Sample records for tay-sachs disease tsd

  1. Tay-Sachs disease

    MedlinePlus

    GM2 gangliosidosis - Tay-Sachs; Lysosomal storage disease - Tay-Sachs disease ... called gangliosides. Without this protein, gangliosides, particularly ganglioside GM2, build up in cells, often nerve cells in ...

  2. Tay-Sachs Disease

    MedlinePlus

    ... Is at Risk for Tay-Sachs? Screening Prenatal Diagnosis Signs and Symptoms Helping a Child With Tay-Sachs Print en español La enfermedad de Tay-Sachs Healthy babies develop vision, movement, hearing, and other vital functions in part because enzymes clear out fatty ...

  3. Tay-Sachs Disease: MedlinePlus Health Topic

    MedlinePlus

    ... Genetics See, Play and Learn Videos and Tutorials Research Clinical Trials Journal Articles Resources Find an Expert For You Patient Handouts Summary Tay-Sachs disease is a rare, inherited disease. It is a type of lipid metabolism disorder . It causes too much of a ...

  4. Novel Tay-Sachs disease mutations from China.

    PubMed

    Akalin, N; Shi, H P; Vavougios, G; Hechtman, P; Lo, W; Scriver, C R; Mahuran, D; Kaplan, F

    1992-01-01

    We describe three HEXA mutations associated with infantile Tay-Sachs disease (TSD) in three unrelated nonconsanguineous Chinese families. Novel mutations were found in two of these families. The third is a previously reported mutation (G-->A transition at nt 1444) (Nakano et al., 1988). Direct sequencing of PCR products identified a novel insertion of an A after nt 547 in family 1. This change generates an early termination codon 6 bp downstream from the insertion site. Allele-specific oligonucleotide hybridization confirmed homozygosity in the proband. Single strand conformational polymorphism analysis and direct sequencing of amplified exon 13 revealed a T-->C transition at nt 1453 with the corresponding amino acid substitution W485R in the second family. This mutation creates an Fnu4HI restriction site. The proband is homozygous for this allele. When the site-specific mutagenized alpha cDNA carrying the T-->C transition at nt 1453 was expressed in COS 1 cells hexosaminidase S activity was not detectable above background. A G-->A transition at nt 1444 (exon 13) corresponding to the E482K substitution was found in the third family. This mutation occurs at a CpG dinucleotide. It has been reported in an Italian TSD proband and causes defective intracellular transport of the alpha-subunit from the rough endoplasmic reticulum to the Golgi apparatus.

  5. Tay Sachs and Related Storage Diseases: Family Planning

    ERIC Educational Resources Information Center

    Schneiderman, Gerald; And Others

    1978-01-01

    Based on interviews with 24 families, the article discusses family planning and the choices available to those families in which a child has previously died from Tay-Sachs or related lipid storage diseases. (IM)

  6. Lyso-GM2 ganglioside: a possible biomarker of Tay-Sachs disease and Sandhoff disease.

    PubMed

    Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-Ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

    2011-01-01

    To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease.

  7. Lyso-GM2 Ganglioside: A Possible Biomarker of Tay-Sachs Disease and Sandhoff Disease

    PubMed Central

    Kodama, Takashi; Togawa, Tadayasu; Tsukimura, Takahiro; Kawashima, Ikuo; Matsuoka, Kazuhiko; Kitakaze, Keisuke; Tsuji, Daisuke; Itoh, Kohji; Ishida, Yo-ichi; Suzuki, Minoru; Suzuki, Toshihiro; Sakuraba, Hitoshi

    2011-01-01

    To find a new biomarker of Tay-Sachs disease and Sandhoff disease. The lyso-GM2 ganglioside (lyso-GM2) levels in the brain and plasma in Sandhoff mice were measured by means of high performance liquid chromatography and the effect of a modified hexosaminidase (Hex) B exhibiting Hex A-like activity was examined. Then, the lyso-GM2 concentrations in human plasma samples were determined. The lyso-GM2 levels in the brain and plasma in Sandhoff mice were apparently increased compared with those in wild-type mice, and they decreased on intracerebroventricular administration of the modified Hex B. The lyso-GM2 levels in plasma of patients with Tay-Sachs disease and Sandhoff disease were increased, and the increase in lyso-GM2 was associated with a decrease in Hex A activity. Lyso-GM2 is expected to be a potential biomarker of Tay-Sachs disease and Sandhoff disease. PMID:22205997

  8. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    PubMed

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2015-08-12

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 25 June 2015.Date of latest search of all other sources: 10 December 2014. Any randomised or quasi-randomised control trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease

  9. Preconception risk assessment for thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease.

    PubMed

    Hussein, Norita; Weng, Stephen F; Kai, Joe; Kleijnen, Jos; Qureshi, Nadeem

    2018-03-14

    Globally, about five per cent of children are born with congenital or genetic disorders. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in specific patient populations. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if genetic counselling is only offered in an antenatal setting. This is an update of a previously published review. To assess the effectiveness of systematic preconception genetic risk assessment to improve reproductive outcomes in women and their partners who are identified as carriers of thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease in healthcare settings when compared to usual care. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Registers. In addition, we searched for all relevant trials from 1970 (or the date at which the database was first available if after 1970) to date using electronic databases (MEDLINE, Embase, CINAHL, PsycINFO), clinical trial databases (National Institutes of Health, Clinical Trials Search portal of the World Health Organization, metaRegister of controlled clinical trials), and hand searching of key journals and conference abstract books from 1998 to date (European Journal of Human Genetics, Genetics in Medicine, Journal of Community Genetics). We also searched the reference lists of relevant articles, reviews and guidelines and also contacted subject experts in the field to request any unpublished or other published trials.Date of latest search of the registers: 20 June 2017.Date of latest search of all other sources: 16 November 2017. Any randomised or quasi-randomised controlled trials (published or unpublished) comparing reproductive outcomes of systematic preconception genetic risk assessment for thalassaemia, sickle

  10. Crystallographic structure of human beta-hexosaminidase A: interpretation of Tay-Sachs mutations and loss of GM2 ganglioside hydrolysis.

    PubMed

    Lemieux, M Joanne; Mark, Brian L; Cherney, Maia M; Withers, Stephen G; Mahuran, Don J; James, Michael N G

    2006-06-16

    Lysosomal beta-hexosaminidase A (Hex A) is essential for the degradation of GM2 gangliosides in the central and peripheral nervous system. Accumulation of GM2 leads to severely debilitating neurodegeneration associated with Tay-Sachs disease (TSD), Sandoff disease (SD) and AB variant. Here, we present the X-ray crystallographic structure of Hex A to 2.8 A resolution and the structure of Hex A in complex with NAG-thiazoline, (NGT) to 3.25 A resolution. NGT, a mechanism-based inhibitor, has been shown to act as a chemical chaperone that, to some extent, prevents misfolding of a Hex A mutant associated with adult onset Tay Sachs disease and, as a result, increases the residual activity of Hex A to a level above the critical threshold for disease. The crystal structure of Hex A reveals an alphabeta heterodimer, with each subunit having a functional active site. Only the alpha-subunit active site can hydrolyze GM2 gangliosides due to a flexible loop structure that is removed post-translationally from beta, and to the presence of alphaAsn423 and alphaArg424. The loop structure is involved in binding the GM2 activator protein, while alphaArg424 is critical for binding the carboxylate group of the N-acetyl-neuraminic acid residue of GM2. The beta-subunit lacks these key residues and has betaAsp452 and betaLeu453 in their place; the beta-subunit therefore cleaves only neutral substrates efficiently. Mutations in the alpha-subunit, associated with TSD, and those in the beta-subunit, associated with SD are discussed. The effect of NGT binding in the active site of a mutant Hex A and its effect on protein function is discussed.

  11. GM2-Gangliosidosis (Sandhoff and Tay Sachs disease): Diagnosis and Neuroimaging Findings (An Iranian Pediatric Case Series).

    PubMed

    Karimzadeh, Parvaneh; Jafari, Narjes; Nejad Biglari, Habibeh; Jabbeh Dari, Sayena; Ahmad Abadi, Farzad; Alaee, Mohammad-Reza; Nemati, Hamid; Saket, Sasan; Tonekaboni, Seyed Hasan; Taghdiri, Mohammad-Mahdi; Ghofrani, Mohammad

    2014-01-01

    GM2-Gangliosidosis disease is a rare autosomal recessive genetic disorder that includes two disorders (Tay-Sachs and Sandhoff disease).These disorders cause a progressive deterioration of nerve cells and inherited deficiency in creating hexosaminidases A, B, and AB. Patients who were diagnosed withGM2-Gangliosidosis in the Neurology Department of Mofid Children's Hospital in Tehran, Iran from October 2009 to February 2014were included in our study. The disorder was confirmed by neurometabolic and enzyme level detection of hexosaminidases A, B, and AB in reference to Wagnester Laboratory in Germany. We assessed age, gender, past medical history, developmental status, clinical manifestations, and neuroimaging findings of 9 patients with Sandhoff disease and 9 with Tay Sachs disease. 83% of our patients were the offspring of consanguineous marriages. All of them had a developmental disorder as a chief complaint. 38%of patients had a history of developmental delay or regression and 22% had seizures. The patients with Sandhoff and Tay Sachs disease were followed for approximately 5 years and the follow-up showed all patients were bedridden or had expired due to refractory seizures, pneumonia aspiration, or swallowing disorders. Neuro-imaging findings included bilateral thalamic involvement, brain atrophy, and hypo myelination in near half of our patients (48%). According to the results of this study, we suggest that cherry-red spots, hyperacusis, refractory seizures, and relative parents in children with developmental delay and/or regression should be considered for assessment of GM2-Gangliosidosis disease.

  12. Pathological alterations typical of human Tay-Sachs disease, in the retina of a deep-sea fish.

    PubMed

    Fishelson, L; Delarea, Y; Galil, B S

    2000-08-01

    Micrographs of retinas from the deep-sea fish Cataetyx laticeps revealed visual cells containing membranous whorls in the ellipsoids of the inner segments resulting from stretching and modifications of the mitochondria membranes and their cristae. These pathological structures seem to be homologous to the whorls observed in retinas of human carriers of Tay-Sachs disease. This disease, a genetic disorder, is found in humans and some mammals. Our findings in fish suggest that the gene responsible can be found throughout the vertebrate evolutionary tree, possibly dormant in most taxa.

  13. Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis.

    PubMed

    Frisch, Amos; Colombo, Roberto; Michaelovsky, Elena; Karpati, Mazal; Goldman, Boleslaw; Peleg, Leah

    2004-03-01

    The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene mutation causing Tay-Sachs disease (TSD), one of the four lysosomal storage diseases (LSDs) occurring at elevated frequencies among Ashkenazi Jews (AJs). To investigate the genetic history of this mutation in the AJ population, a conserved haplotype (D15S981:175-D15S131:240-D15S1050:284-D15S197:144-D15S188:418) was identified in 1278insTATC chromosomes from 55 unrelated AJ individuals (15 homozygotes and 40 heterozygotes for the TSD mutation), suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the insertion was found to be 40+/-12 generations (95% confidence interval: 30-50 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 8th-9th century. This corresponds with the demographic expansion of AJs in central Europe, following the founding of the Ashkenaz settlement in the early Middle Ages. The results are consistent with the geographic distribution of the main TSD mutation, 1278insTATC being more common in central Europe, and with the coalescent times of mutations causing two other LSDs, Gaucher disease and mucolipidosis type IV. Evidence for the absence of a determinant positive selection (heterozygote advantage) over the mutation is provided by a comparison between the estimated age of 1278insTATC and the probability of the current AJ frequency of the mutant allele as a function of its age, calculated by use of a branching-process model. Therefore, the founder effect in a rapidly expanding population arising from a bottleneck provides a robust parsimonious hypothesis explaining the spread of 1278insTATC-linked TSD in AJ individuals.

  14. Crystal Structure of Human [Beta]-Hexosaminidase B: Understanding the Molecular Basis of Sandhoff and Tay-Sachs Disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mark, Brian L.; Mahuran, Don J.; Cherney, Maia M.

    2010-12-01

    In humans, two major {beta}-hexosaminidase isoenzymes exist: Hex A and Hex B. Hex A is a heterodimer of subunits {alpha} and {beta} (60% identity), whereas Hex B is a homodimer of {beta}-subunits. Interest in human {beta}-hexosaminidase stems from its association with Tay-Sachs and Sandhoff disease; these are prototypical lysosomal storage disorders resulting from the abnormal accumulation of G{sub M2}-ganglioside (G{sub M2}). Hex A degrades G{sub M2} by removing a terminal N-acetyl-D-galactosamine ({beta}-GalNAc) residue, and this activity requires the G{sub M2}-activator, a protein which solubilizes the ganglioside for presentation to Hex A. We present here the crystal structure of human Hexmore » B, alone (2.4 {angstrom}) and in complex with the mechanistic inhibitors GalNAc-isofagomine (2.2 {angstrom}) or NAG-thiazoline (2.5 {angstrom}). From these, and the known X-ray structure of the G{sub M2}-activator, we have modeled Hex A in complex with the activator and ganglioside. Together, our crystallographic and modeling data demonstrate how {alpha} and {beta}-subunits dimerize to form either Hex A or Hex B, how these isoenzymes hydrolyze diverse substrates, and how many documented point mutations cause Sandhoff disease ({beta}-subunit mutations) and Tay-Sachs disease ({alpha}-subunit mutations).« less

  15. Novel Vector Design and Hexosaminidase Variant Enabling Self-Complementary Adeno-Associated Virus for the Treatment of Tay-Sachs Disease

    PubMed Central

    Karumuthil-Melethil, Subha; Kalburgi, Sahana Nagabhushan; Thompson, Patrick; Tropak, Michael; Kaytor, Michael D.; Keimel, John G.; Mark, Brian L.; Mahuran, Don; Walia, Jagdeep S.; Gray, Steven J.

    2016-01-01

    GM2 gangliosidosis is a family of three genetic neurodegenerative disorders caused by the accumulation of GM2 ganglioside (GM2) in neuronal tissue. Two of these are due to the deficiency of the heterodimeric (α–β), “A” isoenzyme of lysosomal β-hexosaminidase (HexA). Mutations in the α-subunit (encoded by HEXA) lead to Tay-Sachs disease (TSD), whereas mutations in the β-subunit (encoded by HEXB) lead to Sandhoff disease (SD). The third form results from a deficiency of the GM2 activator protein (GM2AP), a substrate-specific cofactor for HexA. In their infantile, acute forms, these diseases rapidly progress with mental and psychomotor deterioration resulting in death by approximately 4 years of age. After gene transfer that overexpresses one of the deficient subunits, the amount of HexA heterodimer formed would empirically be limited by the availability of the other endogenous Hex subunit. The present study used a new variant of the human HexA α-subunit, μ, incorporating critical sequences from the β-subunit that produce a stable homodimer (HexM) and promote functional interactions with the GM2AP– GM2 complex. We report the design of a compact adeno-associated viral (AAV) genome using a synthetic promoter–intron combination to allow self-complementary (sc) packaging of the HEXM gene. Also, a previously published capsid mutant, AAV9.47, was used to deliver the gene to brain and spinal cord while having restricted biodistribution to the liver. The novel capsid and cassette design combination was characterized in vivo in TSD mice for its ability to efficiently transduce cells in the central nervous system when delivered intravenously in both adult and neonatal mice. This study demonstrates that the modified HexM is capable of degrading long-standing GM2 storage in mice, and it further demonstrates the potential of this novel scAAV vector design to facilitate widespread distribution of the HEXM gene or potentially other similar-sized genes to the

  16. The Val192Leu mutation in the alpha-subunit of beta-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease.

    PubMed

    Hou, Y; Vavougios, G; Hinek, A; Wu, K K; Hechtman, P; Kaplan, F; Mahuran, D J

    1996-07-01

    Substitution mutations adversely affecting the alpha-subunit of beta-hexosaminidase A (alphabeta) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-alpha chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an "active-site" residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all alpha-specific activity. This biochemical phenotype is referred to as the "B1-variant form" of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and both subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, alpha-Val192Leu. Chinese hamster ovary cells were permanently cotransfected with an alpha-cDNA-construct encoding the substitution and a mutant beta-cDNA (beta-Arg211Lys), encoding a beta-subunit that is inactive but normal in all other respects. We were surprised to find that the Val192Leu substitution, produced a pro-alpha chain that did not form alpha-beta dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val192Leu substitution does not specifically affect the alpha-active site.

  17. The Val192Leu mutation in the alpha-subunit of beta-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease.

    PubMed Central

    Hou, Y.; Vavougios, G.; Hinek, A.; Wu, K. K.; Hechtman, P.; Kaplan, F.; Mahuran, D. J.

    1996-01-01

    Substitution mutations adversely affecting the alpha-subunit of beta-hexosaminidase A (alphabeta) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-alpha chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an "active-site" residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all alpha-specific activity. This biochemical phenotype is referred to as the "B1-variant form" of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and both subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, alpha-Val192Leu. Chinese hamster ovary cells were permanently cotransfected with an alpha-cDNA-construct encoding the substitution and a mutant beta-cDNA (beta-Arg211Lys), encoding a beta-subunit that is inactive but normal in all other respects. We were surprised to find that the Val192Leu substitution, produced a pro-alpha chain that did not form alpha-beta dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val192Leu substitution does not specifically affect the alpha-active site. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8659543

  18. The Val{sup 192}Leu mutation in the {alpha}-subunit of {beta}-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hou, Y.; Vavougios, G.; Hinek, A.

    1996-07-01

    Substitution mutations adversely affecting the {alpha}-subunit of {beta}-hexosaminidase A ({alpha}{beta}) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-{alpha} chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an {open_quotes}active-site{close_quotes} residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all {alpha}-specific activity. This biochemical phenotype is referred to as the {open_quotes}B1-variant form{close_quotes} of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and bothmore » subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, {alpha}-Val{sup 192}Leu. Chinese hamster ovary cells were permanently cotransfected with an {alpha}-cDNA-construct encoding the substitution and a mutant {beta}-cDNA ({beta}-Arg{sup 211}Lys), encoding a {beta}-subunit that is inactive but normal in all other respects. We were surprised to find that the Val{sup 192}Leu substitution produced a pro-{alpha} chain that did not form {alpha}-{beta} dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val{sup 192}Leu substitution does not specifically affect the {alpha}-active site. 23 refs., 4 figs., 2 tabs.« less

  19. Tay-Sachs disease preconception screening in Australia: self-knowledge of being an Ashkenazi Jew predicts carrier state better than does ancestral origin, although there is an increased risk for c.1421 + 1G > C mutation in individuals with South African heritage.

    PubMed

    Lew, Raelia; Burnett, Leslie; Proos, Anné

    2011-12-01

    The Australasian Community Genetics Program provided a preconception screening for Tay-Sachs disease (TSD) to 4,105 Jewish high school students in Sydney and Melbourne over the 12-year period 1995-2007. By correlating the frequencies of mutant HEXA, MIM *606869 (gene map locus 15q23-q24) alleles with subjects' nominated ethnicity (Ashkenazi/Sephardi/Mixed) and grandparental birthplaces, we established that Ashkenazi ethnicity is a better predictor of TSD carrier status than grandparental ancestral origins. Screening self-identified Ashkenazi subjects detected 95% of TSD carriers (carrier frequency 1:25). Having mixed Ashkenazi and non-Ashkenazi heritage reduced the carrier frequency (1:97). South African heritage conveyed a fourfold risk of c.1421 + 1G > C mutation compared with other AJ subjects (odds ratio (OR), 4.19; 95% confidence interval (CI), 1.83-9.62, p = 0.001), but this was the only specific case of ancestral origin improving diagnostic sensitivity over that based on determining Ashkenazi ethnicity. Carriers of c.1278insTATC mutations were more likely to have heritage from Western Europe (OR, 1.65 (95% CI, 1.04-2.60), p = 0.032) and South Eastern Europe (OR, 1.77 (95% CI, 1.14-2.73), p = 0.010). However, heritage from specific European countries investigated did not significantly alter the overall odds of TSD carrier status.

  20. Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease.

    PubMed

    Seyrantepe, Volkan; Demir, Secil Akyildiz; Timur, Zehra Kevser; Von Gerichten, Johanna; Marsching, Christian; Erdemli, Esra; Oztas, Emin; Takahashi, Kohta; Yamaguchi, Kazunori; Ates, Nurselin; Dönmez Demir, Buket; Dalkara, Turgay; Erich, Katrin; Hopf, Carsten; Sandhoff, Roger; Miyagi, Taeko

    2018-01-01

    Tay-Sachs disease is a severe lysosomal storage disorder caused by mutations in Hexa, the gene that encodes for the α subunit of lysosomal β-hexosaminidase A (HEXA), which converts GM2 to GM3 ganglioside. Unexpectedly, Hexa -/- mice have a normal lifespan and show no obvious neurological impairment until at least one year of age. These mice catabolize stored GM2 ganglioside using sialidase(s) to remove sialic acid and form the glycolipid GA2, which is further processed by β-hexosaminidase B. Therefore, the presence of the sialidase (s) allows the consequences of the Hexa defect to be bypassed. To determine if the sialidase NEU3 contributes to GM2 ganglioside degradation, we generated a mouse model with combined deficiencies of HEXA and NEU3. The Hexa -/- Neu3 -/- mice were healthy at birth, but died at 1.5 to 4.5months of age. Thin-layer chromatography and mass spectrometric analysis of the brains of Hexa -/- Neu3 -/- mice revealed the abnormal accumulation of GM2 ganglioside. Histological and immunohistochemical analysis demonstrated cytoplasmic vacuolation in the neurons. Electron microscopic examination of the brain, kidneys and testes revealed pleomorphic inclusions of many small vesicles and complex lamellar structures. The Hexa -/- Neu3 -/- mice exhibited progressive neurodegeneration with neuronal loss, Purkinje cell depletion, and astrogliosis. Slow movement, ataxia, and tremors were the prominent neurological abnormalities observed in these mice. Furthermore, radiographs revealed abnormalities in the skeletal bones of the Hexa -/- Neu3 -/- mice. Thus, the Hexa -/- Neu3 -/- mice mimic the neuropathological and clinical abnormalities of the classical early-onset Tay-Sachs patients, and provide a suitable model for the future pre-clinical testing of potential treatments for this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients.

    PubMed

    Gort, Laura; de Olano, Natalia; Macías-Vidal, Judit; Coll, M A Josep

    2012-09-10

    The GM2 gangliosidoses are autosomal recessive lysosomal storage diseases caused by a deficiency of the β-hexosaminidase A enzyme. This enzyme is composed of two polypeptide chains designated the α- and β- subunits and it interacts with the GM2 activator protein. The HEXA and HEXB genes encode the α-subunit and the β-subunit, respectively. Mutations in these genes are causative of Tay-Sachs disease (HEXA) and Sandhoff disease (HEXB). We analyzed the complete HEXA gene in 34 Spanish patients with Tay-Sachs disease and the HEXB gene in 14 Spanish patients with Sandhoff disease. We identified 27 different mutations, 14 of which were novel, in the HEXA gene and 14 different mutations, 8 of which unreported until now, in the HEXB gene, and we attempted to correlate these mutations with the clinical presentation of the patients. We found a high frequency of c.459+5G>A (IVS4+5G>A) mutation in HEXA affected patients, 22 of 68 alleles, which represent the 32.4%. This is the highest percentage found of this mutation in a population. All patients homozygous for mutation c.459+5G>A presented with the infantile form of the disease and, as previously reported, patients carrying mutation p.R178H in at least one of the alleles presented with a milder form. In HEXB affected patients, the novel deletion c.171delG accounts for 21.4% of the mutant alleles (6/28). All patients with this deletion showed the infantile form of the disease. The Spanish GM2 gangliosidoses affected patients show a great mutational heterogeneity as seen in other inherited lisosomal diseases in this country. Copyright © 2012. Published by Elsevier B.V.

  2. Therapeutic potential of intracerebroventricular replacement of modified human β-hexosaminidase B for GM2 gangliosidosis.

    PubMed

    Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

    2011-06-01

    To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB.

  3. Therapeutic Potential of Intracerebroventricular Replacement of Modified Human β-Hexosaminidase B for GM2 Gangliosidosis

    PubMed Central

    Matsuoka, Kazuhiko; Tamura, Tomomi; Tsuji, Daisuke; Dohzono, Yukie; Kitakaze, Keisuke; Ohno, Kazuki; Saito, Seiji; Sakuraba, Hitoshi; Itoh, Kohji

    2011-01-01

    To develop a novel enzyme replacement therapy for neurodegenerative Tay-Sachs disease (TSD) and Sandhoff disease (SD), which are caused by deficiency of β-hexosaminidase (Hex) A, we designed a genetically engineered HEXB encoding the chimeric human β-subunit containing partial amino acid sequence of the α-subunit by structure-based homology modeling. We succeeded in producing the modified HexB by a Chinese hamster ovary (CHO) cell line stably expressing the chimeric HEXB, which can degrade artificial anionic substrates and GM2 ganglioside in vitro, and also retain the wild-type (WT) HexB-like thermostability in the presence of plasma. The modified HexB was efficiently incorporated via cation-independent mannose 6-phosphate receptor into fibroblasts derived from Tay-Sachs patients, and reduced the GM2 ganglioside accumulated in the cultured cells. Furthermore, intracerebroventricular administration of the modified HexB to Sandhoff mode mice restored the Hex activity in the brains, and reduced the GM2 ganglioside storage in the parenchyma. These results suggest that the intracerebroventricular enzyme replacement therapy involving the modified HexB should be more effective for Tay-Sachs and Sandhoff than that utilizing the HexA, especially as a low-antigenic enzyme replacement therapy for Tay-Sachs patients who have endogenous WT HexB. PMID:21487393

  4. Tay-Sachs Disease

    MedlinePlus

    ... better understanding of how neurological deficits arise in lipid storage diseases and on the development of new treatments targeting disease mechanisms. Specific research on the gangliodisoses including expanding the use of ...

  5. Diagnosing Lysosomal Storage Disorders: The GM2 Gangliosidoses.

    PubMed

    Hall, Patricia; Minnich, Sara; Teigen, Claire; Raymond, Kimiyo

    2014-10-01

    The GM2 gangliosidoses are a group of autosomal recessive lysosomal storage disorders caused by defective β-hexosaminidase. There are three clinical conditions in this group: Tay-Sachs disease (TSD), Sandhoff disease (SD), and hexosaminidase activator deficiency. The three conditions are clinically indistinguishable. TSD and SD have been identified with infantile, juvenile, and adult onset forms. The activator deficiency is only known to present with infantile onset. Diagnosis of TSD and SD is based on decreased hexosaminidase activity and a change in the percentage of activity between isoforms. There are no biochemical tests currently available for activator deficiency. This unit provides a detailed procedure for identifying TSD and SD in affected individuals and carriers from leukocyte samples, the most robust sample type available. Copyright © 2014 John Wiley & Sons, Inc.

  6. Molecular characterization of both alleles in an unusual Tay-Sachs disease BI variant

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Coulter-Mackie, M.B.

    1994-06-01

    In a recent report, the authors described an exon 6 mutation in a Tay-Sachs B1 variant patient, first reported by Gordon et al. (1988), who displayed a typical B1 variant biochemical phenotype - i.e., (a) significant levels of hexosaminidase A (Hex A) activity in an assay with a neutral synthetic substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide, and (b) <2% of control Hex A in a test on the sulfated substrate, 4-methylumbelliferyl-[beta]-N-acetylglucosamide-6-sulfate. The patient was found to carry a double mutation (G[sub 574][yields]C [val[sub 192][yields]leu] and G[sub 598][yields]A [val[sub 200][yields]met]) inherited from her mother. Only the 574 mutation produced a deleterious effect on Hex Amore » activity in transfected COS0-1 cells, producing a B1 variant biochemical phenotype. The paternal allele apparently caused decreased abundance of mRNA, since no candidate paternal mutations were found in cloned reverse transcription-PCR (RT-PCR) products in the reported study. The biochemical phenotype of the original patient and the properties of the cDNA carrying the G[sub 574] [yields] C mutation in transient expression studies were compatible with a B1 variant mutation. The possibility remained that there might be some contribution from the paternal allele to the patient's phenotype. However, the paternal allele produces relatively low yields of a largely mis-spliced mRNA whose product would not be functional. Therefore, the G[sub 574] [yields] C (val[yields]leu) mutation in the maternal allele is clearly confirmed as a B1 variant mutation with all the ramifications for the substrate binding site and/or catalytic center that this implies.« less

  7. Sandhoff Disease

    MedlinePlus

    ... Coordinating Committees CounterACT Rigor & Transparency Scientific Resources Animal Models Cell/Tissue/DNA Clinical and Translational Resources Gene ... virus-delivered gene therapy seen in an animal model of Tay-Sachs and Sandhoff diseases for use ...

  8. UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

    ClinicalTrials.gov

    2018-03-15

    Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn; Alpha-Mannosidosis; Sanfilippo Mucopolysaccharidoses

  9. A double mutation in exon 6 of the [beta]-hexosaminidase [alpha] subunit in a patient with the B1 variant of Tay-Sachs disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ainsworth, P.J.; Coulter-Mackie, M.B.

    1992-10-01

    The B1 variant form of Tay-Sachs disease is enzymologically unique in that the causative mutation(s) appear to affect the active site in the [alpha] subunit of [beta]-hexosaminidase A without altering its ability to associate with the [beta] subunit. Most previously reported B1 variant mutations were found in exon 5 within codon 178. The coding sequence of the [alpha] subunit gene of a patient with the B1 variant form was examined with a combination of reverse transcription of mRNA to cDNA, PCR, and dideoxy sequencing. A double mutation in exon 6 has been identified: a G[sub 574][yields]C transversion causing a val[submore » 192][yields]leu change and a G[sub 598][yields] A transition resulting in a val[sub 200][yields]met alteration. The amplified cDNAs were otherwise normal throughout their sequence. The 574 and 598 alterations have been confirmed by amplification directly from genomic DNA from the patient and her mother. Transient-expression studies of the two exon 6 mutations (singly or together) in COS-1 cells show that the G[sub 574][yields]C change is sufficient to cause the loss of enzyme activity. The biochemical phenotype of the 574 alteration in transfection studies is consistent with that expected for a B1 variant mutation. As such, this mutation differs from previously reported B1 variant mutations, all of which occur in exon 5. 31 refs., 2 figs., 2 tabs.« less

  10. Genetics Home Reference: Tay-Sachs disease

    MedlinePlus

    ... NIH Resources (4 links) GeneEd National Human Genome Research Institute National Institute of Neurological Disorders and Stroke: Lipid Storage Diseases Fact Sheet National Institute of Neurological ...

  11. A Drosophila protein family implicated in pheromone perception is related to Tay-Sachs GM2-activator protein.

    PubMed

    Starostina, Elena; Xu, Aiguo; Lin, Heping; Pikielny, Claudio W

    2009-01-02

    Low volatility, lipid-like cuticular hydrocarbon pheromones produced by Drosophila melanogaster females play an essential role in triggering and modulating mating behavior, but the chemosensory mechanisms involved remain poorly understood. Recently, we showed that the CheB42a protein, which is expressed in only 10 pheromone-sensing taste hairs on the front legs of males, modulates progression to late stages of male courtship behavior in response to female-specific cuticular hydrocarbons. Here we report that expression of all 12 genes in the CheB gene family is predominantly or exclusively gustatory-specific, and occurs in many different, often non-overlapping patterns. Only the Gr family of gustatory receptor genes displays a comparable variety of gustatory-specific expression patterns. Unlike Grs, however, expression of all but one CheB gene is sexually dimorphic. Like CheB42a, other CheBs may therefore function specifically in gustatory perception of pheromones. We also show that CheBs belong to the ML superfamily of lipid-binding proteins, and are most similar to human GM2-activator protein (GM2-AP). In particular, GM2-AP residues involved in ligand binding are conserved in CheBs but not in other ML proteins. Finally, CheB42a is specifically secreted into the inner lumen of pheromone-sensing taste hairs, where pheromones interact with membrane-bound receptors. We propose that CheB proteins interact directly with lipid-like Drosophila pheromones and modulate their detection by the gustatory signal transduction machinery. Furthermore, as loss of GM2-AP in Tay-Sachs disease prevents degradation of GM2 gangliosides and results in neurodegeneration, the function of CheBs in pheromone response may involve biochemical mechanisms critical for lipid metabolism in human neurons.

  12. DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDowell, G.A.; Blitzer, M.G.; Mules, E.H.

    A study was undertaken to characterize the mutation(s) responsible for Tay-Sachs disease (TSD) in a Cajun population in southwest Louisiana and to identify the origins of these mutations. Eleven of 12 infantile TSD alleles examined in six families had the [beta]-hexosaminidase A (Hex A) [alpha]-subunit exon 11 insertion mutation that is present in approximately 70% of Ashkenazi Jewish TSD heterozygotes. The mutation in the remaining allele was a single-base transition in the donor splice site of the [alpha]-subunit intron 9. To determine the origins of these two mutations in the Cajun population, the TSD carrier status was enzymatically determined formore » 90 members of four of the six families, and extensive pedigrees were constructed for all carriers. A single ancestral couple from France was found to be common to most of the carriers of the exon 11 insertion. Pedigree data suggest that this mutation has been in the Cajun population since its founding over 2 centuries ago and that it may be widely distributed within the population. In contrast, the intron 9 mutation apparently was introduced within the last century and probably is limited to a few Louisiana families. 29 refs., 4 figs.« less

  13. GM2 gangliosidosis in British Jacob sheep.

    PubMed

    Wessels, M E; Holmes, J P; Jeffrey, M; Jackson, M; Mackintosh, A; Kolodny, E H; Zeng, B J; Wang, C B; Scholes, S F E

    2014-01-01

    GM2 gangliosidosis (Tay-Sachs disease) was diagnosed in 6- to 8-month-old pedigree Jacob lambs from two unrelated flocks presenting clinically with progressive neurological dysfunction of 10 day's to 8 week's duration. Clinical signs included hindlimb ataxia and weakness, recumbency and proprioceptive defects. Histopathological examination of the nervous system identified extensive neuronal cytoplasmic accumulation of material that stained with periodic acid--Schiff and Luxol fast blue. Electron microscopy identified membranous cytoplasmic bodies within the nervous system. Serum biochemistry detected a marked decrease in hexosaminidase A activity in the one lamb tested, when compared with the concentration in age matched controls and genetic analysis identified a mutation in the sheep hexa allele G444R consistent with Tay-Sachs disease in Jacob sheep in North America. The identification of Tay-Sachs disease in British Jacob sheep supports previous evidence that the mutation in North American Jacob sheep originated from imported UK stock. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  14. Stem Cell Transplant for Inborn Errors of Metabolism

    ClinicalTrials.gov

    2017-12-03

    Adrenoleukodystrophy; Metachromatic Leukodystrophy; Globoid Cell Leukodystrophy; Gaucher's Disease; Fucosidosis; Wolman Disease; Niemann-Pick Disease; Batten Disease; GM1 Gangliosidosis; Tay Sachs Disease; Sandhoff Disease

  15. The natural history of juvenile or subacute GM2 gangliosidosis: 21 new cases and literature review of 134 previously reported.

    PubMed

    Maegawa, Gustavo H B; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T R

    2006-11-01

    Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal beta-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, beta-hexosaminidase enzyme activity, and mutation analysis was collected. In our cohort of patients, the mean (+/-SD) age of onset of symptoms was 5.3 +/- 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 +/- 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 +/- 5.5 years. The mean age of onset of speech problems was 7.0 +/- 5.6 years, with a mean time of progression to anarthria of 5.6 +/- 5.3 years. Muscle wasting (10.6 +/- 7.4 years), proximal weakness (11.1 +/- 7.7 years), and incontinence of sphincters (14.6 +/- 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence of R178H and R

  16. Tay-Sachs and Sandhoff Diseases

    MedlinePlus

    ... birth and infant mortality. Solving premature birth Featured articles Accomplishments and lessons learned since the establishment of ... The impact of premature birth on society Featured articles How long should you wait before getting pregnant ...

  17. Learning about Tay-Sachs Disease

    MedlinePlus

    ... New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About ... Genome Exhibition Talking Glossary: English Talking Glossary: Español Issues ... Contacts Media Resources NHGRI-Related News Journal Articles ...

  18. NN′-Diacetylchitobiase activity in Tay–Sachs disease and Sandhoff's disease (Short Communication)

    PubMed Central

    Stirling, John L.

    1974-01-01

    In Tay–Sachs disease and Sandhoff's disease respectively, one of the N-acetyl-β-hexosaminidases (form A) or both (forms A and B) are absent, but glycosaminoglycans containing N-acetylhexosamines are not accumulated. The presence of NN′-diacetylchitobiase in livers from patients with these diseases raises the possibility that this new enzyme is involved in the metabolism of glycosaminoglycans rather than the enzymes previously described. PMID:4455225

  19. The Natural History of Juvenile or Subacute GM2 Gangliosidosis: 21 New Cases and Literature Review of 134 Previously Reported

    PubMed Central

    Maegawa, Gustavo H. B.; Stockley, Tracy; Tropak, Michael; Banwell, Brenda; Blaser, Susan; Kok, Fernando; Giugliani, Roberto; Mahuran, Don; Clarke, Joe T. R.

    2010-01-01

    OBJECTIVE Juvenile GM2 gangliosidosis is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal β-hexosaminidase resulting in GM2 ganglioside accumulation in brain. The purpose of this study was to delineate the natural history of the condition and identify genotype-phenotype correlations that might be helpful in predicting the course of the disease in individual patients. METHODS A cohort of 21 patients with juvenile GM2 gangliosidosis, 15 with the Tay-Sachs variant and 6 with the Sandhoff variant, was studied prospectively in 2 centers. Our experience was compared with previously published reports on 134 patients. Information about clinical features, β-hexosaminidase enzyme activity, and mutation analysis was collected. RESULTS In our cohort of patients, the mean (±SD) age of onset of symptoms was 5.3 ± 4.1 years, with a mean follow-up time of 8.4 years. The most common symptoms at onset were gait disturbances (66.7%), incoordination (52.4%), speech problems (28.6%), and developmental delay (28.6%). The age of onset of gait disturbances was 7.1 ± 5.6 years. The mean time for progression to becoming wheelchair-bound was 6.2 ± 5.5 years. The mean age of onset of speech problems was 7.0 ± 5.6 years, with a mean time of progression to anarthria of 5.6 ± 5.3 years. Muscle wasting (10.6 ± 7.4 years), proximal weakness (11.1 ± 7.7 years), and incontinence of sphincters (14.6 ± 9.7 years) appeared later in the course of the disease. Psychiatric disturbances and neuropathy were more prevalent in patients with the Sandhoff variant than in those with the Tay-Sachs variant. However, dysphagia, sphincter incontinence, and sleep problems occurred earlier in those with the Tay-Sachs variant. Cerebellar atrophy was the most common finding on brain MRI (52.9%). The median survival time among the studied and reviewed patients was 14.5 years. The genotype-phenotype correlation revealed that in patients with the Tay-Sachs variant, the presence

  20. Hypotonia

    MedlinePlus

    ... can be seen in Down syndrome, muscular dystrophy, cerebral palsy, Prader-Willi syndrome, myotonic dystrophy, and Tay-Sachs ... can be seen in Down syndrome, muscular dystrophy, cerebral palsy, Prader-Willi syndrome, myotonic dystrophy, and Tay-Sachs ...

  1. SAChES: Scalable Adaptive Chain-Ensemble Sampling.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swiler, Laura Painton; Ray, Jaideep; Ebeida, Mohamed Salah

    We present the development of a parallel Markov Chain Monte Carlo (MCMC) method called SAChES, Scalable Adaptive Chain-Ensemble Sampling. This capability is targed to Bayesian calibration of com- putationally expensive simulation models. SAChES involves a hybrid of two methods: Differential Evo- lution Monte Carlo followed by Adaptive Metropolis. Both methods involve parallel chains. Differential evolution allows one to explore high-dimensional parameter spaces using loosely coupled (i.e., largely asynchronous) chains. Loose coupling allows the use of large chain ensembles, with far more chains than the number of parameters to explore. This reduces per-chain sampling burden, enables high-dimensional inversions and the usemore » of computationally expensive forward models. The large number of chains can also ameliorate the impact of silent-errors, which may affect only a few chains. The chain ensemble can also be sampled to provide an initial condition when an aberrant chain is re-spawned. Adaptive Metropolis takes the best points from the differential evolution and efficiently hones in on the poste- rior density. The multitude of chains in SAChES is leveraged to (1) enable efficient exploration of the parameter space; and (2) ensure robustness to silent errors which may be unavoidable in extreme-scale computational platforms of the future. This report outlines SAChES, describes four papers that are the result of the project, and discusses some additional results.« less

  2. Phase I/II Pilot Study of Mixed Chimerism to Treat Inherited Metabolic Disorders

    ClinicalTrials.gov

    2017-11-15

    Hurler Syndrome (MPS I); Hurler-Scheie Syndrome; Hunter Syndrome (MPS II); Sanfilippo Syndrome (MPS III); Krabbe Disease (Globoid Leukodystrophy); Metachromatic Leukodystrophy (MLD); Adrenoleukodystrophy (ALD and AMN); Sandhoff Disease; Tay Sachs Disease; Pelizaeus Merzbacher (PMD); Niemann-Pick Disease; Alpha-mannosidosis

  3. Therapeutic evaluation of GM2 gangliosidoses by ELISA using anti-GM2 ganglioside antibodies.

    PubMed

    Tsuji, Daisuke; Higashine, Yukari; Matsuoka, Kazuhiko; Sakuraba, Hitoshi; Itoh, Kohji

    2007-03-01

    GM2 gangliosidoses, including Tay-Sachs disease, Sandhoff disease and the AB variant, comprise deficiencies of beta-hexosaminidase isozymes and GM2 ganglioside activator protein associated with accumulation of GM2 ganglioside (GM2) in lysosomes and neurosomatic clinical manifestations. A simple assay system for intracellular quantification of GM2 is required to evaluate the therapeutic effects on GM2-gangliosidoses. We newly established a cell-ELISA system involving anti-GM2 monoclonal antibodies for measuring GM2 storage in fibroblasts from Tay-Sachs and Sandhoff disease patients. We succeeded in detecting the corrective effect of enzyme replacement on elimination of GM2 in the cells with this ELISA system. This simple and sensitive system should be useful as additional diagnosis tool as well as therapeutic evaluation of GM2 gangliosidoses.

  4. [Molecular pathogenesis and therapeutic approach of GM2 gangliosidosis].

    PubMed

    Tsuji, Daisuke

    2013-01-01

    Tay-Sachs and Sandhoff diseases (GM2 gangliosidoses) are autosomal recessive lysosomal storage diseases caused by gene mutations in HEXA and HEXB, each encoding human lysosomal β-hexosaminidase α-subunits and β-subunits, respectively. In Tay-Sachs disease, excessive accumulation of GM2 ganglioside (GM2), mainly in the central nervous system, is caused by a deficiency of the HexA isozyme (αβ heterodimer), resulting in progressive neurologic disorders. In Sandhoff disease, combined deficiencies of HexA and HexB (ββ homodimer) cause not only the accumulation of GM2 but also of oligosaccharides carrying terminal N-acetylhexosamine residues (GlcNAc-oligosaccharides), resulting in systemic manifestations including hepatosplenomegaly as well as neurologic symptoms. Hence there is little clinically effective treatment for these GM2 gangliosidoses. Recent studies on the molecular pathogenesis in Sandhoff disease patients and disease model mice have shown the involvement of microglial activation and chemokine induction in neuroinflammation and neurodegeneration in this disease. Experimental and therapeutic approaches, including recombinant enzyme replacement, have been performed using Sandhoff disease model mice, suggesting the future application of novel techniques to treat GM2 gangliosidoses (Hex deficiencies), including Sandhoff disease as well as Tay-Sachs disease. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice and demonstrated abnormalities of glial cells. Moreover, we demonstrated the therapeutic effect of an intracerebroventricular administration of novel recombinant human HexA carrying a high content of M6P residue in Sandhoff disease model mice.

  5. 75 FR 14379 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG (RRD) Models Tay 620-15, Tay 650-15...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ...: Following a review of operational data of the Tay 651-54 engine, it has been found that the actual stress... found that the actual stress levels in the Tay 651-54 engine High Pressure Compressor (HPC) stages 1, 3... actual stress levels in the Tay 651-54 engine High Pressure Compressor (HPC) stages 1, 3, 6, 7 and 12...

  6. An economic evaluation of a genetic screening program for Tay-Sachs disease.

    PubMed Central

    Nelson, W B; Swint, J M; Caskey, C T

    1978-01-01

    The resolution of policy questions relating to medical genetic screening programs will not be without considerable difficulty. Examples include such issues as the optimal degree of screening program expansion, the relative values of screening for different genetic diseases, the appropriate sources of program funding (public vs. private), and the relative value of funding expanded genetic screening programs vs. research directed toward elimination of genetic traits themselves. Information on the net impact of the relevant alternatives is greatly needed, and this need will increase if the National Genetics Act receives funding approval. We have provided what is hopefully a contribution toward this end. While our analysis pertains to a specific disease and a specific screening program for that disease, the methodology is readily generalizable to other genetic diseases, as well as programs of any size or structure. Hopefully, this will serve to stimulate further research efforts that we believe are needed for the objective consideration of resource allocation alternatives. PMID:418675

  7. An economic evaluation of a genetic screening program for Tay-Sachs disease.

    PubMed

    Nelson, W B; Swint, J M; Caskey, C T

    1978-03-01

    The resolution of policy questions relating to medical genetic screening programs will not be without considerable difficulty. Examples include such issues as the optimal degree of screening program expansion, the relative values of screening for different genetic diseases, the appropriate sources of program funding (public vs. private), and the relative value of funding expanded genetic screening programs vs. research directed toward elimination of genetic traits themselves. Information on the net impact of the relevant alternatives is greatly needed, and this need will increase if the National Genetics Act receives funding approval. We have provided what is hopefully a contribution toward this end. While our analysis pertains to a specific disease and a specific screening program for that disease, the methodology is readily generalizable to other genetic diseases, as well as programs of any size or structure. Hopefully, this will serve to stimulate further research efforts that we believe are needed for the objective consideration of resource allocation alternatives.

  8. Gene transfer corrects acute GM2 gangliosidosis--potential therapeutic contribution of perivascular enzyme flow.

    PubMed

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-08-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay-Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity-as opposed to tremor-ataxia-were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue-long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system.

  9. An open-label Phase I/II clinical trial of pyrimethamine for the treatment of patients affected with chronic GM2 gangliosidosis (Tay-Sachs or Sandhoff variants).

    PubMed

    Clarke, Joe T R; Mahuran, Don J; Sathe, Swati; Kolodny, Edwin H; Rigat, Brigitte A; Raiman, Julian A; Tropak, Michael B

    2011-01-01

    Late-onset GM2 gangliosidosis is an autosomal recessive, neurodegenerative, lysosomal storage disease, caused by deficiency of ß-hexosaminidase A (Hex A), resulting from mutations in the HEXA (Tay-Sachs variant) or the HEXB (Sandhoff variant) genes. The enzyme deficiency in many patients with juvenile or adult onset forms of the disease results from the production of an unstable protein, which becomes targeted for premature degradation by the quality control system of the smooth endoplasmic reticulum and is not transported to lysosomes. In vitro studies have shown that many mutations in either the α or β subunit of Hex A can be partially rescued, i.e. enhanced levels of both enzyme protein and activity in lysosomes, following the growth of patient cells in the presence of the drug, pyrimethamine. The objectives of the present clinical trial were to establish the tolerability and efficacy of the treatment of late-onset GM2 gangliosidosis patients with escalating doses of pyrimethamine, to a maximum of 100 mg per day, administered orally in a single daily dose, over a 16-week period . The primary objective, tolerability, was assessed by regular clinical examinations, along with a panel of hematologic and biochemical studies. Although clinical efficacy could not be assessed in this short trial, treatment efficacy was evaluated by repeated measurements of leukocyte Hex A activity, expressed relative to the activity of lysosomal ß-glucuronidase. A total of 11 patients were enrolled, 8 males and 3 females, aged 23 to 50 years. One subject failed the initial screen, another was omitted from analysis because of the large number of protocol violations, and a third was withdrawn very early as a result of adverse events which were not drug-related. For the remaining 8 subjects, up to a 4-fold enhancement of Hex A activity at doses of 50 mg per day or less was observed. Additionally marked individual variations in the pharmacokinetics of the drug among the patients were

  10. Longitudinal Study of Neurodegenerative Disorders

    ClinicalTrials.gov

    2018-01-31

    MLD; Krabbe Disease; ALD; MPS I; MPS II; MPS III; Vanishing White Matter Disease; GM3 Gangliosidosis; PKAN; Tay-Sachs Disease; NP Deficiency; Osteopetrosis; Alpha-Mannosidosis; Sandhoff Disease; Niemann-Pick Diseases; MPS IV; Gaucher Disease; GAN; GM1 Gangliosidoses; Morquio Disease; S-Adenosylhomocysteine Hydrolase Deficiency; Batten Disease; Pelizaeus-Merzbacher Disease; Leukodystrophy; Lysosomal Storage Diseases; Purine Nucleoside Phosphorylase Deficiency; Multiple Sulfatase Deficiency Disease

  11. Animal models of GM2 gangliosidosis: utility and limitations.

    PubMed

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.

  12. Genetic Counseling in Mental Retardation.

    ERIC Educational Resources Information Center

    Bowen, Peter

    The task of the genetic counselor who identifies genetic causes of mental retardation and assists families to understand risk of recurrence is described. Considered are chromosomal genetic disorders such as Down's syndrome, inherited disorders such as Tay-Sachs disease, identification by testing the amniotic fluid cells (amniocentresis) in time…

  13. 75 FR 24825 - Airworthiness Directives; Rolls-Royce Deutschland Ltd. & Co. KG (RRD) Models Tay 650-15 and Tay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-06

    ... for corrosion attack are required. The action specified by this European Aviation Safety Agency (EASA... Deutschland Ltd. & Co. KG (RRD) Models Tay 650-15 and Tay 651-54 Turbofan Engines AGENCY: Federal Aviation...-pressure turbine disks stage 2 and stage 3. The corrosion is considered to be caused by the environment in...

  14. How deformed are the TSD bands in odd Lu isotopes?

    NASA Astrophysics Data System (ADS)

    Ragnarsson, I.

    2017-12-01

    The experimental fingerprints for large deformation in the triaxial strongly deformed (TSD) bands of 163,165,167Lu are discussed. It is argued that these fingerprints are not very convincing. On the contrary, especially the fact that there exist strong interactions between the TSD bands and normal-deformed (ND) bands indicates that the deformation of the TSD bands cannot be very different from that of the ND bands. The need for detailed new experimental data is underlined.

  15. Emissions Inventory Final Rule TSD

    EPA Pesticide Factsheets

    This technical support document (TSD) provides the details of emissions data processing done in support of EPA's final rulemaking effort for the Federal Transport Rule, now known as the Cross-State Air Pollution Rule.

  16. Judaism, genetic screening and genetic therapy.

    PubMed

    Rosner, F

    1998-01-01

    Genetic screening, gene therapy and other applications of genetic engineering are permissible in Judaism when used for the treatment, cure, or prevention of disease. Such genetic manipulation is not considered to be a violation of God's natural law, but a legitimate implementation of the biblical mandate to heal. If Tay-Sachs disease, diabetes, hemophilia, cystic fibrosis, Huntington's disease or other genetic diseases can be cured or prevented by "gene surgery," then it is certainly permitted in Jewish law. Genetic premarital screening is encouraged in Judaism for the purpose of discouraging at-risk marriages for a fatal illness such as Tay-Sachs disease. Neonatal screening for treatable conditions such as phenylketonuria is certainly desirable and perhaps required in Jewish law. Preimplantation screening and the implantation of only "healthy" zygotes into the mother's womb to prevent the birth of an affected child are probably sanctioned in Jewish law. Whether or not these assisted reproduction techniques may be used to choose the sex of one's offspring, to prevent the birth of a child with a sex-linked disease such as hemophilia, has not yet been ruled on by modern rabbinic decisions. Prenatal screening with the specific intent of aborting an affected fetus is not allowed according to most rabbinic authorities, although a minority view permits it "for great need." Not to have children if both parents are carriers of genetic diseases such as Tay-Sachs is not a Jewish option. Preimplantation screening is preferable. All screening test results must remain confidential. Judaism does not permit the alteration or manipulation of physical traits and characteristics such as height, eye and hair color, facial features and the like, when such change provides no useful benefit to mankind. On the other hand, it is permissible to clone organisms and microorganisms to facilitate the production of insulin, growth hormone, and other agents intended to benefit mankind and to

  17. GM2 gangliosidosis AB variant: novel mutation from India - a case report with a review.

    PubMed

    Sheth, Jayesh; Datar, Chaitanya; Mistri, Mehul; Bhavsar, Riddhi; Sheth, Frenny; Shah, Krati

    2016-07-11

    GM2 gangliosidosis-AB variants a rare autosomal recessive neurodegenerative disorder occurring due to deficiency of GM2 activator protein resulting from the mutation in GM2A gene. Only seven mutations in nine cases have been reported from different population except India. Present case is a one year old male born to 3rd degree consanguineous Indian parents from Maharashtra. He was presented with global developmental delay, hypotonia and sensitive to hyperacusis. Horizontal nystagmus and cherry red spot was detected during ophthalmic examination. MRI of brain revealed putaminal hyperintensity and thalamic hypointensity with some unmyelinated white matter in T2/T1 weighted images. Initially he was suspected having Tay-Sachs disease and finally diagnosed as GM2 gangliosidosis, AB variant due to truncated protein caused by nonsense mutation c.472 G > T (p.E158X) in GM2Agene. Children with phenotypic presentation as GM2 gangliosidosis (Tay-Sachs or Sandhoff disease) and normal enzyme activity of β-hexosaminidase-A and -B in leucocytes need to be investigated for GM2 activator protein deficiency.

  18. Compulsory DNA Sampling of Service Members for Inclusion in the DOD DNA Registry: Remains Identification With a Risk

    DTIC Science & Technology

    1996-04-01

    for Tay-Sachs disease, cystic fibrosis, Huntingtons disease, Duchenne muscular dystrophy , 26alcoholism, and susceptibility to certain types of cancer...and an increased risk of infection and injury to muscle , nerves, and blood vessels was sufficiently compelling to outweigh the state’s interest in...them into electrical impulses. These surgically implanted devices could produce electronic impulses to induce paralyzed muscles to contract and

  19. Comprehensive Carrier Screening and Molecular Diagnostic Testing for Recessive Childhood Diseases

    PubMed Central

    Kingsmore, Stephen

    2012-01-01

    Of 7,028 disorders with suspected Mendelian inheritance, 1,139 are recessive and have an established molecular basis. Although individually uncommon, Mendelian diseases collectively account for ~20% of infant mortality and ~18% of pediatric hospitalizations. Molecular diagnostic testing is currently available for only ~300 recessive disorders. Preconception screening, together with genetic counseling of carriers, has resulted in remarkable declines in the incidence of several severe recessive diseases including Tay-Sachs disease and cystic fibrosis. However, extension of preconception screening and molecular diagnostic testing to most recessive disease genes has hitherto been impractical. Recently, we reported a preconception carrier screen / molecular diagnostic test for 448 recessive childhood diseases. The current status of this test is reviewed here. Currently, this reports analytical validity of the comprehensive carrier test. As the clinical validity and clinical utility in the contexts described is ascertained, this article will be updated. PMID:22872815

  20. In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.

    PubMed

    Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J; Samulski, R Jude; Wakarchuk, Warren; Mark, Brian L; Mahuran, Don J

    2013-01-01

    The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside.

  1. In Cellulo Examination of a Beta-Alpha Hybrid Construct of Beta-Hexosaminidase A Subunits, Reported to Interact with the GM2 Activator Protein and Hydrolyze GM2 Ganglioside

    PubMed Central

    Sinici, Incilay; Yonekawa, Sayuri; Tkachyova, Ilona; Gray, Steven J.; Samulski, R. Jude; Wakarchuk, Warren; Mark, Brian L.; Mahuran, Don J.

