( s , 1h ) , 11.77 ( s , 1h ) , 8.44 ( s , 1h ) , 8.15 ( s , 1h ) , 8.04 ( s , 1h ) , 7.63 ( s , 1h ) , 7.29 ( s , 1h ) , 7.18 ( s , 1h ) , 4.15 ( s , 3h ) , 3.88 ( m , 1h ) , 3.30 ( s , 3h ) , 3.16 ( m , 1h ) , 2.08 ( m , 2h ) , 1.91 ( m , 2h ) , 1.55 ( m , 2h ) , 1.29 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 162.43 , 160.94 , 157.47 , 133.49 , 131.33 , 122.29 , 120.83 , 120.59 , 120.28 , 112.32 , 77.73 , 56.05 , 55.05 , 46.72 , 30.28 , 29.83 . lrms ( es ) : m / z 373 [ m + h ] . hrms ( es ) : calcd for c19h25n4o4 [ m + h ] 373.1870 , found 373.1873 . h nmr ( dmso - d6 ) ( ppm ) 13.32 ( br s , 1h ) , 10.93 ( s , 1h ) , 9.53 ( s , 1h ) , 8.31 ( s , 1h ) , 8.28 ( d , j = 8.5 hz , 1h ) , 7.68 ( dd , j = 8.0 , 1.4 hz , 1h ) , 7.43 ( m , 1h ) , 7.337.28 ( m , 3h ) , 7.167.14 ( m , 2h ) , 7.016.96 ( m , 2h ) , 3.82 ( m , 1h ) , 3.35 ( s , 1h ) , 3.25 ( s , 3h ) , 3.09 ( m , 1h ) , 2.03 ( br d , j = 12.0 hz , 2h ) , 1.81 ( br d , j = 12.0 hz , 2h ) , 1.48 ( m , 2h ) , 1.20 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 164.84 , 162.97 , 144.57 , 141.62 , 132.81 , 129.33 , 128.04 , 122.32 , 122.00 , 120.01 , 119.63 , 119.26 , 118.30 , 116.49 , 77.74 , 55.06 , 46.95 , 30.33 , 29.73 . lrms ( es ) : m / z 434 [ m + h ] . hrms ( es ) : calcd for c24h28n5o3 [ m + h ] 434.2187 , found 434.2165 . h nmr ( dmso - d6 ) ( ppm ) 13.35 ( br s , 1h ) , 10.89 ( s , 1h ) , 9.53 ( s , 1h ) , 8.33 ( s , 1h ) , 7.63 ( dd , j = 8.1 , 1.4 hz , 1h ) , 7.34 ( m , 1h ) , 7.117.09 ( m , 2h ) , 6.996.97 ( m , 1h ) , 6.87 ( m , 1h ) , 6.82 ( dd , j = 8.4 , 1.0 hz , 1h ) , 3.84 ( m , 1h ) , 3.35 ( s , 1h ) , 3.25 ( s , 3h ) , 3.09 ( m , 1h ) , 2.29 ( s , 3h ) , 2.14 ( s , 3h ) , 2.03 ( br d , j = 12.0 hz , 2h ) , 1.82 ( br d , j = 12.0 hz , 2h ) , 1.49 ( m , 2h ) , 1.21 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 165.36 , 163.08 , 147.05 , 138.87 , 137.74 , 132.95 , 132.72 , 130.25 , 127.52 , 125.96 , 125.74 , 122.41 , 120.79 , 119.98 , 117.44 , 115.36 , 114.63 , 77.74 , 55.06 , 46.95 , 30.33 , 29.75 , 20.25 , 13.64 . lrms ( es ) : m / z 462 [ m + h ] . hrms ( es ) : calcd for c26h32n5o3 [ m + h ] 462.2500 , found 462.2503 . h nmr ( dmso - d6 ) ( ppm ) 13.28 ( s , 1h ) , 9.75 ( s , 1h ) , 8.29 ( s , 1h ) , 8.20 ( d , j = 8.4 hz , 1h ) , 7.39 ( t , j = 8.5 hz , 1h ) , 6.75 ( d , j = 8.5 hz , 2h ) , 3.76 ( s , 6h ) , 3.70 ( m , 1h ) , 3.22 ( s , 3h ) , 3.06 ( m , 1h ) , 2.00 ( m , 2h ) , 1.76 ( m , 2h ) , 1.45 ( m , 2h ) , 1.13 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 162.79 , 161.21 , 156.88 , 132.21 , 131.08 , 122.52 , 119.81 , 115.03 , 104.28 , 77.66 , 55.81 , 55.08 , 46.93 , 30.29 , 29.66 . lrms ( es ) : . hrms ( es ) : calcd for c20h27n4o5 [ m + h ] 403.1976 , found 403.1960 . h nmr ( cd3od ) ( ppm ) 8.36 ( s , 1h ) , 6.17 ( s , 2h ) , 3.84 ( s , 3h ) , 3.82 ( s , 6h ) , 3.35 ( s , 3h ) , 3.22 ( m , 1h ) , 2.08 ( m , 4h ) , 1.36 ( m , 4h ) . c nmr ( cd3od ) ( ppm ) 164.90 , 164.72 , 164.35 , 160.74 , 134.07 , 124.36 , 122.58 , 108.39 , 92.09 , 79.74 , 57.05 , 56.89 , 56.62 , 48.71 , 31.61 , 31.40 . lrms ( es ) : m / z 433 [ m + h ] . hrms ( es ) : calcd for c21h29n4o6 [ m + h ] 433.2082 , found 433.2065 . h nmr ( dmso - d6 ) ( ppm ) 13.24 ( s , 1h ) , 10.89 ( d , j = 10.2 hz , 1h ) , 8.33 ( s , 1h ) , 8.09 ( q , j = 8.7 hz , 1h ) , 8.05 ( d , j = 8.4 hz , 1h ) , 7.39 ( m , 1h ) , 7.24 ( m , 1h ) , 3.82 ( m , 1h ) , 3.25 ( s , 3h ) , 3.10 ( m , 1h ) , 2.02 ( d , j = 10.3 hz , 2h ) , 1.84 ( d , j = 11.6 hz , 2h ) , 1.47 ( q , j = 12.0 hz , 2h ) , 1.22 ( q , j = 12.5 hz , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 164.3 ( q , j = 250.6 , 10.9 hz ) , 162.71 , 160.3 ( q , j = 250.8 , 14.5 hz ) , 158.03 , 133.26 , 133.18 , 132.82 , 122.12 , 120.50 , 117.39 , 117.31 , 112.59 , 112.42 , 104.96 , 104.75 , 104.52 , 79.12 , 78.84 , 78.58 , 77.71 , 55.07 , 46.89 , 30.09 , 29.76;. lrms ( es ) : m / z 379 [ m + h ] . hrms ( es ) : calcd for c18h21f2n4o3 [ m + h ] 379.1576 , found 379.1567 . h nmr ( dmso - d6 ) ( ppm ) 13.39 ( s , 1h ) , 10.77 ( s , 1h ) , 8.34 ( d , j = 8.5 hz , 1h ) , 8.30 ( s , 1h ) , 7.59 ( m , 1h ) , 7.52 ( m , 2h ) , 3.84 ( m , 1h ) , 3.24 ( s , 3h ) , 3.09 ( m , 1h ) , 2.02 ( d , j = 10.7 hz , 2h ) , 1.81 ( d , j = 10.7 hz , 2h ) , 1.49 ( q , j = 11.8 hz , 2h ) , 1.20 ( q , j = 11.8 hz , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 162.8 , 162.5(q , j = 250.7 , 14.4 hz ) , 160.3 , 137.16 127.75 , 126.59 , 124.12 , 122.13 , 118.94 , 110.2 ( q , j = 22.0 , 14.5 hz ) , 107.5 ( t , j = 27.0 hz ) , 77.71 , 55.06 , 46.99 , 30.29 , 29.76 . lrms ( es ) : m / z 379 [ m + h ] . hrms ( es ) : calcd for c18h21f2n4o3 [ m + h ] 379.1576 , found 379.1568 . h nmr ( cdcl3 ) ( ppm ) 10.34 ( s , 1h ) , 8.23 ( s , 1h ) , 7.60 ( d , j = 1.9 hz , 2h ) , 7.31 ( t , j = 1.8 hz , 1h ) , 7.05 ( s , 1h ) , 6.58 ( d , 1h ) , 3.77 ( m , 1h ) , 3.15 ( s , 3h ) , 2.98 ( m , 1h ) , 1.91 ( m , 4h ) , 1.18 ( m , 4h ) . c nmr ( dmso - d6 ) ( ppm ) 163.12 , 161.74 , 136.46 , 135.73 , 131.89 , 128.34 , 126.03 , 125.79 , 121.09 , 78.10 , 55.91 , 47.48 , 30.69 , 30.08 . lrms ( es ) : m / z 411 [ m + h ] . hrms ( es ) : calcd for c18h21cl2n4o3 [ m + h ] 411.0985 , found 411.0966 . h nmr ( cdcl3 ) ( ppm ) 10.65 ( s , 1h ) , 8.48 ( s , 1h ) , 8.02 ( d , j = 8.6 hz , 2h ) , 7.24 ( d , j = 8.6 hz , 2h ) , 6.84 ( d , j = 8.3 hz , 1h ) , 6.62 ( t , j = 73.2 hz , 1h ) , 4.00 ( m , 1h ) , 3.39 ( s , 3h ) , 3.22 ( m , 1h ) , 2.15 ( m , 4h ) , 1.42 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 163.28 , 163.20 , 154.0 ( t , j = 2.9 hz ) , 133.56 , 130.28 , 129.24 , 123.64 , 120.74 , 119.22 , 118.94 , 115.47 , 112.01 , 78.11 , 55.94 , 47.53 , 30.67 , 30.12 . hrms ( es ) : calcd for c19h23f2n4o4 [ m + h ] 409.1682 , found 409.1649 . h nmr ( cdcl3 ) ( ppm ) 10.44 ( s , 1h ) , 8.49 ( s , 1h ) , 7.89 ( d , j = 8.8 hz , 2h ) , 6.85 ( d , j = 8.3 hz , 1h ) , 6.62 ( d , j = 8.8 hz , 2h ) , 4.01 ( m , 1h ) , 3.39 ( m , 7h ) , 3.20 ( m , 1h ) , 2.15 ( m , 4h ) , 2.06 ( m , 4h ) , 1.41 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 