    2013-01-01

    The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # 3.2.1.52 (encoded by the HEXA and HEXB genes, respectively), and the GM2-activator protein (GM2AP, encoded by the GM2A gene). Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750). Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1) and a new more extensive hybrid (H2), with our documented in cellulo (live cell- based) assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside. PMID:23483939

  2. Final Revisions Rule Significant Contribution Assessment TSD

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) presents quantitative assessments of the relationship between final revisions to the Transport Rule and the original analysis conducted for the final Transport Rule.

  3. Assurance Penalty Level Analysis Final Rule TSD

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) supports EPA’s determination that the final Transport Rule’s assurance provision penalty requirement provides sufficient deterrence against a state exceeding its assurance level.

  4. Rapid and cost-effective method for the detection of the c.533G>A mutation in the HEXA gene.

    PubMed

    Ribeiro, Diogo; Duarte, Ana Joana; Amaral, Olga

    2011-03-01

    Tay-Sachs disease is a rare autosomal recessive neurodegenerative disorder that results from mutations in the HEXA gene, leading to β-hexosaminidase A (HexA) α subunit deficiency. An unusual variant of Tay-Sachs disease is known as the B1 variant. Previous studies indicated that, in northern Portugal, this is not only the most common variant but also one of the most prevalent lysosomal storage diseases. Additionally, this variant might also show a higher prevalence in populations of Portuguese and Spanish ancestry. A single mutation is invariably present in at least one of the alleles of B1 variant patients, HEXA mutation c.533G >A. To implement a method for c.533G >A testing in individuals and populations, we have optimized two distinct mutation analysis techniques, one based on restriction fragment length polymorphism analysis and the other based on allelic discrimination. We present the comparison of both methods and their advantages. Mutation screening by allelic discrimination proved to be particularly useful for the studying of large samples of individuals. It is time saving and highly reproducible, and under the conditions used, its cost is lower than the cost of polymerase chain reaction-based restriction fragment length polymorphism analysis.

  5. Gangliosidoses.

    PubMed

    Patterson, Marc C

    2013-01-01

    The gangliosidoses comprise a family of lysosomal storage diseases characterized by the accumulation of complex glycosphingolipids in the nervous system and other tissues, secondary to the deficient activity of lysosomal hydrolases or their associated activator proteins. GM1 and GM2 gangliosidosis are associated with deficiency of β-galactosidase and β-hexosaminidase respectively. All gangliosidoses are characterized by progressive neurodegeneration, the severity of which is proportional to the residual enzyme activity. The GM1 gangliosidoses are characterized by dysostosis, organomegaly and coarsening in their most severe forms, whereas children with classic infantile GM2 gangliosidosis (Tay-Sachs disease) are usually spared systemic involvement, except in the case of the Sandhoff variant, in which organomegaly may occur. Cherry-red macular spots occur in the early onset forms of the gangliosidoses, but are less frequently seen in the less severe, later onset phenotypes. Macrocephaly, an exaggerated startle response, cognitive decline, seizures, ataxia, and progressive muscular atrophy may occur in different forms of gangliosidosis. The diagnosis is made by assay of enzyme activity, and can be confirmed by mutation analysis. Carrier screening for Tay-Sachs disease has been remarkably successful in reducing the incidence of this disease in the at-risk Ashkenazi population. There are no proven disease-modifying therapies for the gangliosidoses. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Tay's syndrome: MRI.

    PubMed

    Porto, L; Weis, R; Schulz, C; Reichel, P; Lanfermann, H; Zanella, F E

    2000-11-01

    Tay's syndrome is a trichothiodystrophy associated with congenital ichthyosis. We report the findings on MRI and spectroscopy in a young girl with sparse, short, ruffled hair, dry skin and delayed milestones. T2-weighted images showed prominent diffuse confluent increase in signal symmetrically in all the supratentorial white matter. These findings are similar to those in a previously described case, and consistent with dysmyelination. Spectroscopy showed increased myoinositol and decreased choline.

  7. Screening Jews and genes: a consideration of the ethics of genetic screening within the Jewish community: challenges and responses.

    PubMed

    Levin, M

    1999-01-01

    Screening for genetic disorders, particularly Tay-Sachs Disease, has been traditionally welcome by the Jewish community. I review the history of genetic screening among Jews and the views from the Jewish tradition on the subject, and then discuss ethical challenges of screening and the impact of historical memories upon future acceptance of screening programs. Some rational principles to guide future design of genetic screening programs among Jews are proposed.

  8. Final June Revisions Rule Significant Contribution Assessment TSD

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) presents quantitative assessments of the relationship between the final February revisions to the Transport Rule, the final June revisions rule, and the original analysis conducted for the final Transport Rule.

  9. Constant mean curvature slicings of Kantowski-Sachs spacetimes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Heinzle, J. Mark

    2011-04-15

    We investigate existence, uniqueness, and the asymptotic properties of constant mean curvature (CMC) slicings in vacuum Kantowski-Sachs spacetimes with positive cosmological constant. Since these spacetimes violate the strong energy condition, most of the general theorems on CMC slicings do not apply. Although there are in fact Kantowski-Sachs spacetimes with a unique CMC foliation or CMC time function, we prove that there also exist Kantowski-Sachs spacetimes with an arbitrary number of (families of) CMC slicings. The properties of these slicings are analyzed in some detail.

  10. Total System Design (TSD) Methodology Assessment.

    DTIC Science & Technology

    1983-01-01

    hardware implementation. Author: Martin - Marietta Aerospace Title: Total System Design Methodology Source: Martin - Marietta Technical Report MCR -79-646...systematic, rational approach to computer systems design is needed. Martin - Marietta has produced a Total System Design Methodology to support such design...gathering and ordering. The purpose of the paper is to document the existing TSD methoeology at Martin - Marietta , describe the supporting tools, and

  11. Julius Sachs (1868): The father of plant physiology.

    PubMed

    Kutschera, Ulrich; Niklas, Karl J

    2018-05-17

    The year 2018 marks the 150th anniversary of the first publication of Julius von Sachs' (1832-1897) Lehrbuch der Botanik (Textbook of Botany), which provided a comprehensive summary of what was then known about the plant sciences. Three years earlier, in 1865, Sachs produced the equally impressive Handbuch der Experimental-Physiologie der Pflanzen (Handbook of Experimental Plant Physiology), which summarized the state of knowledge in all aspects of the discipline known today as plant physiology. Both of these books provided numerous insights based on Sachs' seminal experiments. By virtue of a reliance on detailed empirical observation and the rigorous application of chemical and physical principles, it is fair to say that the publication of these two monumental works marked the beginning of what can be called "modern-day" plant science. Moreover, Sachs' Lehrbuch der Botanik prefigured the ascendance of plant molecular biology and the systems biology of photoautotrophic organisms. Regrettably, many of the insights of this great scientist have been forgotten by the generations who followed. It is only fitting, therefore, that the anniversary of the publication of the Lehrbuch der Botanik and the career of "the father of plant physiology" should be honored and reviewed, particularly because Sachs established the physiology of green organisms as an integral branch of botany and incorporated a Darwinian perspective into plant biology. Here we highlight key insights, with particular emphasis on Sachs' detailed discussion of sexual reproduction at the cellular level and his endorsement of Darwinian evolution. © 2018 Botanical Society of America.

  12. Classification of Kantowski-Sachs metric via conformal Ricci collineations

    NASA Astrophysics Data System (ADS)

    Hussain, Tahir; Khan, Fawad; Bokhari, Ashfaque H.; Akhtar, Sumaira Saleem

    In this paper, we present a classification of the Kantowski-Sachs spacetime metric according to its conformal Ricci collineations (CRCs). Solving the CRC equations, it is shown that the Kantowski-Sachs metric admits 15-dimensional Lie algebra of CRCs when its Ricci tensor is non-degenerate and an infinite dimensional group of CRCs when the Ricci tensor is degenerate. Some examples of Kantowski-Sachs metric admitting nontrivial CRCs are presented and their physical interpretation is provided.

  13. Establishment of the Fox Chase Network Breast Cancer Risk Registry

    DTIC Science & Technology

    1996-10-01

    Neurofibromatosis, type I h) Non-insulin dependent diabetes i) Turner Syndrome j) Tay Sachs Disease k) Marfan Syndrome 1) Cancer (tricky!) 2. Human chromosomes are...gastrointestinal and genitourinary cancers (4). Altogether, over 12 genetic-cancer syndromes have been localized to a specific gene (5). Some families suffer...component of the rare help test the best ways to Risk Registry._5, cases of breast cancer tions are likely to result Li-Fraumeni syndrome , only and up to

  14. Tectonic Evolution of Jabal Tays Ophiolite Complex, Eastern Arabian Shield, Saudi Arabia

    NASA Astrophysics Data System (ADS)

    AlHumidan, Saad; Kassem, Osama; Almutairi, Majed; Al-Faifi, Hussain; Kahal, Ali

    2017-04-01

    Microstructural analysis is important for investigation of tectonic evaluation of Jable Tays area. Furthermore, the Jable Tays ophiolite complex is effected by Al Amar -Idsas fault. The nature of the Al Amar-Idsas fault is a part of the Eastern Arabian Shield, which was subjected to multiple interpretations. Through fieldwork investigation, microscopic examination, and microstructural analysis, we aim to understand the evolution and tectonic setting of the Jable Tays area. Finite-strain data displays that the Abt schist, the metavolcanics and the metagranites are highly to moderately deformed. The axial ratios in the XZ section range from 1.40 to 2.20. The long axes of the finite-strain ellipsoids trend NW- SE and W-E in the Jable Tays area while, their short axes are subvertical to subhorizontal foliations. The strain magnitude does not increase towards the tectonic contacts between the Abt schist and metavolcano-sedimentary. While majority of the obtained data indicate a dominant oblate with minor prolate strain symmetries in the Abt schist, metavolcano-sedimentary and metagranites. The strain data also indicate flattening with some constriction. We assume that the Abt schist and the metavolcano-sedimentry rocks have similar deformation behavior. The finite strain in the studied rocks accumulated during the metamorphism that effected by thrusting activity. Based on these results, we finally concluded that the contact between Abt schist and metavolcano-sedimentary rocks were formed during the progressive thrusting under brittle to semi-ductile deformation conditions by simple shear that also involved a component of vertical shortening, causing subhorizontal foliation in Jable Tays area.

  15. Lysosomal storage diseases

    PubMed Central

    Ferreira, Carlos R.; Gahl, William A.

    2016-01-01

    Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively. PMID:29152458

  16. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo.

    PubMed

    Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

    2016-01-01

    Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels.

  17. Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

    PubMed Central

    Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

    2016-01-01

    Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

  18. Julius Sachs (1832–1897) and the Unity of Life

    PubMed Central

    Kutschera, Ulrich; Baluška, František

    2015-01-01

    In 1865, the German botanist Julius Sachs published a seminal monograph entitled Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) and hence became the founder of a new scientific discipline that originated 150 y ago. Here, we outline the significance of the achievements of Sachs. In addition, we document, with reference to his Vorlesungen über Pflanzen-Physiologie (Lectures on the Physiology of Plants, 1882), that Sachs was one of the first experimentalists who proposed the functional unity of all organisms alive today (humans, animals, plants and other “vegetable” organisms, such as algae, cyanophyceae, fungi, myxomycetes, and bacteria). PMID:26359706

  19. Fingerprinting of bed sediment in the Tay Estuary, Scotland: an environmental magnetism approach

    NASA Astrophysics Data System (ADS)

    Jenkins, Pierre A.; Duck, Rob W.; Rowan, John S.; Walden, John

    Sediment fingerprinting is commonly used for sediment provenance studies in lakes, rivers and reservoirs and on hillslopes and floodplains. This investigation explores the mixing of terrestrial and marine-derived sediment in the Tay Estuary, Scotland, using mineral magnetic attributes for fingerprinting. Samples representative of the estuary sediments and of four sources (end-members) were subjected to a suite of magnetic susceptibility and remanence measurements. Sediment samples from the beds of the Rivers Tay and Earn represented fluvial inputs while samples from the Angus and Fife coasts represented marine input. Multivariate discriminant and factor analysis showed that the sources could be separated on the basis of six magnetic parameters in a simple multivariate unmixing model to identify source contributions to estuarine bed sediments. Multi-domain magnetite signatures, characteristic of unweathered bedrock, dominate the magnetic measurements. Overall contributions of 3% from the River Earn, 17% from the River Tay, 29% from the Angus coast and 51% from the Fife coast source end-members, demonstrated the present-day regime of marine sediment derivation in the Tay Estuary. However, this conceals considerable spatial variability both along-estuary and in terms of sub-environments, with small-scale variations in sediment provenance reflecting local morphology, particularly areas of channel convergence.

  20. Significant Contribution Assessment of Proposed Revisions Technical Support Document (TSD)

    EPA Pesticide Factsheets

    This TSD demonstrates EPA’s analysis to quantify the SO2 emissions that significantly contribute to nonattainment or interfere with maintenance of the National Ambient Air Quality Standards in downwind states for the Revisions to the Transport Rule.

  1. GM2 gangliosidosis in a UK study of children with progressive neurodegeneration: 73 cases reviewed.

    PubMed

    Smith, Nicholas J; Winstone, Anne Marie; Stellitano, Lesley; Cox, Timothy M; Verity, Christopher M

    2012-02-01

    To report the demographic, phenotypic, and time-to-diagnosis characteristics of children with GM2 gangliosidosis referred to the UK study of Progressive Intellectual and Neurological Deterioration. Case notification is made via monthly surveillance card, administered by the British Paediatric Surveillance Unit to all UK-based paediatricians; children with GM2 gangliosidosis were identified from cases satisfying inclusion in the UK study of Progressive Intellectual and Neurological Deterioration and analysed according to phenotypic and biochemical categories. Between May 1997 and January 2010, 73 individuals with GM2 gangliosidoses were reported: 40 with Tay-Sachs disease, 31 with Sandhoff disease, and two with GM2 activator protein deficiency. Together they account for 6% (73/1164) of all diagnosed cases of progressive intellectual and neurological deterioration. The majority (62/73) were sporadic index cases with no family history. Children of Pakistani ancestry were overrepresented in all subtypes, particularly juvenile Sandhoff disease, accounting for 10 of 11 notified cases. Infantile-onset variants predominated (55/73); the mean age at onset of symptoms was 6.2 and 4.7 months for infantile-onset Tay-Sachs and Sandhoff disease respectively, and 26.2 and 34.7 months for the corresponding juvenile-onset variants. Time to diagnosis averaged 7.4 months and 28.0 months in infantile- and juvenile-onset disease respectively. GM2 gangliosidosis is a significant cause of childhood neurodegenerative disease; timely diagnosis relies upon improved clinical recognition, which may be increasingly important as specific therapies become available. There is a potential benefit from the introduction of screening programmes for high-risk ethnic groups. © The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

  2. Cross-State Air Pollution Rule Update Allowance Allocation Final Rule TSD

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) provides information that supports EPA’s determination of unit-level allocations for existing and new units under the final Cross-State Air Pollution Rule Update.

  3. Fish with thermolabile sex determination (TSD) as models to study brain sex differentiation.

    PubMed

    Blázquez, Mercedes; Somoza, Gustavo M

    2010-05-01

    As fish are ectothermic animals, water temperature can affect their basic biological processes such as larval development, growth and reproduction. Similar to reptiles, the incubation temperature during early phases of development is capable to modify sex ratios in a large number of fish species. This phenomenon, known as thermolabile sex determination (TSD) was first reported in Menidia menidia, a species belonging to the family Atherinopsidae. Since then, an increasing number of fish have also been found to exhibit TSD. Traditionally, likewise in reptiles, several TSD patterns have been described in fish, however it has been recently postulated that only one, females at low temperatures and males at high temperatures, may represent the "real" or "true" TSD. Many studies regarding the influence of temperature on the final sex ratios have been focused on the expression and activity of gonadal aromatase, the enzyme involved in the conversion of androgens into estrogens and encoded by the cyp19a1a gene. In this regard, teleost fish, may be due to a whole genome duplication event, produce another aromatase enzyme, commonly named brain aromatase, encoded by the cyp19a1b gene. Contrary to what has been described in other vertebrates, fish exhibit very high levels of aromatase activity in the brain and therefore they synthesize high amounts of neuroestrogens. However, its biological significance is still not understood. In addition, the mechanism whereby temperature can induce the development of a testis or an ovary still remains elusive. In this context the present review is aimed to discuss several theories about the possible role of brain aromatase using fish as models. The relevance of brain aromatase and therefore of neuroestrogens as the possible cue for gonadal differentiation is raised. In addition, the possible role of brain aromatase as the way to keep the high levels of neurogenesis in fish is also considered. Several key examples of how teleosts and aromatase

  4. GM1 and GM2 gangliosides: recent developments.

    PubMed

    Bisel, Blaine; Pavone, Francesco S; Calamai, Martino

    2014-03-01

    GM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer's and Parkinson's diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction.

  5. Rice putative methyltransferase gene OsTSD2 is required for root development involving pectin modification

    PubMed Central

    Qu, Lianghuan; Wu, Chunyan; Zhang, Fei; Wu, Yangyang; Fang, Chuanying; Jin, Cheng; Liu, Xianqing; Luo, Jie

    2016-01-01

    Pectin synthesis and modification are vital for plant development, although the underlying mechanisms are still not well understood. Here, we report the functional characterization of the OsTSD2 gene, which encodes a putative methyltransferase in rice. All three independent T-DNA insertion lines of OsTSD2 displayed dwarf phenotypes and serial alterations in different zones of the root. These alterations included abnormal cellular adhesion and schizogenous aerenchyma formation in the meristematic zone, inhibited root elongation in the elongation zone, and higher lateral root density in the mature zone. Immunofluorescence (with LM19) and Ruthenium Red staining of the roots showed that unesterified homogalacturonan (HG) was increased in Ostsd2 mutants. Biochemical analysis of cell wall pectin polysaccharides revealed that both the monosaccharide composition and the uronic acid content were decreased in Ostsd2 mutants. Increased endogenous ABA content and opposite roles performed by ABA and IAA in regulating cellular adhesion in the Ostsd2 mutants suggested that OsTSD2 is required for root development in rice through a pathway involving pectin synthesis/modification. A hypothesis to explain the relationship among OsTSD2, pectin methylesterification, and root development is proposed, based on pectin’s function in regional cell extension/division in a zone-dependent manner. PMID:27497286

  6. 17 CFR 249.619 - Form TA-Y2K, information required of transfer agents pursuant to section 17 of the Securities...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Form TA-Y2K, information... Certain Exchange Members, Brokers, and Dealers § 249.619 Form TA-Y2K, information required of transfer... affecting Form TA-Y2K, see the List of CFR Sections Affected, which appears in the Finding Aids section of...

  7. Technical Revisions to State Budgets and New Unit Set-Asides TSD

    EPA Pesticide Factsheets

    EPA proposed revising the Transport Rule's new unit set-asides (NUSAs) in certain states. This technical support document (TSD) shows underlying data and calculations and provides the information used to determine revised NUSAs in certain states.

  8. Proper Conformal Killing Vectors in Kantowski-Sachs Metric

    NASA Astrophysics Data System (ADS)

    Hussain, Tahir; Farhan, Muhammad

    2018-04-01

    This paper deals with the existence of proper conformal Killing vectors (CKVs) in Kantowski-Sachs metric. Subject to some integrability conditions, the general form of vector filed generating CKVs and the conformal factor is presented. The integrability conditions are solved generally as well as in some particular cases to show that the non-conformally flat Kantowski-Sachs metric admits two proper CKVs, while it admits a 15-dimensional Lie algebra of CKVs in the case when it becomes conformally flat. The inheriting conformal Killing vectors (ICKVs), which map fluid lines conformally, are also investigated.

  9. CO2 Storage Potential of the Eocene Tay Sandstone, Central North Sea, UK

    NASA Astrophysics Data System (ADS)

    Gent, Christopher; Williams, John

    2017-04-01

    Carbon Capture and Storage (CCS) is crucial for low-carbon industry, climate mitigation and a sustainable energy future. The offshore capacity of the UK is substantial and has been estimated at 78 Gt of CO2 in saline aquifers and hydrocarbon fields. The early-mid Eocene Tay Sandstone Member of the Central North Sea (CNS) is a submarine-fan system and potential storage reservoir with a theoretical capacity of 123 Mt of CO2. The Tay Sandstone comprises of 4 sequences, amalgamating into a fan complex 125km long and 40 km at a minimum of 1500 m depth striking NW-SE, hosting several hydrocarbon fields including Gannett A, B, D and Pict. In order to better understand the storage potential and characteristics, the Tay Sandstone over Quadrant 21 has been interpreted using log correlation and 3D seismic. Understanding the internal and external geometry of the sandstone as well as the lateral extent of the unit is essential when considering CO2 vertical and horizontal fluid flow pathways and storage security. 3D seismic mapping of a clear mounded feature has revealed the youngest sequence of the Tay complex; a homogenous sand-rich channel 12 km long, 1.5 km wide and on average 100 m thick. The sandstone has porosity >35%, permeability >5 D and a net to gross of 0.8, giving a total pore volume of 927x106 m3. The remaining three sequences are a series of stacked channels and interbedded mudstones which are more quiescent on the seismic, however, well logs indicate each subsequent sequence reduce in net to gross with age as mud has a greater influence in the early fan system. Nevertheless, the sandstone properties remain relatively consistent and are far more laterally extensive than the youngest sequence. The Tay Sandstone spatially overlaps several other potential storage sites including the older Tertiary sandstones of the Cromarty, Forties and Mey Members and deeper Jurassic reservoirs. This favours the Tay Sandstone to be considered in a secondary or multiple stacked

  10. Rice putative methyltransferase gene OsTSD2 is required for root development involving pectin modification.

    PubMed

    Qu, Lianghuan; Wu, Chunyan; Zhang, Fei; Wu, Yangyang; Fang, Chuanying; Jin, Cheng; Liu, Xianqing; Luo, Jie

    2016-10-01

    Pectin synthesis and modification are vital for plant development, although the underlying mechanisms are still not well understood. Here, we report the functional characterization of the OsTSD2 gene, which encodes a putative methyltransferase in rice. All three independent T-DNA insertion lines of OsTSD2 displayed dwarf phenotypes and serial alterations in different zones of the root. These alterations included abnormal cellular adhesion and schizogenous aerenchyma formation in the meristematic zone, inhibited root elongation in the elongation zone, and higher lateral root density in the mature zone. Immunofluorescence (with LM19) and Ruthenium Red staining of the roots showed that unesterified homogalacturonan (HG) was increased in Ostsd2 mutants. Biochemical analysis of cell wall pectin polysaccharides revealed that both the monosaccharide composition and the uronic acid content were decreased in Ostsd2 mutants. Increased endogenous ABA content and opposite roles performed by ABA and IAA in regulating cellular adhesion in the Ostsd2 mutants suggested that OsTSD2 is required for root development in rice through a pathway involving pectin synthesis/modification. A hypothesis to explain the relationship among OsTSD2, pectin methylesterification, and root development is proposed, based on pectin's function in regional cell extension/division in a zone-dependent manner. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  11. Critical role of CA1 muscarinic receptors on memory acquisition deficit induced by total (TSD) and REM sleep deprivation (RSD).

    PubMed

    Javad-Moosavi, Bibi-Zahra; Vaezi, Gholamhassan; Nasehi, Mohammad; Haeri-Rouhani, Seyed-Ali; Zarrindast, Mohammad-Reza

    2017-10-03

    Despite different theories regarding sleep physiological function, an overall census indicates that sleep is useful for neural plasticity which eventually strengthens cognition and brain performance. Different studies show that sleep deprivation (SD) leads to impaired learning and hippocampus dependent memory. According to some studies, cholinergic system plays an important role in sleep (particularly REM sleep), learning, memory, and its retrieval. So this study has been designed to investigate the effect of CA1 Cholinergic Muscarinic Receptors on memory acquisition deficit induced by total sleep deprivation (TSD) and REM sleep deprivation (RSD). A modified water box (locomotor activity may be provide a limiting factor in this method of SD) or multiple platforms were used for induction of TSD or RSD, respectively. Inhibitory passive avoidance apparatus has been used to determine the effects of SD and its changes by physostigmine (as cholinesterase inhibitor) or scopolamine (muscarinic receptor antagonist) on memory formation. Because locomotor activity and pain perception induce critical roles in passive avoidance memory formation, we also measured these factors by open field and hot-plate instruments, respectively. The results showed that TSD and RSD for 24 hours impaired memory formation but they did not alter locomotor activity. TSD also induced analgesia effect, but RSD did not alter it. Intra-CA1 injection of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) did not alter memory acquisition in the sham-TSD or sham-RSD, by themselves. Moreover, intra-CA1 injection of sub-threshold dose of physostigmine (0.0001μg/rat) and scopolamine (0.01μg/rat) could restore the memory acquisition deficit induced by RSD, while scopolamine could restore TSD-induced amnesia. Both drugs reversed analgesia induced by TSD. None of previous interventions altered locomotor activity. According to this study, CA1 cholinergic muscarinic receptors play an important role in

  12. Final June Revisions Rule State Budgets and New Unit Set-Asides TSD

    EPA Pesticide Factsheets

    This technical support document (TSD) for the final revisions to the Transport Rule shows the underlying data and calculations used to quantify the state budget revisions and new unit set-aside revisions.

  13. 78 FR 26407 - Goldman Sachs Trust II, et al.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-06

    ... Sachs Trust II, et al.; Notice of Application April 29, 2013. AGENCY: Securities and Exchange Commission... would grant relief from certain disclosure requirements. APPLICANTS: Goldman Sachs Trust II (the ``Trust...'', each of GSAM and GSAMI an ``Adviser'' and collectively, ``Advisers,'' and together with the Trust...

  14. Mendelian diseases among Roman Jews: implications for the origins of disease alleles.

    PubMed

    Oddoux, C; Guillen-Navarro, E; Ditivoli, C; Dicave, E; Cilio, M R; Clayton, C M; Nelson, H; Sarafoglou, K; McCain, N; Peretz, H; Seligsohn, U; Luzzatto, L; Nafa, K; Nardi, M; Karpatkin, M; Aksentijevich, I; Kastner, D; Axelrod, F; Ostrer, H

    1999-12-01

    The Roman Jewish community has been historically continuous in Rome since pre-Christian times and may have been progenitor to the Ashkenazi Jewish community. Despite a history of endogamy over the past 2000 yr, the historical record suggests that there was admixture with Ashkenazi and Sephardic Jews during the Middle Ages. To determine whether Roman and Ashkenazi Jews shared common signature mutations, we tested a group of 107 Roman Jews, representing 176 haploid sets of chromosomes. No mutations were found for Bloom syndrome, BRCA1, BRCA2, Canavan disease, Fanconi anemia complementation group C, or Tay-Sachs disease. Two unrelated individuals were positive for the 3849 + 10C->T cystic fibrosis mutation; one carried the N370S Gaucher disease mutation, and one carried the connexin 26 167delT mutation. Each of these was shown to be associated with the same haplotype of tightly linked microsatellite markers as that found among Ashkenazi Jews. In addition, 14 individuals had mutations in the familial Mediterranean fever gene and three unrelated individuals carried the factor XI type III mutation previously observed exclusively among Ashkenazi Jews. These findings suggest that the Gaucher, connexin 26, and familial Mediterranean fever mutations are over 2000 yr old, that the cystic fibrosis 3849 + 10kb C->T and factor XI type III mutations had a common origin in Ashkenazi and Roman Jews, and that other mutations prevalent among Ashkenazi Jews are of more recent origin.

  15. Suggestions for CAP-TSD mesh and time-step input parameters

    NASA Technical Reports Server (NTRS)

    Bland, Samuel R.

    1991-01-01

    Suggestions for some of the input parameters used in the CAP-TSD (Computational Aeroelasticity Program-Transonic Small Disturbance) computer code are presented. These parameters include those associated with the mesh design and time step. The guidelines are based principally on experience with a one-dimensional model problem used to study wave propagation in the vertical direction.

  16. [Physician satire and patient scorn in Hans Sachs' old Nürnberg and the physicians].

    PubMed

    Sauerbeck, K O

    1993-01-01

    Among the best poems of Hans Sachs quite a few describe patient-physician relationships in 16th century Nuremberg. These poems offer a vivid impression of the technical aspects as well as of the social context of medical treatment at the time. Hans Sachs ridiculed the doctors and their patients, implying that everybody attempted to cheat the other side, and he provides evidence of a great influence of charlatans on the country population. The poems of Hans Sachs are extraordinary pieces or art; their aesthetics, though, appear unusual to us today. Medical satire is part of all European cultures, and has been written throughout medical history. Most motives of later satires focussing on physicians may be traced to Hans Sachs' poetry.

  17. Basic versus applied research: Julius Sachs (1832-1897) and the experimental physiology of plants.

    PubMed

    Kutschera, Ulrich

    2015-01-01

    The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This "plant-microbe-view" of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845-1920), so that the term "Sachs-Pfeffer-Principle of Experimental Plant Research" appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria).

  18. Different Role of CA1 5HT3 Serotonin Receptors on Memory Acquisition Deficit Induced by Total (TSD) and REM Sleep Deprivation (RSD).

    PubMed

    Eydipour, Zainab; Vaezi, Gholamhassan; Nasehi, Mohammad; Haeri-Rouhani, Seyed-Ali; Zarrindast, Mohammad-Reza

    2017-09-01

    Serotonin receptors such as 5-HT3 plays critical role in regulation of sleep, wake cycle and cognitive process. Thus, we investigated the role of CA1 5HT3 serotonin receptors in memory acquisition deficit induced by total sleep deprivation (TSD; for 24 hour) and REM sleep deprivation (RSD; for 24 hour). Pain perception and locomotor activity were also assessed as factors that may affect the memory process. Modified water box and multi-platform apparatus were used to induce TSD or RSD, respectively. Passive avoidance, hot plate and open field devices were used for assessment of memory acquisition, pain and locomotor activity, respectively. Totally, 152 male Wistar rats were used in the study. Pre-training, intra-CA1 injection of 5-HT3 receptor agonist Chlorophenylbiguanide (Mchl; 0.01 and 0.001 µg/rat; P < 0.001) and antagonist Y-25130 (0.1 µg/rat; P < 0.001) reduced memory acquisition and did not alter pain response, while higher dose of both drugs increased locomotor activity in normal rats. Both TSD and RSD reduced memory acquisition (P < 0.001) and did not alter locomotor activity, while TSD (P < 0.001) but not RSD induced analgesia effect. The amnesia induced by TSD was restored by subthreshold dose of Y25130 (0.001 µg/rat; P < 0.001) but not Mchl (0.0001 µg/rat), while both drugs reversed TSD-induced analgesia effect (P < 0.01 for Mchl and P < 0.05 for Y25130), and Y25130 increased locomotor activity in TSD rats (P < 0.05). In RSD rats, subthreshold dose of both drugs did not alter memory acquisition deficit and increased locomotor activity (P < 0.001 for Mchl and P < 0.01 for Y25130), while the Y25130 (P < 0.001), but not Mchl induced analgesia in the RSD rats. Based on the above data, CA1 5HT3 receptors seem to play a critical role in cognitive and non-cognitive behaviors induced by TSD and RSD.

  19. 75 FR 44031 - Goldman, Sachs & Co., et al.; Notice of Application and Temporary Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-27

    ... International (``GSAMI''), Goldman Sachs Hedge Fund Strategies LLC (``GSHFS''), Commonwealth Annuity and Life... marketing materials used in connection with residential mortgage-related securities offerings by Goldman... marketing materials, (iv) where Goldman Sachs is the lead underwriter of an offering of residential mortgage...

  20. GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening.

    PubMed

    Kaya, Namik; Al-Owain, Mohammad; Abudheim, Nada; Al-Zahrani, Jawaher; Colak, Dilek; Al-Sayed, Moeen; Milanlioglu, Aysel; Ozand, Pinar T; Alkuraya, Fowzan S

    2011-06-01

    The GM2 gangliosidose, Tay-Sachs and Sandhoff diseases, are a class of lysosomal storage diseases in which relentless neurodegeneration results in devastating neurological disability and premature death. Primary prevention is the most effective intervention since no effective therapy is currently available. An extremely successful model for the prevention of GM2 gangliosidosis in the Ashkenazi Jewish community is largely attributable to the very limited number of founder mutations in that population. Consistent with our previous observation of allelic heterogeneity in consanguineous populations, we show here that these diseases are largely caused by private mutations which present a major obstacle in replicating the Ashkenazi success story. Alternative solutions are proposed which can also be implemented for other autosomal recessive diseases in our population. Copyright © 2011 Wiley-Liss, Inc.

  1. Natural History of Infantile GM2 Gangliosidosis

    PubMed Central

    Bley, Annette E.; Giannikopoulos, Ourania A.; Hayden, Doug; Kubilus, Kim; Tifft, Cynthia J.

    2011-01-01

    OBJECTIVE: GM2 gangliosidoses are caused by an inherited deficiency of lysosomal β-hexosaminidase and result in ganglioside accumulation in the brain. Onset during infancy leads to rapid neurodegeneration and death before 4 years of age. We set out to quantify the rate of functional decline in infantile GM2 gangliosidosis on the basis of patient surveys and a comprehensive review of existing literature. METHODS: Patients with infantile GM2 gangliosidosis (N = 237) were surveyed via questionnaire by the National Tay Sachs & Allied Diseases Association (NTSAD). These data were supplemented by survival data from the NTSAD database and a literature survey. Detailed retrospective surveys from 97 patients were available. Five patients who had received hematopoietic stem cell transplantation were evaluated separately. The mortality rate of the remaining 92 patients was comparable to that of the 103 patients from the NTSAD database and 121 patients reported in the literature. RESULTS: Common symptoms at onset were developmental arrest (83%), startling (65%), and hypotonia (60%). All 55 patients who had learned to sit without support lost that ability within 1 year. Individual functional measures correlated with each other but not with survival. Gastric tube placement was associated with prolonged survival. Tay Sachs and Sandhoff variants did not differ. Hematopoietic stem cell transplantation was not associated with prolonged survival. CONCLUSIONS: We studied the timing of regression in 97 cases of infantile GM2 gangliosidosis and conclude that clinical disease progression does not correlate with survival, likely because of the impact of improved supportive care over time. However, functional measures are quantifiable and can inform power calculations and study design of future interventions. PMID:22025593

  2. Basic versus applied research: Julius Sachs (1832–1897) and the experimental physiology of plants

    PubMed Central

    Kutschera, Ulrich

    2015-01-01

    The German biologist Julius Sachs was the first to introduce controlled, accurate, quantitative experimentation into the botanical sciences, and is regarded as the founder of modern plant physiology. His seminal monograph Experimental-Physiologie der Pflanzen (Experimental Physiology of Plants) was published 150 y ago (1865), when Sachs was employed as a lecturer at the Agricultural Academy in Poppelsdorf/Bonn (now part of the University). This book marks the beginning of a new era of basic and applied plant science. In this contribution, I summarize the achievements of Sachs and outline his lasting legacy. In addition, I show that Sachs was one of the first biologists who integrated bacteria, which he considered to be descendants of fungi, into the botanical sciences and discussed their interaction with land plants (degradation of wood etc.). This “plant-microbe-view” of green organisms was extended and elaborated by the laboratory botanist Wilhelm Pfeffer (1845–1920), so that the term “Sachs-Pfeffer-Principle of Experimental Plant Research” appears to be appropriate to characterize this novel way of performing scientific studies on green, photoautotrophic organisms (embryophytes, algae, cyanobacteria). PMID:26146794

  3. The white matter of the human cerebrum: Part I The occipital lobe by Heinrich Sachs

    PubMed Central

    Forkel, Stephanie J.; Mahmood, Sajedha; Vergani, Francesco; Catani, Marco

    2015-01-01

    This is the first complete translation of Heinrich Sachs' outstanding white matter atlas dedicated to the occipital lobe. This work is accompanied by a prologue by Prof Carl Wernicke who for many years was Sachs' mentor in Breslau and enthusiastically supported his work. PMID:25527430

  4. Step-by-Step Technique for Segmental Reconstruction of Reverse Hill-Sachs Lesions Using Homologous Osteochondral Allograft.

    PubMed

    Alkaduhimi, Hassanin; van den Bekerom, Michel P J; van Deurzen, Derek F P

    2017-06-01

    Posterior shoulder dislocations are accompanied by high forces and can result in an anteromedial humeral head impression fracture called a reverse Hill-Sachs lesion. This reverse Hill-Sachs lesion can result in serious complications including posttraumatic osteoarthritis, posterior dislocations, osteonecrosis, persistent joint stiffness, and loss of shoulder function. Treatment is challenging and depends on the amount of bone loss. Several techniques have been reported to describe the surgical treatment of lesions larger than 20%. However, there is still limited evidence with regard to the optimal procedure. Favorable results have been reported by performing segmental reconstruction of the reverse Hill-Sachs lesion with bone allograft. Although the procedure of segmental reconstruction has been used in several studies, its technique has not yet been well described in detail. In this report we propose a step-by-step description of the technique how to perform a segmental reconstruction of a reverse Hill-Sachs defect.

  5. Assessment of Non-EGU NOx Emission Controls, Cost of Controls, and Time for Compliance Final TSD

    EPA Pesticide Factsheets

    The purpose of this Technical Support Document (TSD) is to discuss the currently available information on emissions and control measures for sources of NOX other than electric generating units (EGUs).

  6. GM2 gangliosidosis associated with a HEXA missense mutation in Japanese Chin dogs: a potential model for Tay Sachs disease.

    PubMed

    Sanders, Douglas N; Zeng, Rong; Wenger, David A; Johnson, Gary S; Johnson, Gayle C; Decker, Jared E; Katz, Martin L; Platt, Simon R; O'Brien, Dennis P

    2013-01-01

    GM2 gangliosidosis is a fatal lysosomal storage disease caused by a deficiency of β-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an α and a β subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two β subunits. Hexosaminidase A requires an activator protein encoded by GM2A to catabolize GM2 ganglioside, but even in the absence of the activator protein, it can hydrolyze the synthetic substrates commonly used to assess enzyme activity. GM2 gangliosidosis has been reported in Japanese Chin dogs, and we identified the disease in two related Japanese Chin dogs based on clinical signs, histopathology and elevated brain GM2 gangliosides. As in previous reports, we found normal or elevated hexosaminidase activity when measured with the synthetic substrates. This suggested that the canine disease is analogous to human AB variant of G(M2) gangliosidosis, which results from mutations in GM2A. However, only common neutral single nucleotide polymorphisms were found upon sequence analysis of the canine ortholog of GM2A from the affected Japanese Chins. When the same DNA samples were used to sequence HEXA, we identified a homozygous HEXA:c967G>A transition which predicts a p.E323K substitution. The glutamyl moiety at 323 is known to make an essential contribution to the active site of hexosaminidase A, and none of the 128 normal Japanese Chins and 92 normal dogs of other breeds that we tested was homozygous for HEXA:c967A. Thus it appears that the HEXA:c967G>A transition is responsible for the GM2 gangliosidosis in Japanese Chins. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Application of the CAP-TSD unsteady transonic small disturbance program to wing flutter. [Computational Aeroelasticity Program

    NASA Technical Reports Server (NTRS)

    Bennett, Robert M.; Batina, John T.

    1989-01-01

    The application and assessment of a computer program called CAP-TSD (Computational Aeroelasticity Program - Transonic Small Disturbance) for flutter predictions are described. Flutter calculations are presented for two thin swept-and-tapered wing planforms with well-defined modal properties. One planform is a series of 45-degree swept wings and the other planform is a clipped delta wing. Comparisons are made between the results of CAP-TSD using the linear equation and no airfoil thickness and the results obtained from a subsonic kernel function analysis. The calculations cover a Mach number range from low subsonic to low supersonic values, including the transonic range, and are compared with subsonic linear theory and experimental data. It is noted that since both wings have very thin airfoil sections, the effects of thickness are minimal.

  8. Calculating the Sachs-Wolfe Effect from Solutions of Null Geodesics in Perturbed FRW Spacetime

    NASA Astrophysics Data System (ADS)

    Arroyo-Cárdenas, C. A.; Muñoz-Cuartas, J. C.

    2017-07-01

    In the upcoming precision era in cosmology, fine grained effects will be measured accurately. In particular, the late integrated Sachs-Wolfe (ISW) effect measurements will be improved to levels of unprecedented precision. The ISW consists on temperature fluctuations in the CMB due to gravitational redshift induced by the evolving potential well of large scale structure in the Universe. Currently there is large controversy related to the actual observability of the ISW effect. In principle, it is expected that, as an effect of the late accelerated expansion of the universe motivated by the current amount of dark energy, large scale structures may evolve rapidly, inducing an observable signature in the CMB photons in the way of a ISW anisotropy in the CMB. Tension arises since using galaxy redshift surveys some works report a temperature fluctuations with amplitude smaller than predicted by the Lambda-CDM. We argue that these discrepancies may be originated in the approximation that one has to make to get the classic Sachs-Wolfe effect. In this work, we compare the classic Sachs-Wolfe approximation with an exact solution to the propagation of photons in a dynamical background. We solve numerically the null geodesics on a perturbed FRW spacetime in the Newtonian gauge. From null geodesics, temperature fluctuations in the CMB due to the evolving potential has been calculated. Since solving geodesics accounts for more terms than solving the Sachs-Wolfe (approximated) integral, our results are more accurate. We have been able to substract the background cosmological redshift with the information provided by null geodesics, which allows to get an estimate of the integrated Sachs-Wolfe effect contribution to the temperature of the CMB.

  9. Geographic Distribution of Disease Mutations in the Ashkenazi Jewish Population Supports Genetic Drift over Selection

    PubMed Central

    Risch, Neil; Tang, Hua; Katzenstein, Howard; Ekstein, Josef

    2003-01-01

    The presence of four lysosomal storage diseases (LSDs) at increased frequency in the Ashkenazi Jewish population has suggested to many the operation of natural selection (carrier advantage) as the driving force. We compare LSDs and nonlysosomal storage diseases (NLSDs) in terms of the number of mutations, allele-frequency distributions, and estimated coalescence dates of mutations. We also provide new data on the European geographic distribution, in the Ashkenazi population, of seven LSD and seven NLSD mutations. No differences in any of the distributions were observed between LSDs and NLSDs. Furthermore, no regular pattern of geographic distribution was observed for LSD versus NLSD mutations—with some being more common in central Europe and others being more common in eastern Europe, within each group. The most striking disparate pattern was the geographic distribution of the two primary Tay-Sachs disease mutations, with the first being more common in central Europe (and likely older) and the second being exclusive to eastern Europe (primarily Lithuania and Russia) (and likely much younger). The latter demonstrates a pattern similar to two other recently arisen Lithuanian mutations, those for torsion dystonia and familial hypercholesterolemia. These observations provide compelling support for random genetic drift (chance founder effects, one ∼11 centuries ago that affected all Ashkenazim and another ∼5 centuries ago that affected Lithuanians), rather than selection, as the primary determinant of disease mutations in the Ashkenazi population. PMID:12612865

  10. CMB anisotropies at all orders: the non-linear Sachs-Wolfe formula

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roldan, Omar, E-mail: oaroldan@if.ufrj.br

    2017-08-01

    We obtain the non-linear generalization of the Sachs-Wolfe + integrated Sachs-Wolfe (ISW) formula describing the CMB temperature anisotropies. Our formula is valid at all orders in perturbation theory, is also valid in all gauges and includes scalar, vector and tensor modes. A direct consequence of our results is that the maps of the logarithmic temperature anisotropies are much cleaner than the usual CMB maps, because they automatically remove many secondary anisotropies. This can for instance, facilitate the search for primordial non-Gaussianity in future works. It also disentangles the non-linear ISW from other effects. Finally, we provide a method which canmore » iteratively be used to obtain the lensing solution at the desired order.« less

  11. The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease

    PubMed Central

    Gan-Or, Ziv; Ozelius, Laurie J.; Bar-Shira, Anat; Saunders-Pullman, Rachel; Mirelman, Anat; Kornreich, Ruth; Gana-Weisz, Mali; Raymond, Deborah; Rozenkrantz, Liron; Deik, Andres; Gurevich, Tanya; Gross, Susan J.; Schreiber-Agus, Nicole; Giladi, Nir; Bressman, Susan B.

    2013-01-01

    Objective: To study the possible association of founder mutations in the lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs, Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson disease (PD). Methods: Two PD patient cohorts of Ashkenazi Jewish (AJ) ancestry, that included a total of 938 patients, were studied: a cohort of 654 patients from Tel Aviv, and a replication cohort of 284 patients from New York. Eight AJ founder mutations in the HEXA, SMPD1, and MCOLN1 genes were analyzed. The frequencies of these mutations were compared to AJ control groups that included large published groups undergoing prenatal screening and 282 individuals matched for age and sex. Results: Mutation frequencies were similar in the 2 groups of patients with PD. The SMPD1 p.L302P was strongly associated with a highly increased risk for PD (odds ratio 9.4, 95% confidence interval 3.9–22.8, p < 0.0001), as 9/938 patients with PD were carriers of this mutation compared to only 11/10,709 controls. Conclusions: The SMPD1 p.L302P mutation is a novel risk factor for PD. Although it is rare on a population level, the identification of this mutation as a strong risk factor for PD may further elucidate PD pathogenesis and the role of lysosomal pathways in disease development. PMID:23535491

  12. Cloning and sequence analysis of a cDNA encoding the alpha-subunit of mouse beta-N-acetylhexosaminidase and comparison with the human enzyme.

    PubMed Central

    Beccari, T; Hoade, J; Orlacchio, A; Stirling, J L

    1992-01-01

    cDNAs encoding the mouse beta-N-acetylhexosaminidase alpha-subunit were isolated from a mouse testis library. The longest of these (1.7 kb) was sequenced and showed 83% similarity with the human alpha-subunit cDNA sequence. The 5' end of the coding sequence was obtained from a genomic DNA clone. Alignment of the human and mouse sequences showed that all three putative N-glycosylation sites are conserved, but that the mouse alpha-subunit has an additional site towards the C-terminus. All eight cysteines in the human sequence are conserved in the mouse. There are an additional two cysteines in the mouse alpha-subunit signal peptide. All amino acids affected in Tay-Sachs-disease mutations are conserved in the mouse. Images Fig. 1. PMID:1379046

  13. Sachs' free data in real connection variables

    NASA Astrophysics Data System (ADS)

    De Paoli, Elena; Speziale, Simone

    2017-11-01

    We discuss the Hamiltonian dynamics of general relativity with real connection variables on a null foliation, and use the Newman-Penrose formalism to shed light on the geometric meaning of the various constraints. We identify the equivalent of Sachs' constraint-free initial data as projections of connection components related to null rotations, i.e. the translational part of the ISO(2) group stabilising the internal null direction soldered to the hypersurface. A pair of second-class constraints reduces these connection components to the shear of a null geodesic congruence, thus establishing equivalence with the second-order formalism, which we show in details at the level of symplectic potentials. A special feature of the first-order formulation is that Sachs' propagating equations for the shear, away from the initial hypersurface, are turned into tertiary constraints; their role is to preserve the relation between connection and shear under retarded time evolution. The conversion of wave-like propagating equations into constraints is possible thanks to an algebraic Bianchi identity; the same one that allows one to describe the radiative data at future null infinity in terms of a shear of a (non-geodesic) asymptotic null vector field in the physical spacetime. Finally, we compute the modification to the spin coefficients and the null congruence in the presence of torsion.

  14. Proposed Unit Level Ozone Season NOx Allowance Allocations to Existing Units in Six States: Supplemental Proposed Rule TSD

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) presents the proposed unit-level allocations based on the existing-unit portion of each state’s ozone season NOx emission budget to covered existing units in Iowa, Kansas, Michigan, Missouri, Oklahoma, and Wisconsin.

  15. Simultaneous quantification of GM1 and GM2 gangliosides by isotope dilution tandem mass spectrometry.

    PubMed

    Gu, Jianghong; Tifft, Cynthia J; Soldin, Steven J

    2008-04-01

    Gangliosides (GGs) are considered as diagnostic biomarkers and therapeutic targets and agents. The goal of this study was to develop a tandem mass spectrometry (MS/MS) method for the simultaneous measurement of both GM1 and GM2 gangliosides in human cerebrospinal fluid (CSF) samples in order to be able to determine their concentrations in patients with Tay-Sachs and Sandhoff disease and assess whether drugs or transplantation affect their concentrations. An API-4000 tandem mass spectrometer equipped with TurboIonSpray source and Shimadzu HPLC system was employed to perform the analysis using isotope dilution with deuterium labeled internal standards. To a 1.5 mL conical plastic Eppendorf centrifuge tube, 40 microL of human CSF sample was added and mixed with 400 microL of internal standard solution for deproteinization. After centrifugation, 100 microL of supernatant was injected onto a C-18 column. After a 2.5 min wash, the switching valve was activated and the analytes were eluted from the column with a water/methanol gradient into the MS/MS system. Quantification by multiple reaction-monitoring (MRM) analysis was performed in the negative mode. The within-day coefficients of variation were <3% for GM1 and <2% for GM2 and the between-day coefficients of variation were <5% for both GM1 and GM2 at all concentrations tested. Accuracy ranged between 98% and 102% for both analytes. Good linearity was also obtained within the concentration range of 10-200 ng/mL (6.5-129.3 nmol/L) for GM1 and 5-100 ng/mL (3.6-72.3 nmol/L) for GM2 (r> or =0.995). A new simple, accurate, and fast isotope dilution tandem mass spectrometry method was developed for the simultaneous quantification of GM1 and GM2 gangliosides in a small amount of human CSF. Concentrations were measured in "normal" CSF and in CSF from patients with Tay-Sachs disease.

  16. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Petroulakis, E.; Cao, Z.; Salo, T.

    Mutations in the HEXA gene that encodes the {alpha}-subunit of the heterodimeric lysosomal enzyme {beta}-hexosaminidase A, or Hex A ({alpha}{beta}), cause G{sub M2} gangliosidosis, type 1. The infantile form (Tay-Sachs disease) results when there is no residual Hex A activity, while less severe and more variable clinical phenotypes result when residual Hex A activity is present. A non-Jewish male who presented with an acute psychotic episode at age 16 was diagnosed with a subacute encephalopathic form of G{sub M2} gangliosidosis. At age 19, chronic psychosis with intermittent acute exacerbations remains the most disabling symptom in this patient and his affectedmore » brother although both exhibit some ataxia and moderately severe dysarthria. We have found a 4 bp insertion (+TATC 1278) associated with infantile Tay-Sachs disease on one allele; no previously identified mutation was found on the second allele. SSCP analysis detected a shift in exon 13 and sequencing revealed a G1422C mutation in the second allele that results in a Trp474Cys substitution. The presence of the mutation was confirmed by the loss of HaeIII and ScrFI sites in exon 13 PCR products from the subjects and their father. The mutation was introduced into the {alpha}-subunit cDNA and Hex S ({alpha}{alpha}) and Hex A ({alpha}{beta}) were transiently expressed in monkey COS-7 cells. The Trp474Cys mutant protein had approximately 5% and 12% of wild-type Hex S and Hex A activity, respectively. Western blot analysis revealed a small amount of residual mature {alpha}-subunit and a normal level of precursor protein. We conclude that the Trp474Cys mutation is the cause of the Hex A deficiency associated with a subacute (juvenile-onset) phenotype in this patient. Like other mutations in exon 13 of HEXA, it appears to affect intracellular processing. Studies of the defect in intracellular processing are in progress.« less

  17. Stigmatization of carrier status: social implications of heterozygote genetic screening programs.

    PubMed Central

    Kenen, R H; Schmidt, R M

    1978-01-01

    Possible latent psychological and social consequences ensuing from genetic screening programs need to be investigated during the planning phase of national genetic screening programs. The relatively few studies which have been performed to determine psychological, social, and economic consequences resulting from a genetic screening program are reviewed. Stigmatization of carrier-status, having major psychosocial implications in heterozygote genetic screening programs, is discussed and related to Erving Goffman's work in the area of stigmatization. Questions are raised regarding the relationship between such variables as religiosity and sex of the individual and acceptance of the status of newly identified carrier of a mutant gene. Severity of the deleterious gene and visibility of the carrier status are two important factors to consider in an estimation of potential stigma. Specific implications are discussed for four genetic diseases: Tay-Sachs, Sickle-Cell Anemia, Huntington's disease and Hemophilia. PMID:152585

  18. 78 FR 24447 - Goldman Sachs Trust, et al.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-25

    ... SECURITIES AND EXCHANGE COMMISSION [Investment Company Act Release No. 30471; 812-14075] Goldman Sachs Trust, et al.; Notice of Application April 19, 2013. AGENCY: Securities and Exchange Commission..., or cause more than 10% of the acquired company's voting stock to be owned by investment companies and...

  19. Tilted Kantowski-Sachs cosmological model in Brans-Dicke theory of gravitation

    NASA Astrophysics Data System (ADS)

    Pawar, D. D.; Shahare, S. P.; Dagwal, V. J.

    2018-02-01

    Tilted Kantowski-Sachs cosmological model in Brans-Dicke theory for perfect fluid has been investigated. The general solution of field equations in Brans-Dicke theory for the combined scalar and tensor field are obtained by using power law relation. Also, some physical and geometrical parameters are obtained and discussed.

  20. Current practices of commercial cryobanks in screening prospective donors for genetic disease and reproductive risk.

    PubMed

    Conrad, E A; Fine, B; Hecht, B R; Pergament, E

    1996-01-01

    To determine how the screening practices of commercial semen banks vary from published guidelines, which factors influence cryobanks to exclude prospective semen donors for genetic reasons, and the current role of clinical geneticists/genetic counselors in evaluating prospective semen donors. The genetic screening of prospective donors by commercial semen banks was evaluated using written questionnaires completed by bank directors. Responses were analyzed to determine exclusion criteria, adherence to published guidelines, and contribution of genetic professionals. Semen banks were selected on the basis of membership in the American Association of Tissue Banks and commercial use of semen for artificial insemination by donor. Semen bank practices as reported by commercial semen bank directors. Of 37 eligible banks, 16 responded. All screen prospective donors by medical/family history and physical examination, 94% have upper age limits; 63% examine for minor physical defects; 56% routinely karyotype; 81% screen men of ethnic groups at risk for Tay Sachs disease, sickle cell disease and thalassemia; 19% screen all donors; 25% screen all donors for cystic fibrosis and 50% only screen if family history positive. Donor rejection was based on three criteria: mode of inheritance of familial disorder, severity of disease, and availability of carrier/confirmatory testing of donor genotype. Ten of 16 banks have no genetic professional on staff. Commercial semen banks primarily rely on family history as the major exclusion criterion in genetic screening of donors. Considerable differences exist among semen bank practices in accordance with guidelines published by national agencies. Genetic professionals have a minimal effect overall on evaluation of semen donors.

  1. Determination of frequencies of alleles, associated with the pseudodeficiency of lysosomal hydrolases, in population of Ukraine.

    PubMed

    Olkhovych, N V; Gorovenko, N G

    2016-01-01

    The pseudodeficiency of lysosomal hydrolases described as a significant reduction in enzyme activi­ty in vitro in clinically healthy individuals, can lead to diagnostic errors in the process of biochemical analysis of lysosomal storage disease in case of its combination with pathology of another origin. Pseudodeficiency is mostly caused by some non-pathogenic changes in the corresponding gene. These changes lead to the in vitro lability of the enzyme molecule, whereas in vivo the enzyme retains its functional activity. To assess the prevalence of the most common lysosomal hydrolases pseudodeficiency alleles in Ukraine, we have determined the frequency of alleles c.1055A>G and c.* 96A>G in the ARSA gene, substitutions c.739C>T (R247W) and c.745C>T (R249W) in the HEXA gene, c.1726G>A (G576S) and c.2065G>A (E689K) in the GAA gene, c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene in a group of 117 healthy individuals from different regions of the country and 14 heterozygous carriers of pathogenic mutations in the HEXA gene (parents of children with confirmed diagnosis of Tay-Sachs disease). The total frequency of haplotypes, associated with arylsulfatase A pseudodeficiency, in healthy people in Ukraine (c.1055G/c.*96G and c.1055G/c.*96A haplotypes) was 10.3%. The frequency of c.739C>T (R247W) allele, associated with hexo­saminidase A pseudodeficiency, among Tay-Sachs carriers from Ukraine was 7.1%. The total frequency of α-glucosidase pseudodeficiency haplotypes in healthy individuals in Ukraine (c.1726A/c.2065A and c.1726G/c.2065A haplotypes) was 2.6%. No person among examined individuals with the substitution c.937G>T (D313Y) in the GLA1 gene and c.898G>A (A300T) in the IDUA gene was found. The differential diagnostics of lysosomal storage diseases requires obligatory determination of the presence of the pseudodeficiency alleles, particularly the ones with high incidence in the total population. Ignoring phenomenon of pseudodeficiency may

  2. The Kantowski-Sachs Quantum Model with Stiff Matter Fluid

    NASA Astrophysics Data System (ADS)

    Alvarenga, F. G.; Fracalossi, R.; Freitas, R. C.; Gonçalves, S. V. B.

    2018-05-01

    In this paper, we study the quantum cosmological Kantowski-Sachs model and we solve the Wheeler-DeWitt equation in minisuperspace to obtain the wave function of the corresponding universe. The perfect fluid is described by Schutz's canonical formalism, which allows to attribute dynamical degrees of freedom to matter. The time is introduced phenomenologically using the fluid's degrees of freedom. In particular, we adopt a stiff matter fluid. The viability of this model is analyzed and discussed.

  3. Black Hole Entropy from Bondi-Metzner-Sachs Symmetry at the Horizon.

    PubMed

    Carlip, S

    2018-03-09

    Near the horizon, the obvious symmetries of a black hole spacetime-the horizon-preserving diffeomorphisms-are enhanced to a larger symmetry group with a three-dimensional Bondi-Metzner-Sachs algebra. Using dimensional reduction and covariant phase space techniques, I investigate this augmented symmetry and show that it is strong enough to determine the black hole entropy in any dimension.

  4. Application of DNA Machineries for the Barcode Patterned Detection of Genes or Proteins.

    PubMed

    Zhou, Zhixin; Luo, Guofeng; Wulf, Verena; Willner, Itamar

    2018-06-05

    The study introduces an analytical platform for the detection of genes or aptamer-ligand complexes by nucleic acid barcode patterns generated by DNA machineries. The DNA machineries consist of nucleic acid scaffolds that include specific recognition sites for the different genes or aptamer-ligand analytes. The binding of the analytes to the scaffolds initiate, in the presence of the nucleotide mixture, a cyclic polymerization/nicking machinery that yields displaced strands of variable lengths. The electrophoretic separation of the resulting strands provides barcode patterns for the specific detection of the different analytes. Mixtures of DNA machineries that yield, upon sensing of different genes (or aptamer ligands), one-, two-, or three-band barcode patterns are described. The combination of nucleic acid scaffolds acting, in the presence of polymerase/nicking enzyme and nucleotide mixture, as DNA machineries, that generate multiband barcode patterns provide an analytical platform for the detection of an individual gene out of many possible genes. The diversity of genes (or other analytes) that can be analyzed by the DNA machineries and the barcode patterned imaging is given by the Pascal's triangle. As a proof-of-concept, the detection of one of six genes, that is, TP53, Werner syndrome, Tay-Sachs normal gene, BRCA1, Tay-Sachs mutant gene, and cystic fibrosis disorder gene by six two-band barcode patterns is demonstrated. The advantages and limitations of the detection of analytes by polymerase/nicking DNA machineries that yield barcode patterns as imaging readout signals are discussed.

  5. The effect of a combined glenoid and Hill-Sachs defect on glenohumeral stability: a biomechanical cadaveric study using 3-dimensional modeling of 142 patients.

    PubMed

    Arciero, Robert A; Parrino, Anthony; Bernhardson, Andrew S; Diaz-Doran, Vilmaris; Obopilwe, Elifho; Cote, Mark P; Golijanin, Petr; Mazzocca, Augustus D; Provencher, Matthew T

    2015-06-01

    Bone loss in anterior glenohumeral instability occurs on both the glenoid and the humerus; however, existing biomechanical studies have evaluated glenoid and humeral head defects in isolation. Thus, little is known about the combined effect of these bony lesions in a clinically relevant model on glenohumeral stability. The purpose of this study was to determine the biomechanical efficacy of a Bankart repair in the setting of bipolar (glenoid and humeral head) bone defects determined via computer-generated 3-dimensional (3D) modeling of 142 patients with recurrent anterior shoulder instability. The null hypothesis was that adding a bipolar bone defect will have no effect on glenohumeral stability after soft tissue Bankart repair. Controlled laboratory study. A total of 142 consecutive patients with recurrent anterior instability were analyzed with 3D computed tomography scans. Two Hill-Sachs lesions were selected on the basis of volumetric size representing the 25th percentile (0.87 cm(3); small) and 50th percentile (1.47 cm(3); medium) and printed in plastic resin with a 3D printer. A total of 21 cadaveric shoulders were evaluated on a custom shoulder-testing device permitting 6 degrees of freedom, and the force required to translate the humeral head anteriorly 10 mm at a rate of 2.0 mm/s with a compressive load of 50 N was determined at 60° of glenohumeral abduction and 60° of external rotation. All Bankart lesions were made sharply from the 2- to 6-o'clock positions for a right shoulder. Subsequent Bankart repair with transosseous tunnels using high-strength suture was performed. Hill-Sachs lesions were made in the cadaver utilizing a plastic mold from the exact replica off the 3D printer. Testing was conducted in the following sequence for each specimen: (1) intact, (2) posterior capsulotomy, (3) Bankart lesion, (4) Bankart repair, (5) Bankart lesion with 2-mm glenoid defect, (6) Bankart repair, (7) Bankart lesion with 2-mm glenoid defect and Hill-Sachs lesion

  6. What influences participation in genetic carrier testing? Results from a discrete choice experiment.

    PubMed

    Hall, Jane; Fiebig, Denzil G; King, Madeleine T; Hossain, Ishrat; Louviere, Jordan J

    2006-05-01

    This study explores factors that influence participation in genetic testing programs and the acceptance of multiple tests. Tay Sachs and cystic fibrosis are both genetically determined recessive disorders with differing severity, treatment availability, and prevalence in different population groups. We used a discrete choice experiment with a general community and an Ashkenazi Jewish sample; data were analysed using multinomial logit with random coefficients. Although Jewish respondents were more likely to be tested, both groups seem to be making very similar tradeoffs across attributes when they make genetic testing choices.

  7. [The plant physiologist Julius von Sachs and the academic education of women].

    PubMed

    Gimmler, Hartmut

    2005-01-01

    The attitude of the famous plant physiologist Julius von Sachs (1832-1897) to higher education of women is described on the basis of some new documents. Generally, Sachs was in favour of academic education of women at universities, but initially wanted to exclude females from the study of medicine. However, by the example of a bright young Russian lady, who studied medicine in St. Petersburg and who worked 1871 in his laboratory in Würzburg on lower fungi for some time (presumably illegally, since the access for woman to the university was at that time officially forbidden in Würzburg), he changed his mind: 1) In contrast to many colleagues of his time he granted females similar intelligence and skills as males and stated that women had legal rights for the access to the university. 2) He favoured the general necessity of higher education (in particular in science) for women and did not see any contrast in respect to this to the role of women in the society as wives, mothers, and housewives. 3) Access to the university would stimulate the development of young women and thereby would be an improvement for our society. However, in conclusion he asked himself, whether the higher education of females should take place at special women colleges (not existing at that time in Germany) or at universities and whether girl students should preferentially become teachers at high schools for daughters of the high society. He admitted that he also felt uncomfortable because of the threatening job competition between young academic male (traditionally the majority of students in science) and female students. The liberal view of Sachs in respect to higher education of women is compared to the rather conservative view of his former student and friend Hugo Thiel.

  8. Simple, explicitly time-dependent, and regular solutions of the linearized vacuum Einstein equations in Bondi-Sachs coordinates

    NASA Astrophysics Data System (ADS)

    Mädler, Thomas

    2013-05-01

    Perturbations of the linearized vacuum Einstein equations in the Bondi-Sachs formulation of general relativity can be derived from a single master function with spin weight two, which is related to the Weyl scalar Ψ0, and which is determined by a simple wave equation. By utilizing a standard spin representation of tensors on a sphere and two different approaches to solve the master equation, we are able to determine two simple and explicitly time-dependent solutions. Both solutions, of which one is asymptotically flat, comply with the regularity conditions at the vertex of the null cone. For the asymptotically flat solution we calculate the corresponding linearized perturbations, describing all multipoles of spin-2 waves that propagate on a Minkowskian background spacetime. We also analyze the asymptotic behavior of this solution at null infinity using a Penrose compactification and calculate the Weyl scalar Ψ4. Because of its simplicity, the asymptotically flat solution presented here is ideally suited for test bed calculations in the Bondi-Sachs formulation of numerical relativity. It may be considered as a sibling of the Bergmann-Sachs or Teukolsky-Rinne solutions, on spacelike hypersurfaces, for a metric adapted to null hypersurfaces.

  9. Pathology of GM2 gangliosidosis in Jacob sheep.

    PubMed

    Porter, B F; Lewis, B C; Edwards, J F; Alroy, J; Zeng, B J; Torres, P A; Bretzlaff, K N; Kolodny, E H

    2011-07-01

    The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model. © The Authors 2011

  10. Identification of an active acidic residue in the catalytic site of beta-hexosaminidase.

    PubMed

    Tse, R; Vavougios, G; Hou, Y; Mahuran, D J

    1996-06-11

    Human beta-hexosaminidases A and B (EC 3.2.1.52) are dimeric lysosomal glycosidases composed of evolutionarily related alpha and/or beta subunits. Both isozymes hydrolyze terminal beta-linked GalNAc or GlcNAc residues from numerous artificial and natural substrates; however, in vivo GM2 ganglioside is a substrate for only the heterodimeric A isozyme. Thus, mutations in either gene encoding its alpha or beta subunits can result in GM2 ganglioside storage and Tay-Sachs or Sandhoff disease, respectively. All glycosyl hydrolases ae believed to have one or more acidic residues in their catalytic site. We demonstrate that incubation of hexosaminidase with a chemical modifier specific for carboxyl side chains produces a time-dependent loss of activity, and that this effect can be blocked by the inclusion of a strong competitive inhibitor in the reaction mix. We hypothesized that the catalytic acid residue(s) should be located in a region of overall homology and be invariant within the aligned deduced primary sequences of the human alpha and beta subunits, as well as hexosaminidases from other species, including bacteria. Such a region is encoded by exons 5-6 of the HEXA and HEXB genes. This region includes beta Arg211 (invariant in 15 sequences), which we have previously shown to be an active residue. This region also contains two invariant and one conserved acidic residues. A fourth acidic residue, Asp alpha 258, beta 290, in exon 7 was also investigated because of its association with the B1 variant of Tay-Sachs disease. Conservative substitutions were made at each candidate residue by in vitro mutagenesis of a beta cDNA, followed by cellular expression. Of these, only the beta Asp196Asn substitution decreased the kcat (350-910-fold) without any noticeable effect on the K(m). Mutagenesis of either beta Asp240 or beta Asp290 to Asn decreased kcat by 10- or 1.4-fold but also raised the K(m) of the enzyme 11- of 3-fold, respectively. The above results strongly suggest that

  11. Fragments of Science: Festschrift for Mendel Sachs

    NASA Astrophysics Data System (ADS)

    Ram, Michael

    1999-11-01

    The Table of Contents for the full book PDF is as follows: * Preface * Sketches at a Symposium * For Mendel Sachs * The Constancy of an Angular Point of View * Information-Theoretic Logic and Transformation-Theoretic Logic * The Invention of the Transistor and the Realization of the Hole * Mach's Principle, Newtonian Gravitation, Absolute Space, and Einstein * The Sun, Our Variable Star * The Inconstant Sun: Symbiosis of Time Variations of Sunspots, Atmospheric Radiocarbon, Aurorae, and Tree Ring Growth * Other Worlds * Super-Classical Quantum Mechanics * A Probabilistic Approach to the Phase Problem of X-Ray Crystallography * A Nonlinear Twist on Inertia Gives Unified Electroweak Gravitation * Neutrino Oscillations * On an Incompleteness in the General-Relativistic Description of Gravitation * All Truth is One * Ideas of Physics: Correspondence between Colleagues * The Influence of the Physics and Philosophy of Einstein's Relativity on My Attitudes in Science: An Autobiography

  12. Generalized Bondi-Sachs equations for characteristic formalism of numerical relativity

    NASA Astrophysics Data System (ADS)

    Cao, Zhoujian; He, Xiaokai

    2013-11-01

    The Cauchy formalism of numerical relativity has been successfully applied to simulate various dynamical spacetimes without any symmetry assumption. But discovering how to set a mathematically consistent and physically realistic boundary condition is still an open problem for Cauchy formalism. In addition, the numerical truncation error and finite region ambiguity affect the accuracy of gravitational wave form calculation. As to the finite region ambiguity issue, the characteristic extraction method helps much. But it does not solve all of the above issues. Besides the above problems for Cauchy formalism, the computational efficiency is another problem. Although characteristic formalism of numerical relativity suffers the difficulty from caustics in the inner near zone, it has advantages in relation to all of the issues listed above. Cauchy-characteristic matching (CCM) is a possible way to take advantage of characteristic formalism regarding these issues and treat the inner caustics at the same time. CCM has difficulty treating the gauge difference between the Cauchy part and the characteristic part. We propose generalized Bondi-Sachs equations for characteristic formalism for the Cauchy-characteristic matching end. Our proposal gives out a possible same numerical evolution scheme for both the Cauchy part and the characteristic part. And our generalized Bondi-Sachs equations have one adjustable gauge freedom which can be used to relate the gauge used in the Cauchy part. Then these equations can make the Cauchy part and the characteristic part share a consistent gauge condition. So our proposal gives a possible new starting point for Cauchy-characteristic matching.

  13. δ-Tocopherol Reduces Lipid Accumulation in Niemann-Pick Type C1 and Wolman Cholesterol Storage Disorders*

    PubMed Central

    Xu, Miao; Liu, Ke; Swaroop, Manju; Porter, Forbes D.; Sidhu, Rohini; Finkes, Sally; Ory, Daniel S.; Marugan, Juan J.; Xiao, Jingbo; Southall, Noel; Pavan, William J.; Davidson, Cristin; Walkley, Steven U.; Remaley, Alan T.; Baxa, Ulrich; Sun, Wei; McKew, John C.; Austin, Christopher P.; Zheng, Wei

    2012-01-01

    Niemann-Pick disease type C (NPC) and Wolman disease are two members of a family of storage disorders caused by mutations of genes encoding lysosomal proteins. Deficiency in function of either the NPC1 or NPC2 protein in NPC disease or lysosomal acid lipase in Wolman disease results in defective cellular cholesterol trafficking. Lysosomal accumulation of cholesterol and enlarged lysosomes are shared phenotypic characteristics of both NPC and Wolman cells. Utilizing a phenotypic screen of an approved drug collection, we found that δ-tocopherol effectively reduced lysosomal cholesterol accumulation, decreased lysosomal volume, increased cholesterol efflux, and alleviated pathological phenotypes in both NPC1 and Wolman fibroblasts. Reduction of these abnormalities may be mediated by a δ-tocopherol-induced intracellular Ca2+ response and subsequent enhancement of lysosomal exocytosis. Consistent with a general mechanism for reduction of lysosomal lipid accumulation, we also found that δ-tocopherol reduces pathological phenotypes in patient fibroblasts from other lysosomal storage diseases, including NPC2, Batten (ceroid lipofuscinosis, neuronal 2, CLN2), Fabry, Farber, Niemann-Pick disease type A, Sanfilippo type B (mucopolysaccharidosis type IIIB, MPSIIIB), and Tay-Sachs. Our data suggest that regulated exocytosis may represent a potential therapeutic target for reduction of lysosomal storage in this class of diseases. PMID:23035117

  14. Posterior shoulder dislocation with a reverse Hill-Sachs lesion treated with frozen femoral head bone allograft combined with osteochondral autograft transfer.

    PubMed

    Mastrokalos, Dimitrios S; Panagopoulos, Georgios N; Galanopoulos, Ioannis P; Papagelopoulos, Panayiotis J

    2017-10-01

    Management of a posterior shoulder dislocation with an associated reverse Hill-Sachs lesion is challenging, both diagnostically and therapeutically. Diagnosis is frequently delayed or missed, whereas the resulting humeral head defect is often larger and more difficult to salvage than in anterior shoulder dislocations. This report presents the case of a 29-year-old male with a recurrent posterior shoulder dislocation associated with a large reverse Hill-Sachs defect, treated with bone augmentation of the lesion with a combination of fresh femoral head allograft and a locally harvested humeral head autograft transfer, with a successful outcome. Level of evidence V.

  15. Integrated Sachs-Wolfe effect in massive bigravity

    NASA Astrophysics Data System (ADS)

    Enander, Jonas; Akrami, Yashar; Mörtsell, Edvard; Renneby, Malin; Solomon, Adam R.

    2015-04-01

    We study the integrated Sachs-Wolfe (ISW) effect in ghost-free, massive bigravity. We focus on the infinite-branch bigravity (IBB) model which exhibits viable cosmic expansion histories and stable linear perturbations, while the cosmological constant is set to zero and the late-time accelerated expansion of the Universe is due solely to the gravitational interaction terms. The ISW contribution to the CMB auto-correlation power spectrum is predicted, as well as the cross-correlation between the CMB temperature anisotropies and large-scale structure. We use ISW amplitudes as inferred from the WMAP 9-year temperature data together with galaxy and AGN data provided by the WISE mission in order to compare the theoretical predictions to the observations. The ISW amplitudes in IBB are found to be larger than the corresponding ones in the standard Λ CDM model by roughly a factor of 1.5, but are still consistent with the observations.

  16. Genetics and Therapies for GM2 Gangliosidosis.

    PubMed

    Cachon-Gonzalez, María Begona; Zaccariotto, Eva; Cox, Timothy Martin

    2018-04-04

    Tay-Sachs disease, caused by impaired β-N-acetylhexosaminidase activity, was the first GM2 gangliosidosis to be studied and one of the most severe and earliest lysosomal diseases to be described. The condition, associated with the pathological build-up of GM2 ganglioside, has acquired almost iconic status and serves as a paradigm in the study of lysosomal storage diseases. Inherited as a classical autosomal recessive disorder, this global disease of the nervous system induces developmental arrest with regression of attained milestones; neurodegeneration progresses rapidly to cause premature death in young children. There is no effective treatment beyond palliative care, and while the genetic basis of GM2 gangliosidosis is well established, the molecular and cellular events, from disease-causing mutations and glycosphingolipid storage to disease manifestations, remain to be fully delineated. Several therapeutic approaches has been attempted in patients, including enzymatic augmentation, bone marrow transplantation, enzyme enhancement, and substrate reduction therapy. Hitherto, none of these stratagems has materially altered the course of the disease. Authentic animal models of GM2 gangliodidosis have facilitated in-depth evaluation of innovative applications such as gene transfer, which in contrast to other interventions, shows great promise. This review outlines current knowledge pertaining the pathobiology as well as potential innovative treatments for the GM2 gangliosidoses. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. Gene Transfer Corrects Acute GM2 Gangliosidosis—Potential Therapeutic Contribution of Perivascular Enzyme Flow

    PubMed Central

    Cachón-González, M Begoña; Wang, Susan Z; McNair, Rosamund; Bradley, Josephine; Lunn, David; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2012-01-01

    The GM2 gangliosidoses are fatal lysosomal storage diseases principally affecting the brain. Absence of β-hexosaminidase A and B activities in the Sandhoff mouse causes neurological dysfunction and recapitulates the acute Tay–Sachs (TSD) and Sandhoff diseases (SD) in infants. Intracranial coinjection of recombinant adeno-associated viral vectors (rAAV), serotype 2/1, expressing human β-hexosaminidase α (HEXA) and β (HEXB) subunits into 1-month-old Sandhoff mice gave unprecedented survival to 2 years and prevented disease throughout the brain and spinal cord. Classical manifestations of disease, including spasticity—as opposed to tremor-ataxia—were resolved by localized gene transfer to the striatum or cerebellum, respectively. Abundant biosynthesis of β-hexosaminidase isozymes and their global distribution via axonal, perivascular, and cerebrospinal fluid (CSF) spaces, as well as diffusion, account for the sustained phenotypic rescue—long-term protein expression by transduced brain parenchyma, choroid plexus epithelium, and dorsal root ganglia neurons supplies the corrective enzyme. Prolonged survival permitted expression of cryptic disease in organs not accessed by intracranial vector delivery. We contend that infusion of rAAV into CSF space and intraparenchymal administration by convection-enhanced delivery at a few strategic sites will optimally treat neurodegeneration in many diseases affecting the nervous system. PMID:22453766

  18. Efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc) and sp(2)-iminosugar conjugates: Novel hexosaminidase inhibitors with discrimination capabilities between the mature and precursor forms of the enzyme.

    PubMed

    de la Fuente, Alex; Rísquez-Cuadro, Rocío; Verdaguer, Xavier; García Fernández, José M; Nanba, Eiji; Higaki, Katsumi; Ortiz Mellet, Carmen; Riera, Antoni

    2016-10-04

    Due to their capacity to inhibit hexosaminidases, 2-acetamido-1,2-dideoxy-iminosugars have been widely studied as potential therapeutic agents for various diseases. An efficient stereoselective synthesis of 2-acetamido-1,2-dideoxyallonojirimycin (DAJNAc), the most potent inhibitor of human placenta β-N-acetylglucosaminidase (β-hexosaminidase) among the epimeric series, is here described. This novel procedure can be easily scaled up, providing enough material for structural modifications and further biological tests. Thus, two series of sp(2)-iminosugar conjugates derived from DAJNAc have been prepared, namely monocyclic DAJNAc-thioureas and bicyclic 2-iminothiazolidines, and their glycosidase inhibitory activity evaluated. The data evidence the utmost importance of developing diversity-oriented synthetic strategies allowing optimization of electrostatic and hydrophobic interactions to achieve high inhibitory potencies and selectivities among isoenzymes. Notably, strong differences in the inhibition potency of the compounds towards β-hexosaminidase from human placenta (mature) or cultured fibroblasts (precursor form) were encountered. The ensemble of data suggests that the ratio between them, and not the inhibition potency towards the placenta enzyme, is a good indication of the chaperoning potential of TaySachs disease-associated mutant hexosaminidase. Copyright © 2015 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  19. [Dr Mavro Sachs (1817-1888): the first lecturer of Zagreb University].

    PubMed

    Dugacki, Vladimir

    2010-01-01

    Mavro Sachs (Jánosháza, Hungary, 1817 % emdash; Rijeka, 1888.) was a Zagreb student since 1828. In 1846 he graduated in medicine from the University of Vienna and returned to Zagreb to be the city physician. In 1849, he started to teach forensic medicine at the School of Law of the Royal Academy of Sciences in Zagreb and continued teaching the same subject at the Zagreb University Faculty of Law in the capacity of docent (corresponds to lecturer in the British system). He also taught medical law at pharmaceutical studies of Zagreb University. From 1855 to 1860, he presided over the Jewish Community of Zagreb.

  20. The OSU1/QUA2/TSD2-Encoded Putative Methyltransferase Is a Critical Modulator of Carbon and Nitrogen Nutrient Balance Response in Arabidopsis

    PubMed Central

    Zheng, Zhi-Liang

    2008-01-01

    The balance between carbon (C) and nitrogen (N) nutrients must be tightly coordinated so that cells can optimize their opportunity for metabolism, growth and development. However, the C and N nutrient balance perception and signaling mechanism remains poorly understood. Here, we report the isolation and characterization of two allelic oversensitive to sugar1 mutants (osu1-1, osu1-2) in Arabidopsis thaliana. Using the cotyledon anthocyanin accumulation and root growth inhibition assays, we show that the osu1 mutants are more sensitive than wild-type to both of the imbalanced C/N conditions, high C/low N and low C/high N. However, under the balanced C/N conditions (low C/low N or high C/high N), the osu1 mutants have similar anthocyanin levels and root lengths as wild-type. Consistently, the genes encoding two MYB transcription factors (MYB75 and MYB90) and an Asn synthetase isoform (ASN1) are strongly up-regulated by the OSU1 mutation in response to high C/low N and low C/high N, respectively. Furthermore, the enhanced sensitivity of osu1-1 to high C/low N with respect to anthocyanin accumulation but not root growth inhibition can be suppressed by co-suppression of MYB75, indicating that MYB75 acts downstream of OSU1 in the high C/low N imbalance response. Map-based cloning reveals that OSU1 encodes a member of a large family of putative methyltransferases and is allelic to the recently reported QUA2/TSD2 locus identified in genetic screens for cell-adhesion-defective mutants. Accumulation of OSU1/QUA2/TSD2 transcript was not regulated by C and N balance, but the OSU1 promoter was slightly more active in the vascular system. Taken together, our results show that the OSU1/QUA2/TSD2-encoded putative methyltransferase is required for normal C/N nutrient balance response in plants. PMID:18167546

  1. The effect of a Hill-Sachs defect on glenohumeral translations, in situ capsular forces, and bony contact forces.

    PubMed

    Sekiya, Jon K; Jolly, John; Debski, Richard E

    2012-02-01

    Hill-Sachs defects have been associated with failed repairs for anterior shoulder instability. However, the biomechanical consequences of these defects are not well understood because of the complicated interaction between the passive soft tissue and bony stabilizers. The creation of a 25% Hill-Sachs defect would not significantly alter the glenohumeral translations but would increase the in situ forces in the glenohumeral capsule as well as the glenohumeral bony contact forces. Controlled laboratory study. A robotic/universal force-moment sensor (UFS) testing system was used to apply joint compression (22 N) and an anterior or posterior load (44 N) to cadaveric shoulders (n = 9) with the skin and deltoid removed (intact) at 3 glenohumeral joint positions (abduction/external rotation): 0°/0°, 30°/30°, and 60°/60° (corresponds to 90°/90° of shoulder abduction/external rotation). A 25% bony defect on the posterolateral humeral head (defect) was then created in the most common position of anterior shoulder dislocation (90°/90°), and the loading protocol was repeated. A nonparametric repeated-measures Friedman test with a Wilcoxon signed-rank post hoc test was performed to compare translations, in situ forces in the capsule, and bony contact forces between each state (P < .05). At 0°/0°, anterior translation significantly increased from 15.3 ± 8.2 mm to 16.6 ± 9.0 mm (P < .05) in response to an anterior load. At 30°/30°, anterior and posterior translations, respectively, significantly increased in response to both anterior (intact: 13.6 ± 7.1 mm vs defect: 14.2 ± 7 mm; P < .05) and posterior loads (intact: 15.7 ± 5.8 mm vs defect: 17.7 ± 5.1 mm; P < .05). In situ force in the capsule during anterior loading was increased in the defect state at both 60°/60° (intact: 38.9 ± 14.4 N vs defect: 43.2 ± 15.9 N; P < .05) and 30°/30° (intact: 39.6 ± 13.8 N vs defect: 45.6 ± 9.3 N; P < .05). The medial bony contact forces were also increased in the

  2. Kantowski-Sachs Einstein-æther perfect fluid models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Latta, Joey; Leon, Genly; Paliathanasis, Andronikos, E-mail: lattaj@mathstat.dal.ca, E-mail: genly.leon@pucv.cl, E-mail: anpaliat@phys.uoa.gr

    We investigate Kantowski-Sachs models in Einstein-æ ther theory with a perfect fluid source using the singularity analysis to prove the integrability of the field equations and dynamical system tools to study the evolution. We find an inflationary source at early times, and an inflationary sink at late times, for a wide region in the parameter space. The results by A.A. Coley, G. Leon, P. Sandin and J. Latta ( JCAP 12 (2015) 010), are then re-obtained as particular cases. Additionally, we select other values for the non-GR parameters which are consistent with current constraints, getting a very rich phenomenology. Inmore » particular, we find solutions with infinite shear, zero curvature, and infinite matter energy density in comparison with the Hubble scalar. We also have stiff-like future attractors, anisotropic late-time attractors, or both, in some special cases. Such results are developed analytically, and then verified by numerics. Finally, the physical interpretation of the new critical points is discussed.« less

  3. Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model

    PubMed Central

    Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi

    2016-01-01

    GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside–degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses. PMID:27018595

  4. Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model.

    PubMed

    Kitakaze, Keisuke; Mizutani, Yasumichi; Sugiyama, Eiji; Tasaki, Chikako; Tsuji, Daisuke; Maita, Nobuo; Hirokawa, Takatsugu; Asanuma, Daisuke; Kamiya, Mako; Sato, Kohei; Setou, Mitsutoshi; Urano, Yasuteru; Togawa, Tadayasu; Otaka, Akira; Sakuraba, Hitoshi; Itoh, Kohji

    2016-05-02

    GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside-degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses.

  5. Sachs equations for light bundles in a cold plasma

    NASA Astrophysics Data System (ADS)

    Schulze-Koops, Karen; Perlick, Volker; Schwarz, Dominik J.

    2017-11-01

    We study the propagation of light bundles in non-empty spacetime, as most of the Universe is filled by baryonic matter in the form of a (dilute) plasma. Here we restrict to the case of a cold (i.e. pressureless) and non-magnetised plasma. Then the influence of the medium on the light rays is encoded in the spacetime dependent plasma frequency. Our result for a general spacetime generalises the Sachs equations to the case of a cold plasma Universe. We find that the reciprocity law (Etherington theorem), the relation that connects area distance with luminosity distance, is modified. Einstein’s field equation is not used, i.e. our results apply independently of whether or not the plasma is self-gravitating. As an example, our findings are applied to a homogeneous plasma in a Robertson-Walker spacetime. We find small modifications of the cosmological redshift of frequencies and of the Hubble law.

  6. Non-minimally coupled scalar field in Kantowski-Sachs model and symmetry analysis

    NASA Astrophysics Data System (ADS)

    Dutta, Sourav; Lakshmanan, Muthusamy; Chakraborty, Subenoy

    2018-06-01

    The paper deals with a non-minimally coupled scalar field in the background of homogeneous but anisotropic Kantowski-Sachs space-time model. The form of the coupling function of the scalar field with gravity and the potential function of the scalar field are not assumed phenomenologically, rather they are evaluated by imposing Noether symmetry to the Lagrangian of the present physical system. The physical system gets considerable mathematical simplification by a suitable transformation of the augmented variables (a , b , ϕ) →(u , v , w) and by the use of the conserved quantities due to the geometrical symmetry. Finally, cosmological solutions are evaluated and analyzed from the point of view of the present evolution of the Universe.

  7. On the structure and applications of the Bondi-Metzner-Sachs group

    NASA Astrophysics Data System (ADS)

    Alessio, Francesco; Esposito, Giampiero

    This work is a pedagogical review dedicated to a modern description of the Bondi-Metzner-Sachs (BMS) group. Minkowski space-time has an interesting and useful group of isometries, but, for a generic space-time, the isometry group is simply the identity and hence provides no significant informations. Yet symmetry groups have important role to play in physics; in particular, the Poincaré group describing the isometries of Minkowski space-time plays a role in the standard definitions of energy-momentum and angular-momentum. For this reason alone it would seem to be important to look for a generalization of the concept of isometry group that can apply in a useful way to suitable curved space-times. The curved space-times that will be taken into account are the ones that suitably approach, at infinity, Minkowski space-time. In particular we will focus on asymptotically flat space-times. In this work, the concept of asymptotic symmetry group of those space-times will be studied. In the first two sections we derive the asymptotic group following the classical approach which was basically developed by Bondi, van den Burg, Metzner and Sachs. This is essentially the group of transformations between coordinate systems of a certain type in asymptotically flat space-times. In the third section the conformal method and the notion of “asymptotic simplicity” are introduced, following mainly the works of Penrose. This section prepares us for another derivation of the BMS group which will involve the conformal structure, and is thus more geometrical and fundamental. In the subsequent sections we discuss the properties of the BMS group, e.g. its algebra and the possibility to obtain as its subgroup the Poincaré group, as we may expect. The paper ends with a review of the BMS invariance properties of classical gravitational scattering discovered by Strominger, that are finding application to black hole physics and quantum gravity in the literature.

  8. Mapping the integrated Sachs-Wolfe effect

    NASA Astrophysics Data System (ADS)

    Manzotti, A.; Dodelson, S.

    2014-12-01

    On large scales, the anisotropies in the cosmic microwave background (CMB) reflect not only the primordial density field but also the energy gain when photons traverse decaying gravitational potentials of large scale structure, what is called the integrated Sachs-Wolfe (ISW) effect. Decomposing the anisotropy signal into a primordial piece and an ISW component, the main secondary effect on large scales, is more urgent than ever as cosmologists strive to understand the Universe on those scales. We present a likelihood technique for extracting the ISW signal combining measurements of the CMB, the distribution of galaxies, and maps of gravitational lensing. We test this technique with simulated data showing that we can successfully reconstruct the ISW map using all the data sets together. Then we present the ISW map obtained from a combination of real data: the NRAO VLA sky survey (NVSS) galaxy survey, temperature anisotropies, and lensing maps made by the Planck satellite. This map shows that, with the data sets used and assuming linear physics, there is no evidence, from the reconstructed ISW signal in the Cold Spot region, for an entirely ISW origin of this large scale anomaly in the CMB. However a large scale structure origin from low redshift voids outside the NVSS redshift range is still possible. Finally we show that future surveys, thanks to a better large scale lensing reconstruction will be able to improve the reconstruction signal to noise which is now mainly coming from galaxy surveys.

  9. [The "Chapter on health preservation" in the Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr by Avenzoar (1095-1162)].

    PubMed

    Peña, Carmen; Girón, Fernando

    2010-01-01

    The Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr (The Method of Preparing Medicines and Diet) was written in Arabic by Avenzoar (1095-1162). It has yet to be translated into any Western modern language, and we wish to take on this task. We begin by offering an annotated Spanish translation (with commentary) of its preliminary "Chapter on the preservation of health". The Al-mohad caliph 'Abd al-Mu'min, for whom Avenzoar served as court physician, requested the book for his personal use. The work begins with this chapter, which contains measures for preventing and curing certain diseases. This section is followed by the main body of the book. It consists of a complete list of diseases working from head to toe and including their description, symptoms and treatment. The translated chapter is an atypical and concise treatise on the subject. It is presented in a quasi-aphoristic style that appears to have been used by Avenzoar to rapidly deal with the prevention area, in order to concentrate his efforts on what is surely one of the finest and most extensive mediaeval nosographies. We make this claim because our author does not exclusively use for this purpose the so-called "non-naturals"--the usual focus of health preservation measures of the time. Rather, he makes wide use of simple medicines with preventative ends--an unusual practice. Moreover, he indiscriminately intersperses prevention elements with others that are intended to cure. In order to better understand the meaning of this text, we previously refer to the foundations of health preservation practices in the mediaeval world, to the reasons why Avenzoar wrote the Kitāb al-taysīr fī l-mudāwāt wa-l-tadbīr, and to the characteristics of its translated chapter. We also examine the medical sources and contents of this chapter.

  10. Representations of the Bondi—Metzner—Sachs group in three space—time dimensions

    NASA Astrophysics Data System (ADS)

    Melas, Evangelos

    2017-01-01

    The original Bondi-Metzner-Sachs group B is the common asymptotic symmetry group of all asymptotically at Lorentzian 4-dim space-times. As such, B is the best candidate for the universal symmetry group of General Relativity (G.R.). In 1973, with this motivation, P. J. McCarthy classified all relativistic B-invariant systems in terms of strongly continuous irreducible unitary representations (IRS) of B. Here, we construct the IRS of B(2, 1), the analogue of B, in 3 space-time dimensions. The IRS are induced from ‘little groups’ which are compact. The finite ‘little groups’ are cyclic groups of even order. The inducing construction is exhaustive notwithstanding the fact that B(2, 1) is not locally compact in the employed Hilbert topology.

  11. Conserved charges of the extended Bondi-Metzner-Sachs algebra

    NASA Astrophysics Data System (ADS)

    Flanagan, Éanna É.; Nichols, David A.

    2017-02-01

    Isolated objects in asymptotically flat spacetimes in general relativity are characterized by their conserved charges associated with the Bondi-Metzner-Sachs (BMS) group. These charges include total energy, linear momentum, intrinsic angular momentum and center-of-mass location, and, in addition, an infinite number of supermomentum charges associated with supertranslations. Recently, it has been suggested that the BMS symmetry algebra should be enlarged to include an infinite number of additional symmetries known as super-rotations. We show that the corresponding charges are finite and well defined, and can be divided into electric parity "super center-of-mass" charges and magnetic parity "superspin" charges. The supermomentum charges are associated with ordinary gravitational-wave memory, and the super center-of-mass charges are associated with total (ordinary plus null) gravitational-wave memory, in the terminology of Bieri and Garfinkle. Superspin charges are associated with the ordinary piece of spin memory. Some of these charges can give rise to black hole hair, as described by Strominger and Zhiboedov. We clarify how this hair evades the no-hair theorems.

  12. Synthesis and electrochemical characterization of TixTayAlzN1-δOγ for fuel cell catalyst supports

    NASA Astrophysics Data System (ADS)

    Wakabayashi, Ryo H.; Abruña, Héctor D.; DiSalvo, Francis J.

    2017-02-01

    Quinary TixTayAlzN1-δOγ of various compositions have been prepared by a co-precipitation method followed by ammonolysis. The nitride samples were examined as potential catalyst supports in polymer electrolyte membrane fuel cells. The nitride products crystallized in the rock salt (NaCl) structure over a wide range of compositions. The addition of Ta and Al was highly beneficial towards improving the chemical and electrochemical stability of TiN, without a significant loss of electrical conductivity. Platinum particles were successfully deposited on the (oxy)nitride samples, and the composite samples at some compositions were found to be comparable to Pt/carbon in their stability and catalytic activity even without optimizing the Pt deposition and dispersion processes.

  13. Challenges of Pre- and Post-Test Counseling for Orthodox Jewish Individuals in the Premarital Phase.

    PubMed

    Rose, E; Schreiber-Agus, N; Bajaj, K; Klugman, S; Goldwaser, T

    2016-02-01

    The Jewish community has traditionally taken ownership of its health, and has taken great strides to raise awareness about genetic issues that affect the community, such as Tay-Sachs disease and Hereditary Breast and Ovarian Cancer syndrome. Thanks in part to these heightened awareness efforts, many Orthodox Jewish individuals are now using genetics services as they begin to plan their families. Due to unique cultural and religious beliefs and perceptions, the Orthodox Jewish patients who seek genetic counseling face many barriers to a successful counseling session, and often seek the guidance of programs such as the Program for Jewish Genetic Health (PJGH). In this article, we present clinical vignettes from the PJGH's clinical affiliate, the Reproductive Genetics practice at the Montefiore Medical Center. These cases highlight unique features of contemporary premarital counseling and screening within the Orthodox Jewish Community, including concerns surrounding stigma, disclosure, "marriageability," the use of reproductive technologies, and the desire to include a third party in decision making. Our vignettes demonstrate the importance of culturally-sensitive counseling. We provide strategies and points to consider when addressing the challenges of pre- and post-test counseling as it relates to genetic testing in this population.

  14. Insights into the genetic epidemiology of Crohn's and rare diseases in the Ashkenazi Jewish population

    PubMed Central

    Rivas, Manuel A.; Avila, Brandon E.; Koskela, Jukka; Stevens, Christine; Pirinen, Matti; Neale, Benjamin M.; Ganna, Andrea; Graham, Daniel; Glaser, Benjamin; Peter, Inga; Atzmon, Gil; Barzilai, Nir; Levine, Adam P.; Schiff, Elena; Weisburd, Ben; Lek, Monkol; Bloom, Jonathan; Minikel, Eric V.; Petersen, Britt-Sabina; Beaugerie, Laurent; Seksik, Philippe; Cosnes, Jacques; Schreiber, Stefan; Bokemeyer, Bernd; Bethge, Johannes; Ahmad, Tariq; Plagnol, Vincent; Segal, Anthony W.; Targan, Stephan; Turner, Dan; Saavalainen, Paivi; Farkkila, Martti; Kontula, Kimmo; Palotie, Aarno; Brant, Steven R.; Duerr, Richard H.; Silverberg, Mark S.; Weersma, Rinse K.; Franke, Andre; Jostins, Luke; Barrett, Jeffrey C.; MacArthur, Daniel G.; Jalas, Chaim; Sokol, Harry; Xavier, Ramnik J.; Pulver, Ann; Cho, Judy H.; McGovern, Dermot P. B.; Daly, Mark J.

    2018-01-01

    As part of a broader collaborative network of exome sequencing studies, we developed a jointly called data set of 5,685 Ashkenazi Jewish exomes. We make publicly available a resource of site and allele frequencies, which should serve as a reference for medical genetics in the Ashkenazim (hosted in part at https://ibd.broadinstitute.org, also available in gnomAD at http://gnomad.broadinstitute.org). We estimate that 34% of protein-coding alleles present in the Ashkenazi Jewish population at frequencies greater than 0.2% are significantly more frequent (mean 15-fold) than their maximum frequency observed in other reference populations. Arising via a well-described founder effect approximately 30 generations ago, this catalog of enriched alleles can contribute to differences in genetic risk and overall prevalence of diseases between populations. As validation we document 148 AJ enriched protein-altering alleles that overlap with "pathogenic" ClinVar alleles (table available at https://github.com/macarthur-lab/clinvar/blob/master/output/clinvar.tsv), including those that account for 10–100 fold differences in prevalence between AJ and non-AJ populations of some rare diseases, especially recessive conditions, including Gaucher disease (GBA, p.Asn409Ser, 8-fold enrichment); Canavan disease (ASPA, p.Glu285Ala, 12-fold enrichment); and Tay-Sachs disease (HEXA, c.1421+1G>C, 27-fold enrichment; p.Tyr427IlefsTer5, 12-fold enrichment). We next sought to use this catalog, of well-established relevance to Mendelian disease, to explore Crohn's disease, a common disease with an estimated two to four-fold excess prevalence in AJ. We specifically attempt to evaluate whether strong acting rare alleles, particularly protein-truncating or otherwise large effect-size alleles, enriched by the same founder-effect, contribute excess genetic risk to Crohn's disease in AJ, and find that ten rare genetic risk factors in NOD2 and LRRK2 are enriched in AJ (p < 0.005), including several novel

  15. The integrated Sachs-Wolfe signal from BOSS superstructures

    NASA Astrophysics Data System (ADS)

    Granett, B. R.; Kovács, A.; Hawken, A. J.

    2015-12-01

    Cosmic structures leave an imprint on the microwave background radiation through the integrated Sachs-Wolfe (ISW) effect. We construct a template map of the linear signal using the Sloan Digital Sky Survey-III Baryon Acoustic Oscillation Survey at redshift 0.43 < z < 0.65. We verify the imprint of this map on the Planck cosmic microwave background (CMB) temperature map at the 97 per cent confidence level and show consistency with the density-temperature cross-correlation measurement. Using this ISW reconstruction as a template, we investigate the presence of ISW sources and further examine the properties of the Granett-Neyrinck-Szapudi supervoid and supercluster catalogue. We characterize the three-dimensional density profiles of these structures for the first time and demonstrate that they are significant structures. Model fits demonstrate that the supervoids are elongated along the line of sight and we suggest that this special orientation may be picked out by the void-finding algorithm in photometric redshift space. We measure the mean temperature profiles in Planck maps from public void and cluster catalogues. In an attempt to maximize the stacked ISW signal, we construct a new catalogue of superstructures based upon local peaks and troughs of the gravitational potential. However, we do not find a significant correlation between these structures and the CMB temperature.

  16. Production, crystallization and preliminary crystallographic analysis of Allochromatium vinosum thiosulfate dehydrogenase TsdA, an unusual acidophilic c-type cytochrome

    PubMed Central

    Brito, José A.; Gutierres, André; Denkmann, Kevin; Dahl, Christiane; Archer, Margarida

    2014-01-01

    The ability to perform the very simple oxidation of two molecules of thiosulfate to tetrathionate is widespread among prokaryotes. Despite the prevalent occurrence of tetrathionate formation and its well documented significance within the sulfur cycle, little is known about the enzymes that catalyze the oxidative condensation of two thiosulfate anions. To fill this gap, the thiosulfate dehydrogenase (TsdA) enzyme from the purple sulfur bacterium Allochromatium vinosum was recombinantly expressed in Escherichia coli, purified and crystallized, and a crystallographic data set was collected. The crystals belonged to the monoclinic space group C2, with unit-cell parameters a = 79.2, b = 69.9, c = 57.9 Å, β = 129.3°, contained one monomer per asymmetric unit and diffracted to a resolution of 1.98 Å. PMID:25286955

  17. Right services to right patients at right time in right setting in Tays Eye Centre.

    PubMed

    Tuulonen, Anja; Kataja, Marko; Syvänen, Ulla; Miettunen, Sirpa; Uusitalo, Hannu

    2016-11-01

    The report describes the concepts behind procedures implemented in Tays Eye Centre to enable improved access to care and improved productivity. The strategy was developed in 2009 after hospital district decided to construct a new eye hospital which was opened in 2012. The following principles were implemented: (i) identification of high-volume patient groups: the 'big four' eye diseases accounting for 70% of patient visits and costs: age-related macular degeneration (AMD), glaucoma, retinal diseases and cataract; (ii) stratification and prioritization of patient care based on risk of permanent visual disability; (iii) standardization of services for low-risk patients; (iv) maximization of productivity; and (v) shared care. The impact of the new strategy on access to care and productivity is reported for years 2011-2015. In 2011-2015, the total number of services provided increased 46% while the work contribution increased 15%. The number of referrals increased 76% and the number of outpatient appointments increased 2.5-fold. Simultaneously, the number of delayed follow-up visits decreased to zero. Age-related macular degeneration (AMD) injections increased 1.8-fold. However, after 50% yearly increase in Age-related macular degeneration (AMD) injections, a plateau was reached in 2014 with a 3% decline in 2014-2015 with no changes in treatment indications. In the beginning of 2016, the number of injections has started to increase again (+9% compared to 2015).  The total number of surgical procedures increased 98%. The annual number of cataract surgeries increased 64% and bilateral surgeries from 11% to 39%. Revised operational concepts and new facilities together with a 15% increase in work contribution led to a 46% increase in overall productivity, improved access to care and the clearance of delayed services. Efforts continue to further refine cost-effective care and to define the appropriate levels of services. © 2016 Acta Ophthalmologica Scandinavica Foundation

  18. Quaternions, Torsion and the Physical Vacuum: Theories of M. Sachs and G. Shipov Compared

    NASA Astrophysics Data System (ADS)

    Cyganski, David; Page, William S.

    Of several developments of unified field theories in the spirit of Einstein's original objective of a fully geometric description of all classical fields as well as quantum mechanics, two are particularly noteworthy. The works of Mendel Sachs and Gennady Shipov stand apart as major life works comprising tens of papers, several monographs and decades of effort. Direct comparison of these theories is hampered however by differences in notation and conceptual view-point. Despite these differences, there are many parallels between the fundamental mathematical structures appearing in each. In this paper we discuss the main tenets of the two approaches and demonstrate that they both give rise to a factorization of the invariant interval of general relativity.

  19. Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity[S

    PubMed Central

    Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

    2015-01-01

    Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. PMID:26175473

  20. [Transhumeral head plasty and massive osteocartilaginous allograft transplantation for the management of large hill-sachs lesions].

    PubMed

    Hart, R; Okál, F; Komzák, M

    2010-10-01

    The aim of this presentation is to inform the medical community about causal therapy (transhumeral head plasty or massive osteochondral allograft transplantation) for large Hill-Sachs lesions which frequently cause failure of anterior stabilisation following ventral shoulder dislocations. Seven men with an average age of 26 years (19 to 33 years) undergoing surgery in 2006 and 2007 were evaluated. The minimum follow-up was 18 months (41 to 18 months). Impressions on more than 30 % of the articular surface, or those whose critical size was larger than one-eighth of the humeral diameter (on CT scan) were taken as indications for surgery. Four patients had had previous surgery for anterior instability and three had a primary procedure. Four men underwent acute surgery and three had elective operations.Trans- humeral head plasty was used in five and massive osteochondral allograft in two patients. In the patients with large lesions in the anterior aspect of the shoulder joint, transhumeral head plasty involving repair of the ventral structures from the anterior approach was indicatedúúú in those with an isolated posterior bony defect, a massive osteochondral allograft was transplanted through the posterior approach. The Constant-Murley score was used to assess clinical status before (not in acute conditions) and after surgery. All patients reported improved clinical status. The average Constant-Murley score at final follow-up was 95.9 points (83-100 points). In the patients not having an acute procedure in whom pre-operative Constant-Murley scores were obtained, the average improvement was by 22.7 points (8 - 37 points). No general surgical complications were recorded. All patients reported subjective satisfaction and willingness to undergo surgery under the same conditions again. A Hill-Sachs lesion is a frequent injury to the humeral head resulting from anterior shoulder dislocation. To distinguish between major and minor defects in terms of clinical significance

  1. A SENSITIVE FLUORESCENCE-BASED ASSAY FOR MONITORING GM2 GANGLIOSIDE HYDROLYSIS IN LIVE PATIENT CELLS AND THEIR LYSATES

    PubMed Central

    Tropak, Michael B.; Bukovac, Scott W.; Rigat, Brigitte A.; Yonekawa, Sayuri; Wakarchuk, Warren; Mahuran, Don J.

    2010-01-01

    Enzyme enhancement therapy, utilizing small molecules as pharmacological chaperones, is anattractive approach for the treatment of lysosomal storage diseases that are associated with protein misfolding. However, pharmacological chaperones are alsoinhibitors of their target enzyme. Thus, a major concern with this approach is that, despite enhancing protein folding within, and intracellular transport of the functional mutant enzyme out of the endoplasmic reticulum, the chaperone will continue to inhibit the enzyme in the lysosome, preventing substrate clearance. Herewe demonstrate that the in vitro hydrolysis of a fluorescent derivative of lyso-GM2 ganglioside, like natural GM2 ganglioside, is specifically carried out by the β-hexosaminidase A isozyme, requires the GM2 activator protein as a co-factor, increases when the derivative is incorporated into anionic liposomes and follows similar Michaelis-Menten kinetics. This substrate can also be used to differentiate between lysates from normal and GM2 activator-deficient cells. When added to the growth medium of cells, the substrate is internalized and primarily incorporated into lysosomes. Utilizing adult Tay-Sachs fibroblasts that have been pre-treated with the pharmacological chaperone Pyrimethamine and subsequently loaded with this substrate, we demonstrate an increase in both the levels of mutant β-hexosaminidase A and substrate-hydrolysis as compared to mock treated cells. PMID:19917668

  2. A sensitive fluorescence-based assay for monitoring GM2 ganglioside hydrolysis in live patient cells and their lysates.

    PubMed

    Tropak, Michael B; Bukovac, Scott W; Rigat, Brigitte A; Yonekawa, Sayuri; Wakarchuk, Warren; Mahuran, Don J

    2010-03-01

    Enzyme enhancement therapy, utilizing small molecules as pharmacological chaperones, is an attractive approach for the treatment of lysosomal storage diseases that are associated with protein misfolding. However, pharmacological chaperones are also inhibitors of their target enzyme. Thus, a major concern with this approach is that, despite enhancing protein folding within, and intracellular transport of the functional mutant enzyme out of the endoplasmic reticulum, the chaperone will continue to inhibit the enzyme in the lysosome, preventing substrate clearance. Here we demonstrate that the in vitro hydrolysis of a fluorescent derivative of lyso-GM2 ganglioside, like natural GM2 ganglioside, is specifically carried out by the beta-hexosaminidase A isozyme, requires the GM2 activator protein as a co-factor, increases when the derivative is incorporated into anionic liposomes and follows similar Michaelis-Menten kinetics. This substrate can also be used to differentiate between lysates from normal and GM2 activator-deficient cells. When added to the growth medium of cells, the substrate is internalized and primarily incorporated into lysosomes. Utilizing adult Tay-Sachs fibroblasts that have been pre-treated with the pharmacological chaperone Pyrimethamine and subsequently loaded with this substrate, we demonstrate an increase in both the levels of mutant beta-hexosaminidase A and substrate-hydrolysis as compared to mock-treated cells.

  3. Carrier screening in the era of expanding genetic technology.

    PubMed

    Arjunan, Aishwarya; Litwack, Karen; Collins, Nick; Charrow, Joel

    2016-12-01

    The Center for Jewish Genetics provides genetic education and carrier screening to individuals of Jewish descent. Carrier screening has traditionally been performed by targeted mutation analysis for founder mutations with an enzyme assay for Tay-Sachs carrier detection. The development of next-generation sequencing (NGS) allows for higher detection rates regardless of ethnicity. Here, we explore differences in carrier detection rates between genotyping and NGS in a primarily Jewish population. Peripheral blood samples or saliva samples were obtained from 506 individuals. All samples were analyzed by sequencing, targeted genotyping, triplet-repeat detection, and copy-number analysis; the analyses were carried out at Counsyl. Of 506 individuals screened, 288 were identified as carriers of at least 1 condition and 8 couples were carriers for the same disorder. A total of 434 pathogenic variants were identified. Three hundred twelve variants would have been detected via genotyping alone. Although no additional mutations were detected by NGS in diseases routinely screened for in the Ashkenazi Jewish population, 26.5% of carrier results and 2 carrier couples would have been missed without NGS in the larger panel. In a primarily Jewish population, NGS reveals a larger number of pathogenic variants and provides individuals with valuable information for family planning.Genet Med 18 12, 1214-1217.

  4. Membrane lipids regulate ganglioside GM2 catabolism and GM2 activator protein activity.

    PubMed

    Anheuser, Susi; Breiden, Bernadette; Schwarzmann, Günter; Sandhoff, Konrad

    2015-09-01

    Ganglioside GM2 is the major lysosomal storage compound of Tay-Sachs disease. It also accumulates in Niemann-Pick disease types A and B with primary storage of SM and with cholesterol in type C. Reconstitution of GM2 catabolism with β-hexosaminidase A and GM2 activator protein (GM2AP) at uncharged liposomal surfaces carrying GM2 as substrate generated only a physiologically irrelevant catabolic rate, even at pH 4.2. However, incorporation of anionic phospholipids into the GM2 carrying liposomes stimulated GM2 hydrolysis more than 10-fold, while the incorporation of plasma membrane stabilizing lipids (SM and cholesterol) generated a strong inhibition of GM2 hydrolysis, even in the presence of anionic phospholipids. Mobilization of membrane lipids by GM2AP was also inhibited in the presence of cholesterol or SM, as revealed by surface plasmon resonance studies. These lipids also reduced the interliposomal transfer rate of 2-NBD-GM1 by GM2AP, as observed in assays using Förster resonance energy transfer. Our data raise major concerns about the usage of recombinant His-tagged GM2AP compared with untagged protein. The former binds more strongly to anionic GM2-carrying liposomal surfaces, increases GM2 hydrolysis, and accelerates intermembrane transfer of 2-NBD-GM1, but does not mobilize membrane lipids. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Qualitative analysis of Kantowski-Sachs metric in a generic class of f(R) models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leon, Genly; Roque, Armando A., E-mail: genly.leon@ucv.cl, E-mail: arestrada@ucf.edu.cu

    2014-05-01

    In this paper we investigate, from the dynamical systems perspective, the evolution of a Kantowski-Sachs metric in a generic class of f(R) models. We present conditions (i.e., differentiability conditions, existence of minima, monotony intervals, etc.) for a free input function related to the f(R), that guarantee the asymptotic stability of well-motivated physical solutions, specially, self-accelerated solutions, allowing to describe both inflationary- and late-time acceleration stages of the cosmic evolution. We discuss which f(R) theories allows for a cosmic evolution with an acceptable matter era, in correspondence to the modern cosmological paradigm. We find a very rich behavior, and amongst othersmore » the universe can result in isotropized solutions with observables in agreement with observations, such as de Sitter, quintessence-like, or phantom solutions. Additionally, we find that a cosmological bounce and turnaround are realized in a part of the parameter-space as a consequence of the metric choice.« less

  6. Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis.