164.74 , 163.48 , 150.26 , 133.26 , 128.99 , 124.26 , 120.52 , 119.42 , 111.20 , 78.20 , 55.92 , 47.66 , 47.39 , 30.73 , 30.18 , 25.46 . hrms ( es ) : calcd for c22h30n5o3 [ m + h ] 412.2343 , found 412.2338 . h nmr ( cdcl3 ) ( ppm ) 10.48 ( s , 1h ) , 8.47 ( s , 1h ) , 7.90 ( d , j = 8.8 hz , 2h ) , 6.94 ( d , j = 8.8 hz , 2h ) , 6.83 ( m , 1h ) , 4.00 ( m , 1h ) , 3.39 ( s , 3h ) , 3.37 ( t , j = 5 hz , 4h ) , 3.20 ( m , 1h ) , 2.60 ( t , j = 5 hz , 4h ) , 2.38 ( s , 3h ) , 2.14 ( m , 4h ) , 1.41 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 164.17 , 163.44 , 153.54 , 133.33 , 128.81 , 124.05 , 122.92 , 120.61 , 114.27 , 78.17 , 55.92 , 54.79 , 47.62 , 47.41 , 46.11 , 30.72 , 30.17 . lrms ( es ) : m / z 441 [ m + h ] . hrms ( es ) : calcd for c23h33n6o3 [ m + h ] 441.2609 , found 441.2597 . h nmr ( cdcl3 ) ( ppm ) 10.76 ( s , 1h ) , 8.53 ( s , 1h ) , 7.70 ( d , j = 7.5 hz , 1h ) , 7.66 ( d , j = 8.4 hz , 1h ) , 7.59 ( d , j = 0.9 hz , 1h ) , 7.46 ( t , j = 7.8 hz , 1h ) , 7.33 ( t , j = 7.5 hz , 1h ) , 6.85 ( d , j = 8.4 hz , 1h ) , 4.07 ( m , 1h ) , 3.40 ( s , 3h ) , 3.22 ( m , 1h ) , 2.16 ( m , 4h ) , 1.43 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 163.03 , 156.21 , 155.22 , 148.18 , 133.76 , 129.23 , 127.56 , 127.24 , 123.77 , 122.59 , 121.20 , 112.41 , 111.23 , 78.15 , 55.91 , 47.41 , 30.74 , 30.14 . hrms ( es ) : calcd for c20h23n4o4 [ m + h ] 383.1714 , found 383.1703 . h nmr ( dmso - d6 ) ( ppm ) 13.30 ( s , 1h ) , 11.01 ( s , 1h ) , 8.83 ( d , j = 7.0 hz , 1h ) , 8.37 ( s , 1h ) , 8.15 ( d , j = 8.4 hz , 1h ) , 7.82 ( d , j = 8.9 hz , 1h ) , 7.34 ( t , j = 7.7 hz , 1h ) , 7.09 ( t , j = 6.9 hz , 1h ) , 3.85 ( m , 1h ) , 3.26 ( s , 3h ) , 3.11 ( m , 1h ) , 2.04 ( d , j = 10.3 hz , 2h ) , 1.84 ( d , j = 10.7 hz , 2h ) , 1.49 ( m , 2h ) , 1.23 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 162.70 , 158.15 , 146.85 , 141.15 , 132.80 , 128.99 , 124.60 , 122.00 , 120.08 , 119.14 , 114.53 , 97.79 , 77.74 , 55.06 , 46.95 , 30.33 , 29.79 . lrms ( es ) : m / z 383 [ m + h ] . hrms ( es ) : calcd for c19h23n6o3 [ m + h ] 383.1826 , found 383.1812 . h nmr ( meod - d4 ) ( ppm ) 9.57 ( d , j = 6.9 hz , 1h ) , 8.31 ( d , j = 8.3 hz , 2h ) , 7.74 ( d , j = 9.0 hz , 1h ) , 7.57 ( td , j = 6.9 , 1.2 hz , 1h ) , 7.19 ( t , j = 6.9 , 1.2 hz , 1h ) , 3.94 ( m , 1h ) , 3.39 ( s , 3h ) , 3.27 ( m , 1h ) , 2.12 ( m , 4h ) , 1.50 ( m , 2h ) , 1.39 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 162.89 , 156.52 , 147.37 , 136.35 , 127.61 , 127.41 , 122.12 , 119.89 , 117.57 , 117.46 , 114.43 , 77.71 , 55.07 , 46.90 , 30.30 , 29.76 . lrms ( es ) : m / z 383 [ m + h ] . hrms ( es ) : calcd for c19h23n6o3 [ m + h ] 383.1826 , found 383.1811 . h nmr ( cdcl3 ) ( ppm ) 10.88 ( s , 1h ) , 10.24 ( s , 1h ) , 9.58 ( d , j = 6.9 hz , 1h ) , 8.51 ( s , 1h ) , 7.67 ( d , j = 9.0 hz , 1h ) , 7.41 ( t , j = 7.9 hz , 1h ) , 6.99 ( t , j = 6.9 hz , 1h ) , 6.80 ( d , j = 7.9 hz , 1h ) , 4.01 ( m , 1h ) , 3.39 ( s , 3h ) , 3.21 ( m , 1h ) , 3.02 ( s , 3h ) , 2.14 ( m , 4h ) , 1.41 ( m , 4h ) . c nmr ( dmso - d6 ) ( ppm ) 162.73 , 157.27 , 146.18 , 145.49 , 127.61 , 127.42 , 122.35 , 120.04 , 116.31 , 114.46 , 113.62 , 77.74 , 55.06 , 46.77 , 30.24 , 29.81 , 16.52 . lrms ( es ) : m / z 397 [ m + h ] . hrms ( es ) : calcd for c20h25n6o3 [ m + h ] 397.1983 , found 397.1972 . h nmr ( cdcl3 ) : ( ppm ) 10.61 ( s , 1h ) , 8.49 ( s , 1h ) , 7.84 ( m , 2h ) , 7.48 ( t , j = 7.5 hz , 2h ) , 7.38 ( t , j = 7.4 hz , 1h ) , 7.31 ( t , j = 3.6 hz , 1h ) , 6.85 ( d , j = 8.5 hz , 1h ) , 6.80 ( d , j = 3.6 hz , 1h ) , 4.07 ( m , 1h ) , 3.40 ( s , 3h ) , 3.22 ( m , 1h ) , 2.16 ( m , 4h ) , 1.42 ( m , 4h ) . c nmr ( cdcl3 ) ( ppm ) 163.03 , 156.39 , 155.72 , 146.33 , 133.74 , 129.49 , 128.94 , 128.80 , 124.72 , 122.85 , 120.91 , 117.13 , 107.30 , 78.18 , 55.88 , 47.25 , 30.78 , 30.14 . lrms ( es ) : m / z 409 [ m + h ] . hrms ( es ) : calcd for c22h25n4o4 [ m + h ] 409.1870 , found 409.1832 . h nmr ( dmso - d6 ) ( ppm ) 13.30 ( s , 1h ) , 11.20 ( s , 1h ) , 8.68 ( s , 1h ) , 8.38 ( s , 1h ) , 8.30 ( m , 2h ) , 8.14 ( d , j = 8.4 hz , 1h ) , 7.587.51 ( m , 3h ) , 3.83 ( m , 1h ) , 3.26 ( s , 3h ) , 3.11 ( m , 1h ) , 2.04 ( d , j = 10.5 hz , 2h ) , 1.84 ( d , j = 11.0 hz , 2h ) , 1.49 ( q , j = 12.5 hz , 2h ) , 1.23 ( q , j = 11.5 hz , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 162.64 , 157.34 , 151.99 , 150.43 , 132.90 , 130.23 , 128.50 , 128.07 , 127.92 , 126.62 , 121.89 , 120.02 , 77.74 , 55.06 , 47.00 , 30.33 , 29.76 . lrms ( es ) : m / z 410 [ m + h ] . hrms ( es ) : calcd for c21h24n5o4 [ m + h ] 410.1823 , found 410.1807 . a 100 ml three - necked round - bottomed flask equipped with a magnetic stirring bar and fitted with a dropping funnel was charged with 4-nitro-1h - pyrazole-3-carboxylic acid ( 4.0 g , 25.5 mmol ) and methanol ( 40 ml ) . the flask was cooled to 0 c , and thionyl chloride ( 2.1 ml , 28.9 mmol ) was added to the vigorously stirred solution over a period of 10 min . the mixture was stirred for an additional 12 h at room temperature , after which time tlc indicated complete consumption of the starting acid . the reaction mixture was concentrated under reduced pressure at 40 c and the residue treated with toluene and reconcentrated ( 3 20 ml ) under reduced pressure at 40 c to give methyl ester 5 as an off - white solid . h nmr ( dmso - d6 ) ( ppm ) 14.39 ( br s , 1h ) , 9.98 ( s , 1h ) , 3.90 ( s , 3h ) . c nmr ( dmso - d6 ) ( ppm ) 161.15 , 138.13 , 133.20 , 130.90 , 52.84 . lrms ( es ) : m / z 172 [ m + h ] . a 100 ml round - bottomed flask equipped with digital thermometer and stirrer was charged with 10% palladium on carbon ( 0.621 g ) under argon . in a separate vessel , a slurry of methyl ester 5 ( 4.42 g , 25.8 mmol ) in ethanol ( 45 ml ) was warmed to 35 c to effect dissolution and the solution added to the catalyst under argon . following a nitrogen hydrogen purge sequence , an atmosphere of hydrogen was introduced and the reaction mixture maintained at 30 c until