    PubMed

    Tsuji, Daisuke; Akeboshi, Hiromi; Matsuoka, Kazuhiko; Yasuoka, Hiroko; Miyasaki, Eri; Kasahara, Yoshiko; Kawashima, Ikuo; Chiba, Yasunori; Jigami, Yoshifumi; Taki, Takao; Sakuraba, Hitoshi; Itoh, Kohji

    2011-04-01

    Novel recombinant human lysosomal β-hexosaminidase A (HexA) was developed for enzyme replacement therapy (ERT) for Tay-Sachs and Sandhoff diseases, ie, autosomal recessive GM2 gangliosidoses, caused by HexA deficiency. A recombinant human HexA (Om4HexA) with a high mannose 6-phosphate (M6P)-type-N-glycan content, which was produced by a methylotrophic yeast strain, Ogataea minuta, overexpressing the OmMNN4 gene, was intracerebroventricularly (ICV) administered to Sandhoff disease model mice (Hexb⁻/⁻ mice) at different doses (0.5-2.5 mg/kg), and then the replacement and therapeutic effects were examined. The Om4HexA was widely distributed across the ependymal cell layer, dose-dependently restored the enzyme activity due to uptake via cell surface cation-independent M6P receptor (CI-M6PR) on neural cells, and reduced substrates, including GM2 ganglioside (GM2), asialo GM2 (GA2), and oligosaccharides with terminal N-acetylglucosamine residues (GlcNAc-oligosaccharides), accumulated in brain parenchyma. A significant inhibition of chemokine macrophage inflammatory protein-1 α (MIP-1α) induction was also revealed, especially in the hindbrain (< 63%). The decrease in central neural storage correlated with an improvement of motor dysfunction as well as prolongation of the lifespan. This lysosome-directed recombinant human enzyme drug derived from methylotrophic yeast has the high therapeutic potential to improve the motor dysfunction and quality of life of the lysosomal storage diseases (LSDs) patients with neurological manifestations. We emphasize the importance of neural cell surface M6P receptor as a delivery target of neural cell-directed enzyme replacement therapy (NCDERT) for neurodegenerative metabolic diseases. Copyright © 2010 American Neurological Association.

  7. The Influence of Arthroscopic Remplissage for Engaging Hill-Sachs Lesions Combined with Bankart Repair on Redislocation and Shoulder Function Compared with Bankart Repair Alone.

    PubMed

    Ko, Sang-Hun; Cha, Jae-Ryong; Lee, Chae-Chil; Hwang, Il-Yeong; Choe, Chang-Gyu; Kim, Min-Seok

    2016-12-01

    Recurrence of glenohumeral dislocation after arthroscopic Bankart repair can be associated with a large osseous defect in the posterosuperior part of the humeral head. Our hypothesis is that remplissage is more effective to prevent recurrence of glenohumeral instability without a severe motion deficit. Engaging Hill-Sachs lesions were observed in 48 of 737 patients (6.5%). Twenty-four patients underwent arthroscopic Bankart repair combined with remplissage (group I) and the other 24 patients underwent arthroscopic Bankart repair alone (group II). Clinical outcomes were prospectively evaluated by assessing the range of motion. Complications, recurrence rates, and functional results were assessed utilizing the American Shoulder and Elbow Surgeons (ASES) score, Rowe score, and the Korean Shoulder Score for Instability (KSSI) score. Capsulotenodesis healing after remplissage was evaluated with magnetic resonance imaging. The average ASES, Rowe, and KSSI scores were statistically significantly higher in group I than group II. The frequency of recurrence was statistically significantly higher in group II. The average loss in external rotation measured with the arm positioned at the side of the trunk was greater in group II and that in abduction was also higher in group II. Compared to single arthroscopic Bankart repair, the remplissage procedure combined with arthroscopic Bankart repair was more effective to prevent the recurrence of anterior shoulder instability without significant impact on shoulder mobility in patients who had huge Hill-Sachs lesions.

  8. The cross-correlation between 3D cosmic shear and the integrated Sachs-Wolfe effect

    NASA Astrophysics Data System (ADS)

    Zieser, Britta; Merkel, Philipp M.

    2016-06-01

    We present the first calculation of the cross-correlation between 3D cosmic shear and the integrated Sachs-Wolfe (iSW) effect. Both signals are combined in a single formalism, which permits the computation of the full covariance matrix. In order to avoid the uncertainties presented by the non-linear evolution of the matter power spectrum and intrinsic alignments of galaxies, our analysis is restricted to large scales, I.e. multipoles below ℓ = 1000. We demonstrate in a Fisher analysis that this reduction compared to other studies of 3D weak lensing extending to smaller scales is compensated by the information that is gained if the additional iSW signal and in particular its cross-correlation with lensing data are considered. Given the observational standards of upcoming weak-lensing surveys like Euclid, marginal errors on cosmological parameters decrease by 10 per cent compared to a cosmic shear experiment if both types of information are combined without a cosmic wave background (CMB) prior. Once the constraining power of CMB data is added, the improvement becomes marginal.

  9. Degeneracy between nonadiabatic dark energy models and Λ CDM : Integrated Sachs-Wolfe effect and the cross correlation of CMB with galaxy clustering data

    NASA Astrophysics Data System (ADS)

    Velten, Hermano; Fazolo, Raquel Emy; von Marttens, Rodrigo; Gomes, Syrios

    2018-05-01

    As recently pointed out in [Phys. Rev. D 96, 083502 (2017), 10.1103/PhysRevD.96.083502] the evolution of the linear matter perturbations in nonadiabatic dynamical dark energy models is almost indistinguishable (quasidegenerated) to the standard Λ CDM scenario. In this work we extend this analysis to CMB observables in particular the integrated Sachs-Wolfe effect and its cross-correlation with large scale structure. We find that this feature persists for such CMB related observable reinforcing that new probes and analysis are necessary to reveal the nonadiabatic features in the dark energy sector.

  10. Defect Characteristics of Reverse Hill-Sachs Lesions.

    PubMed

    Moroder, Philipp; Tauber, Mark; Scheibel, Markus; Habermeyer, Peter; Imhoff, Andreas B; Liem, Dennis; Lill, Helmut; Buchmann, Stefan; Wolke, Julia; Guevara-Alvarez, Alberto; Salmoukas, Katharina; Resch, Herbert

    2016-03-01

    Little scientific evidence regarding reverse Hill-Sachs lesions (RHSLs) in posterior shoulder instability exists. Recently, standardized measurement methods of the size and localization were introduced, and the biomechanical effect of the extent and position of the defects on the risk of re-engagement was determined. To analyze the characteristics and patterns of RHSLs in a large case series using standardized measurements and to interpret the results based on the newly available biomechanical findings. Case series; Level of evidence, 4. In this multicenter study, 102 cases of RHSLs in 99 patients were collected from 7 different shoulder centers between 2004 and 2013. Patient- as well as injury-specific information was gathered, and defect characteristics in terms of the size, localization, and depth index were determined on computed tomography or magnetic resonance imaging scans by means of standardized measurements. Additionally, the position (gamma angle) of the posterior defect margin as a predictor of re-engagement was analyzed. Three types of an RHSL were distinguished based on the pathogenesis and chronicity of the lesion: dislocation (D), locked dislocation (LD), and chronic locked dislocation (CLD). While the localization of the defects did not vary significantly between the subgroups (P = .072), their mean size differed signficantly (D: 32.6° ± 11.7°, LD: 49.4° ± 17.2°, CLD: 64.1° ± 20.7°; P < .001). The mean gamma angle as a predictor of re-engagement was similarly significantly different between groups (D: 83.8° ± 14.5°, LD: 96.5° ± 17.9°, CLD: 108.7° ± 18.4°; P < .001). The orientation of the posterior defect margin was consistently quite parallel to the humeral shaft axis, with a mean difference of 0.3° ± 8.1°. The distinction between the 3 different RHSL types based on the pathogenesis and chronicity of the defect helps identify defects prone to re-engagement. The gamma angle as a measurement of the position of the posterior

  11. GM2 Activator Deficiency Caused by a Homozygous Exon 2 Deletion in GM2A.

    PubMed

    Hall, Patricia L; Laine, Regina; Alexander, John J; Ankala, Arunkanth; Teot, Lisa A; Lidov, Hart G W; Anselm, Irina

    2018-01-01

    GM2 activator (GM2A) deficiency (OMIM 613109) is a rare lysosomal storage disorder, with onset typically in infancy or early childhood. Clinically, it is almost indistinguishable from Tay-Sachs disease (OMIM 272800) or Sandhoff disease (OMIM 268800); however, traditionally available biochemical screening tests will most likely reveal normal results. We report a 2-year-old male with initially normal development until the age of 9 months, when he presented with developmental delay and regression. Workup at that time was unrevealing; at 15 months, he had abnormal brain MRI findings and a cherry red spot on ophthalmological examination. Family history and all laboratory studies were uninformative. The combination of a cherry red spot and developmental regression was strongly suggestive of a lysosomal storage disorder. Sequence analysis of GM2A did not reveal any pathogenic variants; however, exon 2 of GM2A could not be amplified by PCR, raising suspicion for a large, homozygous deletion. Subsequent copy number analysis confirmed a homozygous deletion of exon 2 in GM2A. This is the first reported case of GM2A deficiency being caused by a whole exon deletion. We describe previously unreported electron microscopy findings in this disease, thus expanding the clinical and variant spectrum for GM2 activator deficiency. These findings demonstrate the increased degree of suspicion required for diagnosis of this rare disorder. Brief Summary: This case of GM2 activator deficiency was caused by a homozygous deletion in GM2A, demonstrating the need to include exon level copy number analysis in any workup to fully exclude this disorder.

  12. Combined replacement effects of human modified β-hexosaminidase B and GM2 activator protein on GM2 gangliosidoses fibroblasts.

    PubMed

    Kitakaze, Keisuke; Tasaki, Chikako; Tajima, Youichi; Hirokawa, Takatsugu; Tsuji, Daisuke; Sakuraba, Hitoshi; Itoh, Kohji

    2016-09-01

    GM2 gangliosidoses are autosomal recessive lysosomal storage diseases (LSDs) caused by mutations in the HEXA , HEXB and GM2A genes, which encode the human lysosomal β-hexosaminidase (Hex) α- and β-subunits, and GM2 activator protein (GM2A), respectively. These diseases are associated with excessive accumulation of GM2 ganglioside (GM2) in the brains of patients with neurological symptoms. Here we established a CHO cell line overexpressing human GM2A, and purified GM2A from the conditioned medium, which was taken up by fibroblasts derived from a patient with GM2A deficiency, and had the therapeutic effects of reducing the GM2 accumulated in fibroblasts when added to the culture medium. We also demonstrated for the first time that recombinant GM2A could enhance the replacement effect of human modified HexB (modB) with GM2-degrading activity, which is composed of homodimeric altered β-subunits containing a partial amino acid sequence of the α-subunit, including the GSEP loop necessary for binding to GM2A, on reduction of the GM2 accumulated in fibroblasts derived from a patient with Tay-Sachs disease, a HexA (αβ heterodimer) deficiency, caused by HEXA mutations. We predicted the same manner of binding of GM2A to the GSEP loop located in the modified HexB β-subunit to that in the native HexA α-subunit on the basis of the x-ray crystal structures. These findings suggest the effectiveness of combinational replacement therapy involving the human modified HexB and GM2A for GM2 gangliosidoses.

  13. 78 FR 71532 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. [[Page 71533... (AD) 2007-03- 02 for all Rolls-Royce Deutschland (RRD) Tay 620-15, Tay 650-15, and Tay 651-54 turbofan..., January 29, 2007) (``AD 2007-03-02'') for certain RRD Tay 611-8 and Tay 620-15 turbofan engines with LP...

  14. Molecular imaging of enhanced Na + expression in the liver of total sleep deprived rats by TOF-SIMS

    NASA Astrophysics Data System (ADS)

    Chang, Hung-Ming; Chen, Bo-Jung; Wu, Un-In; Huang, Yi-Lun; Mai, Fu-Der

    2008-12-01

    Sleep disorder is associated with metabolic disturbances, which was related to oxidative stress and subsequently sodium overload. Since liver plays important roles in metabolic regulation, present study is aimed to determine whether hepatic sodium, together with oxidative stress, would significantly alter after total sleep deprivation (TSD). Sodium ion was investigated by time-of-flight secondary ion mass spectrometry (TOF-SIMS). Parameter for oxidative stress was examined by heat shock protein-25 (HSP-25) immunohistochemistry. TOF-SIMS spectrum indicated that hepatic Na +/K + ratio counting as 82.41 ± 9.5 was obtained in normal rats. Sodium ions were distributed in hepatocytes with several aggregations. However, following TSD, the intensity for Na +/K + ratio was relatively increased (101.94 ± 6.9) and signals for sodium image were strongly expressed throughout hepatocytes without spatial localization. Quantitative analysis revealed that HSP-25 staining intensity is 1.78 ± 0.27 in TSD rats, which was significantly higher than that of normal ones (0.68 ± 0.15). HSP-25 augmentation suggests that hepatocytes suffer from oxidative stress following TSD. Concerning oxidative stress induced sodium overload would impair metabolic function; enhanced hepatic sodium expression after TSD may be a major cause of TSD relevant metabolic diseases.

  15. Integrated Sachs-Wolfe map reconstruction in the presence of systematic errors

    NASA Astrophysics Data System (ADS)

    Weaverdyck, Noah; Muir, Jessica; Huterer, Dragan

    2018-02-01

    The decay of gravitational potentials in the presence of dark energy leads to an additional, late-time contribution to anisotropies in the cosmic microwave background (CMB) at large angular scales. The imprint of this so-called integrated Sachs-Wolfe (ISW) effect to the CMB angular power spectrum has been detected and studied in detail, but reconstructing its spatial contributions to the CMB map, which would offer the tantalizing possibility of separating the early- from the late-time contributions to CMB temperature fluctuations, is more challenging. Here, we study the technique for reconstructing the ISW map based on information from galaxy surveys and focus in particular on how its accuracy is impacted by the presence of photometric calibration errors in input galaxy maps, which were previously found to be a dominant contaminant for ISW signal estimation. We find that both including tomographic information from a single survey and using data from multiple, complementary galaxy surveys improve the reconstruction by mitigating the impact of spurious power contributions from calibration errors. A high-fidelity reconstruction further requires one to account for the contribution of calibration errors to the observed galaxy power spectrum in the model used to construct the ISW estimator. We find that if the photometric calibration errors in galaxy surveys can be independently controlled at the level required to obtain unbiased dark energy constraints, then it is possible to reconstruct ISW maps with excellent accuracy using a combination of maps from two galaxy surveys with properties similar to Euclid and SPHEREx.

  16. 78 FR 17079 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... certain Rolls-Royce Deutschland Ltd & Co KG (RRD) models Tay 620-15 and Tay 650-15 turbofan engines. This... Tay 620-15 and Tay 650-15 turbofan engines with a low-pressure compressor (LPC) rotor disc assembly...

  17. Reproductive health and genetic testing in the Third World.

    PubMed

    Penchaszadeh, V B

    1993-09-01

    New reproductive genetics means recently developed techniques to prevent the birth of children with specific defects or genetic diseases by testing individuals for sickle cell anemia, the thalassemias, Tay-Sachs disease, cystic fibrosis, or Down syndrome. Third World health services have many deficiencies with high maternal mortality rates (30-40 fold higher than in developed countries), the low percentage of births delivered by health personnel, the high rates of low birth weight babies, and high child malnutrition and infant mortality rates. The main issues in women's reproductive health are fertility regulation, abortion, maternal mortality, sexually transmitted diseases, and infertility. As a result of expansion in contraceptive use worldwide, the total fertility rate in developing countries has declined from 6.1 in 1965 to 3.9 in 1990. It is estimated that, worldwide, 36-53 million induced abortions are performed each year, most of them in developing nations. WHO estimates that more than 500,000 women die each year because of complications of pregnancy, most in developing countries. More than 95% of the 13 million estimated deaths of children under 5 years of age have occurred in these countries. Approximately 200 million people carry a potentially pathologic hemoglobinopathy gene, and about 250,000 children are born every year with hemoglobinopathy, most of them in the developing world. Reproductive genetic testing in big cities and in private for-profit ventures cater to the socioeconomic elite. Amniocentesis is often misused for fetal sex determination to abort female fetuses in India. Currently, in Cuba virtually every pregnant woman is tested for sickle cell trait and maternal serum alpha-fetoprotein levels between 15 and 20 weeks of gestation. It is predicted that the judicious use of reproductive genetic testing will be possible when health and quality of life issues are addressed properly.

  18. Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease

    PubMed Central

    Brandt-Rauf, Sherry I.; Raveis, Victoria H.; Drummond, Nathan F.; Conte, Jill A.; Rothman, Sheila M.

    2006-01-01

    We explored the advantages and disadvantages of using ethnic categories in genetic research. With the discovery that certain breast cancer gene mutations appeared to be more prevalent in Ashkenazi Jews, breast cancer researchers moved their focus from high-risk families to ethnicity. The concept of Ashkenazi Jews as genetically unique, a legacy of Tay–Sachs disease research and a particular reading of history, shaped this new approach even as methodological imprecision and new genetic and historical research challenged it. Our findings cast doubt on the accuracy and desirability of linking ethnic groups to genetic disease. Such linkages exaggerate genetic differences among ethnic groups and lead to unequal access to testing and therapy. PMID:17018815

  19. Up-regulation of Na + expression in the area postrema of total sleep deprived rats by TOF-SIMS analysis

    NASA Astrophysics Data System (ADS)

    Mai, Fu-Der; Chen, Bo-Jung; Ling, Yong-Chien; Wu, Un-In; Huang, Yi-Lun; Chang, Hung-Ming

    2008-12-01

    Area postrema (AP) is a circumventricular organ plays an important role in sodium homeostasis and cardiovascular regulation. Since sleep deficiency will cause cardiovascular dysfunction, the present study aims to determine whether sodium level would significantly alter in AP following total sleep deprivation (TSD). Sodium level was investigated in vivo by time-of-flight secondary ion mass spectrometry (TOF-SIMS). Clinical manifestation of cardiovascular function was demonstrated by mean arterial pressure (MAP) values. Results indicated that in normal rats, TOF-SIMS spectrum revealed a major peak of sodium ion counting as 5.61 × 10 5 at m/ z 23. The sodium ions were homogeneous distributed in AP without specific localization. However, following TSD, the sodium intensity was relatively increased (6.73 × 10 5) and the signal for sodium image was strongly expressed throughout AP with definite spatial distribution. MAP of TSD rats is 138 ± 5 mmHg, which is significantly higher than that of normal ones (121 ± 3 mmHg). Regarding AP is an important area for sodium sensation and development of hypernatremic related sympatho-excitation; up-regulation of sodium expression following TSD suggests that high sodium level might over-activate AP, through complex neuronal networks involving in sympathetic regulation, which could lead to the formation of TSD relevant cardiovascular diseases.

  20. Magnification-temperature correlation: The dark side of integrated Sachs-Wolfe measurements

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    LoVerde, Marilena; Hui, Lam; Gaztanaga, Enrique

    2007-02-15

    Integrated Sachs-Wolfe (ISW) measurements, which involve cross-correlating the microwave background anisotropies with the foreground large-scale structure (e.g. traced by galaxies/quasars), have proven to be an interesting probe of dark energy. We show that magnification bias, which is the inevitable modulation of the foreground number counts by gravitational lensing, alters both the scale dependence and amplitude of the observed ISW signal. This is true especially at high redshifts because (1) the intrinsic galaxy-temperature signal diminishes greatly back in the matter-dominated era, (2) the lensing efficiency increases with redshift and (3) the number count slope generally steepens with redshift in a magnitudemore » limited sample. At z > or approx. 2, the magnification-temperature correlation dominates over the intrinsic galaxy-temperature correlation and causes the observed ISW signal to increase with redshift, despite dark energy subdominance--a result of the fact that magnification probes structures all the way from the observer to the sources. Ignoring magnification bias therefore can lead to (significantly) erroneous conclusions about dark energy. While the lensing modulation opens up an interesting high z window for ISW measurements, high redshift measurements are not expected to add much new information to low redshift ones if dark energy is indeed the cosmological constant. This is because lensing introduces significant covariance across redshifts. The most compelling reasons for pursuing high redshift ISW measurements are to look for potential surprises such as early dark energy domination or signatures of modified gravity. We conclude with a discussion of existing measurements, the highest redshift of which is at the margin of being sensitive to the magnification effect. We also develop a formalism which might be of more general interest: to predict biases in estimating parameters when certain physical effects are ignored in interpreting

  1. The concept of wrongful life in the law.

    PubMed

    Kasper, A S

    1983-01-01

    In the history of the law the concept of wrongful life is not new, but it has become of interest recently due to changing social attitudes and advances in contraceptive and genetic technologies. This discussion tries to assess the effects of wrongful life as a legal concept on the rights of childbearing women and their offspring. An unborn child had no rights under common law, which held that a fetus in utero had no existence separate from its mother. Consequently, a child had no right of action for personal harm brought upon it by another person. On occasion early courts disagreed with this view, but the majority of courts maintained that a child had no existence as a human being during gestation. The effect that this concept of common law would have on current abortion laws would be to make it considerably easier to argue for a woman's right to choose an abortion. The notion of wrongful life initially appeared in cases of illegitimate births. In Zepeda v. Zepeda, 1963, and Williams v. State of New York, 1966, the plaintiffs maintained that the children's births and existence were wrongful because they were unintended and illegitimate. In Williams the court ruled that birth under 1 set of circumstances and not another is not a recoverable injury. These cases failed to meet the requirements of tort law, and the court rejected the notion of children finding legal recourse for being born to a poor family or being born to a less desired race or class. A series of cases followed in which recovery for physical injury or birth deformities were claimed by parents for themselves and their children. In June 1980 a California appeals court reversed the decision of a lower court, addressing the fundamental principles of wrongful life as a legal concept. In Curlender v. Bio-Science Laboratories an infant brought suit alleging that the laboratories failed to correctly inform her parents of their status as carriers of Tay-Sachs disease during the mother's pregnancy. The infant

  2. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides.

    PubMed

    Pan, Xuefang; De Aragão, Camila De Britto Pará; Velasco-Martin, Juan P; Priestman, David A; Wu, Harry Y; Takahashi, Kohta; Yamaguchi, Kazunori; Sturiale, Luisella; Garozzo, Domenico; Platt, Frances M; Lamarche-Vane, Nathalie; Morales, Carlos R; Miyagi, Taeko; Pshezhetsky, Alexey V

    2017-08-01

    Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling in neurons. Metabolic blocks in processing and catabolism of gangliosides result in the development of severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration and neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 and 4, play important roles in catabolic processing of brain gangliosides by cleaving terminal sialic acid residues in their glycan chains. In neuraminidase 3 and 4 double-knockout mice, G M3 ganglioside is stored in microglia, vascular pericytes, and neurons, causing micro- and astrogliosis, neuroinflammation, accumulation of lipofuscin bodies, and memory loss, whereas their cortical and hippocampal neurons have lower rate of neuritogenesis in vitro Double-knockout mice also have reduced levels of G M1 ganglioside and myelin in neuronal axons. Furthermore, neuraminidase 3 deficiency drastically increased storage of G M2 in the brain tissues of an asymptomatic mouse model of Tay-Sachs disease, a severe human gangliosidosis, indicating that this enzyme is responsible for the metabolic bypass of β-hexosaminidase A deficiency. Together, our results provide the first in vivo evidence that neuraminidases 3 and 4 have important roles in CNS function by catabolizing gangliosides and preventing their storage in lipofuscin bodies.-Pan, X., De Britto Pará De Aragão, C., Velasco-Martin, J. P., Priestman, D. A., Wu, H. Y., Takahashi, K., Yamaguchi, K., Sturiale, L., Garozzo, D., Platt, F. M., Lamarche-Vane, N., Morales, C. R., Miyagi, T., Pshezhetsky, A. V. Neuraminidases 3 and 4 regulate neuronal function by catabolizing brain gangliosides. © FASEB.

  3. Description of new species of Pterygorhabditis Timm, and Aspidonema (Sachs, ) Andrássy, (Nematoda: Bunonematoidea) in aquatic habitats from India.

    PubMed

    Tahseen, Q; Khan, R; Ahlawat, S

    2016-07-01

    The paper contains descriptions of two new species of the genera Pterygorhabditis Timm, 1957 and Aspidonema (Sachs, 1949) Andrássy, 1958 belonging to the families Pterygorhabditidae Goodey 1963 and Bunonematidae Micoletzky 1922, respectively. Species were procured from fixed samples, collected earlier from aquatic habitats. Pterygorhabditis punctata n. sp. is characterized by a cuticle with flattened hexagonal blocks arranged in eight longitudinal rows in both sexes; each metastegostomal plate with a minute denticle, and males with long, slender, fused spicules and nine pairs of post-cloacal, prominently setose genital papillae. Aspidonema formosa n. sp. is the first report of the genus from India. The species is characterized by the right side provided with 35-48 pairs of warts flanking a row of smooth membranous shields and surrounded by a well-developed network and an anisomorphic metastegostom without discernible armature. Species are compared with other congeners, together with the diagnoses of amended genera, and keys to the identification of species are provided.

  4. Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects GM2 Gangliosidosis in Sandhoff Mice.

    PubMed

    Osmon, Karlaina J L; Woodley, Evan; Thompson, Patrick; Ong, Katalina; Karumuthil-Melethil, Subha; Keimel, John G; Mark, Brian L; Mahuran, Don; Gray, Steven J; Walia, Jagdeep S

    2016-07-01

    mouse phenotype for long-term. Our data could have implications not only for treatment of SD but also for Tay-Sachs disease (α-subunit deficiency) and similar brain disorders.

  5. Planck 2015 results: XXI. The integrated Sachs-Wolfe effect

    DOE PAGES

    Ade, P. A. R.; Aghanim, N.; Arnaud, M.; ...

    2016-09-20

    Here, this paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and themore » NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that Ω Λ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by

  6. Planck 2015 results. XXI. The integrated Sachs-Wolfe effect

    NASA Astrophysics Data System (ADS)

    Planck Collaboration; Ade, P. A. R.; Aghanim, N.; Arnaud, M.; Ashdown, M.; Aumont, J.; Baccigalupi, C.; Banday, A. J.; Barreiro, R. B.; Bartolo, N.; Basak, S.; Battaner, E.; Benabed, K.; Benoît, A.; Benoit-Lévy, A.; Bernard, J.-P.; Bersanelli, M.; Bielewicz, P.; Bock, J. J.; Bonaldi, A.; Bonavera, L.; Bond, J. R.; Borrill, J.; Bouchet, F. R.; Bucher, M.; Burigana, C.; Butler, R. C.; Calabrese, E.; Cardoso, J.-F.; Casaponsa, B.; Catalano, A.; Challinor, A.; Chamballu, A.; Chiang, H. C.; Christensen, P. R.; Church, S.; Clements, D. L.; Colombi, S.; Colombo, L. P. L.; Combet, C.; Couchot, F.; Coulais, A.; Crill, B. P.; Curto, A.; Cuttaia, F.; Danese, L.; Davies, R. D.; Davis, R. J.; de Bernardis, P.; de Rosa, A.; de Zotti, G.; Delabrouille, J.; Désert, F.-X.; Diego, J. M.; Dole, H.; Donzelli, S.; Doré, O.; Douspis, M.; Ducout, A.; Dupac, X.; Efstathiou, G.; Elsner, F.; Enßlin, T. A.; Eriksen, H. K.; Fergusson, J.; Fernandez-Cobos, R.; Finelli, F.; Forni, O.; Frailis, M.; Fraisse, A. A.; Franceschi, E.; Frejsel, A.; Galeotta, S.; Galli, S.; Ganga, K.; Génova-Santos, R. T.; Giard, M.; Giraud-Héraud, Y.; Gjerløw, E.; González-Nuevo, J.; Górski, K. M.; Gratton, S.; Gregorio, A.; Gruppuso, A.; Gudmundsson, J. E.; Hansen, F. K.; Hanson, D.; Harrison, D. L.; Henrot-Versillé, S.; Hernández-Monteagudo, C.; Herranz, D.; Hildebrandt, S. R.; Hivon, E.; Hobson, M.; Holmes, W. A.; Hornstrup, A.; Hovest, W.; Huffenberger, K. M.; Hurier, G.; Ilić, S.; Jaffe, A. H.; Jaffe, T. R.; Jones, W. C.; Juvela, M.; Keihänen, E.; Keskitalo, R.; Kisner, T. S.; Kneissl, R.; Knoche, J.; Kunz, M.; Kurki-Suonio, H.; Lagache, G.; Lähteenmäki, A.; Lamarre, J.-M.; Langer, M.; Lasenby, A.; Lattanzi, M.; Lawrence, C. R.; Leonardi, R.; Lesgourgues, J.; Levrier, F.; Liguori, M.; Lilje, P. B.; Linden-Vørnle, M.; López-Caniego, M.; Lubin, P. M.; Ma, Y.-Z.; Macías-Pérez, J. F.; Maggio, G.; Maino, D.; Mandolesi, N.; Mangilli, A.; Marcos-Caballero, A.; Maris, M.; Martin, P. G.; Martínez-González, E.; Masi, S.; Matarrese, S.; McGehee, P.; Meinhold, P. R.; Melchiorri, A.; Mendes, L.; Mennella, A.; Migliaccio, M.; Mitra, S.; Miville-Deschênes, M.-A.; Moneti, A.; Montier, L.; Morgante, G.; Mortlock, D.; Moss, A.; Munshi, D.; Murphy, J. A.; Naselsky, P.; Nati, F.; Natoli, P.; Netterfield, C. B.; Nørgaard-Nielsen, H. U.; Noviello, F.; Novikov, D.; Novikov, I.; Oxborrow, C. A.; Paci, F.; Pagano, L.; Pajot, F.; Paoletti, D.; Pasian, F.; Patanchon, G.; Perdereau, O.; Perotto, L.; Perrotta, F.; Pettorino, V.; Piacentini, F.; Piat, M.; Pierpaoli, E.; Pietrobon, D.; Plaszczynski, S.; Pointecouteau, E.; Polenta, G.; Popa, L.; Pratt, G. W.; Prézeau, G.; Prunet, S.; Puget, J.-L.; Rachen, J. P.; Reach, W. T.; Rebolo, R.; Reinecke, M.; Remazeilles, M.; Renault, C.; Renzi, A.; Ristorcelli, I.; Rocha, G.; Rosset, C.; Rossetti, M.; Roudier, G.; Rubiño-Martín, J. A.; Rusholme, B.; Sandri, M.; Santos, D.; Savelainen, M.; Savini, G.; Schaefer, B. M.; Scott, D.; Seiffert, M. D.; Shellard, E. P. S.; Spencer, L. D.; Stolyarov, V.; Stompor, R.; Sudiwala, R.; Sunyaev, R.; Sutton, D.; Suur-Uski, A.-S.; Sygnet, J.-F.; Tauber, J. A.; Terenzi, L.; Toffolatti, L.; Tomasi, M.; Tristram, M.; Tucci, M.; Tuovinen, J.; Valenziano, L.; Valiviita, J.; Van Tent, F.; Vielva, P.; Villa, F.; Wade, L. A.; Wandelt, B. D.; Wehus, I. K.; Yvon, D.; Zacchei, A.; Zonca, A.

    2016-09-01

    This paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and the NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that ΩΛ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by combining the

  7. Planck 2015 results: XXI. The integrated Sachs-Wolfe effect

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ade, P. A. R.; Aghanim, N.; Arnaud, M.

    Here, this paper presents a study of the integrated Sachs-Wolfe (ISW) effect from the Planck 2015 temperature and polarization data release. This secondary cosmic microwave background (CMB) anisotropy caused by the large-scale time-evolving gravitational potential is probed from different perspectives. The CMB is cross-correlated with different large-scale structure (LSS) tracers: radio sources from the NVSS catalogue; galaxies from the optical SDSS and the infrared WISE surveys; and the Planck 2015 convergence lensing map. The joint cross-correlation of the CMB with the tracers yields a detection at 4σ where most of the signal-to-noise is due to the Planck lensing and themore » NVSS radio catalogue. In fact, the ISW effect is detected from the Planck data only at ≈3σ (through the ISW-lensing bispectrum), which is similar to the detection level achieved by combining the cross-correlation signal coming from all the galaxy catalogues mentioned above. We study the ability of the ISW effect to place constraints on the dark-energy parameters; in particular, we show that Ω Λ is detected at more than 3σ. This cross-correlation analysis is performed only with the Planck temperature data, since the polarization scales available in the 2015 release do not permit significant improvement of the CMB-LSS cross-correlation detectability. Nevertheless, the Planck polarization data are used to study the anomalously large ISW signal previously reported through the aperture photometry on stacked CMB features at the locations of known superclusters and supervoids, which is in conflict with ΛCDM expectations. We find that the current Planck polarization data do not exclude that this signal could be caused by the ISW effect. In addition, the stacking of the Planck lensing map on the locations of superstructures exhibits a positive cross-correlation with these large-scale structures. Finally, we have improved our previous reconstruction of the ISW temperature fluctuations by

  8. Constraining neutrino masses with the integrated-Sachs-Wolfe-galaxy correlation function

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lesgourgues, Julien; Valkenburg, Wessel; Gaztanaga, Enrique

    2008-03-15

    Temperature anisotropies in the cosmic microwave background (CMB) are affected by the late integrated Sachs-Wolfe (lISW) effect caused by any time variation of the gravitational potential on linear scales. Dark energy is not the only source of lISW, since massive neutrinos induce a small decay of the potential on small scales during both matter and dark energy domination. In this work, we study the prospect of using the cross correlation between CMB and galaxy-density maps as a tool for constraining the neutrino mass. On the one hand massive neutrinos reduce the cross-correlation spectrum because free-streaming slows down structure formation; onmore » the other hand, they enhance it through their change in the effective linear growth. We show that in the observable range of scales and redshifts, the first effect dominates, but the second one is not negligible. We carry out an error forecast analysis by fitting some mock data inspired by the Planck satellite, Dark Energy Survey (DES) and Large Synoptic Survey Telescope (LSST). The inclusion of the cross correlation data from Planck and LSST increases the sensitivity to the neutrino mass m{sub {nu}} by 38% (and to the dark energy equation of state w by 83%) with respect to Planck alone. The correlation between Planck and DES brings a far less significant improvement. This method is not potentially as good for detecting m{sub {nu}} as the measurement of galaxy, cluster, or cosmic shear power spectra, but since it is independent and affected by different systematics, it remains potentially interesting if the total neutrino mass is of the order of 0.2 eV; if instead it is close to the lower bound from atmospheric oscillations, m{sub {nu}}{approx}0.05 eV, we do not expect the ISW-galaxy correlation to be ever sensitive to m{sub {nu}}.« less

  9. Validation of the technique for absolute total electron content and differential code biases estimation

    NASA Astrophysics Data System (ADS)

    Mylnikova, Anna; Yasyukevich, Yury; Yasyukevich, Anna

    2017-04-01

    We have developed a technique for vertical total electron content (TEC) and differential code biases (DCBs) estimation using data from a single GPS/GLONASS station. The algorithm is based on TEC expansion into Taylor series in space and time (TayAbsTEC). We perform the validation of the technique using Global Ionospheric Maps (GIM) computed by Center for Orbit Determination in Europe (CODE) and Jet Propulsion Laboratory (JPL). We compared differences between absolute vertical TEC (VTEC) from GIM and VTEC evaluated by TayAbsTEC for 2009 year (solar activity minimum - sunspot number about 0), and for 2014 year (solar activity maximum - sunspot number 110). Since there is difference between VTEC from CODE and VTEC from JPL, we compare TayAbsTEC VTEC with both of them. We found that TayAbsTEC VTEC is closer to CODE VTEC than to JPL VTEC. The difference between TayAbsTEC VTEC and GIM VTEC is more noticeable for solar activity maximum (2014) than for solar activity minimum (2009) for both CODE and JPL. The distribution of VTEC differences is close to Gaussian distribution, so we conclude that results of TayAbsTEC are in the agreement with GIM VTEC. We also compared DCBs evaluated by TayAbsTEC and DCBs from GIM, computed by CODE. The TayAbsTEC DCBs are in good agreement with CODE DCBs for GPS satellites, but differ noticeable for GLONASS. We used DCBs to correct slant TEC to find out which DCBs give better results. Slant TEC correction with CODE DCBs produces negative and nonphysical TEC values. Slant TEC correction with TayAbsTEC DCBs doesn't produce such artifacts. The technique we developed is used for VTEC and DCBs calculation given only local GPS/GLONASS networks data. The evaluated VTEC data are in GIM framework which is handy when various data analyses are made.

  10. Determination of Time since Death using Vitreous Humor Tryptophan.

    PubMed

    Ansari, Niha; Menon, Shobhana K

    2017-09-01

    Determination of time since death (TSD) plays very important role in forensic examination as it narrows down field of suspects and aids in deceased identification. This study utilizes the fluorescence property of vitreous humor (VH) tryptophan to determine TSD using o-phthalaldehyde (OPA). The detection limit of these fluorometric studies was found to be 8 ppb indicating sensitivity and high accuracy in TSD determination. The study was performed on selected 76 cadaver with known TSD ranging from 3 to 90 h. Excellent correlation between VH tryptophan and TSD was obtained with a coefficient of correlation R 2 = 0.9590. Results showed statistically significant increase in vitreous tryptophan with TSD up to 90 h, and the proposed method was efficaciously applied for prediction of TSD as no systematic error exist. The regression equation obtained from the study is [Trp] = 2.21 + 2.98 * TSD. © 2017 American Academy of Forensic Sciences.

  11. The Late Integrated Sachs-Wolfe Effect and its detectability in galaxy-redshift surveys

    NASA Astrophysics Data System (ADS)

    Valencia-Díaz, D. R.; Muñoz-Cuartas, J. C.

    2017-07-01

    The late Integrated Sachs-Wolfe (ISW) effect is underwent by the Cosmic Microwave Background (CMB) photons due to the presence of the Large-Scale Structures (LSS) in an expanding Universe and can be measured through the temperature fluctuations of the CMB. In this work we use numerical simulations of structure formation to study the detectability of the ISW effect. Our method comprises the estimation of the density field through a Cloud-In-Cell mass assignment scheme. With the help of Fourier transforms we estimate the time derivative of the gravitational potential field in Fourier and in coordinate's space. Finally, this field is integrated numerically to know the ISW contribution. We study the time derivative of the potential in two approaches. First, an exact solution that makes use of the full velocity field. Second, a linear approximation related with the linear theory for the formation of LSS. We apply the method to three cosmological simulations. First, a box of 400 h-1 Mpc; second, the MultiDark1 simulation; third, the MultiDark-Plank simulation. For all cases we obtain coherent results with the expected in the literature for a ΛCDM cosmology: with the exact solution the temperature fluctuation is near the ± 30 μ K; the linear approximation shows a signal in the expected range of ± 20 μ K. This positive detection on simulations is important in order to know an expectation for the results we should obtain when working with observational data and will have important implications due to the lack of consensus about the detection of the ISW effect in previous works. Acknowledgements: This work was supported by Colciencias and Universidad de Antioquia, Convenio Beca-Pasantía Joven Investigador Convocatoria 645 de 2014.

  12. Challenges and Gaps in Understanding Substance Use Problems in Transitional Age Youth.

    PubMed

    Bukstein, Oscar G

    2017-04-01

    Transitional age youth (TAY), developing from adolescence to adulthood, exhibit the highest level of alcohol and other drug use of any other age group. Risk factors mirror those for the development of problems and disorders in adolescents. Early screening of both college students and noncollege high-risk TAY in the community is critical to early and effective intervention. Brief interventions using motivational techniques are effective for many TAY, particularly for those in early stages of problem use on college campuses. Professionals in contact with TAY should be aware of evidence-based interventions and providers for substance use disorders in the community. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.

    PubMed

    Barone, Rita; Sturiale, Luisella; Fiumara, Agata; Palmigiano, Angelo; Bua, Rosaria O; Rizzo, Renata; Zappia, Mario; Garozzo, Domenico

    2016-04-01

    Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  14. Parallel optoelectronic trinary signed-digit division

    NASA Astrophysics Data System (ADS)

    Alam, Mohammad S.

    1999-03-01

    The trinary signed-digit (TSD) number system has been found to be very useful for parallel addition and subtraction of any arbitrary length operands in constant time. Using the TSD addition and multiplication modules as the basic building blocks, we develop an efficient algorithm for performing parallel TSD division in constant time. The proposed division technique uses one TSD subtraction and two TSD multiplication steps. An optoelectronic correlator based architecture is suggested for implementation of the proposed TSD division algorithm, which fully exploits the parallelism and high processing speed of optics. An efficient spatial encoding scheme is used to ensure better utilization of space bandwidth product of the spatial light modulators used in the optoelectronic implementation.

  15. Factors Associated with Suicidal Thought and Help-Seeking Behaviour in Transition-Aged Youth versus Adults.

    PubMed

    MacKinnon, Nathalie; Colman, Ian

    2016-12-01

    Suicide is a leading cause of death for transition-aged youth (TAY), and yet few studies examine correlates of suicidal ideation specifically in this age demographic (age 18-24 years). The transition to adulthood is a unique context, marked by novel stressors (e.g., joining the workforce) and increased independence, which may influence risk factors for suicidal ideation. This study examined correlates of suicidal ideation in TAY and adults and contrasted profiles across age. We used 4 biannual cycles (2005, 2007, 2009, 2011) of the Canadian Community Health Survey, a population-based cross-sectional survey on health. We used logistic regression to assess the association between suicidal ideation and depression, distress, alcohol use, smoking, exercise, sedentary behaviour, chronic illness, restrictions to daily living, perceived physical and mental health, and perceived social support independently in both TAY ( n = 4427) and adults ( n = 14,452). We subsequently assessed possible interactions with age (18-24 v. 25-44 years) and sex and differences in help-seeking behaviour in a combined model. TAY exhibited higher rates of suicidal ideation than adults did ( P < 0.001). Numerous factors were associated with suicidal ideation in TAY. Notably, alcohol abstinence was associated with decreased suicidal ideation in TAY but not for adults. Moreover, when depressed, TAY were significantly less likely to have received professional mental health help than adults (odds ratio = 0.64, 95% CI, 0.43 to 0.94). Suicidal ideation is more prevalent in TAY than adults, and its consequences may be aggravated by poor treatment-seeking behaviour in at-risk (i.e. depressed) individuals. These different risk profiles substantiate the recent shift toward clinical interventions focusing on transition-aged youth, rather than traditional child (<18 years) and adult (>18 years) services.

  16. Temperature-dependent sex determination in fish revisited: prevalence, a single sex ratio response pattern, and possible effects of climate change.

    PubMed

    Ospina-Alvarez, Natalia; Piferrer, Francesc

    2008-07-30

    In gonochoristic vertebrates, sex determination mechanisms can be classified as genotypic (GSD) or temperature-dependent (TSD). Some cases of TSD in fish have been questioned, but the prevalent view is that TSD is very common in this group of animals, with three different response patterns to temperature. We analyzed field and laboratory data for the 59 fish species where TSD has been explicitly or implicitly claimed so far. For each species, we compiled data on the presence or absence of sex chromosomes and determined if the sex ratio response was obtained within temperatures that the species experiences in the wild. If so, we studied whether this response was statistically significant. We found evidence that many cases of observed sex ratio shifts in response to temperature reveal thermal alterations of an otherwise predominately GSD mechanism rather than the presence of TSD. We also show that in those fish species that actually have TSD, sex ratio response to increasing temperatures invariably results in highly male-biased sex ratios, and that even small changes of just 1-2 degrees C can significantly alter the sex ratio from 1:1 (males:females) up to 3:1 in both freshwater and marine species. We demonstrate that TSD in fish is far less widespread than currently believed, suggesting that TSD is clearly the exception in fish sex determination. Further, species with TSD exhibit only one general sex ratio response pattern to temperature. However, the viability of some fish populations with TSD can be compromised through alterations in their sex ratios as a response to temperature fluctuations of the magnitude predicted by climate change.

  17. Thermal Skin Damage During Reirradiation and Hyperthermia Is Time-Temperature Dependent

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bakker, Akke, E-mail: akke.bakker@amc.uva.nl; Kolff, M. Willemijn; Holman, Rebecca

    Purpose: To investigate the relationship of thermal skin damage (TSD) to time–temperature isoeffect levels for patients with breast cancer recurrence treated with reirradiation plus hyperthermia (reRT + HT), and to investigate whether the treatment history of previous treatments (scar tissue) is a risk factor for TSD. Methods and Materials: In this observational study, temperature characteristics of hyperthermia sessions were analyzed in 262 patients with recurrent breast cancer treated in the AMC between 2010 and 2014 with reirradiation and weekly hyperthermia for 1 hour. Skin temperature was measured using a median of 42 (range, 29-82) measurement points per hyperthermia session. Results: Sixty-eight patients (26%) developed 79more » sites of TSD, after the first (n=26), second (n=17), third (n=27), and fourth (n=9) hyperthermia session. Seventy percent of TSD occurred on or near scar tissue. Scar tissue reached higher temperatures than other skin tissue (0.4°C, P<.001). A total of 102 measurement points corresponded to actual TSD sites in 35 of 79 sessions in which TSD developed. Thermal skin damage sites had much higher maximum temperatures than non-TSD sites (2.8°C, P<.001). Generalized linear mixed models showed that the probability of TSD is related to temperature and thermal dose values (P<.001) and that scar tissue is more at risk (odds ratio 0.4, P<.001). Limiting the maximum temperature of a measurement point to 43.7°C would mean that the probability of observing TSD was at most 5%. Conclusion: Thermal skin damage during reRT + HT for recurrent breast cancer was related to higher local temperatures and time–temperature isoeffect levels. Scar tissue reached higher temperatures than other skin tissue, and TSD occurred at lower temperatures and thermal dose values in scar tissue compared with other skin tissue. Indeed, TSD developed often on and around scar tissue from previous surgical procedures.« less

  18. WE-FG-206-08: Pulmonary Functional Imaging Biomarkers of NSCLC to Guide and Optimize Functional Lung Avoidance Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sheikh, Khadija; Capaldi, Dante PI; Parraga, Grace

    Purpose: Functional lung avoidance radiotherapy promises optimized therapy planning by minimizing dose to well-functioning lung and maximizing dose to the rest of the lung. Patients with NSCLC commonly present with co-morbid COPD and heterogeneously distributed ventilation abnormalities stemming from emphysema, airways disease, and tumour burden. We hypothesized that pulmonary functional imaging methods may be used to optimize radiotherapy plans to avoid regions of well-functioning lung and significantly improve outcomes like quality-of-life and survival. To ascertain the utility of functional lung avoidance therapy in clinical practice, we measured COPD phenotypes in NSCLC patients enrolled in a randomized-controlled-clinical-trial prior to curative intentmore » therapy. Methods: Thirty stage IIIA/IIIB NSCLC patients provided written informed consent to a randomized-controlled-clinical-trial ( http://clinicaltrials.gov/ct2/show/NCT02002052 ) comparing outcomes in patients randomized to standard or image-guided radiotherapy. Hyperpolarized noble gas MRI ventilation-defect-percent (VDP) (Kirby et al, Acad Radiol, 2012) as well as CT-emphysema measurements were determined. Patients were stratified based on quantitative imaging evidence of ventilation-defects and emphysema into two subgroups: 1) tumour-specific ventilation defects only (TSD), and, 2) tumour-specific and other ventilation defects with and without emphysema (TSD{sub VE}). Receiver-operating-characteristic (ROC) curves were used to characterize the performance of clinical measures as predictors of the presence of non-tumour specific ventilation defects. Results: Twenty-one out of thirty subjects (70%) had non-tumour specific ventilation defects (TSD{sub VE}) and nine subjects had ONLY tumour-specific defects (TSD). Subjects in the TSD{sub VE} group had significantly greater smoking-history (p=.006) and airflow obstruction (FEV{sub 1}/FVC) (p=.001). ROC analysis demonstrated an 87% classification rate

  19. Public policies and reproductive technology: a feminist critique.

    PubMed

    Mccormack, T

    1991-01-01

    Reproductive technology comprises abortion, contraception, amniocentesis (more than 40 genetic disorders can be diagnosed), chorionic villus sampling, genetic screening (to reduce the risk of chromosomal defects such as Down syndrome, sickle cell anemia, Tay-Sachs disease, and cystic fibrosis), in vitro fertilization, artificial insemination by spouse or donor, the development of sperm banks, storage of frozen sperm (cryopreservation), the development of artificial wombs, techniques for predetermining the sex of a fetus, and nursery environments to maintain a fetus removed from the womb in the 1st trimester. In recent years, the demand for these services has increased because of higher infertility and the drop in the number of babies available for adoption. Surrogacy is especially controversial: it has become a symbol of the dehumanization of modern life and the exploitation of women. The feminist perspective discloses how patriarchal values about the subordinate status of women, about the nature of motherhood, infertility, and the family are both implicit and explicit in prevailing thinking about reproduction. The new technology offers women who wish to remain unmarried the opportunity to have a family, and it enables lesbian women to bear children. The research literature favors a Eurocentric nuclear family without any awareness that in Canada, and in the Western world, new forms of family life have been evolving as couples marry, divorce, and remarry. There is no awareness either that in other cultures this Eurocentric nuclear model is dysfunctional. Because of the rigid notion of the 2-parent nuclear family, the 3rd parties who are involved in either surrogate relationships or artificial insemination are deprecated. The feminist literature is more critical of the nuclear family, but it has been sometimes inconsistent on the relevant issues.

  20. Expression of the GM2 activator protein in mouse testis.

    PubMed

    Li, Yu-Teh; Li, Su-Chen; Chen, I-Li

    2017-12-01

    The GM2-activator protein (GM2-AP), revealed by Li et al. in 1973 in human liver, was initially identified as a protein cofactor that stimulated β-hexosaminidase A to hydrolyze N-acetylgalactosamine from GM2 ganglioside. This cofactor was found to be missing in human variant AB Tay-Sachs disease. Over the years, the GM2-AP has also been shown to be involved in kidney vesicular transport, lipid presentation by CD1 molecule to T-cells, and interaction of human sperm with zona pellucida. Since the expression of the GM2-AP via mRNA detection in mouse tissues was found to be the highest in testis, we became interested in the localization of the GM2-AP at cellular level in mouse testis during spermatogenesis. Using immunohistochemical analysis and electron microscopy, we found that the GM2-AP was predominantly localized in the basal cytoplasm and the attenuated processes of Sertoli cells. The stained structure appeared to be lysosomes. The most interesting finding was the association of the GM2-AP with the acrosomal apparatus in early spermatids. A modest to intense staining was observed in some acrosomal granules and acrosomal caps. The GM2-AP seemed to disappear from acrosomal caps in the later stage of spermatids, in which the nucleus became elongated and condensed. These results suggest that the GM2-AP may be involved in the normal functions of Sertoli cells and play important roles during the development of acrosomal caps in the early spermatids. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  1. A Novel Mechanism for Desulfation of Mucin: Identification and Cloning of a Mucin-Desulfating Glycosidase (Sulfoglycosidase) from Prevotella Strain RS2

    PubMed Central

    Rho, Jung-hyun; Wright, Damian P.; Christie, David L.; Clinch, Keith; Furneaux, Richard H.; Roberton, Anthony M.

    2005-01-01

    A novel enzyme which may be important in mucin degradation has been discovered in the mucin-utilizing anaerobe Prevotella strain RS2. This enzyme cleaves terminal 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sulfate (6-SO3-GlcNAc) residues from sulfomucin and from the model substrate 4-nitrophenyl 2-acetamido-2-deoxy-β-d-glucopyranoside 6-sodium sulfate. The existence of this mucin-desulfating glycosidase (sulfoglycosidase) suggests an alternative mechanism by which this bacterium may desulfate sulfomucins, by glycosidic removal of a sulfated sugar from mucin oligosaccharide chains. Previously, mucin desulfation was thought to take place by the action of a specific desulfating enzyme, which then allowed glycosidases to remove desulfated sugar. Sulfate removal from sulfomucins is thought to be a rate-limiting step in mucin degradation by bacteria in the regions of the digestive tract with a significant bacterial flora. The sulfoglycosidase was induced by growth of the Prevotella strain on mucin and was purified 284-fold from periplasmic extracts. Tryptic digestion and sequencing of peptides from the 100-kDa protein enabled the sulfoglycosidase gene to be cloned and sequenced. Active recombinant enzyme was made in an Escherichia coli expression system. The sulfoglycosidase shows sequence similarity to hexosaminidases. The only other enzyme that has been shown to remove 6-SO3-GlcNAc from glycoside substrates is the human lysosomal enzyme β-N-acetylhexosaminidase A, point mutations in which cause the inheritable, lysosomal storage disorder Tay-Sachs disease. The human enzyme removes GlcNAc from glycoside substrates also, in contrast to the Prevotella enzyme, which acts on a nonsulfated substrate at a rate that is only 1% of the rate observed with a sulfated substrate. PMID:15716424

  2. Environmental sex determination mechanisms in reptiles.

    PubMed

    Merchant-Larios, H; Díaz-Hernández, V

    2013-01-01

    Temperature-dependent sex determination (TSD) was first discovered in reptiles. Since then, a great diversity of sex-determining responses to temperature has been reported. Higher temperatures can produce either males or females, and the temperature ranges and lengths of exposure that influence TSD are remarkably variable among species. In addition, transitory gene regulatory networks leading to gonadal TSD have evolved. Although most genes involved in gonadal development are conserved in vertebrates, including TSD species, temporal and spatial gene expression patterns vary among species. Despite variation in TSD pattern and gene expression heterochrony, the structural framework, the medullary cords, and cortex of the bipotential gonad have been strongly conserved. Aromatase (CYP19), which regulates gonadal estrogen levels, is proposed to be the main target of a putative thermosensitive factor for TSD. However, manipulation of estrogen levels rarely mimics the precise timing of temperature effects on expression of gonadal genes, as occurs with TSD. Estrogen levels may influence sex determination or gonad differentiation depending on the species. Furthermore, the process leading to sex determination under the influence of temperature poses problems that are not encountered by species with genetic sex determination. Yolk steroids of maternal origin and steroids produced by the embryonic nervous system should also be considered as sources of hormones that may play a role in TSD. Copyright © 2012 S. Karger AG, Basel.

  3. Climate change overruns resilience conferred by temperature-dependent sex determination in sea turtles and threatens their survival.

    PubMed

    Santidrián Tomillo, Pilar; Genovart, Meritxell; Paladino, Frank V; Spotila, James R; Oro, Daniel

    2015-08-01

    Temperature-dependent sex determination (TSD) is the predominant form of environmental sex determination (ESD) in reptiles, but the adaptive significance of TSD in this group remains unclear. Additionally, the viability of species with TSD may be compromised as climate gets warmer. We simulated population responses in a turtle with TSD to increasing nest temperatures and compared the results to those of a virtual population with genotypic sex determination (GSD) and fixed sex ratios. Then, we assessed the effectiveness of TSD as a mechanism to maintain populations under climate change scenarios. TSD populations were more resilient to increased nest temperatures and mitigated the negative effects of high temperatures by increasing production of female offspring and therefore, future fecundity. That buffered the negative effect of temperature on the population growth. TSD provides an evolutionary advantage to sea turtles. However, this mechanism was only effective over a range of temperatures and will become inefficient as temperatures rise to levels projected by current climate change models. Projected global warming threatens survival of sea turtles, and the IPCC high gas concentration scenario may result in extirpation of the studied population in 50 years. © 2015 John Wiley & Sons Ltd.

  4. Animal models of GM2 gangliosidosis: utility and limitations

    PubMed Central

    Lawson, Cheryl A; Martin, Douglas R

    2016-01-01

    GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, β-N-acetylhexosaminidase, and includes the closely related Tay–Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay–Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described. PMID:27499644

  5. Updated tomographic analysis of the integrated Sachs-Wolfe effect and implications for dark energy

    NASA Astrophysics Data System (ADS)

    Stölzner, Benjamin; Cuoco, Alessandro; Lesgourgues, Julien; Bilicki, Maciej

    2018-03-01

    We derive updated constraints on the integrated Sachs-Wolfe (ISW) effect through cross-correlation of the cosmic microwave background with galaxy surveys. We improve with respect to similar previous analyses in several ways. First, we use the most recent versions of extragalactic object catalogs, SDSS DR12 photometric redshift (photo-z ) and 2MASS Photo-z data sets, as well as those employed earlier for ISW, SDSS QSO photo-z and NVSS samples. Second, we use for the first time the WISE × SuperCOSMOS catalog, which allows us to perform an all-sky analysis of the ISW up to z ˜0.4 . Third, thanks to the use of photo-z s , we separate each data set into different redshift bins, deriving the cross-correlation in each bin. This last step leads to a significant improvement in sensitivity. We remove cross-correlation between catalogs using masks which mutually exclude common regions of the sky. We use two methods to quantify the significance of the ISW effect. In the first one, we fix the cosmological model, derive linear galaxy biases of the catalogs, and then evaluate the significance of the ISW using a single parameter. In the second approach we perform a global fit of the ISW and of the galaxy biases varying the cosmological model. We find significances of the ISW in the range 4.7 - 5.0 σ thus reaching, for the first time in such an analysis, the threshold of 5 σ . Without the redshift tomography we find a significance of ˜4.0 σ , which shows the importance of the binning method. Finally we use the ISW data to infer constraints on the dark energy redshift evolution and equation of state. We find that the redshift range covered by the catalogs is still not optimal to derive strong constraints, although this goal will be likely reached using future datasets such as from Euclid, LSST, and SKA.

  6. 76 FR 4659 - Science Advisory Board Staff Office; Notification of a Public Teleconference of the Science...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-26

    ...://yosemite.epa.gov/sab/ sabproduct.nsf/fedrgstr--activities/ FL%20Estuaries%20TSD?OpenDocument'' should read ``http:// yosemite.epa.gov/sab/sabproduct.nsf/fedrgstr--activites/ FL%20Estuaries%20TSD?OpenDocument.'' 2.../sabproduct.nsf/fedrgstr--activities/ FL%20Estuaries%20TSD?OpenDocument'' should read ``http:// yosemite.epa...

  7. Free recall of word lists under total sleep deprivation and after recovery sleep.

    PubMed

    de Almeida Valverde Zanini, Gislaine; Tufik, Sérgio; Andersen, Monica Levy; da Silva, Raquel Cristina Martins; Bueno, Orlando Francisco Amodeo; Rodrigues, Camila Cruz; Pompéia, Sabine

    2012-02-01

    One task that has been used to assess memory effects of prior total sleep deprivation (TSD) is the immediate free recall of word lists; however, results have been mixed. A possible explanation for this is task impurity, since recall of words from different serial positions reflects use of distinct types of memory (last words: short-term memory; first and intermediate words: episodic memory). Here we studied the effects of 2 nights of TSD on immediate free recall of semantically unrelated word lists considering the serial position curve. Random allocation to a 2-night TSD protocol followed by one night of recovery sleep or to a control group. Study conducted under continuous behavioral monitoring. 24 young, healthy male volunteers. 2 nights of total sleep deprivation (TSD) and one night of recovery sleep. Participants were shown five 15 unrelated word-lists at baseline, after one and 2 nights of TSD, and after one night of recovery sleep. We also investigated the development of recall strategies (learning) and susceptibility to interference from previous lists. No free recall impairment occurred during TSD, irrespective of serial position. Interference was unchanged. Both groups developed recall strategies, but task learning occurred earlier in controls and was evident in the TSD group only after sleep recovery. Prior TSD spared episodic memory, short-term phonological memory, and interference, allowed the development of recall strategies, but may have decreased the advantage of using these strategies, which returned to normal after recovery sleep.

  8. Trinary signed-digit arithmetic using an efficient encoding scheme

    NASA Astrophysics Data System (ADS)

    Salim, W. Y.; Alam, M. S.; Fyath, R. S.; Ali, S. A.

    2000-09-01

    The trinary signed-digit (TSD) number system is of interest for ultrafast optoelectronic computing systems since it permits parallel carry-free addition and borrow-free subtraction of two arbitrary length numbers in constant time. In this paper, a simple coding scheme is proposed to encode the decimal number directly into the TSD form. The coding scheme enables one to perform parallel one-step TSD arithmetic operation. The proposed coding scheme uses only a 5-combination coding table instead of the 625-combination table reported recently for recoded TSD arithmetic technique.

  9. One-step trinary signed-digit arithmetic using an efficient encoding scheme

    NASA Astrophysics Data System (ADS)

    Salim, W. Y.; Fyath, R. S.; Ali, S. A.; Alam, Mohammad S.

    2000-11-01

    The trinary signed-digit (TSD) number system is of interest for ultra fast optoelectronic computing systems since it permits parallel carry-free addition and borrow-free subtraction of two arbitrary length numbers in constant time. In this paper, a simple coding scheme is proposed to encode the decimal number directly into the TSD form. The coding scheme enables one to perform parallel one-step TSD arithmetic operation. The proposed coding scheme uses only a 5-combination coding table instead of the 625-combination table reported recently for recoded TSD arithmetic technique.

  10. The Prefrontal Model Revisited: Double Dissociations Between Young Sleep Deprived and Elderly Subjects on Cognitive Components of Performance

    PubMed Central

    Tucker, Adrienne M.; Stern, Yaakov; Basner, Robert C.; Rakitin, Brian C.

    2011-01-01

    Study Objectives: The prefrontal model suggests that total sleep deprivation (TSD) and healthy aging produce parallel cognitive deficits. Here we decompose global performance on two common tasks into component measures of specific cognitive processes to pinpoint the source of impairments in elderly and young TSD participants relative to young controls and to each other. Setting: The delayed letter recognition task (DLR) was performed in 3 studies. The psychomotor vigilance task (PVT) was performed in 1 of the DLR studies and 2 additional studies. Subjects: For DLR, young TSD (n = 20, age = 24.60 ± 0.62 years) and young control (n = 17, age = 24.00 ± 2.42); elderly (n = 26, age = 69.92 ± 1.06). For the PVT, young TSD (n = 18, age = 26.65 ± 4.57) and young control (n = 16, age = 25.19 ± 2.90); elderly (n = 21, age = 71.1 ± 4.92). Measurements and Results: Both elderly and young TSD subjects displayed impaired reaction time (RT), our measure of global performance, on both tasks relative to young controls. After decomposing global performance on the DLR, however, a double dissociation was observed as working memory scanning speed was impaired only in elderly subjects while other components of performance were impaired only by TSD. Similarly, for the PVT a second double dissociation was observed as vigilance impairments were present only in TSD while short-term response preparation effects were altered only in the elderly. Conclusions: The similarity between TSD and the elderly in impaired performance was evident only when examining global RT. In contrast, when specific cognitive components were examined double dissociations were observed between TSD and elderly subjects. This demonstrates the heterogeneity in those cognitive processes impaired in TSD versus the elderly. Citation: Tucker AM; Stern Y; Basner RC; Rakitin BC. The prefrontal model revisited: double dissociations between young sleep deprived and elderly subjects on cognitive components of performance

  11. Transcriptomic responses to environmental temperature by turtles with temperature-dependent and genotypic sex determination assessed by RNAseq inform the genetic architecture of embryonic gonadal development.

    PubMed

    Radhakrishnan, Srihari; Literman, Robert; Neuwald, Jennifer; Severin, Andrew; Valenzuela, Nicole

    2017-01-01

    Vertebrate sexual fate is decided primarily by the individual's genotype (GSD), by the environmental temperature during development (TSD), or both. Turtles exhibit TSD and GSD, making them ideal to study the evolution of sex determination. Here we analyze temperature-specific gonadal transcriptomes (RNA-sequencing validated by qPCR) of painted turtles (Chrysemys picta TSD) before and during the thermosensitive period, and at equivalent stages in soft-shell turtles (Apalone spinifera-GSD), to test whether TSD's and GSD's transcriptional circuitry is identical but deployed differently between mechanisms. Our data show that most elements of the mammalian urogenital network are active during turtle gonadogenesis, but their transcription is generally more thermoresponsive in TSD than GSD, and concordant with their sex-specific function in mammals [e.g., upregulation of Amh, Ar, Esr1, Fog2, Gata4, Igf1r, Insr, and Lhx9 at male-producing temperature, and of β-catenin, Foxl2, Aromatase (Cyp19a1), Fst, Nf-kb, Crabp2 at female-producing temperature in Chrysemys]. Notably, antagonistic elements in gonadogenesis (e.g., β-catenin and Insr) were thermosensitive only in TSD early-embryos. Cirbp showed warm-temperature upregulation in both turtles disputing its purported key TSD role. Genes that may convert thermal inputs into sex-specific development (e.g., signaling and hormonal pathways, RNA-binding and heat-shock) were differentially regulated. Jak-Stat, Nf-κB, retinoic-acid, Wnt, and Mapk-signaling (not Akt and Ras-signaling) potentially mediate TSD thermosensitivity. Numerous species-specific ncRNAs (including Xist) were differentially-expressed, mostly upregulated at colder temperatures, as were unannotated loci that constitute novel TSD candidates. Cirbp showed warm-temperature upregulation in both turtles. Consistent transcription between turtles and alligator revealed putatively-critical reptilian TSD elements for male (Sf1, Amh, Amhr2) and female (Crabp2 and Hspb1

  12. A new species of the genus Theloderma Tschudi, 1838 (Amphibia: Anura: Rhacophoridae) from Tay Nguyen Plateau, central Vietnam.

    PubMed

    Poyarkov, Nikolay A; Kropachev, Ivan I; Gogoleva, Svetlana S; Orlov, Nikolai L

    2018-04-20

    A new species of small tree frog from a primary montane tropical forest of central Vietnam, Tay Nguyen Plateau, is described based on morphological, molecular, and acoustic evidence. The Golden Bug-Eyed Frog, Theloderma auratum sp. nov., is distinguishable from its congeners and other small rhacophorid species based on a combination of the following morphological attributes: (1) bony ridges on head absent; (2) smooth skin completely lacking calcified warts or asperities; (3) pointed elongated tapering snout; (4) vocal opening in males absent; (5) vomerine teeth absent; (6) males of small body size (SVL 21.8-26.4 mm); (7) head longer than wide; ED/SVL ratio 13%-15%; ESL/SVL ratio 16%-20%; (8) small tympanum (TD/EL ratio 50%-60%) with few tiny tubercles; (9) supratympanic fold absent; (10) ventral surfaces completely smooth; (11) webbing between fingers absent; (12) outer and inner metacarpal tubercles present, supernumerary metacarpal tubercle single, medial, oval in shape; (13) toes half-webbed: I 2-2¼ II 1½-2¾ III 2-3¼ IV 3-1½ V; (14) inner metatarsal tubercle present, oval; outer metatarsal tubercle absent; (15) iris bicolored; (16) dorsal surfaces golden-yellow with sparse golden-orange speckling or reticulations and few small dark-brown spots; (17) lateral sides of head and body with wide dark reddish-brown to black lateral stripes, clearly separated from lighter dorsal coloration by straight contrasting edge; (18) ventral surfaces of body, throat, and chest greyish-blue with indistinct brown confluent blotches; (19) upper eyelids with few (3-5) very small flat reddish superciliary tubercles; (20) limbs dorsally reddish-brown, ventrally brown with small bluish-white speckles. The new species is also distinct from all congeners in 12S rRNA to 16S rRNA mitochondrial DNA fragment sequences (uncorrected genetic distance P>8.9%). Advertisement call and tadpole morphology of the new species are described. Our molecular data showed Theloderma auratum sp. nov. to

  13. Sex determination, longevity, and the birth and death of reptilian species.

    PubMed

    Sabath, Niv; Itescu, Yuval; Feldman, Anat; Meiri, Shai; Mayrose, Itay; Valenzuela, Nicole

    2016-08-01

    Vertebrate sex-determining mechanisms (SDMs) are triggered by the genotype (GSD), by temperature (TSD), or occasionally, by both. The causes and consequences of SDM diversity remain enigmatic. Theory predicts SDM effects on species diversification, and life-span effects on SDM evolutionary turnover. Yet, evidence is conflicting in clades with labile SDMs, such as reptiles. Here, we investigate whether SDM is associated with diversification in turtles and lizards, and whether alterative factors, such as lifespan's effect on transition rates, could explain the relative prevalence of SDMs in turtles and lizards (including and excluding snakes). We assembled a comprehensive dataset of SDM states for squamates and turtles and leveraged large phylogenies for these two groups. We found no evidence that SDMs affect turtle, squamate, or lizard diversification. However, SDM transition rates differ between groups. In lizards TSD-to-GSD surpass GSD-to-TSD transitions, explaining the predominance of GSD lizards in nature. SDM transitions are fewer in turtles and the rates are similar to each other (TSD-to-GSD equals GSD-to-TSD), which, coupled with TSD ancestry, could explain TSD's predominance in turtles. These contrasting patterns can be explained by differences in life history. Namely, our data support the notion that in general, shorter lizard lifespan renders TSD detrimental favoring GSD evolution in squamates, whereas turtle longevity permits TSD retention. Thus, based on the macro-evolutionary evidence we uncovered, we hypothesize that turtles and lizards followed different evolutionary trajectories with respect to SDM, likely mediated by differences in lifespan. Combined, our findings revealed a complex evolutionary interplay between SDMs and life histories that warrants further research that should make use of expanded datasets on unexamined taxa to enable more conclusive analyses.

  14. Abnormal neural activity of brain regions in treatment-resistant and treatment-sensitive major depressive disorder: a resting-state fMRI study.

    PubMed

    Guo, Wen-bin; Liu, Feng; Chen, Jin-dong; Gao, Keming; Xue, Zhi-min; Xu, Xi-jia; Wu, Ren-rong; Tan, Chang-lian; Sun, Xue-li; Liu, Zhe-ning; Chen, Hua-fu; Zhao, Jing-ping

    2012-10-01

    Patients with treatment-resistant depression (TRD) and those with treatment-sensitive depression (TSD) responded to antidepressants differently. Previous studies have commonly shown that patients with TRD or TSD had abnormal neural activity in different brain regions. In the present study, we used a coherence-based ReHo (Cohe-ReHo) approach to test the hypothesis that patients with TRD or TSD had abnormal neural activity in different brain regions. Twenty-three patients with TRD, 22 with TSD, and 19 healthy subjects (HS) matched with gender, age, and education level participated in the study. ANOVA analysis revealed widespread differences in Cohe-ReHo values among the three groups in different brain regions which included bilateral superior frontal gyrus, bilateral cerebellum, left inferior temporal gyrus, left occipital cortex, and both sides of fusiform gyrus. Compared to HS, lower Cohe-ReHo values were observed in TRD group in bilateral superior frontal gyrus and left cerebellum; in contrast, in TSD group, lower Cohe-ReHo values were mainly found in bilateral superior frontal gyrus. Compared to TSD group, TRD group had lower Cohe-ReHo in bilateral cerebellum and higher Cohe-ReHo in left fusiform gyrus. There was a negative correlation between Cohe-ReHo values of the left fusiform gyrus and illness duration in the pooled patients (r = 0.480, p = 0.001). The sensitivity and specificity of cerebellar Cohe-ReHo values differentiating TRD from TSD were 83% and 86%, respectively. Compared to healthy controls, both TRD and TSD patients shared the majority of brain regions with abnormal neural activity. However, the lower Cohe-ReHo values in the cerebellum might be as a marker to differentiate TRD from TSD with high sensitivity and specificity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Cloning and expression in Escherichia coli of Vibrio parahaemolyticus thermostable direct hemolysin and thermolabile hemolysin genes.

    PubMed

    Taniguchi, H; Ohta, H; Ogawa, M; Mizuguchi, Y

    1985-05-01

    Two hemolysin genes of Vibrio parahaemolyticus WP1, a thermostable direct (TSD) hemolysin gene and a thermolabile hemolysin gene, were cloned into the pBR322 vector in Escherichia coli K-12 C600. A large amount of the TSD hemolysin produced in E. coli K-12 accumulated in the periplasmic space. The TSD hemolysin gene was localized on a 0.9-kilobase HindIII-BamHI fragment by identifying qualitatively the production of the TSD hemolysin by a reverse passive hemagglutination assay in the osmotic shock fluid. The thermolabile hemolysin gene was isolated on a 1.3-kilobase HindIII-PstI fragment by selection with the hemolysin on blood agar. Southern blot hybridization and colony hybridization experiments indicated that the TSD hemolysin gene was present in the chromosomal DNA of 15 Kanagawa phenomenon-positive strains but not in 14 negative strains, whereas the thermolabile hemolysin gene was detected in all strains. No homologous DNA sequences to TSD and thermolabile hemolysin genes were detected in the chromosomes of Vibrio cholerae, Vibrio vulnificus, non-O1 V. cholerae, and Vibrio anguillarum.

  16. Enhancement of solubility and oral bioavailability of manidipine by formation of ternary solid dispersion with d-α-tocopherol polyethylene glycol 1000 succinate and copovidone.

    PubMed

    Chamsai, Benchawan; Limmatvapirat, Sontaya; Sungthongjeen, Srisagul; Sriamornsak, Pornsak

    2017-12-01

    Low bioavailability of oral manidipine (MDP) is due to its low water solubility. The objective of this study was to increase the solubility and bioavailability of MDP by fabricating ternary solid dispersion (tSD) with d-α-tocopherol polyethyleneglycol-1000-succinate and copovidone. In this study, solid ternary phase diagram was applied in order to check the homogeneity of tSD prepared by melting and solidifying with dry ice. The physicochemical properties of different formulations were determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and hot stage microscopy. Their solubility, dissolution, stability and bioavailability were also investigated. The results demonstrated that tSD obtained from ternary phase diagram divided into homogeneous and non-homogeneous regions. In the homogenous region, the transparent characteristics of tSD was observed and considered as a glass solution, which have a higher MDP solubility than that in non-homogenous region. The hot stage microscopy, DSC and PXRD confirmed that solid dispersion was formed in which MDP was molecularly dispersed in the carriers, especially in the homogenous region of phase diagram. FTIR analysis demonstrated strong hydrogen bonding between amine groups of MDP and carbonyl groups of copovidone, which supported a higher solubility and dissolution of tSD. The pharmacokinetic study in Wistar rats showed that the tSD had the greatest effect on oral bioavailability. Immediate hypotensive effect of tSD was also observed in vivo. The improvement of stability, dissolution and oral bioavailability of MDP could be achieved by using tSD technique.

  17. 78 FR 17075 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... certain Rolls-Royce Deutschland Ltd & Co KG (RRD) Tay 611-8 turbofan engines. This AD requires inspection... (RRD) Tay 611-8 turbofan engines, serial numbers 16245, 16256, 16417, 16418, 16584, 16585, 16639, 16640...

  18. Therapeutic self-disclosure in integrative psychotherapy: When is this a clinical error?

    PubMed

    Ziv-Beiman, Sharon; Shahar, Golan

    2016-09-01

    Ascending to prominence in virtually all forms of psychotherapy, therapist self-disclosure (TSD) has recently been identified as a primarily integrative intervention (Ziv-Beiman, 2013). In the present article, we discuss various instances in which using TSD in integrative psychotherapy might constitute a clinical error. First, we briefly review extant theory and empirical research on TSD, followed by our preferred version of integrative psychotherapy (i.e., a version of Wachtel's Cyclical Psychodynamics [Wachtel, 1977, 1997, 2014]), which we title cognitive existential psychodynamics. Next, we provide and discuss three examples in which implementing TSD constitutes a clinical error. In essence, we submit that using TSD constitutes an error when patients, constrained by their representational structures (object relations), experience the subjectivity of the other as impinging, and thus propels them to "react" instead of "emerge." (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  19. Clinical and Epidemiological Correlates of Task-Specific Dystonia in a Large Cohort of Brazilian Music Players.

    PubMed

    Moura, Rita C; de Carvalho Aguiar, Patrícia Maria; Bortz, Graziela; Ferraz, Henrique Ballalai

    2017-01-01

    Musician's dystonia is a task-specific dystonia (TSD) worldwide disabling disorder, and most of the affected individuals may have severe difficulty to play their instrument. Many professional music players may have to quit working as a player. The objective of the present study was to evaluate the clinical characteristics and frequency of TSD in Brazilian music players and to promote awareness of this condition among musicians. We visited orchestras and music schools delivering lectures on TSD and about the scope of our survey. Musicians were invited to answer a questionnaire, and those with possible neurological dysfunction associated with musical performance were recorded by video while playing the instrument. We visited 51 orchestras and music schools in 19 Brazilian cities between March 2013 and March 2015. We collected 2,232 questionnaires, and 72 subjects with suspicion of dystonia were video recorded during specific tasks and evaluated regarding motor impairment. Forty-nine individuals (2.2%) were diagnosed as having TSD (mean age 36.4 years; 92% male). The instruments most associated with TSD were acoustic guitar (36.7%) and brass instruments (30.6%). We concluded that Brazilian TSD music players are mainly male, classical music professionals, around 30 years of age, with arms, hands, or oromandibular muscles affected. TSD is a neurological condition that can impair musical performance and should receive more attention from musicians, teachers, and health professionals.

  20. 78 FR 35574 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... airworthiness directive (AD) for all Rolls-Royce Deutschland Ltd & Co KG (RRD) model Tay 650-15 turbofan engines... Compliance We estimate that this proposed AD affects 52 Tay turbofan engines installed on airplanes of U.S...

  1. (S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa

    PubMed Central

    Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

    2012-01-01

    α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5′-triphosphate (ATP) levels, 3′-5′-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH. PMID:22916194

  2. (S)-α-chlorohydrin inhibits protein tyrosine phosphorylation through blocking cyclic AMP - protein kinase A pathway in spermatozoa.

    PubMed

    Zhang, Hao; Yu, Huan; Wang, Xia; Zheng, Weiwei; Yang, Bei; Pi, Jingbo; He, Gengsheng; Qu, Weidong

    2012-01-01

    α-Chlorohydrin is a common contaminant in food. Its (S)-isomer, (S)-α-chlorohydrin (SACH), is known for causing infertility in animals by inhibiting glycolysis of spermatozoa. The aim of present work was to examine the relationship between SACH and protein tyrosine phosphorylation (PTP), which plays a critical role in regulating mammalian sperm capacitation. In vitro exposure of SACH 50 µM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate dehydrogenase (GAPDS) activities, the intracellular adenosine 5'-triphosphate (ATP) levels, 3'-5'-cyclic adenosine monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished dramatically, indicating that both glycolysis and the cAMP/PKA signaling pathway were impaired by SACH. The inhibition of both PTP and phosphorylation of PKA substrates by SACH could be restored by addition of cAMP analog dibutyryl-cAMP (dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected glycolysis, ATP levels, phosphorylation of PKA substrates and PTP against the influence of SACH. These results suggested SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility associated with SACH.

  3. Total Sleep Deprivation and Recovery Sleep Affect the Diurnal Variation of Agility Performance: The Gender Differences.

    PubMed

    Romdhani, Mohamed; Hammouda, Omar; Smari, Khawla; Chaabouni, Yassine; Mahdouani, Kacem; Driss, Tarak; Souissi, Nizar

    2018-05-30

    Romdhani, M, Hammouda, O, Smari, K, Chaabouni, Y, Mahdouani, K, Driss, T, and Souissi, N. Total sleep deprivation and recovery sleep affect the diurnal variation of agility performance: The gender differences. J Strength Cond Res XX(X): 000-000, 2018-This study aimed to investigate the effects of time-of-day, 24 and 36 hours of total sleep deprivation (TSD), and recovery sleep (RS) on repeated-agility performances. Twenty-two physical education students (11 male and 11 female students) completed 5 repeated modified agility T-test (RMAT) sessions (i.e., 2 after normal sleep night [NSN] [at 07:00 and 17:00 hours], 2 after TSD [at 07:00 hours, i.e., 24-hour TSD and at 17:00 hours, i.e., 36-hour TSD], and 1 after RS at 17:00 hours). The RMAT index decreased from the morning to the afternoon after NSN (p < 0.05, d = 1.05; p < 0.01, d = 0.73) and after TSD (p < 0.001, d = 0.92; d = 1.08), respectively, for total time (TT) and peak time (PT). This finding indicates a diurnal variation in repeated agility, which persisted after TSD. However, the diurnal increase in PT was less marked in the female group after NSN (2.98 vs. 6.24%). Moreover, TT and PT increased, respectively, after 24-hour TSD (p < 0.001; d = 0.84, d = 0.87) and 36-hour TSD (p < 0.001, d = 1.12; p < 0.01, d = 0.65). Female participants' PT was less affected by 24-hour TSD (1.76 vs. 6.81%) compared with male participants' PT. After 36-hour TSD, the amount of decrease was not different between groups, which increased the diurnal amplitude of PT only for male participants. Total sleep deprivation suppressed the diurnal increase of PT and increased the diurnal amplitude of oral temperature only in women. Nevertheless, RS normalized the sleep-loss-induced performance disruption. Conclusively, sleep loss and RS differently affect repeated-agility performance of men and women during the day. Sleep extension postdeprivation could have potent restorative effect on repeated-agility performances, and female

  4. 77 FR 74123 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-13

    ... Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... Rolls-Royce Deutschland Ltd & Co KG (RRD) models Tay 620-15 and Tay 650-15 turbofan engines. This... proposing this AD to prevent failure of the LPC rotor disc assembly, uncontained engine failure, and damage...

  5. Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder.

    PubMed

    He, Zongling; Cui, Qian; Zheng, Junjie; Duan, Xujun; Pang, Yajing; Gao, Qing; Han, Shaoqiang; Long, Zhiliang; Wang, Yifeng; Li, Jiao; Wang, Xiao; Zhao, Jingping; Chen, Huafu

    2016-11-01

    Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Functional brain imaging of a complex navigation task following one night of total sleep deprivation

    NASA Technical Reports Server (NTRS)

    Strangman, Gary; Thompson, John H.; Strauss, Monica M.; Marshburn, Thomas H.; Sutton, Jeffrey P.

    2006-01-01

    Study Objectives: To assess the cerebral effects associated with sleep deprivation in a simulation of a complex, real-world, high-risk task. Design and Interventions: A two-week, repeated measures, cross-over experimental protocol, with counterbalanced orders of normal sleep (NS) and total sleep deprivation (TSD). Setting: Each subject underwent functional magnetic resonance imaging (fMRI) while performing a dual-joystick, 3D sensorimotor navigation task (simulated orbital docking). Scanning was performed twice per subject, once following a night of normal sleep (NS), and once following a single night of total sleep deprivation (TSD). Five runs (eight 24s docking trials each) were performed during each scanning session. Participants: Six healthy, young, right-handed volunteers (2 women; mean age 20) participated. Measurements and Results: Behavioral performance on multiple measures was comparable in the two sleep conditions. Neuroimaging results within sleep conditions revealed similar locations of peak activity for NS and TSD, including left sensorimotor cortex, left precuneus (BA 7), and right visual areas (BA 18/19). However, cerebral activation following TSD was substantially larger and exhibited higher amplitude modulations from baseline. When directly comparing NS and TSD, most regions exhibited TSD>NS activity, including multiple prefrontal cortical areas (BA 8/9,44/45,47), lateral parieto-occipital areas (BA 19/39, 40), superior temporal cortex (BA 22), and bilateral thalamus and amygdala. Only left parietal cortex (BA 7) demonstrated NS>TSD activity. Conclusions: The large network of cerebral differences between the two conditions, even with comparable behavioral performance, suggests the possibility of detecting TSD-induced stress via functional brain imaging techniques on complex tasks before stress-induced failures.

  7. Providing Total Quality Fundamentals: 1995 Workshops for the NASA Lewis Research Center's Technical Services Directorate

    NASA Technical Reports Server (NTRS)

    Antczak, Paul; Jacinto,Gilda; Simek, Jimmy

    1997-01-01

    The National Aeronautics and Space Administration's (NASA) agency-wide movement to cultivate a quality workplace is the basis for Lewis Research Center to implement Total Quality Fundamentals (TQF) initiatives. The Lewis Technical Services Directorate (TSD) introduced the Total Quality Fundamentals (TQF) workshops to its work force as an opportunity to introduce the concepts and principles of TQF. These workshops also provided the participants with the opportunity to dialogue with fellow TSD employees and managers. This report describes, through the perspective of the Lewis TSD TQF Coaches, how the TQF work- shop process was accomplished in TSD. It describes the structure for addressing the need, implementation process, input the TSD Coaches provided, common themes and concerns raised, conclusions, and recommendations. The Coaches concluded that these types of workshops could be the key to open the communication channels that are necessary to help everyone at Lewis understand where they fit in the organization. TQF workshops can strengthen the participant's connection with the Mission, Vision of the Center, and Vision of the Agency. Reconunendations are given based on these conclusions that can help the TSD Quality Board develop attainable measures towards a quality workplace.

  8. Transcriptomic responses to environmental temperature by turtles with temperature-dependent and genotypic sex determination assessed by RNAseq inform the genetic architecture of embryonic gonadal development

    PubMed Central

    Radhakrishnan, Srihari; Literman, Robert; Neuwald, Jennifer; Severin, Andrew

    2017-01-01

    Vertebrate sexual fate is decided primarily by the individual’s genotype (GSD), by the environmental temperature during development (TSD), or both. Turtles exhibit TSD and GSD, making them ideal to study the evolution of sex determination. Here we analyze temperature-specific gonadal transcriptomes (RNA-sequencing validated by qPCR) of painted turtles (Chrysemys picta TSD) before and during the thermosensitive period, and at equivalent stages in soft-shell turtles (Apalone spinifera—GSD), to test whether TSD’s and GSD’s transcriptional circuitry is identical but deployed differently between mechanisms. Our data show that most elements of the mammalian urogenital network are active during turtle gonadogenesis, but their transcription is generally more thermoresponsive in TSD than GSD, and concordant with their sex-specific function in mammals [e.g., upregulation of Amh, Ar, Esr1, Fog2, Gata4, Igf1r, Insr, and Lhx9 at male-producing temperature, and of β-catenin, Foxl2, Aromatase (Cyp19a1), Fst, Nf-kb, Crabp2 at female-producing temperature in Chrysemys]. Notably, antagonistic elements in gonadogenesis (e.g., β-catenin and Insr) were thermosensitive only in TSD early-embryos. Cirbp showed warm-temperature upregulation in both turtles disputing its purported key TSD role. Genes that may convert thermal inputs into sex-specific development (e.g., signaling and hormonal pathways, RNA-binding and heat-shock) were differentially regulated. Jak-Stat, Nf-κB, retinoic-acid, Wnt, and Mapk-signaling (not Akt and Ras-signaling) potentially mediate TSD thermosensitivity. Numerous species-specific ncRNAs (including Xist) were differentially-expressed, mostly upregulated at colder temperatures, as were unannotated loci that constitute novel TSD candidates. Cirbp showed warm-temperature upregulation in both turtles. Consistent transcription between turtles and alligator revealed putatively-critical reptilian TSD elements for male (Sf1, Amh, Amhr2) and female (Crabp2 and

  9. Clinical and Epidemiological Correlates of Task-Specific Dystonia in a Large Cohort of Brazilian Music Players

    PubMed Central

    Moura, Rita C.; de Carvalho Aguiar, Patrícia Maria; Bortz, Graziela; Ferraz, Henrique Ballalai

    2017-01-01

    Musician’s dystonia is a task-specific dystonia (TSD) worldwide disabling disorder, and most of the affected individuals may have severe difficulty to play their instrument. Many professional music players may have to quit working as a player. The objective of the present study was to evaluate the clinical characteristics and frequency of TSD in Brazilian music players and to promote awareness of this condition among musicians. We visited orchestras and music schools delivering lectures on TSD and about the scope of our survey. Musicians were invited to answer a questionnaire, and those with possible neurological dysfunction associated with musical performance were recorded by video while playing the instrument. We visited 51 orchestras and music schools in 19 Brazilian cities between March 2013 and March 2015. We collected 2,232 questionnaires, and 72 subjects with suspicion of dystonia were video recorded during specific tasks and evaluated regarding motor impairment. Forty-nine individuals (2.2%) were diagnosed as having TSD (mean age 36.4 years; 92% male). The instruments most associated with TSD were acoustic guitar (36.7%) and brass instruments (30.6%). We concluded that Brazilian TSD music players are mainly male, classical music professionals, around 30 years of age, with arms, hands, or oromandibular muscles affected. TSD is a neurological condition that can impair musical performance and should receive more attention from musicians, teachers, and health professionals. PMID:28321203

  10. Phenotypic Stability of Energy Balance Responses to Experimental Total Sleep Deprivation and Sleep Restriction in Healthy Adults

    PubMed Central

    Dennis, Laura E.; Spaeth, Andrea M.; Goel, Namni

    2016-01-01

    Experimental studies have shown that sleep restriction (SR) and total sleep deprivation (TSD) produce increased caloric intake, greater fat consumption, and increased late-night eating. However, whether individuals show similar energy intake responses to both SR and TSD remains unknown. A total of N = 66 healthy adults (aged 21–50 years, 48.5% women, 72.7% African American) participated in a within-subjects laboratory protocol to compare daily and late-night intake between one night of SR (4 h time in bed, 04:00–08:00) and one night of TSD (0 h time in bed) conditions. We also examined intake responses during subsequent recovery from SR or TSD and investigated gender differences. Caloric and macronutrient intake during the day following SR and TSD were moderately to substantially consistent within individuals (Intraclass Correlation Coefficients: 0.34–0.75). During the late-night period of SR (22:00–04:00) and TSD (22:00–06:00), such consistency was slight to moderate, and participants consumed a greater percentage of calories from protein (p = 0.01) and saturated fat (p = 0.02) during SR, despite comparable caloric intake (p = 0.12). Similarly, participants consumed a greater percentage of calories from saturated fat during the day following SR than TSD (p = 0.03). Participants also consumed a greater percentage of calories from protein during recovery after TSD (p < 0.001). Caloric intake was greater in men during late-night hours and the day following sleep loss. This is the first evidence of phenotypic trait-like stability and differential vulnerability of energy balance responses to two commonly experienced types of sleep loss: our findings open the door for biomarker discovery and countermeasure development to predict and mitigate this critical health-related vulnerability. PMID:27999367

  11. Free Recall of Word Lists under Total Sleep Deprivation and after Recovery Sleep

    PubMed Central

    de Almeida Valverde Zanini, Gislaine; Tufik, Sérgio; Andersen, Monica Levy; da Silva, Raquel Cristina Martins; Bueno, Orlando Francisco Amodeo; Rodrigues, Camila Cruz; Pompéia, Sabine

    2012-01-01

    Study Objectives: One task that has been used to assess memory effects of prior total sleep deprivation (TSD) is the immediate free recall of word lists; however, results have been mixed. A possible explanation for this is task impurity, since recall of words from different serial positions reflects use of distinct types of memory (last words: short-term memory; first and intermediate words: episodic memory). Here we studied the effects of 2 nights of TSD on immediate free recall of semantically unrelated word lists considering the serial position curve. Design: Random allocation to a 2-night TSD protocol followed by one night of recovery sleep or to a control group. Setting: Study conducted under continuous behavioral monitoring. Participants: 24 young, healthy male volunteers. Intervention: 2 nights of total sleep deprivation (TSD) and one night of recovery sleep. Measurements and Results: Participants were shown five 15 unrelated word-lists at baseline, after one and 2 nights of TSD, and after one night of recovery sleep. We also investigated the development of recall strategies (learning) and susceptibility to interference from previous lists. No free recall impairment occurred during TSD, irrespective of serial position. Interference was unchanged. Both groups developed recall strategies, but task learning occurred earlier in controls and was evident in the TSD group only after sleep recovery. Conclusion: Prior TSD spared episodic memory, short-term phonological memory, and interference, allowed the development of recall strategies, but may have decreased the advantage of using these strategies, which returned to normal after recovery sleep. Citation: Zanini GAV; Tufik S; Andersen ML; da Silva RCM; Bueno OFA; Rodrigues CC; Pompéia S. Free recall of word lists under total sleep deprivation and after recovery sleep. SLEEP 2012;35(2):223-230. PMID:22294812

  12. Phenotypic Stability of Energy Balance Responses to Experimental Total Sleep Deprivation and Sleep Restriction in Healthy Adults.

    PubMed

    Dennis, Laura E; Spaeth, Andrea M; Goel, Namni

    2016-12-19

    Experimental studies have shown that sleep restriction (SR) and total sleep deprivation (TSD) produce increased caloric intake, greater fat consumption, and increased late-night eating. However, whether individuals show similar energy intake responses to both SR and TSD remains unknown. A total of N = 66 healthy adults (aged 21-50 years, 48.5% women, 72.7% African American) participated in a within-subjects laboratory protocol to compare daily and late-night intake between one night of SR (4 h time in bed, 04:00-08:00) and one night of TSD (0 h time in bed) conditions. We also examined intake responses during subsequent recovery from SR or TSD and investigated gender differences. Caloric and macronutrient intake during the day following SR and TSD were moderately to substantially consistent within individuals (Intraclass Correlation Coefficients: 0.34-0.75). During the late-night period of SR (22:00-04:00) and TSD (22:00-06:00), such consistency was slight to moderate, and participants consumed a greater percentage of calories from protein ( p = 0.01) and saturated fat ( p = 0.02) during SR, despite comparable caloric intake ( p = 0.12). Similarly, participants consumed a greater percentage of calories from saturated fat during the day following SR than TSD ( p = 0.03). Participants also consumed a greater percentage of calories from protein during recovery after TSD ( p < 0.001). Caloric intake was greater in men during late-night hours and the day following sleep loss. This is the first evidence of phenotypic trait-like stability and differential vulnerability of energy balance responses to two commonly experienced types of sleep loss: our findings open the door for biomarker discovery and countermeasure development to predict and mitigate this critical health-related vulnerability.

  13. On the representation theory of the Bondi-Metzner-Sachs group and its variants in three space-time dimensions

    NASA Astrophysics Data System (ADS)

    Melas, Evangelos

    2017-07-01

    The original Bondi-Metzner-Sachs (BMS) group B is the common asymptotic symmetry group of all asymptotically flat Lorentzian radiating 4-dim space-times. As such, B is the best candidate for the universal symmetry group of General Relativity (G.R.). In 1973, with this motivation, McCarthy classified all relativistic B-invariant systems in terms of strongly continuous irreducible unitary representations (IRS) of B. Here we introduce the analogue B(2, 1) of the BMS group B in 3 space-time dimensions. B(2, 1) itself admits thirty-four analogues both real in all signatures and in complex space-times. In order to find the IRS of both B(2, 1) and its analogues, we need to extend Wigner-Mackey's theory of induced representations. The necessary extension is described and is reduced to the solution of three problems. These problems are solved in the case where B(2, 1) and its analogues are equipped with the Hilbert topology. The extended theory is necessary in order to construct the IRS of both B and its analogues in any number d of space-time dimensions, d ≥3 , and also in order to construct the IRS of their supersymmetric counterparts. We use the extended theory to obtain the necessary data in order to construct the IRS of B(2, 1). The main results of the representation theory are as follows: The IRS are induced from "little groups" which are compact. The finite "little groups" are cyclic groups of even order. The inducing construction is exhaustive notwithstanding the fact that B(2, 1) is not locally compact in the employed Hilbert topology.

  14. Using traffic speed deflectometer to measure deflections and evaluate bearing capacity of asphalt road pavements at network level

    NASA Astrophysics Data System (ADS)

    Březina, Ilja; Stryk, Josef; Grošek, Jiří

    2017-09-01

    The paper deals with diagnostics of bearing capacity of asphalt pavements by a Traffic Speed Deflectometer (TSD device), which allows to measure pavement deflections continually at the traffic speed on the basis of dynamic loading induced by moving wheel of a reference axle at the speed of up to 80 km/h. The paper aims to inform of a new method to measure road pavement deflections, describes the principles of measuring pavement deflections by TSD device, and presents results of comparative measurements between FWD (Falling Weight Deflectometer) and TSD devices organized by CDV in Italy and Slovakia. Particular attention was paid to the difference between deflections measured by FWD and TSD devices.

  15. The Sachs report: investing in health for economic development--or increasing the size of the crumbs from the rich man's table? Part II.

    PubMed

    Katz, Alison

    2005-01-01

    The Commission on Macroeconomics and Health report (Sachs report of 2001) has been heralded as inspiring and groundbreaking and is being adopted as the blueprint for global health policymaking. This article argues that the report is deeply conservative and unoriginal. It encourages medico-technical solutions to public health problems; it ignores macroeconomic determinants and other root causes of both poor health and poverty; it reverses public health logic and history; it is based on a set of flawed assumptions; it reflects one particular economic perspective to the exclusion of all others; and it recommends greater amounts of charity while preserving the status quo of a deeply unjust and irrational international economic order. Wishful thinking and ideology are presented as established facts to legitimize globalization, and health is conceived primarily as an input to productivity rather than as a human right. The benefits that would result from simple, macroeconomic measures directed toward social justice and the meeting of basic needs are incomparably greater than those that would result from following CMH recommendations in terms of sustainable improvements in both health and economic well-being. The ultimate source of poor health status and miserable living conditions is the extreme concentration of power, nationally and internationally, in the hands of the few.

  16. A new species of the genus Theloderma Tschudi, 1838 (Amphibia: Anura: Rhacophoridae) from Tay Nguyen Plateau, central Vietnam

    PubMed Central

    Poyarkov, Nikolay A.; Kropachev, Ivan I.; Gogoleva, Svetlana S.; Orlov, Nikolai L.

    2018-01-01

    A new species of small tree frog from a primary montane tropical forest of central Vietnam, Tay Nguyen Plateau, is described based on morphological, molecular, and acoustic evidence. The Golden Bug-Eyed Frog, Theloderma auratum sp. nov., is distinguishable from its congeners and other small rhacophorid species based on a combination of the following morphological attributes: (1) bony ridges on head absent; (2) smooth skin completely lacking calcified warts or asperities; (3) pointed elongated tapering snout; (4) vocal opening in males absent; (5) vomerine teeth absent; (6) males of small body size (SVL 21.8–26.4 mm); (7) head longer than wide; ED/SVL ratio 13%–15%; ESL/SVL ratio 16%–20%; (8) small tympanum (TD/EL ratio 50%–60%) with few tiny tubercles; (9) supratympanic fold absent; (10) ventral surfaces completely smooth; (11) webbing between fingers absent; (12) outer and inner metacarpal tubercles present, supernumerary metacarpal tubercle single, medial, oval in shape; (13) toes half-webbed: I 2–2¼ II 1½–2¾ III 2–3¼ IV 3–1½ V; (14) inner metatarsal tubercle present, oval; outer metatarsal tubercle absent; (15) iris bicolored; (16) dorsal surfaces golden-yellow with sparse golden-orange speckling or reticulations and few small dark-brown spots; (17) lateral sides of head and body with wide dark reddish-brown to black lateral stripes, clearly separated from lighter dorsal coloration by straight contrasting edge; (18) ventral surfaces of body, throat, and chest greyish-blue with indistinct brown confluent blotches; (19) upper eyelids with few (3–5) very small flat reddish superciliary tubercles; (20) limbs dorsally reddish-brown, ventrally brown with small bluish-white speckles. The new species is also distinct from all congeners in 12S rRNA to 16S rRNA mitochondrial DNA fragment sequences (uncorrected genetic distance P>8.9%). Advertisement call and tadpole morphology of the new species are described. Our molecular data showed Theloderma

  17. Increased impulsivity in response to food cues after sleep loss in healthy young men

    PubMed Central

    Cedernaes, Jonathan; Brandell, Jon; Ros, Olof; Broman, Jan-Erik; Hogenkamp, Pleunie S; Schiöth, Helgi B; Benedict, Christian

    2014-01-01

    Objective To investigate whether acute total sleep deprivation (TSD) leads to decreased cognitive control when food cues are presented during a task requiring active attention, by assessing the ability to cognitively inhibit prepotent responses. Methods Fourteen males participated in the study on two separate occasions in a randomized, crossover within-subject design: one night of TSD versus normal sleep (8.5 hours). Following each nighttime intervention, hunger ratings and morning fasting plasma glucose concentrations were assessed before performing a go/no-go task. Results Following TSD, participants made significantly more commission errors when they were presented “no-go” food words in the go/no-go task, as compared with their performance following sleep (+56%; P<0.05). In contrast, response time and omission errors to “go” non-food words did not differ between the conditions. Self-reported hunger after TSD was increased without changes in fasting plasma glucose. The increase in hunger did not correlate with the TSD-induced commission errors. Conclusions Our results suggest that TSD impairs cognitive control also in response to food stimuli in healthy young men. Whether such loss of inhibition or impulsiveness is food cue-specific as seen in obesity—thus providing a mechanism through which sleep disturbances may promote obesity development—warrants further investigation. PMID:24839251

  18. Transonic Unsteady Aerodynamics and Aeroelasticity 1987, part 1

    NASA Technical Reports Server (NTRS)

    Bland, Samuel R. (Compiler)

    1989-01-01

    Computational fluid dynamics methods have been widely accepted for transonic aeroelastic analysis. Previously, calculations with the TSD methods were used for 2-D airfoils, but now the TSD methods are applied to the aeroelastic analysis of the complete aircraft. The Symposium papers are grouped into five subject areas, two of which are covered in this part: (1) Transonic Small Disturbance (TSD) theory for complete aircraft configurations; and (2) Full potential and Euler equation methods.

  19. Cell Surface Expression of Biologically Active Influenza C Virus HEF Glycoprotein Expressed from cDNA

    PubMed Central

    Pekosz, Andrew; Lamb, Robert A.

    1999-01-01

    The hemagglutinin, esterase, and fusion (HEF) glycoprotein of influenza C virus possesses receptor binding, receptor destroying, and membrane fusion activities. The HEF cDNAs from influenza C/Ann Arbor/1/50 (HEF-AA) and influenza C/Taylor/1223/47 (HEF-Tay) viruses were cloned and expressed, and transport of HEF to the cell surface was monitored by susceptibility to cleavage by exogenous trypsin, indirect immunofluorescence microscopy, and flow cytometry. Previously it has been found in studies with the C/Johannesburg/1/66 strain of influenza C virus (HEF-JHB) that transport of HEF to the cell surface is severely inhibited, and it is thought that the short cytoplasmic tail, Arg-Thr-Lys, is involved in blocking HEF cell surface expression (F. Oeffner, H.-D. Klenk, and G. Herrler, J. Gen. Virol. 80:363–369, 1999). As the cytoplasmic tail amino acid sequences of HEF-AA and HEF-Tay are identical to that of HEF-JHB, the data indicate that cell surface expression of HEF-AA and HEF-Tay is not inhibited by this amino acid sequence. Furthermore, the abundant cell surface transport of HEF-AA and HEF-Tay indicates that their cell surface expression does not require coexpression of another viral protein. The HEF-AA and HEF-Tay HEF glycoproteins bound human erythrocytes, promoted membrane fusion in a low-pH and trypsin-dependent manner, and displayed esterase activity, indicating that the HEF glycoprotein alone mediates all three known functions at the cell surface. PMID:10482635

  20. Why prioritize when there isn't enough money?

    PubMed

    Wikler, Daniel

    2003-02-26

    In an informal address to the 4th International Conference on Priorities in Health (Oslo, 23 September 2002), Professor Jeffrey Sachs - Chairperson of the WHO Commission on Macroeconomics and Health - maintained that the real causes of the inability of the world's poorest people to receive help for the lethal diseases that burden them did not include the "usual suspects" (corruption, mismanagement, and wrong priorities). Rather, the root cause was argued to be an inherent lack of money, indicating that the burden of disease would be lifted only if rich countries gave more money to poor ones.Without taking exception to anything that Sachs said in his address, there nevertheless remain a number of justifications for efforts to improve priority setting in the face of severely shortages of resources, including the following three defenses: prioritization is needed if we are to know that prioritization is insufficient; prioritization is most important when there is little money; prioritization can itself increase resources.

  1. Why prioritize when there isn't enough money?

    PubMed Central

    Wikler, Daniel

    2003-01-01

    In an informal address to the 4th International Conference on Priorities in Health (Oslo, 23 September 2002), Professor Jeffrey Sachs – Chairperson of the WHO Commission on Macroeconomics and Health – maintained that the real causes of the inability of the world's poorest people to receive help for the lethal diseases that burden them did not include the "usual suspects" (corruption, mismanagement, and wrong priorities). Rather, the root cause was argued to be an inherent lack of money, indicating that the burden of disease would be lifted only if rich countries gave more money to poor ones. Without taking exception to anything that Sachs said in his address, there nevertheless remain a number of justifications for efforts to improve priority setting in the face of severely shortages of resources, including the following three defenses: prioritization is needed if we are to know that prioritization is insufficient; prioritization is most important when there is little money; prioritization can itself increase resources. PMID:12773216

  2. Odontometric evaluation of mandibular premolars with tooth shape deviation: a case-control study.

    PubMed

    Chate, Robert Anthony Clive

    2012-09-01

    To evaluate the mean dimensions and morphologic characteristics of mandibular premolars that had mesiodistally elongated and faciolingually squeezed tooth shape deviations (MnP-TSD) and determine the population prevalence of this anomaly. Clinical photographs and study models were made for all new patients with MnP-TSD teeth who were seen over 20 years. The mesiodistal (MD) and faciolingual (FL) dimensions of the anomalous premolars were measured. MD/FL indices and MD × FL mm(2) occlusal crown areas were calculated and means and standard deviations were derived. Male and female means from the mandibular first and second anomalous premolars (MnP1/MnP2-TSD) were statistically compared against gender-specific means derived from published normative data using Student's t-tests and chi-square tests. Fifty-six individuals (33 male and 23 female) with MnP-TSD were identified, giving a male to female ratio of 1.4:1, while the prevalence rate in the indigenous British population was estimated to be 0.6%. The MD widths of the MnP1-TSD and MnP2-TSD teeth were approximately 1 mm wider than normal, while the FL diameters were about 0.5 mm and 1.5 mm narrower respectively, for the first and second premolar teeth. The MD/FL indices, instead of being under 90 as usual were above 100, while the mean MD/FL mm(2) crown surface areas were normal. This study supplies odontometric dimensional and morphologic data on MnP-TSD teeth that provide a reference source for future comparisons.

  3. Temperature-Dependent Sex Determination under Rapid Anthropogenic Environmental Change: Evolution at a Turtle's Pace?

    PubMed

    Refsnider, Jeanine M; Janzen, Fredric J

    2016-01-01

    Organisms become adapted to their environment by evolving through natural selection, a process that generally transpires over many generations. Currently, anthropogenically driven environmental changes are occurring orders of magnitude faster than they did prior to human influence, which could potentially outpace the ability of some organisms to adapt. Here, we focus on traits associated with temperature-dependent sex determination (TSD), a classic polyphenism, in a model turtle species to address the evolutionary potential of species with TSD to respond to rapid climate change. We show, first, that sex-ratio outcomes in species with TSD are sensitive to climatic variation. We then identify the evolutionary potential, in terms of heritability, of TSD and quantify the evolutionary potential of 3 key traits involved in TSD: pivotal temperature, maternal nest-site choice, and nesting phenology. We find that these traits display different patterns of adaptive potential: pivotal temperature exhibits moderate heritable variation, whereas nest-site choice and nesting phenology, with considerable phenotypic plasticity, have only modest evolutionary potential to alter sex ratios. Therefore, the most likely response of species with TSD to anthropogenically induced climate change may be a combination of microevolution in thermal sensitivity of the sex-determining pathway and of plasticity in maternal nesting behavior. © The American Genetic Association. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Thyroid hormone modulates offspring sex ratio in a turtle with temperature-dependent sex determination

    PubMed Central

    Li, Teng; Mu, Yi; McGlashan, Jessica K.; Georges, Arthur

    2016-01-01

    The adaptive significance of temperature-dependent sex determination (TSD) has attracted a great deal of research, but the underlying mechanisms by which temperature determines the sex of a developing embryo remain poorly understood. Here, we manipulated the level of a thyroid hormone (TH), triiodothyronine (T3), during embryonic development (by adding excess T3 to the eggs of the red-eared slider turtle Trachemys scripta, a reptile with TSD), to test two competing hypotheses on the proximate basis for TSD: the developmental rate hypothesis versus the hormone hypothesis. Exogenous TH accelerated embryonic heart rate (and hence metabolic rate), developmental rate, and rates of early post-hatching growth. More importantly, hyperthyroid conditions depressed expression of Cyp19a1 (the gene encoding for aromatase) and levels of oestradiol, and induced more male offspring. This result is contrary to the direction of sex-ratio shift predicted by the developmental rate hypothesis, but consistent with that predicted by the hormone hypothesis. Our results suggest an important role for THs in regulating sex steroid hormones, and therefore, in affecting gonadal sex differentiation in TSD reptiles. Our study has implications for the conservation of TSD reptiles in the context of global change because environmental contaminants may disrupt the activity of THs, and thereby affect offspring sex in TSD reptiles. PMID:27798296

  5. Increased impulsivity in response to food cues after sleep loss in healthy young men.

    PubMed

    Cedernaes, Jonathan; Brandell, Jon; Ros, Olof; Broman, Jan-Erik; Hogenkamp, Pleunie S; Schiöth, Helgi B; Benedict, Christian

    2014-08-01

    To investigate whether acute total sleep deprivation (TSD) leads to decreased cognitive control when food cues are presented during a task requiring active attention, by assessing the ability to cognitively inhibit prepotent responses. Fourteen males participated in the study on two separate occasions in a randomized, crossover within-subject design: one night of TSD versus normal sleep (8.5 hours). Following each nighttime intervention, hunger ratings and morning fasting plasma glucose concentrations were assessed before performing a go/no-go task. Following TSD, participants made significantly more commission errors when they were presented "no-go" food words in the go/no-go task, as compared with their performance following sleep (+56%; P<0.05). In contrast, response time and omission errors to "go" non-food words did not differ between the conditions. Self-reported hunger after TSD was increased without changes in fasting plasma glucose. The increase in hunger did not correlate with the TSD-induced commission errors. Our results suggest that TSD impairs cognitive control also in response to food stimuli in healthy young men. Whether such loss of inhibition or impulsiveness is food cue-specific as seen in obesity-thus providing a mechanism through which sleep disturbances may promote obesity development-warrants further investigation. Copyright © 2014 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

  6. The effects of caffeine ingestion on the reaction time and short-term maximal performance after 36 h of sleep deprivation.

    PubMed

    Souissi, Makram; Chtourou, Hamdi; Abedelmalek, Salma; Ghozlane, Imen Ben; Sahnoun, Zouhair

    2014-05-28

    The aim of the present study was to investigate the effects of caffeine ingestion on cognitive and physical performances after 36h of sleep deprivation. In randomized order, thirteen healthy male physical education students (age: 21.1±1.1years, body mass: 77.1±7.2kg, height: 1.77±0.06m) completed four test sessions at 18:00h: after placebo or 5mg·kg(-1) of caffeine ingestion during a baseline night (RN) (bed time: from 22:30h to 07:00h) or a night of 36h of sleep deprivation (TSD). During each test session, participants performed the squat jump (SJ), the reaction time, and the 30-s Wingate tests (i.e., for the measurement of the peak (PP) and mean (MP) powers and the fatigue index (FI)). The results showed that PP and MP decreased and FI increased during the TSD compared to RN in the placebo condition (p<0.001). The caffeine ingestion improved PP after TSD compared to RN (p<0.001). SJ decreased significantly after the TSD compared to RN after both placebo and caffeine ingestions (p<0.001). However, SJ increased significantly after caffeine ingestion during RN and TSD (p<0.001). The reaction time increased significantly after TSD compared to RN (p<0.001). However, the reaction time decreased significantly after the caffeine ingestion only during the TSD (p<0.001). Therefore, caffeine is an effective strategy to counteract the effect of 36h of sleep loss on physical and cognitive performances. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Evidence for a founder effect for the IVS4 +4 A{r_arrow}T mutation in the Fanconi anemia gene FACC in a Jewish population

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verlander, P.C.; Kaporis, A.G.; Qian, L.

    1994-09-01

    Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder defined by hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C(FACC) has been cloned. Two common mutations, IVS4 +4 A{r_arrow}T and 322delG, and several rare mutations have recently been reported in affected individuals. We now report the development of amplification refractory mutation system (ARMS) assays for rapid, non-radioactive detection of these known mutations in FACC. Primer pairs specific for variant sequences were designed, with the 3{prime} terminal base of one primer matching the variant base. PCR products are separated by electrophoresis on 2.5% agarose gels; mutationsmore » are indicated by the presence of a band of a specific size. These ARMS assays can be multiplexed to allow screening for all known mutations in two PCR reactions. We have used these assays for detection of FACC mutations in affected individuals in the International Fanconi Anemia Registry (IFAR), and for carrier detection FACC families. IVS4 +4 A{r_arrow}T is the only FACC mutation found in Jewish FA patients and their families, of both Ashkenazi and Sephardic ancestry. This mutation was not found in any affected individual of non-Jewish origin. In addition, DNA samples from 1596 healthy Jewish individuals primarily of Ashkenazi ancestry were supplied to us by Dor Yeshorim. These samples, ascertained for carrier screening for Tay Sachs, cystic fibrosis, and other genetic diseases with a high frequency in the religious Jewish community served by this organization, were tested for both IVS4 +4 A{r_arrow}T and 322delG mutations; seventeen IVS4 +4 A{r_arrow}T are of Sephardic Jewish ancestry. We hypothesize that IVS4 +4 A{r_arrow}T is a very old mutation, predating the divergence of the Ashkenazi and Sephardic populations. Haplotype analysis with microsatellite markers is in progress.« less

  8. Distinct sperm nucleus behaviors between genotypic and temperature-dependent sex determination males are associated with replication and expression-related pathways in a gynogenetic fish.