the reaction completion ( 6 h ) was noted by h nmr analysis . following a purge cycle , the reaction mixture under argon was filtered and the liquors concentrated under reduced pressure to give amine 6 as a solid . h nmr ( dmso - d6 ) ( ppm ) 12.83 ( br s , 1h ) , 7.10 ( s , 1h ) , 4.83 ( br s , 2h ) , 3.78 ( s , 3h ) . c nmr ( dmso - d6 ) ( ppm ) 160.39 , 136.94 , 128.43 , 115.59 , 50.88 . lrms ( es ) : a solution of amine 6 ( 3.57 g , 25.3 mmol ) in 1,4-dioxane ( 50 ml ) under argon was treated with triethylamine ( 4.3 ml , 31 mmol ) followed by 2,6-dimethoxybenzoyl chloride ( 6.13 g , 30.6 mmol ) such that the internal temperature was maintained in the range 2025 c . the reaction mixture was stirred at 25 c until the reaction was complete ( 12 h ) by tlc analysis . the reaction mixture was filtered , the filter - cake washed with 1,4-dioxane , and the combined filtrates progressed to next stage without further isolation . to obtain analytical data for compound 7 and also to determine the yield of this reaction , a 2 g sample was taken out of the homogeneous filtrate solution ( total weight of this solution is 91 g ) . the crude product ( 192 mg ) was purified by column chromatography ( dcm / meoh ) . evaporation of the appropriate fractions yielded finally the desired compound 7 as an amorphous solid ( 161 mg ) . a 5 mg sample was used for to obtain analytical data ; the rest was redissolved for use in the next reaction . h nmr ( dmso - d6 ) 13.68 ( br s , 1h ) , 9.16 ( s , 1h ) , 8.31 ( s , 1h ) , 7.41 ( t , j = 8.4 hz , 1h ) , 6.76 ( d , j = 8.4 hz , 2h ) , 3.83 ( s , 3h ) , 3.77 ( s , 6h ) . c nmr ( dmso - d6 ) ( ppm ) 163.86 , 161.55 , 157.07 , 131.27 , 129.97 , 123.61 , 120.41 , 114.66 , 104.35 , 55.84 , 51.63 . hrms ( es ) : calcd for c14h16n3o5 [ m + h ] 306.1084 , found 306.1081 . to a solution of sodium hydroxide ( 3.32 g , 83 mmol ) in water ( 20 ml ) was charged a solution of ester 7 in one portion ( 7.33 g , 24.0 mmol ; the solution of crude 7 from the previous reaction , plus 156 mg of redissolved pure 7 ) . the reaction mixture was stirred at 25 c until completion as determined by tlc analysis . the reaction mixture was concentrated under reduced pressure at 45 c , the oily residue diluted with water and acidified to ph 1 with concentrated hydrochloric acid , such that the temperature was maintained below 30 c . the resulting precipitate was collected by filtration , washed with water , pulled dry on the filter , and subsequently washed with heptanes . the filter cake was charged to a 200 ml rotary evaporator flask and drying completed azeotropically with toluene . h nmr ( dmso - d6 ) 13.44 ( br s , 2h ) , 9.17 ( br s , 1h ) , 8.29 ( s , 1h ) , 7.40 ( t , j = 8.4 hz , 1h ) , 6.76 ( d , j = 8.4 hz , 2h ) , 3.77 ( s , 6h ) . hrms ( es ) : calcd for c13h14n3o5 [ m + h ] 292.0928 , found 292.0920 . a mixture of carboxylic acid ( 50 mg , 0.17 mmol , 1.2 equiv ) , amine ( 14 mg , 0.14 mmol , 1.0 equiv ) , hydroxybenzotriazole ( 19 mg , 0.14 mmol , 1.0 equiv ) , polymer supported - carbodiimide ( 105 mg , 0.14 mmol , 1.0 equiv ) , and acetonitrile was heated by microwave irradiation for 10 min at 100 c . the final product ( 9c ) was isolated from the reaction mixture by filtering through a short column of si - carbonate under gravity , which scavenged the excess carboxylic acid and hydroxybenzotriazole . removal of the solvent under reduced pressure yielded the required compounds as amorphous solids . h nmr ( cd3od ) ( ppm ) 8.33 ( s , 1h ) , 7.42 ( t , j = 8.5 hz , 1h ) , 6.75 ( d , j = 8.4 hz , 2h ) , 3.86 ( s , 6h ) , 3.82 ( m , 1h ) , 1.88 ( m , 4h ) , 1.68 ( d , j = 12.8 hz , 1h ) , 1.40 ( m , 4h ) , 1.27 ( m , 1h ) . c nmr ( cd3od ) ( ppm ) 165.02 , 164.71 , 159.24 , 134.17 , 132.97 , 123.89 , 121.82 , 115.64 , 105.24 , 56.50 , 49.36 , 33.77 , 26.58 , 26.19 . lrms ( es ) : m / z 373 [ m + h ] . hrms ( es ) : calcd for c19h25n4o4 [ m + h ] 373.1870 , found 373.1850 . h nmr ( cd3od ) ( ppm ) 8.32 ( s , 1h ) , 7.42 ( t , j = 8.4 hz , 1h ) , 6.76 ( d , j = 8.4 hz , 2h ) , 3.86 ( s , 6h ) , 2.79 ( m , 1h ) , 0.80 ( m , 2h ) , 0.65 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 161.32 , 161.20 , 131.10 , 122.44 , 122.30 , 115.01 , 104.28 , 55.82 , 22.13 , and 22.02 ( d , rotamers ) , 5.55 . hrms ( es ) : calcd for c16h19n4o4 [ m + h ] 331.1401 , found 331.1385 . h nmr ( dmso - d6 ) ( ppm ) 13.28 ( s , 1h ) , 9.71 ( s , 1h ) , 8.60 ( d , j = 8.1 hz , 1h ) , 8.30 ( s , 1h ) , 7.40 ( t , j = 8.4 hz , 1h ) , 6.74 ( d , j = 8.4 hz , 2h ) , 4.37 ( sex , j = 8.3 , 1h ) , 3.76 ( s , 6h ) , 2.13 ( m , 4h ) , 1.63 ( m , 2h ) . c nmr ( dmso - d6 ) ( ppm ) 162.53 , 161.23 , 156.93 , 132.14 , 131.07 , 122.61 , 119.84 , 115.07 , 104.32 , 55.82 , 54.86 , 43.39 , 29.81 , 14.62 . lrms ( es ) : m / z 345 [ m + h ] . hrms ( es ) : calcd for c17h21n4o4 [ m + h ] 345.1557 , found 345.1548 . h nmr ( cdcl3 ) ( ppm ) 12.19 ( br s , 1h ) , 9.94 ( s , 1h ) , 8.41 ( s , 1h ) , 7.29 ( t , j = 8.5 hz , 1h ) , 6.98 ( d , j = 8.1 hz , 1h ) , 6.57 ( d , j = 8.5 hz , 2h ) , 4.05 ( m , 1h ) , 3.80 ( s , 6h ) , 2.001.94 ( m , 2h ) , 1.661.45 ( m , 10h ) . c nmr ( cdcl3 ) ( ppm ) 161.75 , 160.98 , 155.95 , 131.18 , 129.57 , 121.16 , 119.75 , 112.84 , 102.24 , 54.19 , 48.30 , 33.28 , 26.12 , 22.39 . lrms ( es ) : m / z 387 [ m + h ] . hrms ( es ) : calcd for c20h27n4o4 [ m + h ] 387.2027 , found 387.2043 . h nmr ( dmso - d6 ) ( ppm ) 11.80 ( br s , 1h ) , 9.72 ( s , 1h ) , 8.28 ( s , 1h ) , 8.00 ( br d , j = 6.9 hz , 1h ) , 7.40 ( t , j = 8.4 hz , 1h ) , 6.75 ( d , j = 8.4 hz , 2h ) , 3.76 ( s , 6h ) , 3.66 ( m , 1h ) , 2.21 ( br s , 1h ) , 2.15 ( br s , 1h ) , 1.631.37 ( m , 5h ) , 1.160.99 ( m , 3h ) . c nmr ( cd3od ) ( ppm ) 165.11 , 164.82 , 159.28 , 133.97 , 133.00 , 124.01 , 122.33 , 115.79 , 105.34 , 56.59 , 53.91 , 43.80 , 40.38 , 37.06 , 36.28 , 29.28 , 27.54 . lrms ( es ) : m / z 385 [ m + h ] . hrms ( es ) : calcd for c20h25n4o4 [ m + h ] 385.1870 , found 385.1857 . h nmr ( dmso - d6 ) ( ppm ) 13.30 ( s , 1h ) , 9.66 ( s , 1h ) , 9.55 ( s , 1h ) , 8.31 ( s , 1h ) , 7.39 ( t , j = 8.4 hz , 1h ) , 6.75 ( d , j = 8.6 hz , 2h ) , 3.76 ( s , 6h ) , 3.62 ( m , 4h ) , 2.84 ( m , 4h ) . c nmr ( dmso - d6 ) ( ppm ) 161.26 , 161.18 , 156.93 , 131.41 , 131.10 , 122.90 , 119.80 , 115.01 , 104.32 , 65.98 , 55.82 , 54.31 . lrms ( es ) : m / z 376 [ m + h ] . hrms ( es ) : calcd for c17h22n5o5 [ m + h ] 376.1615 , found 376.1620 . h nmr ( dmso - d6 ) ( ppm ) 13.15 ( brs , 1h ) , 9.70 ( s , 1h ) , 8.99 ( t , j = 6.3 hz , 1h ) , 8.32 ( s , 1h ) , 7.38 ( t , j = 8.4 hz , 1h ) , 7.317.29 ( m , 4h ) , 7.22 ( m , 1h ) , 6.74 ( d , j = 8.4 hz , 2h ) , 4.41 ( d , j = 6.4 hz , 2h ) , 3.75 ( s , 6h ) . c nmr ( dmso - d6 ) ( ppm ) 163.46 , 161.29 , 156.93 , 139.45 , 131.95 , 131.10 , 128.21 , 127.26 , 126.71 , 122.58 , 120.18 , 115.01 , 104.32 , 55.82 , 41.66 . lrms ( es ) : m / z 381 [ m + h ] . hrms ( es ) : calcd for c20h21n4o4 [ m + h ] 381.1557 , found 381.1543 . h nmr ( dmso - d6 ) ( ppm ) 13.33 ( br s , 1h ) , 9.66 ( s , 1h ) , 8.96 ( t , j = 5.9 , 1h ) , 8.50 ( m , 1h ) , 8.34 ( s , 1h ) , 7.74 ( td , j = 7.7 , 1.9 hz , 1h ) , 7.39 ( t , j = 8.4 hz , 1h ) , 7.30 ( d , j = 7.8 hz , 1h ) , 7.25 ( m , 1h ) , 6.73 ( d , j = 8.4 hz , 2h ) , 4.53 ( d , j = 5.6 hz , 2h ) , 3.75 ( s , 6h ) . c nmr ( dmso - d6 ) ( ppm ) 163.65 , 161.32 , 158.14 , 156.93 , 148.75 , 136.68 , 131.89 , 131.10 , 122.61 , 122.06 , 120.84 , 120.18 , 114.98 , 104.32 , 55.82 , 43.54 . lrms ( es ) : h nmr ( dmso - d6 ) ( ppm ) 13.30 ( br s , 1h ) , 9.68 ( s , 1h ) , 8.72 ( t , j = 5.0 hz , 1h ) , 8.39 ( d , j = 5.0 hz , 1h ) , 8.34 ( s , 1h ) , 7.60 ( d , j = 7.6 hz , 1h ) , 7.39 ( t , j = 8.4 hz , 1h ) , 7.23 ( dd , j = 7.6 , 5.0 hz , 1h ) , 6.75 ( d , j = 8.4 hz , 2h ) , 4.54 ( d , j = 5.0 hz , 2h ) , 3.76 ( s , 6h ) , 2.29 ( s , 3h ) . c nmr ( dmso - d6 ) ( ppm ) 163.28 , 161.29 , 156.96 , 153.98 , 145.81 , 137.64 , 132.10 , 131.13 , 130.64 , 122.47 , 122.24 , 120.04 , 114.98 , 104.32 , 55.84 , 40.96 , 17 , 13 . lrms ( es ) : m / z 396 [ m + h ] . hrms ( es ) : calcd for c20h22n5o4 [ m + h ] 396.1666 , found 396.1656 . h nmr ( cd3od ) ( ppm ) 8.35 ( s. 1h ) , 7.37 ( t , j = 8.4 hz , 1h ) , 6.71 ( d , j = 8.4 hz , 2h ) , 3.82 ( s , 6h ) , 3.17 ( d , j = 7.0 hz , 2h ) , 1.771.64 ( m , 5h ) , 1.55 ( m , 1h ) , 1.281.13 ( m , 3h ) , 1.000.89 ( m , 2h ) . c nmr ( cd3od ) ( ppm ) 165.64 , 165.00 , 159.22 , 134.15 , 132.99 , 123.89 , 122.10 , 115.69 , 105.31 , 56.58 , 46.09 , 39.42 , 32.00 , 27.57 , 27.03 . lrms ( es ) : m / z 386 [ m + h ] . hrms ( es ) : calcd for c20h27n4o4 [ m + h ] 387.2027 , found 387.2008 . yield : 48 mg ( solid ) , 76% . h nmr ( dmso - d6 ) ( ppm ) 13.51 ( s , 1h ) , 10.31 ( s , 1h ) , 9.65 ( s , 1h ) , 8.40 ( s , 1h ) , 7.78 ( d , j = 7.7 hz , 2h ) , 7.41 ( t , j = 8.5 hz , 1h ) , 7.31 ( t , j = 7.8 hz , 2h ) , 7.09 ( t , j = 7.3 hz , 1h ) , 6.76 ( d , j = 8.5 hz , 2h ) , 3.77 ( s , 6h ) . c nmr ( dmso - d6 ) ( ppm ) 162.29 , 161.40 , 157.02 , 138.10 , 132.32 , 131.19 , 128.49 , 123.81 , 123.02 , 120.69 , 120.37 , 114.98 , 104.40 , 55.88 . lrms ( es ) : m / z 367 [ m + h ] . hrms ( es ) : calcd for c19h19n4o4 [ m + h ] 367.1401 , found 367.1402 . h nmr ( dmso - d6 ) ( ppm ) 13.63 ( s , 1h ) , 10.73 ( s , 1h ) , 9.55 ( s , 1h ) , 8.43 ( d , j = 6.4 hz , 3h ) , 7.83 ( d , j = 5.5 hz , 2h ) , 7.42 ( t , j = 8.3 hz , 1h ) , 6.77 ( d , j = 8.4 hz , 2h ) , 3.78 ( s , 6h ) . hrms ( es ) : calcd for c18h18n5o4 [ m + h ] 368.1353 , found 368.1347 . h nmr ( dmso - d6 ) ( ppm ) 13.61 ( s , 1h ) , 9.63 ( s , 1h ) , 9.49 ( s , 1h ) , 8.42 ( s , 1h ) , 8.38 ( br d , j = 4.6 hz , 1h ) , 8.09 ( d , j = 8.4 hz , 1h ) , 7.83 ( m , 1h ) , 7.42 ( t , j = 8.4 hz , 1h ) , 7.18 ( m , 1h ) , 6.77 ( d , j = 8.5 hz , 2h ) , 3.78 ( s , 6h ) . c nmr ( dmso - d6 ) ( ppm ) 161.87 , 161.55 , 157.01 , 150.45 , 148.29 , 138.41 , 131.62 , 131.30 , 123.04 , 120.90 , 120.15 , 114.66 , 113.86 , 104.35 , 55.84 . lrms ( es ) : m / z 368 [ m + h ] . hrms ( es ) : calcd for c18h18n5o4 [ m + h ] 368.1353 , found 368.1335 . h nmr ( dmso - d6 ) ( ppm ) 13.21 ( br s , 1h ) , 9.75 ( s , 1h ) , 8.28 ( s , 1h ) , 8.09 ( d , j = 8.4 hz , 1h ) , 7.39 ( t , j = 8.4 hz , 1h ) , 6.75 ( d , j = 8.4 hz , 2h ) , 4.53 ( br d , j = 3.8 hz , 1h ) , 3.76 ( s , 6h ) , 3.66 ( m , 1h ) , 3.403.33 ( m , 1h ) , 1.82 ( m , 2h ) , 1.73 ( m , 2h ) , 1.44 ( m , 2h ) , 1.19 ( m , 2h ) . c nmr ( dmso - d6 ) 162.67 , 161.25 , 156.91 , 131.07 , 122.56 , 115.10 , 104.32 , 68.11 , 55.82 , 47.00 , 34.19 , 30.00 . lrms ( es ) : m / z 389 [ m + h ] . hrms ( es ) : calcd for c19h25n4o5 [ m + h ] 389.1819 , found 389.1800 . h nmr ( cd3od ) ( ppm ) 8.36 ( s , 0.5h ) , 8.33 ( s , 0.5h ) , 7.39 ( t , j = 8.5 hz , 1h ) , 6.73 ( d , j = 8.5 hz , 2h ) , 4.05 ( m , 0.5h ) , 3.84 ( s , 6h ) , 3.76 ( m , 0.5h ) , 1.961.32 ( m , 8h ) , 1.06 ( m , 1h ) , 0.98 ( d , j = 6.5 hz , 1.5 h ) , 0.92 ( d , j = 6.6 hz , 1.5h ) . c nmr ( cd3od ) ( ppm ) 165.06 , 165.02 , 164.76 , 164.64 , 159.25 , 134.07 , 134.01 , 132.97 , 123.99 , 123.91 , 122.30 , 122.12 , 115.70 , 115.66 , 105.39 , 105.29 , 56.54 , 49.52 , 46.86 , 35.15 , 33.67 , 33.12 , 31.53 , 31.01 , 30.09 , 22.63 , 21.25 . lrms ( es ) : m / z 387 [ m + h ] . hrms ( es ) : calcd for c20h27n4o4 [ m + h ] 387.2027 , found 387.2007 . h nmr ( cd3od ) ( ppm ) 8.35 ( s , 1h ) , 7.37 ( t , j = 8.4 hz , 1h ) , 6.71 ( d , j = 8.4 hz , 2h ) , 4.083.99 ( m , 3h ) , 3.82 ( s , 6h ) , 2.90 ( m , 2h ) , 1.89 ( m , 2h ) , 1.51 ( m , 2h ) , 1.46 ( s , 9h ) . c nmr ( cd3od ) ( ppm ) 165.00 , 164.89 , 159.22 , 156.39 , 134.00 , 132.99 , 124.03 , 122.16 , 115.72 , 105.35 , 81.17 , 56.61 , 47.67 , 44.39 , and 43.61 ( br d , rotamers ) , 32.69 , 28.79 . lrms ( es ) : m / z 474 [ m + h ] . hrms ( es ) : calcd for c23h32n5o6 [ m + h ] 474.2347 , found 474.2324 . h nmr ( cd3od ) ( ppm ) 8.32 ( s , 1h ) , 7.36 ( t , j = 8.4 hz , 1h ) , 7.327.22 ( m , 5h ) , 6.68 ( d , j = 8.4 hz , 2h ) , 4.52 ( m , 1h ) , 3.78 ( s , 6h ) , 3.58 ( d , j = 2.5 hz , 2h ) , 2.76 ( m , 2h ) , 2.58 ( dd , j = 10.0 , 4.3 , 1h ) , 2.43 ( q , j = 8.1 hz , 1h ) , 2.27 ( m , 1h ) , 1.75 ( m , 1h ) . c nmr ( cd3od ) ( ppm ) 165.06 , 165.00 , 159.22 , 139.26 , 133.92 , 132.99 , 130.33 , 129.50 , 128.49 , 124.01 , 122.16 , 115.67 , 105.32 , 61.26 , 61.17 , 56.58 , 53.83 , 49.19 , 32.54 . lrms ( es ) : m / z 450 [ m + h ] . hrms ( es ) : calcd for c24h28n5o4 [ m + h ] 450.2136 , found 450.2113 . h nmr ( cd3od ) ( ppm ) 8.35 ( s. 1h ) , 7.38 ( t , j = 8.4 hz , 1h ) , 6.72 ( d , 8.4 j = 8.4 hz , 2h ) , 3.83 ( s , 6h ) , 3.53 ( s , 4h ) , 3.37 ( s , 3h ) . c nmr ( cd3od ) ( ppm ) 165.76 , 165.05 , 159.26 , 134.10 , 132.99 , 115.71 , 105.32 , 72.07 , 59.03 , 56.56 , 39.52 . lrms ( es ) : m / z 349 [ m + h ] . hrms ( es ) : calcd for c16h21n4o5 [ m + h ] 349.1506 , found 349.1504 . h nmr ( dmso - d6 ) ( ppm ) 13.23 ( br s , 1h ) , 9.74 ( s , 1h ) , 8.38 ( br s , 1h ) , 8.29 ( s , 1h ) , 7.39 ( t , j = 8.5 hz , 1h ) , 6.75 ( d , j = 8.5 hz , 2h ) , 3.76 ( s , 6h ) , 3.19 ( m , 2h ) , 1.49 ( quint , j = 7.2 hz , 2h ) , 1.311.22 ( m , 4h ) , 0.85 ( t , j = 7.0 hz , 3h ) . c nmr ( dmso - d6 ) ( ppm ) 163.39 , 161.20 , 156.93 , 132.25 , 131.07 , 122.35 , 119.79 , 115.05 , 104.32 , 55.82 , 37.95 , 28.77 , 28.57 , 21.78 , 13.87 . lrms ( es ) : m / z 361 [ m + h ] . hrms ( es ) : calcd for c18h25n4o4 [ m + h ] 361.1870 , found 361.1868 . h nmr ( cd3od ) ( ppm ) 8.35 ( s , 1h ) , 7.38 ( t , j = 8.5 hz , 1h ) , 6.71 ( d , j = 8.5 hz , 2h ) , 3.83 ( s , 6h ) , 3.58 ( sept , j = 6.1 hz , 1h ) , 3.53 ( t , j = 6.1 hz , 2h ) , 3.45 ( t , j = 6.6 hz , 2h ) , 1.83 ( quin , j = 6.4 hz , 2h ) , 1.15 ( d , j = 6.1 hz , 6h ) . c nmr ( cd3od ) ( ppm ) 165.58 , 165.00 , 159.22 , 134.17 , 132.99 , 123.82 , 121.99 , 115.69 , 105.32 , 73.08 , 67.50 , 56.61 , 38.06 , 30.72 , 22.49 . lrms ( es ) : m / z 391 [ m + h ] . hrms ( es ) : calcd for c19h27n4o5 [ m + h ] 391.1976 , found 391.1961 . h nmr ( cd3od ) ( ppm ) 8.23 ( s , 1h ) , 7.26 ( t , j = 8.4 hz , 1h ) , 6.59 ( d , j = 8.4 hz , 2h ) , 3.71 ( s , 6h ) , 3.26 ( t , j = 7.5 hz , 2h ) , 2.26 ( t , j = 7.5 hz , 2h ) , 2.11 ( s , 6h ) , 1.65 ( q , j = 7.5 hz , 2h ) . c nmr ( cd3od ) ( ppm ) 165.70 , 164.94 , 159.22 , 134.15 , 132.99 , 123.92 , 122.05 , 115.75 , 105.35 , 58.25 , 56.61 , 45.52 , 38.23 , 28.32 . lrms ( es ) : m / z 376 [ m + h ] . hrms ( es ) : calcd for c18h26n5o4 [ m + h ] 376.1979 , found 376.1965 . h nmr ( cd3od ) ( ppm ) 8.34 ( s , 1h ) , 7.38 ( t , j = 8.4 hz , 1h ) , 6.71 ( d , j = 8.4 hz , 2h ) , 3.83 ( s , 6h ) , 3.51 ( t , j = 6.9 hz , 2h ) , 2.69 ( t , j = 6.9 hz , 2h ) , 2.59 ( m , 4h ) , 1.80 ( m , 4h ) . c nmr ( cd3od ) ( ppm ) 165.69 , 164.97 , 159.22 , 134.09 , 132.99 , 123.89 , 122.01 , 115.72 , 105.32 , 56.58 , 56.32 , 55.08 , 38.64 , 24.31 . hrms ( es ) : calcd for c19h26n5o4 [ m + h ] 388.1979 , found 388.1965 . h nmr ( cd3od ) ( ppm ) 8.34 ( s , 1h ) , 7.40 ( t , j = 8.4 hz , 1h ) , 6.73 ( d , j = 8.4 hz , 2h ) , 3.84 ( s , 6h ) , 3.70 ( t , j = 4.5 hz , 4h ) , 3.5 ( t , j = 6.6 , 2h ) , 2.57 ( t , j = 6.6 hz , 2h ) , 2.52 ( br t , j = 4.5 hz , 4 hz ) . c nmr ( cd3od ) ( ppm ) 165.67 , 165.00 , 159.23 , 134.06 , 132.96 , 123.86 , 122.02 , 115.72 , 105.32 , 67.80 , 58.60 , 56.55 , 54.67 , 36.50 . lrms ( es ) : m / z 404 [ m + h ] . hrms ( es ) : calcd for c19h26n5o5 [ m + h ] 404.1928 , found 404.1929 .

glycogen synthase kinase 3 ( gsk3 ) is a genetically validated drug target for human african trypanosomiasis ( hat ) , also called african sleeping sickness . we report the synthesis and biological evaluation of aminopyrazole derivatives as trypanosoma brucei gsk3 short inhibitors . low nanomolar inhibitors , which had high selectivity over the off - target human cdk2 and good selectivity over human gsk3 enzyme , have been prepared . these potent kinase inhibitors demonstrated low micromolar levels of inhibition of the trypanosoma brucei brucei parasite grown in culture .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Federal Research Public Access Act of 2006''. SEC. 2. FINDINGS. Congress finds that-- (1) the Federal Government funds basic and applied research with the expectation that new ideas and discoveries that result from the research, if shared and effectively disseminated, will advance science and improve the lives and welfare of people of the United States and around the world; and (2) the Internet makes it possible for this information to be promptly available to every scientist, physician, educator, and citizen at home, in school, or in a library. SEC. 3. DEFINITION. In this Act the term ``Federal agency'' means an Executive agency defined under section 105 of title 5, United States Code. SEC. 4. FEDERAL RESEARCH PUBLIC ACCESS POLICY. (a) In General.--Not later than 1 year after the date of enactment of this Act, each Federal agency with extramural research expenditures of over $100,000,000 shall develop a Federal research public access policy that is consistent with and advances purposes of the Federal agency. (b) Content.--Each Federal research public access policy shall provide for-- (1) submission to the Federal agency of an electronic version of the author's final manuscript of original research papers that have been accepted for publication in peer-reviewed journals and result from research supported, in whole or in part, from funding by the Federal Government; (2) the incorporation of all changes resulting from the peer review publication process in the manuscript described under paragraph (1); (3) the replacement of the final manuscript with the final published version if-- (A) the publisher consents to the replacement; and (B) the goals of the Federal agency for functionality and interoperability are retained; (4) free online public access to such final peer-reviewed manuscripts or published versions as soon as practicable, but not later than 6 months after publication in peer-reviewed journals; (5) production of an online bibliography of all research papers that are publicly accessible under the policy, with each entry linking to the corresponding free online full text; and (6) long-term preservation of, and free public access to, published research findings-- (A) in a stable digital repository maintained by the Federal agency; or (B) if consistent with the purposes of the Federal agency, in any repository meeting conditions determined favorable by the Federal agency, including free public access, interoperability, and long-term preservation. (c) Application of Policy.