    PubMed

    Zhu, Yao-Jun; Li, Xi-Yin; Zhang, Jun; Li, Zhi; Ding, Miao; Zhang, Xiao-Juan; Zhou, Li; Gui, Jian-Fang

    2018-06-05

    Coexistence and transition of diverse sex determination strategies have been revealed in some ectothermic species, but the variation between males caused by different sex determination strategies and the underlying mechanism remain unclear. Here, we used the gynogenetic gibel carp (Carassius gibelio) with both genotypic sex determination (GSD) and temperature-dependent sex determination (TSD) strategies to illustrate this issue. We found out that males of GSD and TSD in gibel carp had similar morphology, testicular histology, sperm structure and sperm vitality. However, when maternal individuals were mated with males of GSD, sperm nucleus swelling and fusing with the female pronucleus were observed in the fertilized eggs. On the contrary, when maternal individuals were mated with males of TSD, sperm nucleus remained in the condensed status throughout the whole process. Subsequently, semen proteomics analysis unveiled that DNA replication and gene expression-related pathways were inhibited in the sperm from males of TSD compared to males of GSD, and most differentially expressed proteins associated with DNA replication, transcription and translation were down-regulated. Moreover, via BrdU incorporation and immunofluorescence detection, male nucleus replication was revealed to be present in the fertilized eggs by the sperm from males of GSD, but absent in the fertilized eggs by the sperm from males of TSD. These findings indicate that DNA replication and gene expression-related pathways are associated with the distinct sperm nucleus development behaviors in fertilized eggs in response to the sperm from males of GSD and TSD. And this study is the first attempt to screen the differences between males determined via GSD and TSD in gynogenetic species, which might give a hint for understanding evolutionary adaption of diverse sex determination mechanisms in unisexual vertebrates.

  9. Molecular imaging of in vivo calcium ion expression in area postrema of total sleep deprived rats: Implications for cardiovascular regulation by TOF-SIMS analysis

    NASA Astrophysics Data System (ADS)

    Mai, Fu-Der; Chen, Li-You; Ling, Yong-Chien; Chen, Bo-Jung; Wu, Un-In; Chang, Hung-Ming

    2010-05-01

    Excessive calcium influx in chemosensitive neurons of area postrema (AP) is detrimental for sympathetic activation and participates in the disruption of cardiovascular activities. Since total sleep deprivation (TSD) is a stressful condition known to harm the cardiovascular function, the present study is aimed to determine whether the in vivo calcium expression in AP would significantly alter following TSD by the use of time-of-flight secondary ion mass spectrometry (TOF-SIMS) and calretinin (a specific calcium sensor protein in AP neurons) immunohistochemistry. The results indicated that in normal rats, the calcium intensity was estimated to be 0.5 × 10 5 at m/ z 40.08. However, following TSD, the intensity for calcium ions was greatly increased to 1.2 × 10 5. Molecular imaging revealed that after TSD, various strongly expressed calcium signals were distributed throughout AP with clear identified profiles instead of randomly scattered within this region in normal rats. Immunohistochemical staining corresponded well with ionic image in which a majority of calcium-enriched gathering co-localized with calretinin positive neurons. The functional significance of TSD-induced calcium augmentation was demonstrated by increased heart rate and mean arterial pressure, clinical markers for cardiovascular dysfunction. Considering AP-mediated sympathetic activation is important for cardiovascular regulation, exaggerated calcium influx in AP would render this neurocircuitry more vulnerable to over-excitation, which might serve as the underlying mechanism for the development of TSD-relevant cardiovascular deficiency.

  10. THE INTEGRATION OF THE 241-Z BUILDING DECONTAMINATION & DECOMMISSIONING (D&D) UNDER COMPREHENSIVE ENVIRONMENTAL RESPONSE COMPENSATION & LIABILITY ACT (CERCLA) WITH RESOURCE CONSERVATION & RECOVERY ACT (RCRA) CLOSURE AT THE PLUTONIUM FINISHING PLANT (PFP)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    HOPKINS, A.M.

    2007-02-20

    The 241-Z treatment and storage tanks, a hazardous waste Treatment, Storage and Disposal (TSD) unit permitted pursuant to the ''Resource Conservation and Recovery Act of 1976'' (RCRA) and Washington State ''Hazardous Waste Management Act, RCW 70.105'', have been deactivated and are being actively decommissioned. The 241-Z TSD unit managed non-listed radioactive contaminated waste water, containing trace RCRA characteristic constituents. The 241-Z TSD unit consists of below grade tanks (D-4, D-5, D-7, D-8, and an overflow tank) located in a concrete containment vault, sample glovebox GB-2-241-ZA, and associated ancillary piping and equipment. The tank system is located beneath the 241-Z building.more » The 241-Z building is not a portion of the TSD unit. The sample glovebox is housed in the above-grade building. Waste managed at the TSD unit was received via underground mining from Plutonium Finishing Plant (PFP) sources. Tank D-6, located in the D-6 vault cell, is a past-practice tank that was taken out of service in 1972 and has never operated as a portion of the RCRA TSD unit. CERCLA actions address Tank D-6, its containment vault cell, and soil beneath the cell that was potentially contaminated during past-practice operations and any other potential past-practice contamination identified during 241-Z closure, while outside the scope of the ''Hanford Facility Dangerous Waste Closure Plant, 241-Z Treatment and Storage Tanks''.« less

  11. Sleep deprivation alters choice strategy without altering uncertainty or loss aversion preferences

    PubMed Central

    Mullette-Gillman, O'Dhaniel A.; Kurnianingsih, Yoanna A.; Liu, Jean C. J.

    2015-01-01

    Sleep deprivation alters decision making; however, it is unclear what specific cognitive processes are modified to drive altered choices. In this manuscript, we examined how one night of total sleep deprivation (TSD) alters economic decision making. We specifically examined changes in uncertainty preferences dissociably from changes in the strategy with which participants engage with presented choice information. With high test-retest reliability, we show that TSD does not alter uncertainty preferences or loss aversion. Rather, TSD alters the information the participants rely upon to make their choices. Utilizing a choice strategy metric which contrasts the influence of maximizing and satisficing information on choice behavior, we find that TSD alters the relative reliance on maximizing information and satisficing information, in the gains domain. This alteration is the result of participants both decreasing their reliance on cognitively-complex maximizing information and a concomitant increase in the use of readily-available satisficing information. TSD did not result in a decrease in overall information use in either domain. These results show that sleep deprivation alters decision making by altering the informational strategies that participants employ, without altering their preferences. PMID:26500479

  12. Recoded and nonrecoded trinary signed-digit adders and multipliers with redundant-bit representations

    NASA Astrophysics Data System (ADS)

    Cherri, Abdallah K.; Alam, Mohammed S.

    1998-07-01

    Highly-efficient two-step recoded and one-step nonrecoded trinary signed-digit (TSD) carry-free adders subtracters are presented on the basis of redundant-bit representation for the operands digits. It has been shown that only 24 (30) minterms are needed to implement the two-step recoded (the one-step nonrecoded) TSD addition for any operand length. Optical implementation of the proposed arithmetic can be carried out by use of correlation- or matrix-multiplication-based schemes, saving 50% of the system memory. Furthermore, we present four different multiplication designs based on our proposed recoded and nonrecoded TSD adders. Our multiplication designs require a small number of reduced minterms to generate the multiplication partial products. Finally, a recently proposed pipelined iterative-tree algorithm can be used in the TSD adders multipliers; consequently, efficient use of all available adders can be made.

  13. Recoded and nonrecoded trinary signed-digit adders and multipliers with redundant-bit representations.

    PubMed

    Cherri, A K; Alam, M S

    1998-07-10

    Highly-efficient two-step recoded and one-step nonrecoded trinary signed-digit (TSD) carry-free adders-subtracters are presented on the basis of redundant-bit representation for the operands' digits. It has been shown that only 24 (30) minterms are needed to implement the two-step recoded (the one-step nonrecoded) TSD addition for any operand length. Optical implementation of the proposed arithmetic can be carried out by use of correlation- or matrix-multiplication-based schemes, saving 50% of the system memory. Furthermore, we present four different multiplication designs based on our proposed recoded and nonrecoded TSD adders. Our multiplication designs require a small number of reduced minterms to generate the multiplication partial products. Finally, a recently proposed pipelined iterative-tree algorithm can be used in the TSD adders-multipliers; consequently, efficient use of all available adders can be made.

  14. Estimating the Benefit per Ton of Reducing PM2.5 Precursors from 17 Sectors

    EPA Pesticide Factsheets

    Technical Support Document (TSD) reporting the human health impact and monetized benefits of reducing emissions of PM2.5 and PM2.5 precursors from 17 sectors. This TSD was updated in 2018 to reflect updated demographic and economic data.

  15. The Integration of the 241-Z Building Decontamination and Decommissioning Under Cercla with RCRA Closure at the Plutonium Finishing Plant

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mattlin, E.; Charboneau, S.; Johnston, G.

    2007-07-01

    The 241-Z treatment and storage tanks, a hazardous waste Treatment, Storage and Disposal (TSD) unit permitted pursuant to the Resource Conservation and Recovery Act of 1976 (RCRA) and Washington State Hazardous Waste Management Act, RCW 70.105, , have been deactivated and are being actively decommissioned under the provisions of the Hanford Federal Facility Agreement and Consent Order (HFFACO), RCRA and Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) 42 U.S.C. 9601 et seq. The 241-Z TSD unit managed non-listed radioactive contaminated waste water, containing trace RCRA characteristic constituents. The 241-Z TSD unit consists of below grade tanks (D-4,more » D-5, D-7, D-8, and an overflow tank) located in a concrete containment vault, sample glovebox GB-2-241-ZA, and associated ancillary piping and equipment. The tank system is located beneath the 241-Z building. The 241-Z building is not a portion of the TSD unit. The sample glovebox is housed in the above-grade building. Waste managed at the TSD unit was received via underground piping from Plutonium Finishing Plant (PFP) sources. Tank D-6, located in the D-6 vault cell, is a past-practice tank that was taken out of service in 1972 and has never operated as a portion of the RCRA TSD unit. CERCLA actions will address Tank D-6, its containment vault cell, and soil beneath the cell that was potentially contaminated during past-practice operations and any other potential past-practice contamination identified during 241-Z closure, while outside the scope of the Hanford Facility Dangerous Waste Closure Plan, 241-Z Treatment and Storage Tanks. Under the RCRA closure plan, the 241-Z TSD unit is anticipated to undergo clean closure to the performance standards of the State of Washington with respect to dangerous waste contamination from RCRA operations. The TSD unit will be clean closed if physical closure activities identified in the plan achieve clean closure standards for all

  16. 76 FR 3133 - Science Advisory Board Staff Office; Notification of a Public Teleconference of the Science...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-19

    ... document (TSD), Methods and Approaches for Deriving Numeric Criteria for Nitrogen/Phosphorus Pollution in Florida's Estuaries, Coastal Waters, and Southern Inland Flowing Waters. The draft TSD describes methods... discuss its draft report reviewing EPA's technical support document on development of numeric nutrient...

  17. Iranian EFL Teachers' Perceptions of Teacher Self-Disclosure

    ERIC Educational Resources Information Center

    Rahimi, Ali; Askari Bigdeli, Rouhollah

    2016-01-01

    Teacher self-disclosure (TSD) as a communication behavior can influence students' learning by increasing their engagement and class participation as well as helping them establish effective interpersonal relationships. Owning to its context-sensitive and culture-dependent nature, however, TSD topics, purposes, and considerations may vary…

  18. Factors that Influence Women's Technical Skill Development in Outdoor Adventure

    ERIC Educational Resources Information Center

    Warren, Karen; Loeffler, TA

    2006-01-01

    This article provides a theoretical foundation for understanding women's technical skill development (TSD) in outdoor adventure. An examination of societal and biological factors influencing women's TSD focuses on gender role socialization, sense of competence, technical conditioning, sexism, spatial ability, and risk-taking. The article suggests…

  19. Large-Scale Brain Network Coupling Predicts Total Sleep Deprivation Effects on Cognitive Capacity

    PubMed Central

    Wang, Lubin; Zhai, Tianye; Zou, Feng; Ye, Enmao; Jin, Xiao; Li, Wuju; Qi, Jianlin; Yang, Zheng

    2015-01-01

    Interactions between large-scale brain networks have received most attention in the study of cognitive dysfunction of human brain. In this paper, we aimed to test the hypothesis that the coupling strength of large-scale brain networks will reflect the pressure for sleep and will predict cognitive performance, referred to as sleep pressure index (SPI). Fourteen healthy subjects underwent this within-subject functional magnetic resonance imaging (fMRI) study during rested wakefulness (RW) and after 36 h of total sleep deprivation (TSD). Self-reported scores of sleepiness were higher for TSD than for RW. A subsequent working memory (WM) task showed that WM performance was lower after 36 h of TSD. Moreover, SPI was developed based on the coupling strength of salience network (SN) and default mode network (DMN). Significant increase of SPI was observed after 36 h of TSD, suggesting stronger pressure for sleep. In addition, SPI was significantly correlated with both the visual analogue scale score of sleepiness and the WM performance. These results showed that alterations in SN-DMN coupling might be critical in cognitive alterations that underlie the lapse after TSD. Further studies may validate the SPI as a potential clinical biomarker to assess the impact of sleep deprivation. PMID:26218521

  20. Semiclassical unified description of wobbling motion in even-even and even-odd nuclei

    NASA Astrophysics Data System (ADS)

    Raduta, A. A.; Poenaru, R.; Ixaru, L. Gr.

    2017-11-01

    A unitary description for wobbling motion in even-even and even-odd nuclei is presented. In both cases compact formulas for wobbling frequencies are derived. The accuracy of the harmonic approximation is studied for the yrast as well as for the excited bands in the even-even case. Important results for the structure of the wave function and its behavior inside the two wells of the potential energy function corresponding to the Bargmann representation are pointed out. Applications to 158Er and 163Lu reveal a very good agreement with available data. Indeed, the yrast energy levels in the even-even case and the first four triaxial superdeformed bands, TSD1, TSD2, TSD3, and TSD4, are realistically described. Also, the results agree with the data for the E 2 and M 1 intra- as well as interband transitions. Perspectives for the formalism development and an extensive application to several nuclei from various regions of the nuclides chart are presented.

  1. Trait-Like Vulnerability to Total and Partial Sleep Loss

    PubMed Central

    Rupp, Tracy L.; Wesensten, Nancy J.; Balkin, Thomas J.

    2012-01-01

    Objective: To determine the extent to which individual differences in vulnerability to total sleep deprivation also reflect individual differences in vulnerability to multiple nights of sleep restriction. Design: Two sleep loss conditions (order counterbalanced) separated by 2 to 4 weeks: (a) total sleep deprivation (TSD) of 2 nights (63 h continuous wakefulness); (b) sleep restriction (SR) of 7 nights of 3 h nightly time in bed (TIB). Both conditions were preceded by 7 in-laboratory nights with 10 h nightly TIB; and followed by 3 recovery nights with 8 h nightly TIB. Measures of cognitive performance (psychomotor vigilance, working memory [1-Back], and mathematical processing), objective alertness, subjective sleepiness, and mood were obtained at regular intervals under both conditions. Intra-class correlation coefficients (ICC) were computed using outcome metrics averaged over the last day (08:00-20:00) of TSD and SR. Setting: Residential sleep/performance testing facility. Participants: Nineteen healthy adults (ages 18-39; 11 males, 8 females). Interventions: 2 nights of TSD and 7 nights SR (3 h nightly TIB). Results: Volunteers who displayed greater vulnerability to TSD displayed greater vulnerability to SR on cognitive performance tasks (ICC: PVT lapses = 0.89; PVT speed = 0.86; 1-Back = 0.88; mathematical processing = 0.68, Ps < 0.05). In addition, trait-like responsivity to TSD/SR was found for mood variables vigor (ICC = 0.91), fatigue (ICC = 0.73), and happiness (ICC = 0.85) (all Ps < 0.05). Conclusion: Resilience to sleep loss is a trait-like characteristic that reflects an individual's ability to maintain performance during both types of sleep loss (SR and TSD). Whether the findings extend to sleep schedules other than those investigated here (63 h of TSD and 7 nights of 3 h nightly TIB) will be the focus of future studies. Citation: Rupp TL; Wesensten NJ; Balkin TJ. Trait-like vulnerability to total and partial sleep loss. SLEEP 2012

  2. Removal of two large-scale cosmic microwave background anomalies after subtraction of the integrated Sachs-Wolfe effect

    NASA Astrophysics Data System (ADS)

    Rassat, A.; Starck, J.-L.; Dupé, F.-X.

    2013-09-01

    Context. Although there is currently a debate over the significance of the claimed large-scale anomalies in the cosmic microwave background (CMB), their existence is not totally dismissed. In parallel to the debate over their statistical significance, recent work has also focussed on masks and secondary anisotropies as potential sources of these anomalies. Aims: In this work we investigate simultaneously the impact of the method used to account for masked regions as well as the impact of the integrated Sachs-Wolfe (ISW) effect, which is the large-scale secondary anisotropy most likely to affect the CMB anomalies. In this sense, our work is an update of previous works. Our aim is to identify trends in CMB data from different years and with different mask treatments. Methods: We reconstruct the ISW signal due to 2 Micron All-Sky Survey (2MASS) and NRAO VLA Sky Survey (NVSS) galaxies, effectively reconstructing the low-redshift ISW signal out to z ~ 1. We account for regions of missing data using the sparse inpainting technique. We test sparse inpainting of the CMB, large scale structure and ISW and find that it constitutes a bias-free reconstruction method suitable to study large-scale statistical isotropy and the ISW effect. Results: We focus on three large-scale CMB anomalies: the low quadrupole, the quadrupole/octopole alignment, and the octopole planarity. After sparse inpainting, the low quadrupole becomes more anomalous, whilst the quadrupole/octopole alignment becomes less anomalous. The significance of the low quadrupole is unchanged after subtraction of the ISW effect, while the trend amongst the CMB maps is that both the low quadrupole and the quadrupole/octopole alignment have reduced significance, yet other hypotheses remain possible as well (e.g. exotic physics). Our results also suggest that both of these anomalies may be due to the quadrupole alone. While the octopole planarity significance is reduced after inpainting and after ISW subtraction, however

  3. Role of sleep for encoding of emotional memory.

    PubMed

    Kaida, Kosuke; Niki, Kazuhisa; Born, Jan

    2015-05-01

    Total sleep deprivation (TSD) has been consistently found to impair encoding of information during ensuing wakefulness, probably through suppressing NonREM (non-rapid eye movement) sleep. However, a possible contribution of missing REM sleep to this encoding impairment after TSD has so far not been systematically examined in humans, although such contribution might be suspected in particular for emotional information. Here, in two separate experiments in young healthy men, we compared effects of TSD and of selective REM sleep deprivation (REMD), relative to respective control conditions of undisturbed sleep, on the subsequent encoding of neutral and emotional pictures. The pictures were presented in conjunction with colored frames to also assess related source memory. REMD was achieved by tones presented contingently upon initial signs of REM sleep. Encoding capabilities were examined in the evening (18:00h) after the experimental nights, by a picture recognition test right after encoding. TSD significantly decreased both the rate of correctly recognized pictures and of recalled frames associated with the pictures. The TSD effect was robust and translated into an impaired long term memory formation, as it was likewise observed on a second recognition testing one week after the encoding phase. Contrary to our expectation, REMD did not affect encoding in general, or particularly of emotional pictures. Also, REMD did not affect valence ratings of the encoded pictures. However, like TSD, REMD distinctly impaired vigilance at the time of encoding. Altogether, these findings indicate an importance of NonREM rather than REM sleep for the encoding of information that is independent of the emotionality of the materials. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Catechol-O-methyltransferase (COMT) genotype affects cognitive control during total sleep deprivation.

    PubMed

    Satterfield, Brieann C; Hinson, John M; Whitney, Paul; Schmidt, Michelle A; Wisor, Jonathan P; Van Dongen, Hans P A

    2018-02-01

    Adaptive decision making is profoundly impaired by total sleep deprivation (TSD). This suggests that TSD impacts fronto-striatal pathways involved in cognitive control, where dopamine is a key neuromodulator. In the prefrontal cortex (PFC), dopamine is catabolized by the enzyme catechol-O-methyltransferase (COMT). A functional polymorphism (Val158Met) influences COMT's enzymatic activity, resulting in markedly different levels of prefrontal dopamine. We investigated the effect of this polymorphism on adaptive decision making during TSD. Sixty-six healthy young adults participated in one of two in-laboratory studies. After a baseline day, subjects were randomized to either a TSD group (n = 32) with 38 h or 62 h of extended wakefulness or a well-rested control group (n = 34) with 10 h nighttime sleep opportunities. Subjects performed a go/no-go reversal learning (GNGr) task at well-rested baseline and again during TSD or equivalent control. During the task, subjects were required to learn stimulus-response relationships from accuracy feedback. The stimulus-response relationships were reversed halfway through the task, which required subjects to learn the new stimulus-response relationships from accuracy feedback. Performance on the GNGr task was quantified by discriminability (d') between go and no-go stimuli before and after the stimulus-response reversal. GNGr performance did not differ between COMT genotypes when subjects were well-rested. However, TSD exposed a significant vulnerability to adaptive decision making impairment in subjects with the Val allele. Our results indicate that sleep deprivation degrades cognitive control through a fronto-striatal, dopaminergic mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Differential intron retention in Jumonji chromatin modifier genes is implicated in reptile temperature-dependent sex determination

    PubMed Central

    Deveson, Ira W.; Holleley, Clare E.; Blackburn, James; Marshall Graves, Jennifer A.; Mattick, John S.; Waters, Paul D.; Georges, Arthur

    2017-01-01

    In many vertebrates, sex of offspring is determined by external environmental cues rather than by sex chromosomes. In reptiles, for instance, temperature-dependent sex determination (TSD) is common. Despite decades of work, the mechanism by which temperature is converted into a sex-determining signal remains mysterious. This is partly because it is difficult to distinguish the primary molecular events of TSD from the confounding downstream signatures of sexual differentiation. We use the Australian central bearded dragon, in which chromosomal sex determination is overridden at high temperatures to produce sex-reversed female offspring, as a unique model to identify TSD-specific features of the transcriptome. We show that an intron is retained in mature transcripts from each of two Jumonji family genes, JARID2 and JMJD3, in female dragons that have been sex-reversed by temperature but not in normal chromosomal females or males. JARID2 is a component of the master chromatin modifier Polycomb Repressive Complex 2, and the mammalian sex-determining factor SRY is directly regulated by an independent but closely related Jumonji family member. We propose that the perturbation of JARID2/JMJD3 function by intron retention alters the epigenetic landscape to override chromosomal sex-determining cues, triggering sex reversal at extreme temperatures. Sex reversal may then facilitate a transition from genetic sex determination to TSD, with JARID2/JMJD3 intron retention preserved as the decisive regulatory signal. Significantly, we also observe sex-associated differential retention of the equivalent introns in JARID2/JMJD3 transcripts expressed in embryonic gonads from TSD alligators and turtles, indicative of a reptile-wide mechanism controlling TSD. PMID:28630932

  6. Differential intron retention in Jumonji chromatin modifier genes is implicated in reptile temperature-dependent sex determination.

    PubMed

    Deveson, Ira W; Holleley, Clare E; Blackburn, James; Marshall Graves, Jennifer A; Mattick, John S; Waters, Paul D; Georges, Arthur

    2017-06-01

    In many vertebrates, sex of offspring is determined by external environmental cues rather than by sex chromosomes. In reptiles, for instance, temperature-dependent sex determination (TSD) is common. Despite decades of work, the mechanism by which temperature is converted into a sex-determining signal remains mysterious. This is partly because it is difficult to distinguish the primary molecular events of TSD from the confounding downstream signatures of sexual differentiation. We use the Australian central bearded dragon, in which chromosomal sex determination is overridden at high temperatures to produce sex-reversed female offspring, as a unique model to identify TSD-specific features of the transcriptome. We show that an intron is retained in mature transcripts from each of two Jumonji family genes, JARID2 and JMJD3 , in female dragons that have been sex-reversed by temperature but not in normal chromosomal females or males. JARID2 is a component of the master chromatin modifier Polycomb Repressive Complex 2, and the mammalian sex-determining factor SRY is directly regulated by an independent but closely related Jumonji family member. We propose that the perturbation of JARID2/JMJD3 function by intron retention alters the epigenetic landscape to override chromosomal sex-determining cues, triggering sex reversal at extreme temperatures. Sex reversal may then facilitate a transition from genetic sex determination to TSD, with JARID2/JMJD3 intron retention preserved as the decisive regulatory signal. Significantly, we also observe sex-associated differential retention of the equivalent introns in JARID2/JMJD3 transcripts expressed in embryonic gonads from TSD alligators and turtles, indicative of a reptile-wide mechanism controlling TSD.

  7. Total and partial sleep deprivation: Effects on plasma TNF-αRI, TNF-αRII, and IL-6, and reversal by caffeine operating through adenosine A2 receptor

    NASA Astrophysics Data System (ADS)

    Shearer, William T.; Reuben, James M.; Lee, Bang-Ning; Mullington, Janet; Price, Nicholas; Dinges, David F.

    2000-01-01

    Plasma levels of IL-6 and TNF-α are elevated in individuals who are deprived of sleep. TNF-α regulates expression of its soluble receptors, sTNF-αRI and sTNF-αRII. Sleep deprivation (SD) also increases extracellular adenosine that induces sedation and sleep. An antagonist of adenosine, caffeine, raises exogenous adenosine levels, stimulates the expression of IL-6 and inhibits the release of TNF-α. Our objective was to determine the effect of total SD (TSD) or partial SD (PSD) on the levels of these sleep regulatory molecules in volunteers who experienced SD with or without the consumption of caffeine. Plasma levels of IL-6, sTNF-αRI and sTNF-αRII were assayed by ELISA in samples collected at 90-min intervals from each subject over an 88-hour period. The results were analyzed by the repeated measures ANOVA. Whereas only TSD significantly increased sTNF-αRI over time, caffeine suppressed both sTNF-α receptors in TSD and PSD subjects. The selective increase in the expression of sTNF-αRI and not sTNF-αRII in subjects experiencing TSD with caffeine compared with others experiencing PSD with caffeine has not been previously reported. Moreover, caffeine significantly increased IL-6 in TSD subjects compared with those who did not receive caffeine. However, subjects who were permitted intermittent naps (PSD) ablated the effects of caffeine and reduced their level of IL-6 to that of the TSD group. These data further lend support to the hypothesis that the sTNF-αRI and not the sTNF-αRII plays a significant role in sleep regulation by TNF-α. .

  8. Increased Automaticity and Altered Temporal Preparation Following Sleep Deprivation.

    PubMed

    Kong, Danyang; Asplund, Christopher L; Ling, Aiqing; Chee, Michael W L

    2015-08-01

    Temporal expectation enables us to focus limited processing resources, thereby optimizing perceptual and motor processing for critical upcoming events. We investigated the effects of total sleep deprivation (TSD) on temporal expectation by evaluating the foreperiod and sequential effects during a psychomotor vigilance task (PVT). We also examined how these two measures were modulated by vulnerability to TSD. Three 10-min visual PVT sessions using uniformly distributed foreperiods were conducted in the wake-maintenance zone the evening before sleep deprivation (ESD) and three more in the morning following approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were determined by a tertile split of participants based on the change in the number of behavioral lapses recorded during ESD and TSD. A subset of participants performed six additional 10-min modified auditory PVTs with exponentially distributed foreperiods during rested wakefulness (RW) and TSD to test the effect of temporal distribution on foreperiod and sequential effects. Sleep laboratory. There were 172 young healthy participants (90 males) with regular sleep patterns. Nineteen of these participants performed the modified auditory PVT. Despite behavioral lapses and slower response times, sleep deprived participants could still perceive the conditional probability of temporal events and modify their level of preparation accordingly. Both foreperiod and sequential effects were magnified following sleep deprivation in vulnerable individuals. Only the foreperiod effect increased in nonvulnerable individuals. The preservation of foreperiod and sequential effects suggests that implicit time perception and temporal preparedness are intact during total sleep deprivation. Individuals appear to reallocate their depleted preparatory resources to more probable event timings in ongoing trials, whereas vulnerable participants also rely more on automatic processes. © 2015 Associated Professional Sleep

  9. Unexpected resilience of species with temperature-dependent sex determination at the Cretaceous–Palaeogene boundary

    PubMed Central

    Silber, Sherman; Geisler, Jonathan H.; Bolortsetseg, Minjin

    2011-01-01

    It has been suggested that climate change at the Cretaceous–Palaeogene (K–Pg) boundary, initiated by a bolide impact or volcanic eruptions, caused species with temperature-dependent sex determination (TSD), including dinosaurs, to go extinct because of a skewed sex ratio towards all males. To test this hypothesis, the sex-determining mechanisms (SDMs) of Cretaceous tetrapods of the Hell Creek Formation (Montana, USA) were inferred using parsimony optimizations of SDMs on a tree, including Hell Creek species and their extant relatives. Although the SDMs of non-avian dinosaurs could not be inferred, we were able to determine the SDMs of 62 species; 46 had genotypic sex determination (GSD) and 16 had TSD. The TSD hypothesis for extinctions performed poorly, predicting between 32 and 34 per cent of survivals and extinctions. Most surprisingly, of the 16 species with TSD, 14 of them survived into the Early Palaeocene. In contrast, 61 per cent of species with GSD went extinct. Possible explanations include minimal climate change at the K–Pg, or if climate change did occur, TSD species that survived had egg-laying behaviour that prevented the skewing of sex ratios, or had a sex ratio skewed towards female rather than male preponderance. Application of molecular clocks may allow the SDMs of non-avian dinosaurs to be inferred, which would be an important test of the pattern discovered here. PMID:20980293

  10. Short term total sleep deprivation in the rat increases antioxidant responses in multiple brain regions without impairing spontaneous alternation behavior

    PubMed Central

    Ramanathan, Lalini; Hu, Shuxin; Frautschy, Sally A.; Siegel, Jerome M.

    2009-01-01

    Total sleep deprivation (TSD) induces a broad spectrum of cognitive, behavioral and cellular changes. We previously reported that long term (5–11 days) TSD in the rat, by the disk-over-water method, decreases the activity of the antioxidant enzyme superoxide dismutase (SOD) in the brainstem and hippocampus. To gain insight into the mechanisms causing cognitive impairment, here we explore the early associations between metabolic activity, antioxidant responses and working memory (one form of cognitive impairment). Specifically we investigated the impact of short term (6 h) TSD, by gentle handling, on the levels of the endogenous antioxidant, total glutathione (GSHt), and the activities of the antioxidative enzymes, SOD and glutathione peroxidase (GPx). Short term TSD had no significant impact on SOD activity, but increased GSHt levels in the rat cortex, brainstem and basal forebrain, and GPx activity in the rat hippocampus and cerebellum. We also observed increased activity of hexokinase, (HK), the rate limiting enzyme of glucose metabolism, in the rat cortex and hypothalamus. We further showed that 6h of TSD leads to increased exploratory behavior to a new environment, without impairing spontaneous alternation behavior (SAB) in the Y maze. We conclude that acute (6h) sleep loss may trigger compensatory mechanisms (like increased antioxidant responses) that prevent initial deterioration in working memory. PMID:19850085

  11. Significance of the zero sum principle for circadian, homeostatic and allostatic regulation of sleep-wake state in the rat.

    PubMed

    Stephenson, Richard; Caron, Aimee M; Famina, Svetlana

    2016-12-01

    Sleep-wake behavior exhibits diurnal rhythmicity, rebound responses to acute total sleep deprivation (TSD), and attenuated rebounds following chronic sleep restriction (CSR). We investigated how these long-term patterns of behavior emerge from stochastic short-term dynamics of state transition. Male Sprague-Dawley rats were subjected to TSD (1day×24h, N=9), or CSR (10days×18h TSD, N=7) using a rodent walking-wheel apparatus. One baseline day and one recovery day following TSD and CSR were analyzed. The implications of the zero sum principle were evaluated using a Markov model of sleep-wake state transition. Wake bout duration (a combined function of the probability of wake maintenance and proportional representations of brief and long wake) was a key variable mediating the baseline diurnal rhythms and post-TSD responses of all three states, and the attenuation of the post-CSR rebounds. Post-NREM state transition trajectory was an important factor in REM rebounds. The zero sum constraint ensures that a change in any transition probability always affects bout frequency and cumulative time of at least two, and usually all three, of wakefulness, NREM and REM. Neural mechanisms controlling wake maintenance may play a pivotal role in regulation and dysregulation of all three states. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Does the mechanism of sex determination constrain the potential for sex manipulation? A test in geckos with contrasting sex-determining systems

    NASA Astrophysics Data System (ADS)

    Kratochvíl, Lukáš; Kubička, Lukáš; Landová, Eva

    2008-03-01

    The concentration of yolk steroids was suggested to influence offspring gender in oviparous animals subject to both temperature-dependent sex determination (TSD) and genotypic sex determination (GSD). However, the proposed mechanisms of steroid effects are thought to differ between TSD and GSD: a direct effect of oestrogens on gonad feminisation in TSD species vs a differential induction of male-producing or female-producing gametes in GSD species. Geckos offer an ideal opportunity for testing these suggested mechanisms. Closely related gecko species differ in their modes of sex determination. They lay clutches of two synchronously formed eggs; both eggs share equal steroid levels. If identical hormonal composition and environment during vitellogenesis, gravidity and incubation determine the sex of the progeny, siblings should share the same gender in both TSD and GSD geckos. We found strong support for this prediction in a TSD gecko species. Among clutches that were incubated at the temperature that produced both sexes, there were no clutches with siblings of the opposite sex. On the other hand, about half of the clutches yielded siblings of the opposite sex in four GSD species. These results suggest that sex-determining systems constrain the ability of the female to produce single-sex siblings and, hence, it seems that the GSD mechanism constrains the opportunities for sex ratio manipulation in geckos via yolk steroid manipulation.

  13. Total-System Design: Planning, Delivering, and Sharing Instruction Oriented to Professional Practice and Human Values.

    ERIC Educational Resources Information Center

    Lux, M. Janet

    Aspects of the Total-System Design (TSD) approach to instructional design in medical laboratory science that was implemented at Creighton University are described. In a four-year project, TSD principles were used to produce the uniform, systematic, and complete definition of a medical technology major within a program of study leading to the…

  14. Quality of life among pediatric patients with cancer: Contributions of time since diagnosis and parental chronic stress.

    PubMed

    Hamner, Taralee; Latzman, Robert D; Latzman, Natasha E; Elkin, T David; Majumdar, Suvankar

    2015-07-01

    Pediatric cancer is associated with a host of negative psychosocial consequences; however, outcomes vary extensively suggesting a need to better understand this variation. Empirical research suggests a positive association between time since diagnosis (TSD) and Quality of Life (QoL). In addition to TSD, family stressors have been found to be particularly important in predicting QoL among children. The current study examined parental chronic stress beyond TSD in explanation of QoL functioning among a sample of pediatric patients with cancer. Participants included 43 pediatric patients aged 5-18 years (M(age) = 10.2 ± 3.6) who were undergoing oncological treatment. Parents reported on TSD, child's QoL, and their own chronic stress. TSD was associated with greater physical functioning (r = 0.30, P < 0.05). Parental chronic stress was associated with poorer emotional (r = -0.54, P < 0.01), physical (r = -0.41, P < 0.01), and social functioning (r = -0.44, P < 0.01). Further, hierarchal linear regression analyzes indicated parental chronic stress contributed incrementally beyond TSD in the explanation of physical (β = -0.37, t = -2.58, P < 0.01), emotional (β = -0.47, t = -3.51, P < 0.00), and social functioning (β = -0.38, t = -2.67, P < 0.01). Parental chronic stress is associated with reduced levels of emotional, physical, and social functioning among pediatric patients. Future research is needed to further investigate the process by which chronic stress within the family interferes with adaptive coping among pediatric patients. In addition, clinical services may benefit from increased consideration of family factors, such as parental chronic stress, during oncological treatment. © 2015 Wiley Periodicals, Inc.

  15. Increased Automaticity and Altered Temporal Preparation Following Sleep Deprivation

    PubMed Central

    Kong, Danyang; Asplund, Christopher L.; Ling, Aiqing; Chee, Michael W.L.

    2015-01-01

    Study Objectives: Temporal expectation enables us to focus limited processing resources, thereby optimizing perceptual and motor processing for critical upcoming events. We investigated the effects of total sleep deprivation (TSD) on temporal expectation by evaluating the foreperiod and sequential effects during a psychomotor vigilance task (PVT). We also examined how these two measures were modulated by vulnerability to TSD. Design: Three 10-min visual PVT sessions using uniformly distributed foreperiods were conducted in the wake-maintenance zone the evening before sleep deprivation (ESD) and three more in the morning following approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were determined by a tertile split of participants based on the change in the number of behavioral lapses recorded during ESD and TSD. A subset of participants performed six additional 10-min modified auditory PVTs with exponentially distributed foreperiods during rested wakefulness (RW) and TSD to test the effect of temporal distribution on foreperiod and sequential effects. Setting: Sleep laboratory. Participants: There were 172 young healthy participants (90 males) with regular sleep patterns. Nineteen of these participants performed the modified auditory PVT. Measurements and Results: Despite behavioral lapses and slower response times, sleep deprived participants could still perceive the conditional probability of temporal events and modify their level of preparation accordingly. Both foreperiod and sequential effects were magnified following sleep deprivation in vulnerable individuals. Only the foreperiod effect increased in nonvulnerable individuals. Conclusions: The preservation of foreperiod and sequential effects suggests that implicit time perception and temporal preparedness are intact during total sleep deprivation. Individuals appear to reallocate their depleted preparatory resources to more probable event timings in ongoing trials, whereas vulnerable

  16. The ecology and evolution of temperature-dependent reaction norms for sex determination in reptiles: a mechanistic conceptual model.

    PubMed

    Pezaro, Nadav; Doody, J Sean; Thompson, Michael B

    2017-08-01

    Sex-determining mechanisms are broadly categorised as being based on either genetic or environmental factors. Vertebrate sex determination exhibits remarkable diversity but displays distinct phylogenetic patterns. While all eutherian mammals possess XY male heterogamety and female heterogamety (ZW) is ubiquitous in birds, poikilothermic vertebrates (fish, amphibians and reptiles) exhibit multiple genetic sex-determination (GSD) systems as well as environmental sex determination (ESD). Temperature is the factor controlling ESD in reptiles and temperature-dependent sex determination (TSD) in reptiles has become a focal point in the study of this phenomenon. Current patterns of climate change may cause detrimental skews in the population sex ratios of reptiles exhibiting TSD. Understanding the patterns of variation, both within and among populations and linking such patterns with the selection processes they are associated with, is the central challenge of research aimed at predicting the capacity of populations to adapt to novel conditions. Here we present a conceptual model that innovates by defining an individual reaction norm for sex determination as a range of incubation temperatures. By deconstructing individual reaction norms for TSD and revealing their underlying interacting elements, we offer a conceptual solution that explains how variation among individual reaction norms can be inferred from the pattern of population reaction norms. The model also links environmental variation with the different patterns of TSD and describes the processes from which they may arise. Specific climate scenarios are singled out as eco-evolutionary traps that may lead to demographic extinction or a transition to either male or female heterogametic GSD. We describe how the conceptual principles can be applied to interpret TSD data and to explain the adaptive capacity of TSD to climate change as well as its limits and the potential applications for conservation and management

  17. The homeostatic and circadian sleep recovery responses after total sleep deprivation in mice.

    PubMed

    Dispersyn, Garance; Sauvet, Fabien; Gomez-Merino, Danielle; Ciret, Sylvain; Drogou, Catherine; Leger, Damien; Gallopin, Thierry; Chennaoui, Mounir

    2017-10-01

    Many studies on sleep deprivation effects lack data regarding the recovery period. We investigated the 2-day homeostatic and circadian sleep recovery response to 24 h of total sleep deprivation (TSD) induced by brief rotation of an activity wheel. Eight mice were implanted with telemetry transmitters (DSI F40-EET) that recorded simultaneously their electroencephalography (EEG), locomotor activity and temperature during 24 h of baseline (BSL), TSD and 2 days of recovery (D1 and D2). In a second experiment, two groups of five non-implanted mice underwent TSD or ad libitum sleep, after which they were killed, adrenal glands were weighed and blood was collected for analysis of corticosterone concentration. During TSD mice were awake at least 97% of the time, with a consecutive sleep rebound during D1 that persisted during D2. This was characterized by increases of non-rapid eye movement (NREM) sleep (44.2 ± 6.9% for D1 and 43.0 ± 7.7% for D2 versus 33.8 ± 9.2% for BSL) and the relative delta band power (179.2 ± 34.4% for D1 and 81.9 ± 11.2% for D2). Greater NREM and REM sleep amounts were observed during the 'light' periods. Temperature and locomotor activity characteristics were unchanged during D1 and D2 versus BSL. In non-implanted mice, corticosterone levels as well as adrenal gland and overall body weights did not differ between TSD and ad libitum sleep groups. In conclusion, 24 h of TSD in an activity wheel without stress responses influence homeostatic sleep regulation with no effect on the circadian regulation over at least 2 days of recovery in mice. © 2017 European Sleep Research Society.

  18. Comparison of RCRA SWMU Corrective Action and CERCLA Remedial Action

    DTIC Science & Technology

    1991-09-30

    4. TITLE AND SUBTITLE 5 . FUNDING NUMBERS Comparison of RCRA SWMU Corrective Action and CERCLA Remedial Action 6. AUTHOR(S) Sam Capps Rupe, Major -1...Interim Status for TSD Facilities .................... 19 5 . Closure and Postclosure Requirements for TSD Facilities ........... 25 D. State Role... 65 1. RCRA Facility Assessment . ............................... 65 2. RCRA Facility Investigation . .............................. 66 3

  19. Changes in Attenuated Total Reflection Fourier Transform Infrared Spectra as Blood Dries Out.

    PubMed

    Zhang, Yinming; Wang, Qi; Li, Bing; Wang, Zhijun; Li, Chengzhi; Yao, Yao; Huang, Ping; Wang, Zhenyuan

    2017-05-01

    The time since deposition (TSD) of a bloodstain is a valuable piece of evidence for forensic scientists to determine the time at which a crime took place. The objective of this study was to determine whether attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy could be used to estimate the TSD of a bloodstain in a relatively early period (from 0 min to the time required for the bloodstain to dry out). For this purpose, we used ATR-FTIR to study the variation in absorbance at certain wavelengths as rat and human blood sample dried out. The absorbance at 3308/cm (A3308) was found to have a close correlation with the TSD during this time period, and the changes in A3308 during the drying of rat and human blood drops under the same controlled conditions showed similar results. The current study indicates that ATR-FTIR spectroscopy has potential as a tool for estimating TSD at early time periods of blood deposition. © 2016 American Academy of Forensic Sciences.

  20. A pilot study testing a natural and a synthetic Molluscicide for controlling invasive apple snails (Pomacea maculata)

    USGS Publications Warehouse

    Olivier, Heather M.; Jenkins, Jill A.; Berhow, Mark; Carter, Jacoby

    2016-01-01

    Pomacea maculata (formerly P. insularum), an apple snail native to South America, was discovered in Louisiana in 2008. These snails strip vegetation, reproduce at tremendous rates, and have reduced rice production and caused ecosystem changes in Asia. In this pilot study snails were exposed to two molluscicides, a tea (Camellia sinensis) seed derivative (TSD) or niclosamide monohydrate (Pestanal®, 2′,5-dichloro-4′-nitrosalicylanilide, CAS #73360-56-2). Mortality was recorded after exposure to high or low concentrations (0.03 and 0.015 g/L for TSD, 1.3 and 0.13 mg/L for niclosamide). The TSD induced 100 % mortality at both concentrations. Niclosamide caused 100 % and 17 % mortality at high and low concentrations respectively. These molluscicides were also tested on potential biocontrol agents, the red swamp crayfish (Procambarus clarkii) and redear sunfish (Lepomis microlophus). No crayfish mortalities occurred at either concentration for either chemical, but sunfish experienced 100 % mortality with TSD (0.03 g/L), and 21 % mortality with niclosamide (0.13 mg/L).

  1. Integrated Sachs-Wolfe effect from the cross correlation of WMAP 3year and the NRAO VLA sky survey data: New results and constraints on dark energy

    NASA Astrophysics Data System (ADS)

    Pietrobon, Davide; Balbi, Amedeo; Marinucci, Domenico

    2006-08-01

    We cross correlate the new 3 year Wilkinson Microwave Anistropy Probe (WMAP) cosmic microwave background data with the NRAO VLA Sky Survey radio galaxy data and find further evidence of late integrated Sachs-Wolfe (ISW) effect taking place at late times in cosmic history. Our detection makes use of a novel statistical method (P. Baldi, G. Kerkyacharian, D. Marinucci, and D. Picard, math.ST/0606154 and P. Baldi, G. Kerkyacharian, D. Marinucci, D. Picard, math.ST/0606599) based on a new construction of spherical wavelets, called needlets. The null hypothesis (no ISW) is excluded at more than 99.7% confidence. When we compare the measured cross correlation with the theoretical predictions of standard, flat cosmological models with a generalized dark energy component parameterized by its density, ΩDE, equation of state w and speed of sound cs2, we find 0.3≤ΩDE≤0.8 at 95% C.L., independently of cs2 and w. If dark energy is assumed to be a cosmological constant (w=-1), the bound on density shrinks to 0.41≤ΩDE≤0.79. Models without dark energy are excluded at more than 4σ. The bounds on w depend rather strongly on the assumed value of cs2. We find that models with more negative equation of state (such as phantom models) are a worse fit to the data in the case cs2=1 than in the case cs2=0.

  2. Effects of TEL Confusers on Operator Target Acquisition Performance with SAR Imagery

    DTIC Science & Technology

    1998-12-01

    processing known as the theory of signal detection (TSD) (Gescheider, 1985; Green & Swets, 1966; Macmillan & Creelman , 1991; Wilson, 1992). A TSD...localizations (Hacker & Ratcliff, 1979; Macmillan & Creelman , 1991). The index of bias in a target localization task provides a measure of the operator’s...of correct localizations substituted for hits (Macmillan & Creelman , 1991). Receiver Operating Characteristic Curves. In addition to the calculation

  3. Predicted sex ratio of juvenile Kemp's Ridley sea turtles captured near Steinhatchee, Florida

    USGS Publications Warehouse

    Geis, A.A.; Barichivich, W.J.; Wibbels, T.; Coyne, M.; Landry, A.M.; Owens, D.

    2005-01-01

    The Kemp's Ridley (Lepidochelys kempii) is one of the most endangered sea turtles in the world, and it possesses temperature-dependent sex determination (TSD). Sex ratios produced under TSD can vary widely and can affect the reproductive ecology of a population. Therefore, sex ratios produced from TSD are of ecological and conservation interest. The current study validated and utilized a testosterone radioimmunoassay (RIA) to examine the sex ratio of juvenile Kemp's Ridleys inhabiting the waters near Steinhatchee, Florida. Testosterone levels were measured in blood samples collected from juvenile Kemp's Ridleys captured over a three-year period. Results of this study indicate that a significant female bias (approximately 3.7:1) occurs in the aggregation of juvenile Kemp's Ridleys inhabiting the waters near Steinhatchee.

  4. Operationalizing Economics for Counterinsurgency and Stability Operations

    DTIC Science & Technology

    2009-05-01

    as freedom, described by Amartya Sen provides an improved foundation for military operations and a more complete campaign framework. Within these...peacekeeping.7 Development described by Amartya Sen is based on a concept that promotes freedom, a cornerstone of democracy and U.S. national policy. The...poverty and disease promote state failure.19 The writings of Jeffery Sachs, Thomas Sowell, Paul Collier, Amartya Sen , the World Bank, and many others

  5. Potential contributions of heat shock proteins to temperature-dependent sex determination in the American alligator.

    PubMed

    Kohno, S; Katsu, Y; Urushitani, H; Ohta, Y; Iguchi, T; Guillette, L J

    2010-01-01

    Sex determination in the American alligator depends on the incubation temperature experienced during a thermo-sensitive period (TSP), although sex determination can be 'reversed' by embryonic exposure to an estrogenic compound. Thus, temperature and estrogenic signals play essential roles during temperature-dependent sex determination (TSD). The genetic basis for TSD is poorly understood, although previous studies observed that many of the genes associated with genetic sex determination (GSD) are expressed in species with TSD. Heat shock proteins (HSPs), good candidates because of their temperature-sensitive expression, have not been examined in regard to TSD but HSPs have the ability to modify steroid receptor function. A number of HSP cDNAs (HSP27, DNAJ, HSP40, HSP47, HSP60, HSP70A, HSP70B, HSP70C, HSP75, HSP90alpha, HSP90beta, and HSP108) as well as cold-inducible RNA binding protein (CIRBP) and HSP-binding protein (HSPBP) were cloned, and expression of their mRNA in the gonadal-adrenal-mesonephros complex (GAM) was investigated. Embryonic and neonatal GAMs exhibited mRNA for all of the HSPs examined during and after the TSP. One-month-old GAMs were separated into 3 portions (gonad, adrenal gland, and mesonephros), and sexual dimorphism in the mRNA expression of gonadal HSP27 (male > female), gonadal HSP70A (male < female), and adrenal HSP90 alpha (male > female) was observed. These findings provide new insights on TSD and suggest that further studies examining the role of HSPs during gonadal development are needed. (c) 2009 S. Karger AG, Basel.

  6. Putative Independent Evolutionary Reversals from Genotypic to Temperature-Dependent Sex Determination are Associated with Accelerated Evolution of Sex-Determining Genes in Turtles.

    PubMed

    Literman, Robert; Burrett, Alexandria; Bista, Basanta; Valenzuela, Nicole

    2018-01-01

    The evolutionary lability of sex-determining mechanisms across the tree of life is well recognized, yet the extent of molecular changes that accompany these repeated transitions remain obscure. Most turtles retain the ancestral temperature-dependent sex determination (TSD) from which multiple transitions to genotypic sex determination (GSD) occurred independently, and two contrasting hypotheses posit the existence or absence of reversals back to TSD. Here we examined the molecular evolution of the coding regions of a set of gene regulators involved in gonadal development in turtles and several other vertebrates. We found slower molecular evolution in turtles and crocodilians compared to other vertebrates, but an acceleration in Trionychia turtles and at some phylogenetic branches demarcating major taxonomic diversification events. Of all gene classes examined, hormone signaling genes, and Srd5a1 in particular, evolve faster in many lineages and especially in turtles. Our data show that sex-linked genes do not follow a ubiquitous nor uniform pattern of molecular evolution. We then evaluated turtle nucleotide and protein evolution under two evolutionary hypotheses with or without GSD-to-TSD reversals, and found that when GSD-to-TSD reversals are considered, all transitional branches irrespective of direction, exhibit accelerated molecular evolution of nucleotide sequences, while GSD-to-TSD transitional branches also show acceleration in protein evolution. Significant changes in predicted secondary structure that may affect protein function were identified in three genes that exhibited hastened evolution in turtles compared to other vertebrates or in transitional versus non-transitional branches within turtles, rendering them candidates for a key role during SDM evolution in turtles.

  7. The Degree of Radiation-Induced DNA Strand Breaks Is Altered by Acute Sleep Deprivation and Psychological Stress and Is Associated with Cognitive Performance in Humans.

    PubMed

    Moreno-Villanueva, Maria; von Scheven, Gudrun; Feiveson, Alan; Bürkle, Alexander; Wu, Honglu; Goel, Namni

    2018-03-27

    Sleep deprivation is associated with impaired immune responses, cancer, and morbidity and mortality, and can degrade cognitive performance, although individual differences exist in such responses. Sleep deprivation induces DNA strand breaks and DNA base oxidation in animals, and psychological stress is associated with increased DNA damage in humans. It remains unknown whether sleep deprivation or psychological stress in humans affects DNA damage response from environmental stressors, and whether these responses predict cognitive performance during sleep deprivation. Sixteen healthy adults (ages 29-52;mean age±SD, 36.4±7.1 years;7 women) participated in a 5-day experiment involving two 8 hour time-in-bed [TIB] baseline nights, followed by 39 hours total sleep deprivation (TSD), and two 8-10 hour TIB recovery nights. A modified Trier Social Stress Test was conducted on the day after TSD. Psychomotor Vigilance Tests measured behavioral attention. DNA damage was assessed in blood cells collected at 5 time points, and blood cells were irradiated ex-vivo. TSD, alone or in combination with psychological stress, did not induce significant increases in DNA damage. By contrast, radiation-induced DNA damage decreased significantly in response to TSD, but increased back to baseline when combined with psychological stress. Cognitively-vulnerable individuals had more radiation-induced DNA strand breaks before TSD, indicating their greater sensitivity to DNA damage from environmental stressors. Our results provide novel insights into the molecular consequences of sleep deprivation, psychological stress, and performance vulnerability. They are important for situations involving sleep loss, radiation exposure and cognitive deficits, including cancer therapy, environmental toxicology, and space medicine.

  8. Prazosin for Treatment of Patients With PTSD and Comorbid Alcohol Dependence

    DTIC Science & Technology

    2013-07-01

    treat individuals with comorbid AD and TSD. The use of an alpha-! adrenergic receptor antagonist represents a novel approach to treatment that may... adrenergic ~ceptor antagonist that has been used successfully in the treatment of trauma nightmares and sleep disturbance in combat veterans with TSD, and...stressor, presented randomly. Outcome measures include self-reported measures of alcohol craving and anxiety . Subjects are subsequently randomized

  9. RNA-seq analysis of the gonadal transcriptome during Alligator mississippiensis temperature-dependent sex determination and differentiation.

    PubMed

    Yatsu, Ryohei; Miyagawa, Shinichi; Kohno, Satomi; Parrott, Benjamin B; Yamaguchi, Katsushi; Ogino, Yukiko; Miyakawa, Hitoshi; Lowers, Russell H; Shigenobu, Shuji; Guillette, Louis J; Iguchi, Taisen

    2016-01-25

    The American alligator (Alligator mississippiensis) displays temperature-dependent sex determination (TSD), in which incubation temperature during embryonic development determines the sexual fate of the individual. However, the molecular mechanisms governing this process remain a mystery, including the influence of initial environmental temperature on the comprehensive gonadal gene expression patterns occurring during TSD. Our characterization of transcriptomes during alligator TSD allowed us to identify novel candidate genes involved in TSD initiation. High-throughput RNA sequencing (RNA-seq) was performed on gonads collected from A. mississippiensis embryos incubated at both a male and a female producing temperature (33.5 °C and 30 °C, respectively) in a time series during sexual development. RNA-seq yielded 375.2 million paired-end reads, which were mapped and assembled, and used to characterize differential gene expression. Changes in the transcriptome occurring as a function of both development and sexual differentiation were extensively profiled. Forty-one differentially expressed genes were detected in response to incubation at male producing temperature, and included genes such as Wnt signaling factor WNT11, histone demethylase KDM6B, and transcription factor C/EBPA. Furthermore, comparative analysis of development- and sex-dependent differential gene expression revealed 230 candidate genes involved in alligator sex determination and differentiation, and early details of the suspected male-fate commitment were profiled. We also discovered sexually dimorphic expression of uncharacterized ncRNAs and other novel elements, such as unique expression patterns of HEMGN and ARX. Twenty-five of the differentially expressed genes identified in our analysis were putative transcriptional regulators, among which were MYBL2, MYCL, and HOXC10, in addition to conventional sex differentiation genes such as SOX9, and FOXL2. Inferred gene regulatory network was constructed

  10. Benefit-Cost Analysis of Foot-and-Mouth Disease Vaccination at the Farm-Level in South Vietnam.

    PubMed

    Truong, Dinh Bao; Goutard, Flavie Luce; Bertagnoli, Stéphane; Delabouglise, Alexis; Grosbois, Vladimir; Peyre, Marisa

    2018-01-01

    This study aimed to analyze the financial impact of foot-and-mouth disease (FMD) outbreaks in cattle at the farm-level and the benefit-cost ratio (BCR) of biannual vaccination strategy to prevent and eradicate FMD for cattle in South Vietnam. Production data were collected from 49 small-scale dairy farms, 15 large-scale dairy farms, and 249 beef farms of Long An and Tay Ninh province using a questionaire. Financial data of FMD impacts were collected using participatory tools in 37 villages of Long An province. The net present value, i.e., the difference between the benefits (additional revenue and saved costs) and costs (additional costs and revenue foregone), of FMD vaccination in large-scale dairy farms was 2.8 times higher than in small-scale dairy farms and 20 times higher than in beef farms. The BCR of FMD vaccination over 1 year in large-scale dairy farms, small-scale dairy farms, and beef farms were 11.6 [95% confidence interval (95% CI) 6.42-16.45], 9.93 (95% CI 3.45-16.47), and 3.02 (95% CI 0.76-7.19), respectively. The sensitivity analysis showed that varying the vaccination cost had more effect on the BCR of cattle vaccination than varying the market price. This benefit-cost analysis of biannual vaccination strategy showed that investment in FMD prevention can be financially profitable, and therefore sustainable, for dairy farmers. For beef cattle, it is less certain that vaccination is profitable. Additional benefit-cost analysis study of vaccination strategies at the national-level would be required to evaluate and adapt the national strategy to achieve eradication of this disease in Vietnam.