--Each Federal research public access policy shall-- (1) apply to-- (A) researchers employed by the Federal agency whose works remain in the public domain; and (B) researchers funded by the Federal agency; (2) provide that works described under paragraph (1)(A) shall be-- (A) marked as being public domain material when published; and (B) made immediately available under subsection (b)(4); and (3) make effective use of any law or guidance relating to the creation and reservation of a Government license that provides for the reproduction, publication, release, or other uses of a final manuscript for Federal purposes. (d) Exclusions.--Each Federal research public access policy shall not apply to-- (1) laboratory notes, preliminary data analyses, notes of the author, phone logs, or other information used to produce final manuscripts; (2) classified research, research resulting in works that generate revenue or royalties for authors (such as books) or patentable discoveries, to the extent necessary to protect a copyright or patent; or (3) authors who do not submit their work to a journal or works that are rejected by journals. (e) Patent or Copyright Law.--Nothing in this Act shall be construed to affect any right under the provisions of title 17 or 35, United States Code. (f) Report.-- (1) In general.--Not later than October 1, of each year, the head of each Federal agency shall submit a report on the Federal research public access policy of that agency to-- (A) the Committee on Homeland Security and Governmental Affairs of the Senate; (B) the Committee on Government Reform of the House of Representatives; and (C) any other committee of Congress of appropriate jurisdiction. (2) Content.--Each report under this subsection shall include-- (A) a statement of the effectiveness of the Federal research public access policy in providing the public with free online access to papers on research funded by the Federal agency; (B) a list of papers published in peer-reviewed journals that report on research funded by the Federal agency; (C) a corresponding list of papers made available by the Federal agency as a result of the Federal research public access policy; and (D) a summary of the periods of time between public availability of each paper in a journal and in the online repository of the Federal agency. (3) Public availability.--The Federal agency shall make the statement under paragraph (2)(A) and the lists of papers under subparagraphs (B) and (C) of paragraph (2) available to the public by posting such statement and lists on the website of the Federal agency.

Federal Research Public Access Act of 2006 - Requires each federal agency with extramural research expenditures of over $100 million to develop a specified federal research public access policy that is consistent with and advances the purposes of the agency. Makes each federal research public access policy applicable to: (1) researchers employed by the federal agency whose works remain in the public domain; and (2) researchers funded by the agency. Specifies exclusions. Requires the submission of annual reports by each federal agency on its federal research public access policy.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Dollars to the Classroom Act''. SEC. 2. DIRECT AWARDS OF CERTAIN EDUCATION FUNDING TO STATES. (a) Direct Awards of Certain Education Funding.-- (1) In general.--Notwithstanding any other provision of law, for each fiscal year the Secretary shall award the total amount of funds described in paragraph (2) directly to States in accordance with this subsection. (2) Applicable funding.--The total amount of funds referred to in paragraph (1) are all funds not used to carry out paragraph (6)(B) for the fiscal year that are appropriated for the Department of Education for the fiscal year to carry out programs or activities under the following provisions of law: (A) Title III of the Goals 2000: Educate America Act (20 U.S.C. 5881 et seq.). (B) Title IV of the Goals 2000: Educate America Act (20 U.S.C. 5911 et seq.). (C) Title VI of the Goals 2000: Educate America Act (20 U.S.C. 5951). (D) The Educational Research, Development, Disseminations, and Improvement Act of 1994 (20 U.S.C. 6001 et seq.). (E) Titles II, III, and IV of the School-to-Work Opportunities Act of 1994 (20 U.S.C. 6121 et seq., 6171 et seq., and 6191 et seq.). (F) Part B of title I of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6361 et seq.). (G) Section 1502 of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6492). (H) Part A of title II of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6621 et seq.). (I) Part B of title II of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6641 et seq.). (J) Title III of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6801 et seq.) (other than section 3132 of such title). (K) Section 3132 of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6842 et seq.). (L) Subpart 1 of part A of title IV of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 7111 et seq.). (M) Subpart 2 of part A of title IV of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 7131 et seq.). (N) Part A of title V of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 7201 et seq.). (O) Part B of title V of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 7231 et seq.). (P) Title VI of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 7311 et seq.). (Q) Part B of title IX of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 7901 et seq.). (R) Part C of title IX of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 7931 et seq.). (S) Part A of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8001 et seq.). (T) Part B of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8031 et seq.). (U) Part D of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8091 et seq.). (V) Part F of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8141 et seq.). (W) Part G of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8161 et seq.). (X) Part I of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8241 et seq.). (Y) Part J of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8271 et seq.). (Z) Part K of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8331 et seq.). (AA) Part L of title X of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8351 et seq.). (BB) Part A of title XIII of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8621 et seq.). (CC) Part C of title XIII of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8671 et seq.). (DD) Part B of title VII of the Stewart B. McKinney Homeless Assistance Act (42 U.S.C. 11421 et seq.). (3) Timelines.-- (A) Census determination.-- (i) In general.--Not later than 21 days after the beginning of an academic year, each State shall conduct a census to determine the number of kindergarten through grade 12 students in the State for the academic year. (ii) Submission.--Each State shall submit the number described in clause (i) to the Secretary not later than February 1 of the academic year. (B) Publication.--The Secretary shall publish in the Federal Register not later than March 15 of each fiscal year the amount each State shall receive under this subsection for the succeeding fiscal year. (C) Disbursal.--The Secretary shall disburse the amount awarded to a State under this subsection for a fiscal year not later than July 1 of the fiscal year. (4) Determination of award.--From the total amount made available under paragraph (1) and not used to carry out paragraph (6)(B), the Secretary, using the information provided under paragraph (3), shall award to each State an amount that bears the same relation to the total amount as the number of kindergarten through grade 12 students in the State for the academic year preceding the fiscal year bears to the total number of all such students in all States for the academic year. (5) Penalty.--If the Secretary determines that a State has knowingly submitted false information under paragraph (3) for the purpose of gaining additional funds under paragraph (1), then the State shall be fined an amount equal to twice the difference between the amount the State received under this subsection, and the correct amount the State would have received if the State had submitted accurate information under paragraph (3). (6) Hold harmless.-- (A) In general.--No State shall receive an award under this subsection-- (i) for fiscal year 2000 in an amount that is less than the amount the State would have received to carry out programs or activities under the provisions of law described in subparagraphs (A), (F), (I), (J), (L), (P) and (DD) of paragraph (2) for fiscal year 2000; (ii) for fiscal year 2001 in an amount that is less than 95 percent of the minimum amount the State is eligible to receive under clause (i) for fiscal year 2000; (iii) for fiscal year 2002 in an amount that is less than 90 percent of the minimum amount the State is eligible to receive under clause (ii) for fiscal year 2001; (iv) for fiscal year 2003 in an amount that is less than 85 percent of the minimum amount the State is eligible to receive under clause (iii) for fiscal year 2002; and (v) for fiscal year 2004 in an amount that is less than 80 percent of the minimum amount the State is eligible to receive under clause (iv) for fiscal year 2003. (B) Multiyear awards.--The Secretary shall use funds appropriated to carry out the programs or activities under the provisions of law described in paragraph (2) (other than subparagraphs (A), (F), (I), (J), (L), (P) and (DD) of paragraph (2)) to make payments to eligible recipients under such provisions pursuant to any multiyear award made under such provisions prior to the date of enactment of this Act. (b) Payments and Availability.-- (1) Payments.--Funds awarded to a State under this subsection shall be paid to the Governor of the State. (2) Availability.--The Governor of the State shall make the funds provided under this subsection available to the individual or entity in the State that is responsible for the State administration of Federal education funds pursuant to State law. (c) Use of State Awards.-- (1) In general.--From the amount made available to a State under subsection (a) for a fiscal year, the State-- (A) shall use not more than 5 percent of the amount to support programs or activities, for kindergarten through grade 12 students, that the State determines appropriate, of which the State shall distribute 20 percent of the 5 percent to local educational agencies in the State to pay the administrative expenses of the local educational agencies that are associated with the activities and services assisted under this section; and (B) shall distribute not less than 95 percent of the amount to local educational agencies in the State for the fiscal year to enable the local educational agencies to pay the costs of activities or services, for kindergarten through grade 12 students, that-- (i) the local educational agencies determine appropriate; and (ii) are provided in the classroom. (2) Classroom activities and services.--For the purpose of paragraph (1)(B), the costs of activities and services provided in the classroom-- (A) exclude the administrative expenses associated with the activities and services; and (B) subject to paragraph (1)(B)(i), include nonadministrative expenses associated with statewide or districtwide initiatives directly affecting classroom learning. (d) Regulations.-- (1) In general.--No head of a Federal department or agency other than the Secretary may promulgate regulations under this section. (2) Classroom activities and services.