  11. Short-term memory deficits correlate with hippocampal-thalamic functional connectivity alterations following acute sleep restriction.

    PubMed

    Chengyang, Li; Daqing, Huang; Jianlin, Qi; Haisheng, Chang; Qingqing, Meng; Jin, Wang; Jiajia, Liu; Enmao, Ye; Yongcong, Shao; Xi, Zhang

    2017-08-01

    Acute sleep restriction heavily influences cognitive function, affecting executive processes such as attention, response inhibition, and memory. Previous neuroimaging studies have suggested a link between hippocampal activity and short-term memory function. However, the specific contribution of the hippocampus to the decline of short-term memory following sleep restriction has yet to be established. In the current study, we utilized resting-state functional magnetic resonance imaging (fMRI) to examine the association between hippocampal functional connectivity (FC) and the decline of short-term memory following total sleep deprivation (TSD). Twenty healthy adult males aged 20.9 ± 2.3 years (age range, 18-24 years) were enrolled in a within-subject crossover study. Short-term memory and FC were assessed using a Delay-matching short-term memory test and a resting-state fMRI scan before and after TSD. Seed-based correlation analysis was performed using fMRI data for the left and right hippocampus to identify differences in hippocampal FC following TSD. Subjects demonstrated reduced alertness and a decline in short-term memory performance following TSD. Moreover, fMRI analysis identified reduced hippocampal FC with the superior frontal gyrus (SFG), temporal regions, and supplementary motor area. In addition, an increase in FC between the hippocampus and bilateral thalamus was observed, the extent of which correlated with short-term memory performance following TSD. Our findings indicate that the disruption of hippocampal-cortical connectivity is linked to the decline in short-term memory observed after acute sleep restriction. Such results provide further evidence that support the cognitive impairment model of sleep deprivation.

  12. Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression.

    PubMed

    Dallaspezia, Sara; Locatelli, Clara; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Benedetti, Francesco

    2016-03-01

    Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. PER3 polymorphism influenced changes in total sleep time (F=2.24; p=0.024): while PER3(4/4) and PER3(4/5) patients showed a reduction in it after treatment, PER3(5/5) subjects showed an increase of about 40min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028). Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus.

    PubMed

    Matos, Gabriela; Ribeiro, Daniel A; Alvarenga, Tathiana A; Hirotsu, Camila; Scorza, Fulvio A; Le Sueur-Maluf, Luciana; Noguti, Juliana; Cavalheiro, Esper A; Tufik, Sergio; Andersen, Monica L

    2012-05-02

    The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  14. Procedural performance following sleep deprivation remains impaired despite extended practice and an afternoon nap

    PubMed Central

    Kurniawan, Irma Triasih; Cousins, James Nicholas; Chong, Pearlynne L. H.; Chee, Michael W. L.

    2016-01-01

    The negative impact of sleep loss on procedural memory is well established, yet it remains unclear how extended practice opportunities or daytime naps can modulate the effect of a night of sleep deprivation. Here, participants underwent three training and test conditions on a sequential finger tapping task (SFTT) separated by at least one week. In the first condition they were trained in the evening followed by a night of sleep. Two further conditions took place where evening training was followed by a night of total sleep deprivation (TSD). One of the TSD conditions included a one-hour nap opportunity (15:00). Compared to the condition in which sleep was permitted, a night of TSD resulted in poorer performance across 4 practices the following day (10:00–19:00). The deleterious effect of a single night of TSD on procedural performance, was neither clearly alleviated by an afternoon nap nor by multiple practice opportunities. Interestingly, significant gains in performance were observed in all conditions after a one-week delay. Recovery sleep on subsequent nights thus appeared to nullify the effect of a single night of sleep deprivation, underscoring the importance of offline consolidation on the acquisition of procedural skill. PMID:27782172

  15. Aeroelastic Calculations Using CFD for a Typical Business Jet Model

    NASA Technical Reports Server (NTRS)

    Gibbons, Michael D.

    1996-01-01

    Two time-accurate Computational Fluid Dynamics (CFD) codes were used to compute several flutter points for a typical business jet model. The model consisted of a rigid fuselage with a flexible semispan wing and was tested in the Transonic Dynamics Tunnel at NASA Langley Research Center where experimental flutter data were obtained from M(sub infinity) = 0.628 to M(sub infinity) = 0.888. The computational results were computed using CFD codes based on the inviscid TSD equation (CAP-TSD) and the Euler/Navier-Stokes equations (CFL3D-AE). Comparisons are made between analytical results and with experiment where appropriate. The results presented here show that the Navier-Stokes method is required near the transonic dip due to the strong viscous effects while the TSD and Euler methods used here provide good results at the lower Mach numbers.

  16. Taste, umami-enhance effect and amino acid sequence of peptides separated from silkworm pupa hydrolysate.

    PubMed

    Yu, Zilin; Jiang, Hongrui; Guo, Rongcan; Yang, Bo; You, Gang; Zhao, Mouming; Liu, Xiaoling

    2018-06-01

    Four umami peptides were separated and purified by ultrafiltration, gel filtration chromatography and identified by ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS), the amino acid sequences of four peptides are Val-Pro-Tyr (VPY), Thr-Ala-Tyr (TAY), Ala-Ala-Pro-Tyr (AAPY) and Gly-Phe-Pro (GFP). The result illustrates that the umami amino acids are not the content of umami peptides, but bitter amino acids are included. The threshold of VPY, TAY, AAPY and GFP were 1.65 mmol/L, 1.76 mmol/L, 2.97 mmol/L and 6.26 mmol/L, respectively. The peptide TAY, VPY and AAPY had an umami-enhancement effect on the monosodium glutamate (MSG) + sodium chloride (NaCl) solution, their concentrations were 2.5 g/L, 5 g/L and 5 g/L, respectively, while GFP has no significant umami-enhancement effect in solution. In addition, the peptides have better taste than its composing amino acids, which indicates that the taste of peptide does not depend on its composing amino acids. Copyright © 2018. Published by Elsevier Ltd.

  17. Vogt-Koyanagi-Harada disease: inquiry into the genesis of a disease name in the historical context of Switzerland and Japan.

    PubMed

    Herbort, Carl P; Mochizuki, Manabu

    2007-01-01

    To delineate the historical steps associated with the genesis of the name and the definition of Vogt-Koyanagi-Harada (VKH) disease. A bibliographical review of the major publications that were relevant to the original development of the name of the clinical entity known today as Vogt-Koyanagi-Harada disease, in the historical context of the early 20th century. Three distinct time periods can be considered to be important in terms of providing a historical perspective on VKH disease. Given that the cutaneous manifestations of VKH disease are so characteristic, these could not have been missed even before the actual clinical entity of VKH was recognized in the early 20th century. Indeed, several authors, including the Arabic doctor Mohammad-al-Ghâfiqî in the 12th century as well as Jacobi, Nettelship and Tay in the 19th century, described poliosis, neuralgias and hearing disorders. Many of these cases were probably due to sympathetic ophthalmia, but some were clearly VKH cases. The second phase is characterized by the surge of articles that appeared early in the 20th century that defined the disease more precisely. A number of these authors subsequently became associated with the disease name, the first being Alfred Vogt from Switzerland, followed by Japanese researchers. Yoshizo Koyanagi was in fact not the first Japanese author to describe the disease; this honor goes to the first Japanese Professor of Ophthalmology at the University of Tokyo, Dr. Jujiro Komoto, who published in a German language journal, Klinische Monatsblätter für Augenheilkunde in 1911. Yoshizo Koyanagi published his first report in the Nippon Ganka Gakkai Zasshi 3 years later, in 1914, but it was a much later article, one published in 1929, that definitively associated his name with the disease. In this review article, Koyanagi reported 16 cases, of which six were his own cases, that beautifully illustrate the natural course of the disease. In this same time period, Einosuke Harada, in an

  18. An unbiased approach to identify genes involved in development in a turtle with temperature-dependent sex determination.

    PubMed

    Chojnowski, Jena L; Braun, Edward L

    2012-07-15

    Many reptiles exhibit temperature-dependent sex determination (TSD). The initial cue in TSD is incubation temperature, unlike genotypic sex determination (GSD) where it is determined by the presence of specific alleles (or genetic loci). We used patterns of gene expression to identify candidates for genes with a role in TSD and other developmental processes without making a priori assumptions about the identity of these genes (ortholog-based approach). We identified genes with sexually dimorphic mRNA accumulation during the temperature sensitive period of development in the Red-eared slider turtle (Trachemys scripta), a turtle with TSD. Genes with differential mRNA accumulation in response to estrogen (estradiol-17β; E(2)) exposure and developmental stages were also identified. Sequencing 767 clones from three suppression-subtractive hybridization libraries yielded a total of 581 unique sequences. Screening a macroarray with a subset of those sequences revealed a total of 26 genes that exhibited differential mRNA accumulation: 16 female biased and 10 male biased. Additional analyses revealed that C16ORF62 (an unknown gene) and MALAT1 (a long noncoding RNA) exhibited increased mRNA accumulation at the male producing temperature relative to the female producing temperature during embryonic sexual development. Finally, we identified four genes (C16ORF62, CCT3, MMP2, and NFIB) that exhibited a stage effect and five genes (C16ORF62, CCT3, MMP2, NFIB and NOTCH2) showed a response to E(2) exposure. Here we report a survey of genes identified using patterns of mRNA accumulation during embryonic development in a turtle with TSD. Many previous studies have focused on examining the turtle orthologs of genes involved in mammalian development. Although valuable, the limitations of this approach are exemplified by our identification of two genes (MALAT1 and C16ORF62) that are sexually dimorphic during embryonic development. MALAT1 is a noncoding RNA that has not been implicated

  19. Validity and sensitivity of a brief psychomotor vigilance test (PVT-B) to total and partial sleep deprivation

    NASA Astrophysics Data System (ADS)

    Basner, Mathias; Mollicone, Daniel; Dinges, David F.

    2011-12-01

    The Psychomotor Vigilance Test (PVT) objectively assesses fatigue-related changes in alertness associated with sleep loss, extended wakefulness, circadian misalignment, and time on task. The standard 10-min PVT is often considered impractical in applied contexts. To address this limitation, we developed a modified brief 3-min version of the PVT (PVT-B). The PVT-B was validated in controlled laboratory studies with 74 healthy subjects (34 female, aged 22-45 years) that participated either in a total sleep deprivation (TSD) study involving 33 h awake ( N=31 subjects) or in a partial sleep deprivation (PSD) protocol involving 5 consecutive nights of 4 h time in bed ( N=43 subjects). PVT and PVT-B were performed regularly during wakefulness. Effect sizes of 5 key PVT outcomes were larger for TSD than PSD and larger for PVT than for PVT-B for all outcomes. Effect size was largest for response speed (reciprocal response time) for both the PVT-B and the PVT in both TSD and PSD. According to Cohen's criteria, effect sizes for the PVT-B were still large (TSD) or medium to large (PSD, except for fastest 10% RT). Compared to the 70% decrease in test duration the 22.7% (range 6.9-67.8%) average decrease in effect size was deemed an acceptable trade-off between duration and sensitivity. Overall, PVT-B performance had faster response times, more false starts and fewer lapses than PVT performance (all p<0.01). After reducing the lapse threshold from 500 to 355 ms for PVT-B, mixed model ANOVAs indicated no differential sensitivity to sleep loss between PVT-B and PVT for all outcome variables (all P>0.15) but the fastest 10% response times during PSD ( P<0.001), and effect sizes increased from 1.38 to 1.49 (TSD) and 0.65 to 0.76 (PSD), respectively. In conclusion, PVT-B tracked standard 10-min PVT performance throughout both TSD and PSD, and yielded medium to large effect sizes. PVT-B may be a useful tool for assessing behavioral alertness in settings where the duration of the 10

  20. Modeling transonic aerodynamic response using nonlinear systems theory for use with modern control theory

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.

    1993-01-01

    The presentation begins with a brief description of the motivation and approach that has been taken for this research. This will be followed by a description of the Volterra Theory of Nonlinear Systems and the CAP-TSD code which is an aeroelastic, transonic CFD (Computational Fluid Dynamics) code. The application of the Volterra theory to a CFD model and, more specifically, to a CAP-TSD model of a rectangular wing with a NACA 0012 airfoil section will be presented.

  1. Designs of Optoelectronic Trinary Signed-Digit Multiplication by use of Joint Spatial Encodings and Optical Correlation

    NASA Astrophysics Data System (ADS)

    Cherri, Abdallah K.

    1999-02-01

    Trinary signed-digit (TSD) symbolic-substitution-based (SS-based) optical adders, which were recently proposed, are used as the basic modules for designing highly parallel optical multiplications by use of cascaded optical correlators. The proposed multiplications perform carry-free generation of the multiplication partial products of two words in constant time. Also, three different multiplication designs are presented, and new joint spatial encodings for the TSD numbers are introduced. The proposed joint spatial encodings allow one to reduce the SS computation rules involved in optical multiplication. In addition, the proposed joint spatial encodings increase the space bandwidth product of the spatial light modulators of the optical system. This increase is achieved by reduction of the numbers of pixels in the joint spatial encodings for the input TSD operands as well as reduction of the number of pixels used in the proposed matched spatial filters for the optical multipliers.

  2. Designs of optoelectronic trinary signed-digit multiplication by use of joint spatial encodings and optical correlation.

    PubMed

    Cherri, A K

    1999-02-10

    Trinary signed-digit (TSD) symbolic-substitution-based (SS-based) optical adders, which were recently proposed, are used as the basic modules for designing highly parallel optical multiplications by use of cascaded optical correlators. The proposed multiplications perform carry-free generation of the multiplication partial products of two words in constant time. Also, three different multiplication designs are presented, and new joint spatial encodings for the TSD numbers are introduced. The proposed joint spatial encodings allow one to reduce the SS computation rules involved in optical multiplication. In addition, the proposed joint spatial encodings increase the space-bandwidth product of the spatial light modulators of the optical system. This increase is achieved by reduction of the numbers of pixels in the joint spatial encodings for the input TSD operands as well as reduction of the number of pixels used in the proposed matched spatial filters for the optical multipliers.

  3. Climate change and temperature-dependent sex determination: can individual plasticity in nesting phenology prevent extreme sex ratios?

    PubMed

    Schwanz, Lisa E; Janzen, Fredric J

    2008-01-01

    Under temperature-dependent sex determination (TSD), temperatures experienced by embryos during development determine the sex of the offspring. Consequently, populations of organisms with TSD have the potential to be strongly impacted by climatic warming that could bias offspring sex ratio, a fundamental demographic parameter involved in population dynamics. Moreover, many taxa with TSD are imperiled, so research on this phenomenon, particularly long-term field study, has assumed great urgency. Recently, turtles with TSD have joined the diverse list of taxa that have demonstrated population-level changes in breeding phenology in response to recent climate change. This raises the possibility that any adverse impacts of climate change on populations may be alleviated by individual plasticity in nesting phenology. Here, we examine data from a long-term study on a population of painted turtles (Chrysemys picta) to determine whether changes in phenology are due to individual plasticity and whether individual plasticity in the timing of nesting has the capacity to offset the sex ratio effects of a rise in climatic temperature. We find that individual females show plasticity in the date of first nesting each year, and that this plasticity depends on the climate from the previous winter. First nesting date is not repeatable within individuals, suggesting that it would not respond to selection. Sex ratios of hatchlings within a nest declined nonsignificantly over the nesting season. However, small increases in summer temperature had a much stronger effect on nest sex ratios than did laying nests earlier in the season. For this and other reasons, it seems unlikely that individual plasticity in the timing of nesting will offset the effects of climate change on sex ratios in this population, and we hypothesize that this conclusion applies to other populations with TSD.

  4. MeDIP-seq and nCpG analyses illuminate sexually dimorphic methylation of gonadal development genes with high historic methylation in turtle hatchlings with temperature-dependent sex determination.

    PubMed

    Radhakrishnan, Srihari; Literman, Robert; Mizoguchi, Beatriz; Valenzuela, Nicole

    2017-01-01

    DNA methylation alters gene expression but not DNA sequence and mediates some cases of phenotypic plasticity. Temperature-dependent sex determination (TSD) epitomizes phenotypic plasticity where environmental temperature drives embryonic sexual fate, as occurs commonly in turtles. Importantly, the temperature-specific transcription of two genes underlying gonadal differentiation is known to be induced by differential methylation in TSD fish, turtle and alligator. Yet, how extensive is the link between DNA methylation and TSD remains unclear. Here we test for broad differences in genome-wide DNA methylation between male and female hatchling gonads of the TSD painted turtle Chrysemys picta using methyl DNA immunoprecipitation sequencing, to identify differentially methylated candidates for future study. We also examine the genome-wide nCpG distribution (which affects DNA methylation) in painted turtles and test for historic methylation in genes regulating vertebrate gonadogenesis. Turtle global methylation was consistent with other vertebrates (57% of the genome, 78% of all CpG dinucleotides). Numerous genes predicted to regulate turtle gonadogenesis exhibited sex-specific methylation and were proximal to methylated repeats. nCpG distribution predicted actual turtle DNA methylation and was bimodal in gene promoters (as other vertebrates) and introns (unlike other vertebrates). Differentially methylated genes, including regulators of sexual development, had lower nCpG content indicative of higher historic methylation. Ours is the first evidence suggesting that sexually dimorphic DNA methylation is pervasive in turtle gonads (perhaps mediated by repeat methylation) and that it targets numerous regulators of gonadal development, consistent with the hypothesis that it may regulate thermosensitive transcription in TSD vertebrates. However, further research during embryogenesis will help test this hypothesis and the alternative that instead, most differential methylation

  5. One night of total sleep deprivation promotes a state of generalized hyperalgesia: a surrogate pain model to study the relationship of insomnia and pain.

    PubMed

    Schuh-Hofer, Sigrid; Wodarski, Rachel; Pfau, Doreen B; Caspani, Ombretta; Magerl, Walter; Kennedy, Jeffrey D; Treede, Rolf-Detlef

    2013-09-01

    Sleep disturbances are highly prevalent in chronic pain patients. Understanding their relationship has become an important research topic since poor sleep and pain are assumed to closely interact. To date, human experimental studies exploring the impact of sleep disruption/deprivation on pain perception have yielded conflicting results. This inconsistency may be due to the large heterogeneity of study populations and study protocols previously used. In addition, none of the previous studies investigated the entire spectrum of nociceptive modalities. To address these shortcomings, a standardized comprehensive quantitative sensory protocol was used in order to compare the somatosensory profile of 14 healthy subjects (6 female, 8 male, 23.5 ± 4.1 year; mean ± SD) after a night of total sleep deprivation (TSD) and a night of habitual sleep in a cross-over design. One night of TSD significantly increased the level of sleepiness (P<0.001) and resulted in higher scores of the State Anxiety Inventory (P<0.01). In addition to previously reported hyperalgesia to heat (P<0.05) and blunt pressure (P<0.05), study participants developed hyperalgesia to cold (P<0.01) and increased mechanical pain sensitivity to pinprick stimuli (P<0.05) but no changes in temporal summation. Paradoxical heat sensations or dynamic mechanical allodynia were absent. TSD selectively modulated nociception, since detection thresholds of non-nociceptive modalities remained unchanged. Our findings show that a single night of TSD is able to induce generalized hyperalgesia and to increase State Anxiety scores. In the future, TSD may serve as a translational pain model to elucidate the pathomechanisms underlying the hyperalgesic effect of sleep disturbances. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. Acute sleep deprivation increases food purchasing in men.

    PubMed

    Chapman, Colin D; Nilsson, Emil K; Nilsson, Victor C; Cedernaes, Jonathan; Rångtell, Frida H; Vogel, Heike; Dickson, Suzanne L; Broman, Jan-Erik; Hogenkamp, Pleunie S; Schiöth, Helgi B; Benedict, Christian

    2013-12-01

    To investigate if acute sleep deprivation affects food purchasing choices in a mock supermarket. On the morning after one night of total sleep deprivation (TSD) or after one night of sleep, 14 normal-weight men were given a fixed budget (300 SEK-approximately 50 USD). They were instructed to purchase as much as they could out of a possible 40 items, including 20 high-caloric foods (>2 kcal/g) and 20 low-caloric foods (<2 kcal/g). The prices of the high-caloric foods were then varied (75%, 100% (reference price), and 125%) to determine if TSD affects the flexibility of food purchasing. Before the task, participants received a standardized breakfast, thereby minimizing the potential confound produced by hunger. In addition, morning plasma concentrations of the orexigenic hormone ghrelin were measured under fasting conditions. Independent of both type of food offered and price condition, sleep-deprived men purchased significantly more calories (+9%) and grams (+18%) of food than they did after one night of sleep (both P < 0.05). Morning plasma ghrelin concentrations were also higher after TSD (P < 0.05). However, this increase did not correlate with the effects of TSD on food purchasing. This experiment demonstrates that acute sleep loss alters food purchasing behavior in men. Copyright © 2013 The Obesity Society.

  7. Epidemiological investigation of tattoo-like skin lesions among bottlenose dolphins in Shark Bay, Australia.

    PubMed

    Powell, Sarah N; Wallen, Megan M; Bansal, Shweta; Mann, Janet

    2018-07-15

    Bottlenose dolphins are excellent bioindicators of ocean ecosystem health for three reasons: (a) as long-lived apex predators they accumulate biotoxins and contaminants; (b) they are visible, routinely appearing at the water's surface in coastal areas, often coming into close contact with humans; and, (c) they exhibit a range of pathogenic lesions attributable to environmental degradation. In this study, we analyzed tattoo-like skin lesions in a population of Tursiops aduncus studied for 30+years in Shark Bay, Australia, a UNESCO World Heritage Site. We provide important baseline data by documenting epidemiological patterns of tattoo-like skin lesions in a healthy, free-ranging population that builds on the previous data of tattoo skin disease (TSD) derived from free ranging, stranded, and dead dolphins. Individual dolphins were classified as symptomatic with tattoo-like skin disease if at least one photograph showed a lesion similar to TSD. The average age of infection was 26.6months (±34.8months) with the symptomatic period lasting 137±29.8days. Overall prevalence of tattoo-like skin disease in the population was 19.4%. Age, but not sex, was significant, with yearlings (1-2years) exhibiting tattoo-like lesions more than younger and older calves. Tattoo-like lesions were rare among juvenile and adult dolphins (N=68 calves, 4 juveniles, and 3 adults). We hypothesize that the lower prevalence in youngest calves (<1year) is due to maternal immunity, while older individuals (>2years) have infection-acquired immunity, as reported for other small cetaceans. The low prevalence of tattoo-like lesions in Shark Bay compared to other populations with poxvirus is consistent with reproductive and demographic viability analyses. Furthermore, by documenting the demography of the disease, we can monitor changes in the prevalence of tattoo-like lesions as a sentinel indicator of ecosystem health. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. GRAIN-SCALE FAILURE IN THERMAL SPALLATION DRILLING

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Walsh, S C; Lomov, I; Roberts, J J

    2012-01-19

    Geothermal power promises clean, renewable, reliable and potentially widely-available energy, but is limited by high initial capital costs. New drilling technologies are required to make geothermal power financially competitive with other energy sources. One potential solution is offered by Thermal Spallation Drilling (TSD) - a novel drilling technique in which small particles (spalls) are released from the rock surface by rapid heating. While TSD has the potential to improve drilling rates of brittle granitic rocks, the coupled thermomechanical processes involved in TSD are poorly described, making system control and optimization difficult for this drilling technology. In this paper, we discussmore » results from a new modeling effort investigating thermal spallation drilling. In particular, we describe an explicit model that simulates the grain-scale mechanics of thermal spallation and use this model to examine existing theories concerning spalling mechanisms. We will report how borehole conditions influence spall production, and discuss implications for macro-scale models of drilling systems.« less

  9. High-performance Chinese multiclass traffic sign detection via coarse-to-fine cascade and parallel support vector machine detectors

    NASA Astrophysics Data System (ADS)

    Chang, Faliang; Liu, Chunsheng

    2017-09-01

    The high variability of sign colors and shapes in uncontrolled environments has made the detection of traffic signs a challenging problem in computer vision. We propose a traffic sign detection (TSD) method based on coarse-to-fine cascade and parallel support vector machine (SVM) detectors to detect Chinese warning and danger traffic signs. First, a region of interest (ROI) extraction method is proposed to extract ROIs using color contrast features in local regions. The ROI extraction can reduce scanning regions and save detection time. For multiclass TSD, we propose a structure that combines a coarse-to-fine cascaded tree with a parallel structure of histogram of oriented gradients (HOG) + SVM detectors. The cascaded tree is designed to detect different types of traffic signs in a coarse-to-fine process. The parallel HOG + SVM detectors are designed to do fine detection of different types of traffic signs. The experiments demonstrate the proposed TSD method can rapidly detect multiclass traffic signs with different colors and shapes in high accuracy.

  10. Environmental assessment for proposed energy conservation standards for three types of consumer products: dishwashers, clothes washers and clothes dryers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1989-01-01

    This environmental assessment (EA) evaluates the environmental impacts resulting from new or amended energy-efficiency standards for dishwashers, clothes washers and clothes dryers as mandated by the National Appliance Energy Conservation Act of 1987. A complete description of the Engineering and Economic Analysis of the proposed standards may be found elsewhere in the Technical Support Document (TSD). All eleven of the scenarios for product design changes described in the Engineering Analysis of the TSD are analyzed in the environmental assessment in the form of levels of pollutant reduction. Level 1 represents the least amount of pollutant reduction, while higher numbered levelsmore » represent increasingly more stringent standards, with correspondingly greater reductions in pollutants. Values for energy savings that result from product design changes are taken from the TSD. These energy savings are based on recent data on actual usage rather than DOE test procedures. 12 refs., 1 fig., 12 tabs.« less

  11. [Mortality from respiratory diseases in the provinces of Apulia Region (Southern Italy) from 1933 to 2010].

    PubMed

    Montinari, Maria Rosa; Gianicolo, Emilio Antonio Luca; Vigotti, Maria Angela

    2016-01-01

    OBIETTIVI: valutare l'andamento temporale della mortalità per patologie respiratorie nelle province pugliesi utilizzando dati omogenei per fonte e metodologia di calcolo. DISEGNO: analisi ecologica storica degli andamenti temporali di mortalità per tumori e patologie dell'apparato respiratorio nelle province pugliesi, in Puglia e nelle ripartizioni geografiche italiane dal 1933 al 2010. SETTING E PARTECIPANTI: i dati di mortalità e le popolazioni residenti sono di fonte Istat. Sono state esaminate tutte le cause di decesso, il tumore della laringe, il tumore del polmone, l'insieme dei tumori respiratori, la bronchite, la polmonite e la broncopolmonite considerate congiuntamente, e l'insieme delle patologie respiratorie. Le analisi sono disaggregate per sesso dal 1969. PRINCIPALI MISURE DI OUTCOME: rapporti standardizzati di mortalità (SMR%) in riferimento all'Italia, con intervalli di confidenza al 95%, e tassi di mortalità standardizzati col metodo diretto (TSD ) in riferimento alla popolazione standard europea. RISULTATI: dal 1933 al 2010, i TSD per tumori respiratori e per bronchiti diminuiscono in tutte le aree analizzate. Tuttavia, nelle province di Taranto, Brindisi e Lecce, l'SMR% per tumori respiratori, inferiore al riferimento nazionale fino agli anni Sessanta, si allinea (a Brindisi) e supera (a Lecce e Taranto) il riferimento negli anni successivi. Nelle province di Foggia e Bari il numero dei decessi per tumore del polmone è costantemente inferiore all'atteso. CONCLUSIONI: la ricostruzione storica e l'analisi dei trend temporali di mortalità dal 1933 al 2010 mostrano alcune criticità sanitarie in periodi specifici. L'elaborazione dei dati di mortalità per un arco temporale di circa 80 anni ha messo in evidenza la maggiore rilevanza di queste criticità con l'avvio dello sviluppo industriale.

  12. Molecular marker suggests rapid changes of sex-determining mechanisms in Australian dragon lizards.

    PubMed

    Ezaz, Tariq; Quinn, Alexander E; Sarre, Stephen D; O'Meally, Denis; Georges, Arthur; Graves, Jennifer A Marshall

    2009-01-01

    Distribution of sex-determining mechanisms across Australian agamids shows no clear phylogenetic segregation, suggesting multiple transitions between temperature-dependent (TSD) and genotypic sex determination (GSD). These taxa thus present an excellent opportunity for studying the evolution of sex chromosomes, and evolutionary transitions between TSD and GSD. Here we report the hybridization of a 3 kb genomic sequence (PvZW3) that marks the Z and W microchromosomes of the Australian central bearded dragon (Pogona vitticeps) to chromosomes of 12 species of Australian agamids from eight genera using fluorescence in-situ hybridization (FISH). The probe hybridized to a single microchromosome pair in 11 of these species, but to the tip of the long arm of chromosome pair 2 in the twelfth (Physignathus lesueurii), indicating a micro-macro chromosome rearrangement. Three TSD species shared the marked microchromosome, implying that it is a conserved autosome in related species that determine sex by temperature. C-banding identified the marked microchromosome as the heterochromatic W chromosome in two of the three GSD species. However, in Ctenophorus fordi, the probe hybridized to a different microchromosome from that shown by C-banding to be the heterochromatic W, suggesting an independent origin for the ZW chromosome pair in that species. Given the haphazard distribution of GSD and TSD in this group and the existence of at least two sets of sex microchromosomes in GSD species, we conclude that sex-determining mechanisms in this family have evolved independently, multiple times in a short evolutionary period.

  13. Origin and transition of sex determination mechanisms in a gynogenetic hexaploid fish.

    PubMed

    Li, Xi-Yin; Liu, Xiao-Li; Zhu, Yao-Jun; Zhang, Jun; Ding, Miao; Wang, Ming-Tao; Wang, Zhong-Wei; Li, Zhi; Zhang, Xiao-Juan; Zhou, Li; Gui, Jian-Fang

    2018-02-02

    Most vertebrates reproduce sexually, and plastic sex determination mechanisms including genotypic sex determination (GSD) and environmental sex determination (ESD) have been extensively revealed. However, why sex determination mechanisms evolve diversely and how they correlate with diverse reproduction strategies remain largely unclear. Here, we utilize the superiority of a hexaploid gibel carp (Carassius gibelio) that is able to reproduce by unisexual gynogenesis and contains a rare but diverse proportion of males to investigate these puzzles. A total of 2248 hexaploid specimens were collected from 34 geographic wild populations throughout mainland China, in which 24 populations were revealed to contain 186 males with various incidences ranging from 1.2 to 26.5%. Subsequently, the proportion of temperature-dependent sex determination (TSD) was revealed to be positively correlated to average annual temperature in wild populations, and male incidence in lab gynogenetic progenies was demonstrated to increase with the increasing of larval rearing temperature. Meanwhile, extra microchromosomes were confirmed to play genotypic male determination role as previously reported. Thereby, GSD and TSD were found to coexist in gibel carp, and the proportions of GSD were observed to be much higher than that of TSD in sympatric wild populations. Our findings uncover a potential new mechanism in the evolution of sex determination system in polyploid vertebrates with unisexual gynogenesis ability, and also reveal a possible association of sex determination mechanism transition between TSD and GSD and reproduction mode transition between unisexual gynogenesis and bisexual reproduction.

  14. PULPAL BLOOD FLOW CHANGES IN ABUTMENT TEETH OF REMOVABLE PARTIAL DENTURES

    PubMed Central

    Kunt, Göknil Ergün; Kökçü, Deniz; Ceylan, Gözlem; Yılmaz, Nergiz; Güler, Ahmet Umut

    2009-01-01

    The purpose of this study was to investigate the effect of tooth supported (TSD) and toothtissue supported (TTSD) removable partial denture wearing on pulpal blood flow (PBF) of the abutment teeth by using Laser Doppler Flowmeter (LDF). Measurements were carried out on 60 teeth of 28 patients (28 teeth and 12 patients of TTSD group, 32 teeth and 16 patients of TSD group) who had not worn any type of removable partial dentures before, had no systemic problems and were non smokers. PBF values were recorded by LDF before insertion (day 0) and after insertion of dentures at day 1, day 7 and day 30. Statistical analysis was performed by student t test and covariance analyses of repeated measurements. In the group TTSD, the mean values of PBF decreased statistically significantly at day 1 after insertion when compared with PBF values before insertion (p<0,01). There was no statistically significant difference among PBF mean values on 1st, 7th and 30th day. However, in the group TSD, there was no statistically significant difference among PBF mean values before insertion and on 1st, 7th and 30th day. In other words, PBF mean values in group TSD continued without changing statistically significant on 1st, 7th and 30th day. TTSD wearing may show negative effect on the abutment teeth due to decreasing basal PBF. PMID:20001995

  15. Unrecognized Sleep Loss Accumulated in Daily Life Can Promote Brain Hyperreactivity to Food Cue.

    PubMed

    Katsunuma, Ruri; Oba, Kentaro; Kitamura, Shingo; Motomura, Yuki; Terasawa, Yuri; Nakazaki, Kyoko; Hida, Akiko; Moriguchi, Yoshiya; Mishima, Kazuo

    2017-10-01

    Epidemiological studies have shown that sleep debt increases the risk of obesity. Experimental total sleep deprivation (TSD) has been reported to activate the reward system in response to food stimuli, but food-related responses in everyday sleep habits, which could lead to obesity, have not been addressed. Here, we report that habitual sleep time at home among volunteers without any sleep concerns was shorter than their optimal sleep time estimated by the 9-day extended sleep intervention, which indicates that participants had already been in sleep debt in their usual sleep habits. The amygdala and anterior insula, which are responsible for both affective responses and reward prediction, were found to exhibit significantly lowered activity in the optimal sleep condition. Additionally, a subsequent one-night period of TSD reactivated the right anterior insula in response to food images; however, the activity level of amygdala remained lowered. These findings indicate that (1) our brain is at risk of hyperactivation to food triggers in everyday life, which could be a risk factor for obesity and lifestyle diseases, and (2) optimal sleep appears to reduce this hypersensitivity to food stimuli. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  16. Auditory Pattern Memory

    DTIC Science & Technology

    1990-10-31

    Creelman , 1962; Getty, 1975; Divenyi and Danner, kin et aL (1982) jitter-detection paradigm. An advantage of 1977; Divenyi and Sachs, 1978; and Allen...discrimination of tonal se- Creelman . C. D. (1962). "’Human discrimination ofauditory duration." 3. quences.’" J. Acoust. Soc. Am. 82.1218-1226. Acoust...single marked intervals (Abel, 1972a,b; Creelman , 1962; Getty, 1975; Divenyi and Danner, 1977; Divenyi and Sachs, 1978; Espinoza-Varas and Jamieson

  17. Determination of PCDD/Fs in breast milk of women living in the vicinities of Da Nang Agent Orange hot spot (Vietnam) and estimation of the infant's daily intake.

    PubMed

    Hue, N T M; Nam, V D; Thuong, N V; Huyen, N T; Phuong, N T H; Hung, N X; Tuan, N H; Son, L K; Minh, N H

    2014-09-01

    Seventeen toxic congeners of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were determined in breast milks using the high resolution gas chromatography/high resolution mass spectrometry (HRGC/HRMS) method. Twenty seven breast milk samples were collected from primiparae who have lived over 5 years in wards namely Chinh Gian, An Khe, Khue Trung, and Hoa Thuan Tay which are located near the Da Nang Agent Orange hot spot (the AO/Dioxin hot spot). The samples were then analyzed for PCDD/F residues in order to assess the human exposure to dioxins from the AO/Dioxin hot spot, especially health risk to the breast-fed infants. The average TEQ levels in the four studied cohorts ranged from 8.1 to 26 pg/g lipid, with the highest level up to 51 pg TEQ/g lipid found in the An Khe ward. The TEQ level was correlated with geographical position and ranking in the order of Khue Trung, Hoa Thuan Tay, Chinh Gian and An Khe. The mean estimated PCDD/Fs infant's daily intake in the cohort of Khue Trung, Hoa Thuan Tay, Chinh Gian and An Khe was about 41, 122, 124, and 134 pg TEQ/kg bw/day, respectively, which are much higher than the tolerable daily intake proposed by the World Health Organization (4 pg TEQ/kg bw/day). Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Dmrt1 induces the male pathway in a turtle species with temperature-dependent sex determination.

    PubMed

    Ge, Chutian; Ye, Jian; Zhang, Haiyan; Zhang, Yi; Sun, Wei; Sang, Yapeng; Capel, Blanche; Qian, Guoying

    2017-06-15

    The molecular mechanism underlying temperature-dependent sex determination (TSD) has been a long-standing mystery; in particular, the thermosensitive genetic triggers for gonadal sex differentiation are largely unknown. Here, we have characterized a conserved DM domain gene, Dmrt1 , in the red-eared slider turtle Trachemys scripta ( T. scripta ), which exhibits TSD. We found that Dmrt1 has a temperature-dependent, sexually dimorphic expression pattern, preceding gonadal sex differentiation, and is capable of responding rapidly to temperature shifts and aromatase inhibitor treatment. Most importantly, loss- and gain-of-function analyses provide solid evidence that Dmrt1 is both necessary and sufficient to initiate male development in T. scripta Furthermore, the DNA methylation dynamics of the Dmrt1 promoter are tightly correlated with temperature and could mediate the impact of temperature on sex determination. Collectively, our findings demonstrate that Dmrt1 is a candidate master male sex-determining gene in this TSD species, consistent with the idea that DM domain genes are conserved during the evolution of sex determination mechanisms. © 2017. Published by The Company of Biologists Ltd.

  19. Is the 20th century warming unprecedented in the Siberian north?

    NASA Astrophysics Data System (ADS)

    Sidorova, Olga V.; Saurer, Matthias; Andreev, Andrei; Fritzsche, Diedrich; Opel, Thomas; Naurzbaev, Mukhtar M.; Siegwolf, Rolf

    2013-08-01

    To answer the question "Has the recent warming no analogues in the Siberian north?" we analyzed larch tree samples (Larix gmelinii Rupr.) from permafrost zone in the eastern Taimyr (TAY) (72°N, 102°E) using tree-ring and stable isotope analyses for the Climatic Optimum Period (COP) 4111-3806 BC and Medieval Warm Period (MWP) 917-1150 AD, in comparison to the recent period (RP) 1791-2008 AD. We developed a description of the climatic and environmental changes in the eastern Taimyr using tree-ring width and stable isotope (δ13C, δ18O) data based on statistical verification of the relationships to climatic parameters (temperature and precipitation). Additionally, we compared our new tree-ring and stable isotope data sets with earlier published July temperature and precipitation reconstructions inferred from pollen data of the Lama Lake, Taimyr Peninsula, δ18O ice core data from Akademii Nauk ice cap on Severnaya Zemlya (SZ) and δ18O ice core data from Greenland (GISP2), as well as tree-ring width and stable carbon and oxygen isotope data from northeastern Yakutia (YAK). We found that the COP in TAY was warmer and drier compared to the MWP but rather similar to the RP. Our results indicate that the MWP in TAY started earlier and was wetter than in YAK. July precipitation reconstructions obtained from pollen data of the Lama Lake, oxygen isotope data from SZ and our carbon isotopes in tree cellulose agree well and indicate wetter climate conditions during the MWP. Consistent large-scale patterns were reflected in significant links between oxygen isotope data in tree cellulose from TAY and YAK, and oxygen isotope data from SZ and GISP2 during the MWP and the RP. Finally, we showed that the recent warming is not unprecedented in the Siberian north. Similar climate conditions were recorded by tree-rings, stable isotopes, pollen, and ice core data 6000 years ago.

  20. Shoulder instability in the setting of bipolar (glenoid and humeral head) bone loss: the glenoid track concept.

    PubMed

    Trivedi, Suraj; Pomerantz, Michael L; Gross, Daniel; Golijanan, Petar; Provencher, Matthew T

    2014-08-01

    An assortment of variables has been used in predicting anterior shoulder instability resulting from pathologic engagement of Hill-Sachs lesions on the glenoid. The glenoid track is a unique biomechanical model that relates both Hill-Sachs and bony Bankart lesions to predict shoulder engagement. We examined the glenoid track concept to determine if it provides a model that unifies glenoid rim and humeral head bone loss in predicting engagement. In this review we addressed two questions: (1) How are humeral head and glenoid rim bony defects and their interactions quantified? (2) Why is the concept of the glenoid track important? We performed a systematic review of the literature using PubMed (MEDLINE) and OVID for biomechanical studies and peer-reviewed articles published until March 2013. Twenty-four studies fit the inclusion criteria. These were subdivided into four anatomic studies, four studies quantifying glenohumeral bone loss, nine studies biomechanically defining shoulder engagement, six studies analyzing current treatment models, and one clinical study to be included in the final review. Data demonstrate pathologic engagement is dependent on the medial margin of the Hill-Sachs lesion traveling outside the glenoid track. The width of the glenoid track decreases accordingly if there is a glenoid defect, making engagement more likely. Most treatment models focus on widening the glenoid track before addressing Hill-Sachs lesions. The glenoid track uses both glenoid and humeral head bone loss to predict subsequent risk of humeral head engagement and possible dislocation. The glenoid track shows us that restoring the track to its natural width should be among the surgeon's first priority in restoring shoulder stability. Humeral head lesions, also known as Hill-Sachs lesions, are surgically addressed when they cause clinical symptoms. Symptoms arise when the medial margin of the defect engages the glenoid track.

  1. Differential effects of total and partial sleep deprivation on salivary factors in Wistar rats.

    PubMed

    Lasisi, Dr T J; Shittu, S T; Meludu, C C; Salami, A A

    2017-01-01

    Aim of this study was to investigate the effects of sleep deprivation on salivary factors in rats. Animals were randomly assigned into three groups of 6 animals each as control, total sleep deprivation (TSD) and partial sleep deprivation (PSD) groups. The multiple platform method was used to induce partial and total sleep deprivation for 7days. On the 8th day, stimulated saliva samples were collected for the analysis of salivary lag time, flow rate, salivary amylase activity, immunoglobulin A secretion rate and corticosterone levels using ELISA and standard kinetic enzyme assay. Data were analyzed using ANOVA with Dunnett T3 post hoc tests. Salivary flow rate reduced significantly in the TSD group compared with the PSD group as well as the control group (p=0.01). The secretion rate of salivary IgA was significantly reduced in the TSD group compared with the control group (p=0.04). Salivary amylase activity was significantly elevated in the TSD group compared with the PSD group as well as control group (p<0.001). However, there were no significant changes in the salivary lag time and levels of corticosterone among the groups. These findings suggest that total sleep deprivation is associated with reduced salivary flow rate and secretion rate of IgA as well as elevated levels of salivary amylase activity in rats. However, sleep recovery of four hours in the PSD group produced ameliorative effects on the impaired functions of salivary glands. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 2014 Version 7.0 Technical Support Document (TSD)

    EPA Pesticide Factsheets

    The 2014 Version 7 document describes the processing of emission inventories into inputs for the Community Multiscale Air Quality model for use in the 2014 National Air Toxics Assessment initial modeling.

  3. Saline magnetic resonance arthrography in the evaluation of glenohumeral instability.

    PubMed

    Tirman, P F; Stauffer, A E; Crues, J V; Turner, R M; Nottage, W M; Schobert, W E; Rubin, B D; Janzen, D L; Linares, R C

    1993-01-01

    Sixty-five patients underwent magnetic resonance (MR) shoulder arthrography. Forty-eight of these patients underwent examination under anesthesia (EUA). MR images were retrospectively evaluated for signs felt to be imaging indicators of shoulder instability, including evaluation of various capsular measurements and the presence of glenoid labral tears, as well as Hill-Sachs fractures. Statistical analysis of the results showed that no correlation between capsular indicators with EUA-documented instability was found. However, there was a statistically significant correlation between the presence of a Bankart cartilaginous deformity (p = 0.000) and Hill-Sachs fractures (p = 0.022) with EUA-documented instability. Sensitivity to labral tears was 89% and specificity was 98%, whereas Hill-Sachs fracture detection was 69% and 87%, respectively. We believe that MR saline arthrography is of benefit in the evaluation of the anterior labrum when unenhanced MR imaging is inconclusive, and we speculate on the role of MR arthrography as a primary investigative tool.

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Halsey, W

    This report provides a summary for FY-2008 of activities, analyses and products from the Material Transportation, Storage and Disposal (M-TSD) sub-task of Systems Analysis within the Advanced Fuel Cycle Research & Development area of the Global Nuclear Energy Partnership. The objective of this work is to evaluate near-term material management requirements for initial GNEP facilities and activities, long-term requirements for large-scale GNEP technology deployment, and alternatives and paths forward to meet these needs. For FY-08, the work expanded to include the Integrated Waste Management Strategy as well as integration with the newly formed Waste Forms Campaign. The M-TSD team wasmore » expanded with the addition of support from Savannah River National Lab (SRNL) to the existing team of Lawrence Livermore National Lab (LLNL), Argonne National Lab (ANL), Idaho National Lab (INL), Sandia National Lab (SNL) and University of Nevada - Reno (UN-R). During the first half of the year, analysis was focused on providing supporting technical analysis and documentation to support anticipated high-level decisions on program direction. A number of analyses were conducted and reports prepared as program deliverables. This work is briefly summarized in this report. Analyses provided informally to other program efforts are included in this report to provide documentation. This year-end summary was planned primarily as a compilation of activities following the anticipated programmatic decisions. These decisions were deferred beyond the end of the year, and funds were reallocated in a number of areas, thus reducing the M-TSD activities. This report summarizes the miscellaneous 'ad-hoc' work conducted during the later part of the year, such as support to the draft Programmatic Environmental Impact Statement (PEIS), and support to other program studies. Major programmatic contributions from the M-TSD team during the year included: (1) Completion of the IWMS in March 2008 as the

  5. Climate change and temperature-linked hatchling mortality at a globally important sea turtle nesting site.

    PubMed

    Laloë, Jacques-Olivier; Cozens, Jacquie; Renom, Berta; Taxonera, Albert; Hays, Graeme C

    2017-11-01

    The study of temperature-dependent sex determination (TSD) in vertebrates has attracted major scientific interest. Recently, concerns for species with TSD in a warming world have increased because imbalanced sex ratios could potentially threaten population viability. In contrast, relatively little attention has been given to the direct effects of increased temperatures on successful embryonic development. Using 6603 days of sand temperature data recorded across 6 years at a globally important loggerhead sea turtle rookery-the Cape Verde Islands-we show the effects of warming incubation temperatures on the survival of hatchlings in nests. Incorporating published data (n = 110 data points for three species across 12 sites globally), we show the generality of relationships between hatchling mortality and incubation temperature and hence the broad applicability of our findings to sea turtles in general. We use a mechanistic approach supplemented by empirical data to consider the linked effects of warming temperatures on hatchling output and on sex ratios for these species that exhibit TSD. Our results show that higher temperatures increase the natural growth rate of the population as more females are produced. As a result, we project that numbers of nests at this globally important site will increase by approximately 30% by the year 2100. However, as incubation temperatures near lethal levels, the natural growth rate of the population decreases and the long-term survival of this turtle population is threatened. Our results highlight concerns for species with TSD in a warming world and underline the need for research to extend from a focus on temperature-dependent sex determination to a focus on temperature-linked hatchling mortalities. © 2017 John Wiley & Sons Ltd.

  6. One-night sleep deprivation induces changes in the DNA methylation and serum activity indices of stearoyl-CoA desaturase in young healthy men.

    PubMed

    Skuladottir, Gudrun Valgerdur; Nilsson, Emil Karl; Mwinyi, Jessica; Schiöth, Helgi Birgir

    2016-08-26

    Sleep deprivation has been associated with obesity among adults, and accumulating data suggests that stearoyl-CoA desaturase 1 (SCD1) expression has a relevant impact on fatty acid (FA) composition of lipid pools and obesity. The aim of this study was to investigate the effect of one-night total sleep deprivation (TSD) on DNA methylation in the 5'-prime region of SCD1, and whether detected changes in DNA methylation are associated with SCD activity indices (product to precursor FA ratios; 16:1n-7/16:0 and 18:1n-9/18:0) derived from serum phospholipids (PL). Sixteen young, normal-weight, healthy men completed two study sessions, one with one-night TSD and one with one-night normal sleep (NS). Sleep quality and length was assessed by polysomnography, and consisted of electroencephalography, electrooculography, and electromyography. Fasting whole blood samples were collected on the subsequent morning for analysis of DNA methylation and FAs in serum PL. Linear regression analyses were performed to assess the association between changes in DNA methylation and SCD activity indices. Three CpG sites close to the transcription start site (TSS) of SCD1 (cg00954566, cg24503796, cg14089512) were significantly differentially methylated in dependency of sleep duration (-log10 P-value > 1.3). Both SCD-16 and SCD-18 activity indices were significantly elevated (P < 0.05) following one-night TSD, and significantly associated with DNA methylation changes of the three mentioned probes in the 5' region of SCD1. Our results suggest a relevant link between TSD, hepatic SCD1 expression and de-novo fatty acid synthesis via epigenetically driven regulatory mechanisms.

  7. Extension of a nonlinear systems theory to general-frequency unsteady transonic aerodynamic responses

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.

    1993-01-01

    A methodology for modeling nonlinear unsteady aerodynamic responses, for subsequent use in aeroservoelastic analysis and design, using the Volterra-Wiener theory of nonlinear systems is presented. The methodology is extended to predict nonlinear unsteady aerodynamic responses of arbitrary frequency. The Volterra-Wiener theory uses multidimensional convolution integrals to predict the response of nonlinear systems to arbitrary inputs. The CAP-TSD (Computational Aeroelasticity Program - Transonic Small Disturbance) code is used to generate linear and nonlinear unit impulse responses that correspond to each of the integrals for a rectangular wing with a NACA 0012 section with pitch and plunge degrees of freedom. The computed kernels then are used to predict linear and nonlinear unsteady aerodynamic responses via convolution and compared to responses obtained using the CAP-TSD code directly. The results indicate that the approach can be used to predict linear unsteady aerodynamic responses exactly for any input amplitude or frequency at a significant cost savings. Convolution of the nonlinear terms results in nonlinear unsteady aerodynamic responses that compare reasonably well with those computed using the CAP-TSD code directly but at significant computational cost savings.

  8. Parental attitudes regarding behavior guidance of dental patients with autism.

    PubMed

    Marshall, Jennifer; Sheller, Barbara; Mancl, Lloyd; Williams, Bryan J

    2008-01-01

    The purposes of this study were to evaluate: (1) parents' ability to predict dental treatment cooperation by their autistic child; (2) behavior guidance techniques (BGTs) used during treatment; and (3) parental attitudes regarding basic and advanced BGTs. Data were collected from 85 parent/autistic child pairs and their dentists using surveys and treatment records. Parents most accurately predicted if their child would permit an examination in the dental chair (> or = 88%) and would cooperate for radiographs (> or = 84%). BGTs utilized most often (> 50%) were positive verbal reinforcement (PVR), tell-show-do (TSD), mouthprops, and rewards. In general, basic BGTs were more acceptable (> 81%) than advanced BGTs (>54%). The most acceptable techniques (>90%) in order were: PVR, TSD, distraction, rewards, general anesthesia, hand-holding by parent, and mouth-props. When parents evaluated only BGTs used for their child, all BGTs, including a stabilization device, were highly acceptable (> 91%), except for staff restraint (74%). Parents were accurate in predicting cooperation for some procedures. The most acceptable and efficacious BGTs in order were: PVR, TSD, distraction, rewards, and hand-holding by parent. Parental perceptions of BGTs were influenced by whether or not they had been used for their child.

  9. Mucocutaneous lesions in free-ranging Atlantic bottlenose dolphins Tursiops truncatus from the southeastern USA.

    PubMed

    Bossart, Gregory D; Schaefer, Adam M; McCulloch, Stephen; Goldstein, Juli; Fair, Patricia A; Reif, John S

    2015-08-20

    Mucocutaneous lesions were biopsied from free-ranging Atlantic bottlenose dolphins Tursiops truncatus inhabiting the Indian River Lagoon (IRL), Florida, and estuarine waters of Charleston (CHS), South Carolina, USA, between 2003 and 2013. A total of 78 incisional biopsies from 58 dolphins (n=43 IRL, n=15 CHS) were examined. Thirteen dolphins had 2 lesions biopsied at the same examination, and 6 dolphins were re-examined and re-biopsied at time intervals varying from 1 to 8 yr. Biopsy sites included the skin (n=47), tongue (n=2), and genital mucosa (n=29). Pathologic diagnoses were: orogenital sessile papilloma (39.7%), cutaneous lobomycosis (16.7%), tattoo skin disease (TSD; 15.4%), nonspecific chronic to chronic-active dermatitis (15.4%), and epidermal hyperplasia (12.8%). Pathologic diagnoses from dolphins with 2 lesions were predominately orogenital sessile papillomas (n=9) with nonspecific chronic to chronic-active dermatitis (n=4), TSD (n=3), lobomycosis (n=1), and epidermal hyperplasia (n=1). Persistent pathologic diagnoses from the same dolphins re-examined and re-biopsied at different times included genital sessile papillomas (n=3), lobomycosis (n=2), and nonspecific dermatitis (n=2). This is the first study documenting the various types, combined prevalence, and progression of mucocutaneous lesions in dolphins from the southeastern USA. The data support other published findings describing the health patterns in dolphins from these geographic regions. Potential health impacts related to the observed suite of lesions are important for the IRL and CHS dolphin populations, since previous studies have indicated that both populations are affected by complex infectious diseases often associated with immunologic disturbances and anthropogenic contaminants.

  10. Regulation & Development of Membrane Transport Processes.

    DTIC Science & Technology

    1985-05-15

    221, 733-741. 30. Liu, A. Y. C. and Greengard, P. (1974) Proc. Nall. Acad. Sci. USA, 71, 3869-3873. 31. MacKnight, A. D. C., DiBona , D. R., and Leaf...However, DiBona and Sachs and their collaborators 2. IXO(YI’(YI’IC INSEITION OF OTHER TANSPORT SYSTEMS 155 have challenged this view, suggesting that...the U.S. Public Health Service. REFERENCES I. DiBona , D. R., Ito, S., Berglindh, T.. and Sachs, G. (1979) Proc. Nall. Acad. Sci. USA, 76, 6689-6693. 2

  11. Sustained attention performance during sleep deprivation: evidence of state instability

    NASA Technical Reports Server (NTRS)

    Doran, S. M.; Van Dongen, H. P.; Dinges, D. F.