--The Secretary of Education shall not issue any regulation regarding the type of classroom activities or services that may be assisted under this section. (e) Report.--Each Governor of a State receiving assistance under this section shall prepare and submit, not later than 60 days after the date of enactment of this Act, to the Committee on Labor and Human Resources of the Senate and the Committee on Education and the Workforce of the House of Representatives, a report that describes the classroom activities and services provided in the State under this section. SEC. 3. TITLE I FUNDING. Section 1603 of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6513) is amended by adding at the end the following: ``(d) Dollars to the Classroom.-- ``(1) In general.--Notwithstanding any other provision of law, from the funds made available to a local educational agency under this part for a fiscal year, not less than 95 percent of the funds shall be used for the costs of activities and services that-- ``(A) the local educational agency deems appropriate; and ``(B) are provided in the classroom. ``(2) Classroom activities and services.--For the purpose of paragraph (1), the costs of activities and services provided in the classroom-- ``(A) exclude the administrative expenses associated with the activities and services; and ``(B) subject to paragraph (1)(A), include nonadministrative expenses associated with statewide or districtwide initiatives directly affecting classroom learning. ``(3) Plan.--Not later than 6 months after the date of enactment of the Dollars to the Classroom Act, the Secretary shall-- ``(A) develop and implement a plan for streamlining regulations and eliminating bureaucracy so that 95 percent of the funds made available to local educational agencies under this part are used for the costs of activities and services provided in the classroom; and ``(B) prepare and submit to Congress recommended legislation containing changes to Federal law that are needed for 95 percent of the funds to be so used.''. SEC. 4. PARTICIPATION OF CHILDREN ENROLLED IN PRIVATE AND HOME SCHOOLS. Each local educational agency that receives funds under section 2 shall provide for the participation of children enrolled in private and home schools in the activities and services assisted under such section in the same manner as private school children participate in activities and services under the Elementary and Secondary Education Act of 1965 (20 U.S.C. 6301 et seq.) pursuant to sections 14503, 14504, 14505, and 14506 of such Act (20 U.S.C. 8893, 8894, 8895, and 8896). SEC. 5. DEFINITIONS. In this Act-- (1) the term ``local educational agency'' has the meaning given the term in section 14101 of the Elementary and Secondary Education Act of 1965 (20 U.S.C. 8801); (2) the term ``Secretary'' means the Secretary of Education; and (3) the term ``State'' means each of the several States of the United States, the District of Columbia, the Commonwealth of Puerto Rico, Guam, American Samoa, the Commonwealth of the Northern Mariana Islands, and the United States Virgin Islands.

Dollars to the Classroom Act - Requires the Secretary of Education to award the total amount of certain applicable education funding directly to the States. (Sec. 2) Requires such direct awarding of all the funds (except those used for specified multiyear awards) that are appropriated for the Department of Education for the fiscal year for programs or activities under specified provisions of: (1) the Goals 2000: Educate America Act; (2) the Educational Research, Development, Disseminations, and Improvement Act of 1994; (3) the School-to-Work Opportunities Act of 1994; (4) the Elementary and Secondary Education Act of 1965 (ESEA); and (5) the Stewart B. McKinney Homeless Assistance Act. Sets deadlines for: (1) each State to conduct a census to determine, and report to the Secretary, the number of kindergarten through grade 12 students in the State for the academic year; and (2) the Secretary to publish and disburse the amount each State will receive under this Act for the succeeding fiscal year. Sets forth: (1) a formula for determination of such award amounts, based on relative numbers of such students in each State; and (2) penalties for false information. Provides for continuation of certain multiyear awards made prior to enactment of this Act. Requires award amounts under this Act to be paid to the State Governor, who shall make them available to the individual or entity in the State responsible for the State administration of Federal education funds. Prescribes requirements for the use of such funds, earmarking not less than 95 percent for distribution to local educational agencies (LEAs) for the costs of activities or services provided in the classroom that LEAs determine appropriate, excluding associated administrative expenses, but including nonadministrative expenses associated with statewide or districtwide initiatives directly affecting classroom learning. Prohibits: (1) any head of a Federal department or agency other than the Secretary from promulgating regulations under this Act; and (2) the Secretary from issuing any regulation regarding the type of classroom activities or services that may be assisted under this Act. (Sec. 3) Amends ESEA title I (Helping Disadvantaged Children Meet High Standards) to require the use of at least 95 percent of title I funds for an LEA for a fiscal year according to the requirements of this Act. Directs the Secretary to: (1) develop and implement a plan for streamlining regulations and eliminating bureaucracy so that 95 percent of such ESEA title I funds for LEAs are used for the costs of activities and services provided in the classroom; and (2) recommend to Congress legislation containing changes to Federal law needed for the use of such funds. (Sec. 4) Requires each LEA that receives funds under this Act to provide for the participation of children enrolled in private and home schools.