    2001-01-01

    Nathaniel Kleitman was the first to observe that sleep deprivation in humans did not eliminate the ability to perform neurobehavioral functions, but it did make it difficult to maintain stable performance for more than a few minutes. To investigate variability in performance as a function of sleep deprivation, n = 13 subjects were tested every 2 hours on a 10-minute, sustained-attention, psychomotor vigilance task (PVT) throughout 88 hours of total sleep deprivation (TSD condition), and compared to a control group of n = 15 subjects who were permitted a 2-hour nap every 12 hours (NAP condition) throughout the 88-hour period. PVT reaction time means and standard deviations increased markedly among subjects and within each individual subject in the TSD condition relative to the NAP condition. TSD subjects also had increasingly greater performance variability as a function of time on task after 18 hours of wakefulness. During sleep deprivation, variability in PVT performance reflected a combination of normal timely responses, errors of omission (i.e., lapses), and errors of commission (i.e., responding when no stimulus was present). Errors of omission and errors of commission were highly intercorrelated across deprivation in the TSD condition (r = 0.85, p = 0.0001), suggesting that performance instability is more likely to include compensatory effort than a lack of motivation. The marked increases in PVT performance variability as sleep loss continued supports the "state instability" hypothesis, which posits that performance during sleep deprivation is increasingly variable due to the influence of sleep initiating mechanisms on the endogenous capacity to maintain attention and alertness, thereby creating an unstable state that fluctuates within seconds and that cannot be characterized as either fully awake or asleep.

  12. A novel hypothesis for the adaptive maintenance of environmental sex determination in a turtle.

    PubMed

    Spencer, R-J; Janzen, F J

    2014-08-22

    Temperature-dependent sex determination (TSD) is widespread in reptiles, yet its adaptive significance and mechanisms for its maintenance remain obscure and controversial. Comparative analyses identify an ancient origin of TSD in turtles, crocodiles and tuatara, suggesting that this trait should be advantageous in order to persist. Based on this assumption, researchers primarily, and with minimal success, have employed a model to examine sex-specific variation in hatchling phenotypes and fitness generated by different incubation conditions. The unwavering focus on different incubation conditions may be misplaced at least in the many turtle species in which hatchlings overwinter in the natal nest. If overwintering temperatures differentially affect fitness of male and female hatchlings, TSD might be maintained adaptively by enabling embryos to develop as the sex best suited to those overwintering conditions. We test this novel hypothesis using the painted turtle (Chrysemys picta), a species with TSD in which eggs hatch in late summer and hatchlings remain within nests until the following spring. We used a split-clutch design to expose field-incubated hatchlings to warm and cool overwintering (autumn-winter-spring) regimes in the laboratory and measured metabolic rates, energy use, body size and mortality of male and female hatchlings. While overall mortality rates were low, males exposed to warmer overwintering regimes had significantly higher metabolic rates and used more residual yolk than females, whereas the reverse occurred in the cool temperature regime. Hatchlings from mixed-sex nests exhibited similar sex-specific trends and, crucially, they were less energy efficient and grew less than same-sex hatchlings that originated from single-sex clutches. Such sex- and incubation-specific physiological adaptation to winter temperatures may enhance fitness and even extend the northern range of many species that overwinter terrestrially. © 2014 The Author

  13. Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically regulated in cortical astrocytes following sleep deprivation in mice.

    PubMed

    Petit, Jean-Marie; Gyger, Joël; Burlet-Godinot, Sophie; Fiumelli, Hubert; Martin, Jean-Luc; Magistretti, Pierre J

    2013-10-01

    There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. 6-hour instrumental sleep deprivation (TSD). Animal sleep research laboratory. Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Basal sleep recordings and sleep deprivation achieved using a modified cage where animals were gently forced to move. Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, α-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. This study shows that TSD induces the expression of genes associated with ANLS specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

  14. 75 FR 66759 - Science Advisory Board Staff Office; Notification of a Public Meeting of the Science Advisory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-29

    ... TSD will describe methods and approaches for developing numeric nutrient criteria for Florida's... support document on development of numeric nutrient criteria for Florida's estuarine and coastal waters...

  15. A Profession of Arms

    DTIC Science & Technology

    2011-01-01

    survey of 17,000 civilian technology professionals. Acquisitions, Military Intelligence, Military Investigations, Special Forces, and Military Culinary ...assigned as a career manager at Human Resources Com- mand at Fort Knox, Ky. She holds a Bachelor of Arts in History from Tay- lor University and a

  16. Pain Control

    MedlinePlus

    ... inside the cheek or under the tongue. ■■ Injections (shots): There are two different kinds of shots: • Under the skin: Medicine is placed just under ... Subcutaneous (sub-kyu-TAY-nee-yus) injection : A shot under the skin. Sublingual : Under the tongue. Supplements : ...

  17. 100-D Ponds closure plan. Revision 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Petersen, S.W.

    1997-09-01

    The 100-D Ponds is a Treatment, Storage, and Disposal (TSD) unit on the Hanford Facility that received both dangerous and nonregulated waste. This Closure Plan (Rev. 1) for the 100-D Ponds TSD unit consists of a RCRA Part A Dangerous Waste Permit Application (Rev. 3), a RCRA Closure Plan, and supporting information contained in the appendices to the plan. The closure plan consists of eight chapters containing facility description, process information, waste characteristics, and groundwater monitoring data. There are also chapters containing the closure strategy and performance standards. The strategy for the closure of the 100-D Ponds TSD unit ismore » clean closure. Appendices A and B of the closure plan demonstrate that soil and groundwater beneath 100-D Ponds are below cleanup limits. All dangerous wastes or dangerous waste constituents or residues associated with the operation of the ponds have been removed, therefore, human health and the environment are protected. Discharges to the 100-D Ponds, which are located in the 100-DR-1 operable unit, were discontinued in June 1994. Contaminated sediment was removed from the ponds in August 1996. Subsequent sampling and analysis demonstrated that there is no contamination remaining in the ponds, therefore, this closure plan is a demonstration of clean closure.« less

  18. Expert-guided evolutionary algorithm for layout design of complex space stations

    NASA Astrophysics Data System (ADS)

    Qian, Zhiqin; Bi, Zhuming; Cao, Qun; Ju, Weiguo; Teng, Hongfei; Zheng, Yang; Zheng, Siyu

    2017-08-01

    The layout of a space station should be designed in such a way that different equipment and instruments are placed for the station as a whole to achieve the best overall performance. The station layout design is a typical nondeterministic polynomial problem. In particular, how to manage the design complexity to achieve an acceptable solution within a reasonable timeframe poses a great challenge. In this article, a new evolutionary algorithm has been proposed to meet such a challenge. It is called as the expert-guided evolutionary algorithm with a tree-like structure decomposition (EGEA-TSD). Two innovations in EGEA-TSD are (i) to deal with the design complexity, the entire design space is divided into subspaces with a tree-like structure; it reduces the computation and facilitates experts' involvement in the solving process. (ii) A human-intervention interface is developed to allow experts' involvement in avoiding local optimums and accelerating convergence. To validate the proposed algorithm, the layout design of one-space station is formulated as a multi-disciplinary design problem, the developed algorithm is programmed and executed, and the result is compared with those from other two algorithms; it has illustrated the superior performance of the proposed EGEA-TSD.

  19. Signal detection with criterion noise: applications to recognition memory.

    PubMed

    Benjamin, Aaron S; Diaz, Michael; Wee, Serena

    2009-01-01

    A tacit but fundamental assumption of the theory of signal detection is that criterion placement is a noise-free process. This article challenges that assumption on theoretical and empirical grounds and presents the noisy decision theory of signal detection (ND-TSD). Generalized equations for the isosensitivity function and for measures of discrimination incorporating criterion variability are derived, and the model's relationship with extant models of decision making in discrimination tasks is examined. An experiment evaluating recognition memory for ensembles of word stimuli revealed that criterion noise is not trivial in magnitude and contributes substantially to variance in the slope of the isosensitivity function. The authors discuss how ND-TSD can help explain a number of current and historical puzzles in recognition memory, including the inconsistent relationship between manipulations of learning and the isosensitivity function's slope, the lack of invariance of the slope with manipulations of bias or payoffs, the effects of aging on the decision-making process in recognition, and the nature of responding in remember-know decision tasks. ND-TSD poses novel, theoretically meaningful constraints on theories of recognition and decision making more generally, and provides a mechanism for rapprochement between theories of decision making that employ deterministic response rules and those that postulate probabilistic response rules.

  20. Unsteady transonic flow calculations for realistic aircraft configurations

    NASA Technical Reports Server (NTRS)

    Batina, John T.; Seidel, David A.; Bland, Samuel R.; Bennett, Robert M.

    1987-01-01

    A transonic unsteady aerodynamic and aeroelasticity code has been developed for application to realistic aircraft configurations. The new code is called CAP-TSD which is an acronym for Computational Aeroelasticity Program - Transonic Small Disturbance. The CAP-TSD code uses a time-accurate approximate factorization (AF) algorithm for solution of the unsteady transonic small-disturbance equation. The AF algorithm is very efficient for solution of steady and unsteady transonic flow problems. It can provide accurate solutions in only several hundred time steps yielding a significant computational cost savings when compared to alternative methods. The new code can treat complete aircraft geometries with multiple lifting surfaces and bodies including canard, wing, tail, control surfaces, launchers, pylons, fuselage, stores, and nacelles. Applications are presented for a series of five configurations of increasing complexity to demonstrate the wide range of geometrical applicability of CAP-TSD. These results are in good agreement with available experimental steady and unsteady pressure data. Calculations for the General Dynamics one-ninth scale F-16C aircraft model are presented to demonstrate application to a realistic configuration. Unsteady results for the entire F-16C aircraft undergoing a rigid pitching motion illustrated the capability required to perform transonic unsteady aerodynamic and aeroelastic analyses for such configurations.

  1. Maximizing sensitivity of the psychomotor vigilance test (PVT) to sleep loss.

    PubMed

    Basner, Mathias; Dinges, David F

    2011-05-01

    The psychomotor vigilance test (PVT) is among the most widely used measures of behavioral alertness, but there is large variation among published studies in PVT performance outcomes and test durations. To promote standardization of the PVT and increase its sensitivity and specificity to sleep loss, we determined PVT metrics and task durations that optimally discriminated sleep deprived subjects from alert subjects. Repeated-measures experiments involving 10-min PVT assessments every 2 h across both acute total sleep deprivation (TSD) and 5 days of chronic partial sleep deprivation (PSD). Controlled laboratory environment. 74 healthy subjects (34 female), aged 22-45 years. TSD experiment involving 33 h awake (N = 31 subjects) and a PSD experiment involving 5 nights of 4 h time in bed (N = 43 subjects). In a paired t-test paradigm and for both TSD and PSD, effect sizes of 10 different PVT performance outcomes were calculated. Effect sizes were high for both TSD (1.59-1.94) and PSD (0.88-1.21) for PVT metrics related to lapses and to measures of psychomotor speed, i.e., mean 1/RT (response time) and mean slowest 10% 1/RT. In contrast, PVT mean and median RT outcomes scored low to moderate effect sizes influenced by extreme values. Analyses facilitating only portions of the full 10-min PVT indicated that for some outcomes, high effect sizes could be achieved with PVT durations considerably shorter than 10 min, although metrics involving lapses seemed to profit from longer test durations in TSD. Due to their superior conceptual and statistical properties and high sensitivity to sleep deprivation, metrics involving response speed and lapses should be considered primary outcomes for the 10-min PVT. In contrast, PVT mean and median metrics, which are among the most widely used outcomes, should be avoided as primary measures of alertness. Our analyses also suggest that some shorter-duration PVT versions may be sensitive to sleep loss, depending on the outcome variable

  2. 77 FR 67582 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG Turbofan Engines AGENCY: Federal Aviation... airworthiness directive (AD) for certain Rolls-Royce Deutschland Ltd & Co KG (RRD) Tay 611-8 turbofan engines... properties may have been installed in some engines. This proposed AD would require inspection and replacement...

  3. Alternative Significant Contribution Approaches Evaluated

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) discusses alternative approaches that EPA evaluated for defining emissions that constitute each upwind state’s significant contribution to nonattainment and interference with maintenance downwind.

  4. Behavioral sleep-wake homeostasis and EEG delta power are decoupled by chronic sleep restriction in the rat.

    PubMed

    Stephenson, Richard; Caron, Aimee M; Famina, Svetlana

    2015-05-01

    Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR. A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function. Animal laboratory, rodent walking-wheel apparatus. Male Sprague-Dawley rats. Acute total sleep deprivation (TSD, 1 day × 18 or 24 h, N = 12), CSR (10 days × 18 h TSD, N = 5, or 5 days × 20 h TSD, N = 6). Behavioral rebounds were consistent with model predictions for proportional control of cumulative times in wake, nonrapid eye movement (NREM) and rapid eye movement (REM). Delta (D) energy homeostasis was secondary to behavioral homeostasis; a biphasic NREM D power rebound contributed to the dynamics (rapid response) but not to the magnitude of the rebound in D energy. REM behavioral homeostasis was little affected by CSR. NREM behavioral homeostasis was attenuated in proportion to cumulative NREM deficit, whereas the biphasic NREM D power rebound was only slightly suppressed, indicating decoupled regulatory mechanisms following CSR. We conclude that sleep homeostasis is achieved through behavioral regulation, that the NREM behavioral homeostat is susceptible to attenuation during CSR and that the concept of sleep intensity is not essential in a model of sleep-wake regulation. Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR. A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function. Animal laboratory, rodent walking-wheel apparatus. Male Sprague-Dawley rats. Acute total sleep

  5. Applications of potential theory computations to transonic aeroelasticity

    NASA Technical Reports Server (NTRS)

    Edwards, J. W.

    1986-01-01

    Unsteady aerodynamic and aeroelastic stability calculations based upon transonic small disturbance (TSD) potential theory are presented. Results from the two-dimensional XTRAN2L code and the three-dimensional XTRAN3S code are compared with experiment to demonstrate the ability of TSD codes to treat transonic effects. The necessity of nonisentropic corrections to transonic potential theory is demonstrated. Dynamic computational effects resulting from the choice of grid and boundary conditions are illustrated. Unsteady airloads for a number of parameter variations including airfoil shape and thickness, Mach number, frequency, and amplitude are given. Finally, samples of transonic aeroelastic calculations are given. A key observation is the extent to which unsteady transonic airloads calculated by inviscid potential theory may be treated in a locally linear manner.

  6. U-series dating of impure carbonates: An isochron technique using total-sample dissolution

    USGS Publications Warehouse

    Bischoff, J.L.; Fitzpatrick, J.A.

    1991-01-01

    U-series dating is a well-established technique for age determination of Late Quaternary carbonates. Materials of sufficient purity for nominal dating, however, are not as common as materials with mechanically inseparable aluminosilicate detritus. Detritus contaminates the sample with extraneous Th. We propose that correction for contamination is best accomplished with the isochron technique using total sample dissolution (TSD). Experiments were conducted on artificial mixtures of natural detritus and carbonate and on an impure carbonate of known age. Results show that significant and unpredictable transfer of radionuclides occur from the detritus to the leachate in commonly used selective leaching procedures. The effects of correcting via leachate-residue pairs and isochron plots were assessed. Isochrons using TSD gave best results, followed by isochron plots of leachates only. ?? 1991.

  7. Evaluations of dielectric property and drug release profile of 5-FU patches based on plasma charged electrets

    NASA Astrophysics Data System (ADS)

    Wang, YUAN; Hejuan, LIANG; Ping, HUANG; Xiaoqiang, AN; Jian, JIANG; Lili, CUI

    2018-05-01

    In the present study, the electret 5-fluorouracil patch was developed, the effective surface potential, piezoelectric coefficient d 33, open-circuit thermally stimulated discharge (TSD) current spectra and shear adhesion of the patch were measured. The drug release profile of the patch was determined by using high performance liquid chromatography method. A stable potential difference which was positively dependent on the surface potential of the electret was generated on two sides of the patch. The measurements of d 33 coefficient, TSD current spectra and adhesion performance showed that the electrostatic field of the electret could cause polarization and cohesive strength decreasing of the matrix molecules, change the distribution and interaction of the drug molecules in patch, therefore to increase the release of drug from the transdermal patch.

  8. Further investigations of the aeroelastic behavior of the AFW wind-tunnel model using transonic small disturbance theory

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Bennett, Robert M.

    1992-01-01

    The Computational Aeroelasticity Program-Transonic Small Disturbance (CAP-TSD) code, developed at LaRC, is applied to the active flexible wing wind-tunnel model for prediction of transonic aeroelastic behavior. A semi-span computational model is used for evaluation of symmetric motions, and a full-span model is used for evaluation of antisymmetric motions, and a full-span model is used for evaluation of antisymmetric motions. Static aeroelastic solutions using CAP-TSD are computed. Dynamic deformations are presented as flutter boundaries in terms of Mach number and dynamic pressure. Flutter boundaries that take into account modal refinements, vorticity and entropy corrections, antisymmetric motion, and sensitivity to the modeling of the wing tip ballast stores are also presented with experimental flutter results.

  9. Anomaly Detection in the Right Hemisphere: The Influence of Visuospatial Factors

    ERIC Educational Resources Information Center

    Smith, Stephen D.; Dixon, Michael J.; Tays, William J.; Bulman-Fleming, M. Barbara

    2004-01-01

    Previous research with both brain-damaged and neurologically intact populations has demonstrated that the right cerebral hemisphere (RH) is superior to the left cerebral hemisphere (LH) at detecting anomalies (or incongruities) in objects (Ramachandran, 1995; Smith, Tays, Dixon, & Bulman-Fleming, 2002). The current research assesses whether the RH…

  10. Using Archives for Education.

    ERIC Educational Resources Information Center

    MacKenzie, Douglas

    1996-01-01

    Discusses the use of computer systems for archival applications based on experiences at the Demarco European Arts Foundation (Scotland) and the TAMH Project, an attempt to build a virtual museum of Tay Valley maritime history. Highlights include hardware; development software; data representation, including storage space versus quality;…

  11. Meaning of Muscular Dystrophy

    MedlinePlus

    ... is very similar to Duchenne, except kids with Becker MD may not have problems until much later, when they're teenagers or adults. It takes a long time for their muscles to become weak. How Does a Kid Get Muscular Dystrophy? MD is not contagious (say: con-TAY-juss), ...

  12. Comparison of projection skills of deterministic ensemble methods using pseudo-simulation data generated from multivariate Gaussian distribution

    NASA Astrophysics Data System (ADS)

    Oh, Seok-Geun; Suh, Myoung-Seok

    2017-07-01

    The projection skills of five ensemble methods were analyzed according to simulation skills, training period, and ensemble members, using 198 sets of pseudo-simulation data (PSD) produced by random number generation assuming the simulated temperature of regional climate models. The PSD sets were classified into 18 categories according to the relative magnitude of bias, variance ratio, and correlation coefficient, where each category had 11 sets (including 1 truth set) with 50 samples. The ensemble methods used were as follows: equal weighted averaging without bias correction (EWA_NBC), EWA with bias correction (EWA_WBC), weighted ensemble averaging based on root mean square errors and correlation (WEA_RAC), WEA based on the Taylor score (WEA_Tay), and multivariate linear regression (Mul_Reg). The projection skills of the ensemble methods improved generally as compared with the best member for each category. However, their projection skills are significantly affected by the simulation skills of the ensemble member. The weighted ensemble methods showed better projection skills than non-weighted methods, in particular, for the PSD categories having systematic biases and various correlation coefficients. The EWA_NBC showed considerably lower projection skills than the other methods, in particular, for the PSD categories with systematic biases. Although Mul_Reg showed relatively good skills, it showed strong sensitivity to the PSD categories, training periods, and number of members. On the other hand, the WEA_Tay and WEA_RAC showed relatively superior skills in both the accuracy and reliability for all the sensitivity experiments. This indicates that WEA_Tay and WEA_RAC are applicable even for simulation data with systematic biases, a short training period, and a small number of ensemble members.

  13. Air Quality Modeling Technical Support Document for the Final Cross State Air Pollution Rule Update

    EPA Pesticide Factsheets

    In this technical support document (TSD) we describe the air quality modeling performed to support the final Cross State Air Pollution Rule for the 2008 ozone National Ambient Air Quality Standards (NAAQS).

  14. Air Quality Modeling Technical Support Document for the 2008 Ozone NAAQS Cross-State Air Pollution Rule Proposal

    EPA Pesticide Factsheets

    In this technical support document (TSD) we describe the air quality modeling performed to support the proposed Cross-State Air Pollution Rule for the 2008 ozone National Ambient Air Quality Standards (NAAQS)

  15. Air Quality Modeling

    EPA Pesticide Factsheets

    In this technical support document (TSD) EPA describes the air quality modeling performed to support the Environmental Protection Agency’s Transport Rule proposal (now known as the Cross-State Air Pollution Rule).

  16. Mapping abnormal subcortical brain morphometry in an elderly HIV+ cohort.

    PubMed

    Wade, Benjamin S C; Valcour, Victor G; Wendelken-Riegelhaupt, Lauren; Esmaeili-Firidouni, Pardis; Joshi, Shantanu H; Gutman, Boris A; Thompson, Paul M

    2015-01-01

    Over 50% of HIV + individuals exhibit neurocognitive impairment and subcortical atrophy, but the profile of brain abnormalities associated with HIV is still poorly understood. Using surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 elderly HIV + participants and 31 uninfected controls. The thalamus, caudate, putamen, pallidum, hippocampus, amygdala, brainstem, accumbens, callosum and ventricles were segmented from high-resolution MRIs. To investigate shape-based morphometry, we analyzed the Jacobian determinant (JD) and radial distances (RD) defined on each region's surfaces. We also investigated effects of nadir CD4 + T-cell counts, viral load, time since diagnosis (TSD) and cognition on subcortical morphology. Lastly, we explored whether HIV + participants were distinguishable from unaffected controls in a machine learning context. All shape and volume features were included in a random forest (RF) model. The model was validated with 2-fold cross-validation. Volumes of HIV + participants' bilateral thalamus, left pallidum, left putamen and callosum were significantly reduced while ventricular spaces were enlarged. Significant shape variation was associated with HIV status, TSD and the Wechsler adult intelligence scale. HIV + people had diffuse atrophy, particularly in the caudate, putamen, hippocampus and thalamus. Unexpectedly, extended TSD was associated with increased thickness of the anterior right pallidum. In the classification of HIV + participants vs. controls, our RF model attained an area under the curve of 72%.

  17. Assessing the Item Response Theory with Covariate (IRT-C) Procedure for Ascertaining Differential Item Functioning

    ERIC Educational Resources Information Center

    Tay, Louis; Vermunt, Jeroen K.; Wang, Chun

    2013-01-01

    We evaluate the item response theory with covariates (IRT-C) procedure for assessing differential item functioning (DIF) without preknowledge of anchor items (Tay, Newman, & Vermunt, 2011). This procedure begins with a fully constrained baseline model, and candidate items are tested for uniform and/or nonuniform DIF using the Wald statistic.…

  18. Assessment of Impact of Consent Decree Annual Tonnage Limits on Transport Rule Allocations

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) provides information that supports EPA’s analysis of the impact of emission constraints specified in existing federally-enforceable judicial consent decrees on allowance allocations under the Transport Rule.

  19. 40 CFR 262.90 - Project XL for Public Utilities in New York State.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... section including, but not limited to, the following: (1) Database management for each remote location as... consolidation of waste for economical shipment (including no longer shipping waste directly to a TSD from remote...

  20. 40 CFR 262.90 - Project XL for Public Utilities in New York State.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... section including, but not limited to, the following: (1) Database management for each remote location as... consolidation of waste for economical shipment (including no longer shipping waste directly to a TSD from remote...

  1. 40 CFR 262.90 - Project XL for Public Utilities in New York State.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... section including, but not limited to, the following: (1) Database management for each remote location as... consolidation of waste for economical shipment (including no longer shipping waste directly to a TSD from remote...

  2. 40 CFR 262.90 - Project XL for Public Utilities in New York State.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... section including, but not limited to, the following: (1) Database management for each remote location as... consolidation of waste for economical shipment (including no longer shipping waste directly to a TSD from remote...

  3. State Budgets, Unit Allocations, and Unit Emissions Rates

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) provides information that supports EPA’s determination of state emissions budgets, unit-level allocations, direct control rate limits, and new unit set-asides for the Transport Rule proposal.

  4. Air Quality Modeling Technical Support Document for the 2015 Ozone NAAQS Preliminary Interstate Transport Assessment

    EPA Pesticide Factsheets

    In this technical support document (TSD) EPA describes the air quality modeling performed to support the 2015 ozone National Ambient Air Quality Standards (NAAQS) preliminary interstate transport assessment Notice of Data Availability (NODA).

  5. Draft federal GHG accounting and reporting : technical support document

    DOT National Transportation Integrated Search

    2010-07-01

    This is a technical support document (TSD) that accompanies the Federal Greenhouse Gas Accounting and Reporting Guidance (or Guidance). This document provides detailed information on the inventory reporting process and accepted calculation methodolog...

  6. Genes Involved in the Astrocyte-Neuron Lactate Shuttle (ANLS) Are Specifically Regulated in Cortical Astrocytes Following Sleep Deprivation in Mice

    PubMed Central

    Petit, Jean-Marie; Gyger, Joël; Burlet-Godinot, Sophie; Fiumelli, Hubert; Martin, Jean-Luc; Magistretti, Pierre J.

    2013-01-01

    Study Objectives: There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called “astrocyte-neuron lactate shuttle” (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. Design: 6-hour instrumental sleep deprivation (TSD). Setting: Animal sleep research laboratory. Participants: Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Interventions: Basal sleep recordings and sleep deprivation achieved using a modified cage where animals were gently forced to move. Measurements and Results: Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, α-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, was observed for Ldha, Mct2, and α-3-Na/K pump mRNAs. Conclusions: This study shows that TSD induces the expression of genes associated with ANLS specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle. Citation: Petit JM; Gyger J; Burlet-Godinot S; Fiumelli H; Martin JL; Magistretti PJ. Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically

  7. Maximizing Sensitivity of the Psychomotor Vigilance Test (PVT) to Sleep Loss

    PubMed Central

    Basner, Mathias; Dinges, David F.

    2011-01-01

    Study Objectives: The psychomotor vigilance test (PVT) is among the most widely used measures of behavioral alertness, but there is large variation among published studies in PVT performance outcomes and test durations. To promote standardization of the PVT and increase its sensitivity and specificity to sleep loss, we determined PVT metrics and task durations that optimally discriminated sleep deprived subjects from alert subjects. Design: Repeated-measures experiments involving 10-min PVT assessments every 2 h across both acute total sleep deprivation (TSD) and 5 days of chronic partial sleep deprivation (PSD). Setting: Controlled laboratory environment. Participants: 74 healthy subjects (34 female), aged 22–45 years. Interventions: TSD experiment involving 33 h awake (N = 31 subjects) and a PSD experiment involving 5 nights of 4 h time in bed (N = 43 subjects). Measurements and Results: In a paired t-test paradigm and for both TSD and PSD, effect sizes of 10 different PVT performance outcomes were calculated. Effect sizes were high for both TSD (1.59–1.94) and PSD (0.88–1.21) for PVT metrics related to lapses and to measures of psychomotor speed, i.e., mean 1/RT (response time) and mean slowest 10% 1/RT. In contrast, PVT mean and median RT outcomes scored low to moderate effect sizes influenced by extreme values. Analyses facilitating only portions of the full 10-min PVT indicated that for some outcomes, high effect sizes could be achieved with PVT durations considerably shorter than 10 min, although metrics involving lapses seemed to profit from longer test durations in TSD. Conclusions: Due to their superior conceptual and statistical properties and high sensitivity to sleep deprivation, metrics involving response speed and lapses should be considered primary outcomes for the 10-min PVT. In contrast, PVT mean and median metrics, which are among the most widely used outcomes, should be avoided as primary measures of alertness. Our analyses also suggest

  8. Failure to Find Executive Function Deficits Following One Night’s Total Sleep-Deprivation in University Students under Naturalistic Conditions

    PubMed Central

    Pace-Schott, Edward F.; Hutcherson, Cendri A.; Bemporad, Brenda; Morgan, Alexandra; Kumar, Arjun; Hobson, J. Allan; Stickgold, Robert

    2018-01-01

    Young adult male students participated in a naturalistic, group-design experiment to ascertain the effects of one night’s total sleep deprivation (TSD) on performance of diverse executive function tasks presented as an extended, multi-task battery. On the majority of component tasks in this battery, performance has been reported to be impaired following one night’s TSD when tasks are administered in isolation. However, subjects sleep deprived 35–39 hours showed few performance deficits among tests in this battery when compared with non sleep-deprived controls. Sleep-deprived subjects showed only poorer recognition memory and overconfidence in incorrect temporal judgments. Behavioral and physiological adaptation to chronically sleep-restricting lifestyles may confer resistance to the cognitive effects of sleep deprivation in high-functioning young adults. PMID:19568965

  9. Solid Waste Assurance Program Implementation Plan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Irons, L.G.

    1995-06-19

    On June 6, 1995, a waiver to Hanford Site Solid Waste Acceptance Criteria, was approved by the US Department of Energy Richland Operations Office (RL) to replace the low-level, mixed, and transuranic (TRU) generator assessment programs with the Solid Waste Assurance Program (SWAP). This is associated with a waiver that was approved on March 16, 1995 to replace the Storage/Disposal Approval Record (SDAR) requirements with the Waste Specification System (WSS). This implementation plan and the SWAP applies to Solid Waste Disposal (SWD) functions, facilities, and personnel who perform waste acceptance, verification, receipt, and management functions of dangerous, radioactive, and mixedmore » waste from on- and off-site generators who ship to or within the Hanford Site for treatment, storage, and/or disposal (TSD) at SWD TSD facilities.« less

  10. Using transonic small disturbance theory for predicting the aeroelastic stability of a flexible wind-tunnel model

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Bennett, Robert M.

    1990-01-01

    The CAP-TSD (Computational Aeroelasticity Program - Transonic Small Disturbance) code, developed at the NASA - Langley Research Center, is applied to the Active Flexible Wing (AFW) wind tunnel model for prediction of the model's transonic aeroelastic behavior. Static aeroelastic solutions using CAP-TSD are computed. Dynamic (flutter) analyses are then performed as perturbations about the static aeroelastic deformations of the AFW. The accuracy of the static aeroelastic procedure is investigated by comparing analytical results to those from previous AFW wind tunnel experiments. Dynamic results are presented in the form of root loci at different Mach numbers for a heavy gas and air. The resultant flutter boundaries for both gases are also presented. The effects of viscous damping and angle-of-attack, on the flutter boundary in air, are presented as well.

  11. Proceedings of the Symposium on Research in Biology and Biotechnology in Developing Countries (National University of Singapore, November 2-4, 1983). Selected Papers.

    ERIC Educational Resources Information Center

    Rao, A. N., Ed.

    These proceedings of a symposium designed to increase public awareness of current research in biology and biotechnology include: welcoming addresses by Chau Sian Eng and S. Radhakrishna; an opening address by Tay Eng Soon; five papers; four abstracts; summary; symposium program; and list of participants. The five papers are: (1) "The Role of…

  12. Administrators' Use of Metaphors to Deal with Anger in Jordanian Higher Education Institutions

    ERIC Educational Resources Information Center

    Bin Tareef, Atif Omer

    2014-01-01

    School violence emerged as a topic of interest for the education system during the past decade. School violence covers an array of intentional or reckless behaviors that include physical harm, psychological harm, and property damage. These include behaviors that vary in severity and frequency such as murder (Dwyer, Osher, & Warger, 1998). Tay,…

  13. Central Dogma Goes Digital.

    PubMed

    Lin, Yihan; Elowitz, Michael B

    2016-03-17

    In this issue of Molecular Cell, Tay and colleagues (Albayrak et al., 2016) describe a new technique to digitally quantify the numbers of protein and mRNA in the same mammalian cell, providing a new way to look at the central dogma of molecular biology. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Evaluation and Management of Failed Shoulder Instability Surgery.

    PubMed

    Cartucho, António; Moura, Nuno; Sarmento, Marco

    2017-01-01

    Failed shoulder instability surgery is mostly considered to be the recurrence of shoulder dislocation but subluxation, painful or non-reliable shoulder are also reasons for patient dissatisfaction and should be considered in the notion. The authors performed a revision of the literature and online contents on evaluation and management of failed shoulder instability surgery. When we look at the reasons for failure of shoulder instability surgery we point the finger at poor patient selection, technical error and an additional traumatic event. More than 80% of surgical failures, for shoulder instability, are associated with bone loss. Quantification of glenoid bone loss and investigation of an engaging Hill-Sachs lesion are determining facts. Adequate imaging studies are determinant to assess labrum and capsular lesions and to rule out associated pathology as rotator cuff tears. CT-scan is the method of choice to diagnose and quantify bone loss. Arthroscopic soft tissue procedures are indicated in patients with minimal bone loss and no contact sports. Open soft tissue procedures should be performed in patients with small bone defects, with hiperlaxity and practicing contact sports. Soft tissue techniques, as postero-inferior capsular plication and remplissage, may be used in patients with less than 25% of glenoid bone loss and Hill-Sachs lesions. Bone block procedures should be used for glenoid larger bone defects in the presence of an engaging Hill-Sachs lesion or in the presence of poor soft tissue quality. A tricortical iliac crest graft may be used as a primary procedure or as a salvage procedure after failure of a Bristow or a Latarjet procedure. Less frequently, the surgeon has to address the Hill-Sachs lesion. When a 30% loss of humeral head circumference is present a filling graft should be used. Reasons for failure are multifactorial. In order to address this entity, surgeons must correctly identify the causes and tailor the right solution.

  15. Effect of Battlefield Acupuncture and Physical Therapy Versus Physical Therapy Alone After Shoulder Surgery

    ClinicalTrials.gov

    2018-05-14

    Opioid Use; Pain, Postoperative; SLAP Lesion; Bankart Lesion; Subacromial Impingement Syndrome; Rotator Cuff Tear; Glenohumeral Dislocation; Glenohumeral Subluxation; Hill Sach Lesion; Bony Bankart Lesion; Acromioclavicular Separation

  16. Republication of: A theorem on Petrov types

    NASA Astrophysics Data System (ADS)

    Goldberg, J. N.; Sachs, R. K.

    2009-02-01

    This is a republication of the paper “A Theorem on Petrov Types” by Goldberg and Sachs, Acta Phys. Pol. 22 (supplement), 13 (1962), in which they proved the Goldberg-Sachs theorem. The article has been selected for publication in the Golden Oldies series of General Relativity and Gravitation. Typographical errors of the original publication were corrected by the editor. The paper is accompanied by a Golden Oldie Editorial containing an editorial note written by Andrzej Krasiński and Maciej Przanowski and Goldberg’s brief autobiography. The editorial note explains some difficult parts of the proof of the theorem and discusses the influence of results of the paper on later research.

  17. Power Sector Variability

    EPA Pesticide Factsheets

    This Technical Support Document (TSD) provides information in support of section IV.F, “Emission Reduction Requirements Including Variability”, in the preamble to the proposed Transport Rule (now known as the Cross-State Air Pollution Rule).

  18. Fatigue testing of energy storing prosthetic feet.

    PubMed

    Toh, S L; Goh, J C; Tan, P H; Tay, T E

    1993-12-01

    This paper describes a simple approach to the fatigue testing of prosthetic feet. A fatigue testing machine for prosthetic feet was designed as part of the programme to develop an energy storing prosthetic foot (ESPF). The fatigue tester does not simulate the loading pattern on the foot during normal walking. However, cyclic vertical loads are applied to the heel and forefoot during heel-strike and toe-off respectively, for 500,000 cycles. The maximum load applied was chosen to be 1.5 times that applied by the bodyweight of the amputee and the test frequency was chosen to be 2 Hz to shorten the test duration. Four prosthetic feet were tested: two Lambda feet (a newly developed ESPF), a Kingsley SACH foot and a Proteor SACH foot. It was found that the Lambda feet have very good fatigue properties. The Kingsley SACH foot performed better than the Proteor model, with no signs of wear at the heel. The results obtained using the simple approach was found to be comparable to the results from more complex fatigue machines which simulate the load pattern during normal walking. This suggests that simple load simulating machines, which are less costly and require less maintenance, are useful substitutes in studying the fatigue properties of prosthetic feet.

  19. Study of the human/ITS interface issues on the design of traffic information bulletin board and traffic control signal displays

    DOT National Transportation Integrated Search

    2002-10-01

    The success of automation for intelligent transportation systems is ultimately contingent upon the Interface between the users (humans) and the system (ITS). The issues of variable message signs (VMS) and traffic signal device (TSD) design were studi...

  20. Electric Generation Ownership, Market Concentration and Auction Size

    EPA Pesticide Factsheets

    In this Technical Support Document (TSD), EPA explains in more detail the issues and analyses completed for the alternative remedy of State Budgets/Intrastate Trading described in the proposed Transport Rule preamble in section V.D.5.

  1. 75 FR 67611 - Airworthiness Directives; Rolls-Royce Deutschland Ltd. & Co. KG. (RRD) Models Tay 650-15 and Tay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-03

    ... by this European Aviation Safety Agency (EASA) AD 2008-0122 was intended to avoid a failure of a low... information provided by the European Aviation Safety Agency and determined the unsafe condition exists and is... Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule; request for comments...

  2. 75 FR 51651 - Airworthiness Directives; Rolls-Royce Deutschland Ltd. & Co. KG. (RRD) Models Tay 650-15 and Tay...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-23

    ... by this European Aviation Safety Agency (EASA) AD 2008-0122 was intended to avoid a failure of a low... action specified by this European Aviation Safety Agency (EASA) AD 2008-0122 was intended to avoid a... Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: The FAA is...

  3. River Protection Project (RPP) Dangerous Waste Training Plan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    POHTO, R.E.

    2000-03-09

    This supporting document contains the training plan for dangerous waste management at River Protection Project TSD Units. This document outlines the dangerous waste training program developed and implemented for all Treatment, Storage, and Disposal (TSD) Units operated by River Protection Project (RPP) in the Hanford 200 East, 200 West and 600 Areas and the <90 Day Accumulation Area at 209E. Operating TSD Units managed by RPP are: the Double-Shell Tank (DST) System, 204-AR Waste Unloading Facility, Grout, and the Single-Shell Tank (SST) System. The program is designed in compliance with the requirements of Washington Administrative Code (WAC) 173-303-330 and Titlemore » 40 Code of Federal Regulations (CFR) 265.16 for the development of a written dangerous waste training program and the Hanford Facility Permit. Training requirements were determined by an assessment of employee duties and responsibilities. The RPP training program is designed to prepare employees to operate and maintain the Tank Farms in a safe, effective, efficient, and environmentally sound manner. In addition to preparing employees to operate and maintain the Tank Farms under normal conditions, the training program ensures that employees are prepared to respond in a prompt and effective manner should abnormal or emergency conditions occur. Emergency response training is consistent with emergency responses outlined in the following Building Emergency Plans: HNF-IP-0263-TF and HNF-=IP-0263-209E.« less

  4. Discovery of the youngest sex chromosomes reveals first case of convergent co-option of ancestral autosomes in turtles.

    PubMed

    Montiel, E E; Badenhorst, D; Tamplin, J; Burke, R L; Valenzuela, N

    2017-02-01

    Most turtle species possess temperature-dependent sex determination (TSD), but genotypic sex determination (GSD) has evolved multiple times independently from the TSD ancestral condition. GSD in animals typically involves sex chromosomes, yet the sex chromosome system of only 9 out of 18 known GSD turtles has been characterized. Here, we combine comparative genome hybridization (CGH) and BAC clone fluorescent in situ hybridization (BAC FISH) to identify a macro-chromosome XX/XY system in the GSD wood turtle Glyptemys insculpta (GIN), the youngest known sex chromosomes in chelonians (8-20 My old). Comparative analyses show that GIN-X/Y is homologous to chromosome 4 of Chrysemys picta (CPI) painted turtles, chromosome 5 of Gallus gallus chicken, and thus to the X/Y sex chromosomes of Siebenrockiella crassicollis black marsh turtles. We tentatively assign the gene content of the mapped BACs from CPI chromosome 4 (CPI-4) to GIN-X/Y. Chromosomal rearrangements were detected in G. insculpta sex chromosome pair that co-localize with the male-specific region of GIN-Y and encompass a gene involved in sexual development (Wt1-a putative master gene in TSD turtles). Such inversions may have mediated the divergence of G. insculpta sex chromosome pair and facilitated GSD evolution in this turtle. Our results illuminate the structure, origin, and evolution of sex chromosomes in G. insculpta and reveal the first case of convergent co-option of an autosomal pair as sex chromosomes within chelonians.

  5. TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-TS-D-26 (R) 157.4815. Left (printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

  6. Characterization of Construction Material Properties through Gamma Spectroscopy, X-ray Fluorescence, and Hyper-spectral Imagery for Background Correction Applications in Nuclear Detection

    DTIC Science & Technology

    2014-03-27

    14 Mar 2014 David J. Bunker, Ph.D. (Chairman) Date ____________//signed//_________________ 14 Mar 2014 Tay W. Johannes, Ph.D...Lt Col, USAF (Member) Date ____________//signed//_________________ 12 Mar 2014 Benjamin R. Kowash, Ph.D., Maj, USAF (Member) Date AFIT-ENP...by Test Date ........................ 28 Figure 3: Comparison of background spectra from 6 October (blue) and 16 September (green

  7. Programmatic Agreements for Project-Level Air Quality Analyses : NCHRP 25-25 Task 78

    DOT National Transportation Integrated Search

    2015-09-01

    The research performed under Task 78 was divided into two phases. The first phase involved development of a draft Programmatic Agreement (PA) template and a draft Technical Support Document (TSD) template for project-level carbon monoxide (CO) hot-sp...

  8. TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    TOWER STAIRHALL; SOUTH SOFFIT, SOUTH WEST (R). Glass plate stereopair number PA-1430-139 LC-HABS-GS05-TS-D-26 (R) 157.4815. Right (not printed) - Independence Hall Complex, Independence Hall, 500 Chestnut Street, Philadelphia, Philadelphia County, PA

  9. An outbreak of Streptococcus equi subspecies zooepidemicus associated with consumption of fresh goat cheese

    PubMed Central

    Kuusi, Markku; Lahti, Elina; Virolainen, Anni; Hatakka, Maija; Vuento, Risto; Rantala, Leila; Vuopio-Varkila, Jaana; Seuna, Eija; Karppelin, Matti; Hakkinen, Marjaana; Takkinen, Johanna; Gindonis, Veera; Siponen, Kyosti; Huotari, Kaisa

    2006-01-01

    Background Streptococcus equi subspecies zooepidemicus is a rare infection in humans associated with contact with horses or consumption of unpasteurized milk products. On October 23, 2003, the National Public Health Institute was alerted that within one week three persons had been admitted to Tampere University Central Hospital (TaYS) because of S. equi subsp. zooepidemicus septicaemia. All had consumed fresh goat cheese produced in a small-scale dairy located on a farm. We conducted an investigation to determine the source and the extent of the outbreak. Methods Cases were identified from the National Infectious Disease Register. Cases were persons with S. equi subsp. zooepidemicus isolated from a normally sterile site who had illness onset 15.9-31.10.2003. All cases were telephone interviewed by using a standard questionnaire and clinical information was extracted from patient charts. Environmental and food specimens included throat swabs from two persons working in the dairy, milk from goats and raw milk tank, cheeses made of unpasteurized milk, vaginal samples of goats, and borehole well water. The isolates were characterized by ribotyping and pulsed-field gel electrophoresis (PFGE). Results Seven persons met the case definition; six had septicaemia and one had purulent arthritis. Five were women; the median age was 70 years (range 54–93). None of the cases were immunocompromized and none died. Six cases were identified in TaYS, and one in another university hospital in southern Finland. All had eaten goat cheese produced on the implicated farm. S. equi subsp. zooepidemicus was isolated from throat swabs, fresh goat cheese, milk tank, and vaginal samples of one goat. All human and environmental strains were indistinguishable by ribotyping and PFGE. Conclusion The outbreak was caused by goat cheese produced from unpasteurized milk. Outbreaks caused by S. equi subsp. zooepidemicus may not be detected if streptococcal strains are only typed to the group level. S

  10. [Nuclear magnetic tomography in shoulder dislocation].

    PubMed

    Runkel, M; Kreitner, K F; Wenda, K; Rudig, L; Degreif, J; Grebe, P

    1993-03-01

    Sixty-two patients with anterior shoulder dislocations were examined by magnetic resonance imaging (MRI). After a primary dislocation, 30 patients showed 23 (77%) tears of the glenoid labrum, 13 (45%) anterior-inferior separation of the capsula, 24 (83%) Hill-Sachs lesions, 6 fractures of the greater tuberosity and 4 glenoid rim fractures. Thirty-two patients with recurrent shoulder dislocation had 14 (44%) tears and 15 (47%) defects of the glenoid labrum, 16 (50%) anterior-inferior separation of the capsula, 28 (88%) Hill-Sachs lesions and 3 glenoid rim fractures. MRI permits complete non-invasive documentation of glenohumeral instability if joint effusion is present. In the absence of joint effusion, diagnostic accuracy can be improved by application of a contrast medium.

  11. 2011 Version 6.3 Technical Support Document

    EPA Pesticide Factsheets

    This TSD describes how the emission inventories were prepared for air quality modeling for the years 2011, 2017, and 2025 using the 2011, version 6.2 emissions modeling platform, which is based on the 2011 National Emissions Inventory, Version 3

  12. 2011 Version 6.2 Technical Support Document

    EPA Pesticide Factsheets

    This TSD describes how the emission inventories were prepared for air quality modeling for the years 2011, 2017, and 2025 using the 2011, version 6.2 emissions modeling platform, which is based on the 2011 National Emissions Inventory, Version 2.

  13. 2011 Version 6.1 Technical Support Document

    EPA Pesticide Factsheets

    This TSD describes how the emission inventories were prepared for air quality modeling for the years 2011, 2018, and 2025 using the 2011, version 6.1 emissions modeling platform, which is based on the 2011 National Emissions Inventory, Version 1.

  14. 2011 Version 6.0 Technical Support Document

    EPA Pesticide Factsheets

    This TSD describes how the emission inventories were prepared for air quality modeling for the years 2011, 2018, and 2025 using the 2011, version 6.0 emissions modeling platform, which is based on the 2011 National Emissions Inventory, Version 1

  15. Mapping of past stand-level forest disturbances and estimation of time since disturbance using simulated spaceborne LiDAR data

    NASA Astrophysics Data System (ADS)

    Sanchez Lopez, N.; Hudak, A. T.; Boschetti, L.

    2017-12-01

    Explicit information on the location, the size or the time since disturbance (TSD) at the forest stand level complements field inventories, improves the monitoring of forest attributes and the estimation of biomass and carbon stocks. Even-aged stands display homogenous structural parameters that have often been used as a proxy of stand age. Consequently, performing object-oriented analysis on Light Detection and Ranging (LiDAR) data has potential to detect historical stand-replacing disturbances. Recent research has shown good results in the delineation of forest stands as well as in the prediction of disturbance occurrence and TSD using airborne LiDAR data. Nevertheless, the use of airborne LiDAR for systematic monitoring of forest stands is limited by the sporadic availability of data and its high cost compared to satellite instruments. NASA's forthcoming Global Ecosystem Dynamics Investigations (GEDI) mission will provide systematically data on the vertical structure of the vegetation, but its use presents some challenges compared to the common discrete-return airborne LiDAR. GEDI will be a waveform instrument, hence the summary metrics will be different to those obtained with airborne LiDAR, and the sampling configuration could limit the utility of the data, especially on heterogeneous landscapes. The potential use of GEDI data for forest characterization at the stand level would therefore depend on the predictive power of the GEDI footprint metrics, and on the density of point samples relative to forest stand size (i.e. the number of observation/footprints per stand).In this study, we assess the performance of simulated GEDI-derived metrics for stand characterization and estimation of TSD, and the point density needed to adequately identify forest stands, which translates - due to the fixed sampling configuration - into the minimum temporal interval needed to collect a sufficient number of points. The study area was located in the Clear Creek, Selway River

  16. Investigations of quantum effect semiconductor devices: The tunnel switch diode and the velocity modulation transistor

    NASA Astrophysics Data System (ADS)

    Daniel, Erik Stephen

    In this thesis we present the results of experimental and theoretical studies of two quantum effect devices--the Tunnel Switch Diode (TSD) and the Velocity Modulation Transistor (VMT). We show that TSD devices can be fabricated such that they behave (semi-quantitatively) as predicted by simple analytical models and more advanced drift-diffusion simulations. These devices possess characteristics, such as on-state currents which range over nearly five orders of magnitude, and on/off current ratios which are even larger, which may allow for a practical implementation of a very dense transistorless SRAM architecture and possibly other novel circuit designs. We demonstrate that many TSD properties can be explained by analogy to a thyristor. In particular, we show that the thin oxide layer in the TSD plays a critical role, and that this can be understood in terms of current injection through the oxide, analogous to transport through the "current limiting" layer in a thyristor. As this oxide layer can be subjected to extreme stress during device operation, we have studied the effect of this stress on device behavior. We demonstrate many significant stress-dependent effects, and identify structures and operation modes which minimize these effects. We propose an InAs/GaSb/AlSb VMT which may allow for larger conductance modulation and higher temperature operation than has been demonstrated in similar GaAs/AlAs structures. Fundamental differences in device operation in the two materials systems and unusual transport mechanisms in the InAs/GaSb/AlSb system are identified as a result of the band lineups in the two systems. Boltzmann transport simulations are developed and presented, allowing a qualitative description of the transport in the InAs/GaSb/AlSb structure. Band structure calculations are carried out, allowing for device design. While no working VMT devices were produced, this is believed to be due to processing and crystal growth problems. We present methods used to

  17. Calendar Year 2007 Resource Conservation and Recovery Act Annual Monitoring Report for the U.S. Department of Energy Y-12 National Security Complex, Oak Ridge, Tennessee - RCRA Post-Closure Permit Nos. TNHW-113, TNHW-116, and TNHW-128

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Elvado Environmental

    2008-02-01

    This report contains groundwater quality monitoring data obtained during calendar year (CY) 2007 at the following hazardous waste treatment, storage, and disposal (TSD) units located at the US Department of Energy (DOE) Y-12 National Security Complex (hereafter referenced as Y-12) in Oak Ridge, Tennessee; this S-3 Site, Oil Landfarm, Bear Creek Burial Grounds/Walk-In Pits (BCBG/WIP), Eastern S-3 Site Plume, Chestnut Ridge Security Pits (CRSP), Chestnut Ridge Sediment Disposal Baste (CRSDB), few Hollow Quarry (KHQ), and East Chestnut Ridge Waste Pile (ECRWP). Hit monitoring data were obtained in accordance with the applicable Resource Conservation and Recovery Act of 1976 (RCRA) hazardousmore » waste post-closure permit (PCP). The Tennessee Department of Environment and Conservation (TDEC) - Division of Solid Waste Management issued the PCPs to define the requirements for RCRA post-closure inspection, maintenance, and groundwater monitoring at the specified TSD units located within the Bear Creek Hydrogeologic Regime (PCP no. TNHW-116), Upper East Fork Poplar Creek Hydrogeologic Regime (PCP no. TNHW-113), and Chestnut Ridge Hydrogeologic Regime (PCP no. TNHW-128). Each PCP requires the Submittal of an annual RCRA groundwater monitoring report containing the groundwater sampling information and analytical results obtained at each applicable TSD unit during the preceding CY, along with an evaluation of groundwater low rates and directions and the analytical results for specified RCRA groundwater target compounds; this report is the RCRA annual groundwater monitoring report for CY 2007. The RCRA post-closure groundwater monitoring requirements specified in the above-referenced PCP for the Chestnut Ridge Regime replace those defined in the previous PCP (permit no. TNHW-088), which expired on September 18, 2005, but remained effective until the TDEC issued the new PCP in September 2006. The new PCP defines site-specific groundwater sampling and analysis requirements

  18. 77 FR 13026 - Energy Conservation Program: Energy Conservation Standard for Automatic Commercial Ice Makers

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-05

    ... written comments on these subjects. This document announces an extension of the time period for submitting... preliminary technical support document (preliminary TSD) for automatic commercial ice makers. The comment... published a Federal Register notice announcing the availability of its preliminary technical support...

  19. Fine-Tuning in a Design Experiment

    ERIC Educational Resources Information Center

    Ho, Foo Him; Toh, Pee Choon; Toh, Tin Lam

    2013-01-01

    Quek, Tay, Toh, Leong, and Dindyal (2011) proposed that a design-theory-practice troika should always be considered for a designed package to be acceptable to the research users who, in this case, are teachers and schools. This paper describes the fine-tuning to the MProSE problem-solving design made by the teachers in the school after first round…

  20. Nonisentropic unsteady three dimensional small disturbance potential theory

    NASA Technical Reports Server (NTRS)

    Gibbons, M. D.; Whitlow, W., Jr.; Williams, M. H.

    1986-01-01

    Modifications that allow for more accurate modeling of flow fields when strong shocks are present were made into three dimensional transonic small disturbance (TSD) potential theory. The Engquist-Osher type-dependent differencing was incorporated into the solution algorithm. The modified theory was implemented in the XTRAN3S computer code. Steady flows over a rectangular wing with a constant NACA 0012 airfoil section and an aspect ratio of 12 were calculated for freestream Mach numbers (M) of 0.82, 0.84, and 0.86. The obtained results are compared using the modified and unmodified TSD theories and the results from a three dimensional Euler code are presented. Nonunique solutions in three dimensions are shown to appear for the rectangular wing as aspect ratio increases. Steady and unsteady results are shown for the RAE tailplane model at M = 0.90. Calculations using unmodified theory, modified theory and experimental data are compared.

  1. 75 FR 61343 - Airworthiness Directives; Rolls-Royce Deutschland Ltd & Co KG (RRD) Models Tay 620-15, Tay 650-15...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... receipt. List of Subjects in 14 CFR Part 39 Air transportation, Aircraft, Aviation safety, Incorporation... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 [Docket No. FAA-2010... Docket Operations office is located at Docket Management Facility, U.S. Department of Transportation...

  2. Mitral valve repair in dogs using an ePTFE chordal implantation device: a pilot study.

    PubMed

    Borgarelli, M; Lanz, O; Pavlisko, N; Abbott, J A; Menciotti, G; Aherne, M; Lahmers, S M; Lahmers, K K; Gammie, J S

    2017-06-01

    Mitral valve (MV) regurgitation due to degenerative MV disease is the leading cause of cardiac death in dogs. We carried out preliminary experiments to determine the feasibility and short-term effects of beating-heart MV repair using an expanded polytetrafluorethylene (ePTFE) chordal implantation device (Harpoon TSD-5) in dogs. This study involved six healthy purpose-bred Beagles (weight range 8.9-11.4 kg). Following a mini-thoracotomy performed under general anesthesia, the TSD-5 was used to place 1 or 2 artificial ePTFE cords on the anterior MV leaflet or the posterior MV leaflet via a left-ventricular transapical approach. The procedure was guided and monitored by transesophageal echocardiography. Postoperative antithrombotic treatment consisted of clopidogrel or a combination of clopidogrel and apixaban. Dogs were serially evaluated by transthoracic echocardiography at day 1, 7, 14, 21, and 30. The hearts were then examined for evaluation of tissues reactions and to detect signs of endothelialization. One or two chords were successfully implanted in five dogs. Four dogs completed the 30 days follow-up. One dog died intra-operatively because of aortic perforation. One dog died early post-operatively from a hemorrhagic pleural effusion attributed to overly aggressive antithrombotic treatment. One dog developed a thrombus surrounding both the knot and the synthetic cord. Postmortem exam confirmed secure placement of ePTFE knots in the mitral leaflets in all dogs and the presence of endothelialization of the knots and chords. These preliminary results demonstrate the feasibility of artificial chordal placement using an ePTFE cordal implantation device in dogs. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. A Unified Model of Performance: Validation of its Predictions across Different Sleep/Wake Schedules.

    PubMed

    Ramakrishnan, Sridhar; Wesensten, Nancy J; Balkin, Thomas J; Reifman, Jaques

    2016-01-01

    Historically, mathematical models of human neurobehavioral performance developed on data from one sleep study were limited to predicting performance in similar studies, restricting their practical utility. We recently developed a unified model of performance (UMP) to predict the effects of the continuum of sleep loss-from chronic sleep restriction (CSR) to total sleep deprivation (TSD) challenges-and validated it using data from two studies of one laboratory. Here, we significantly extended this effort by validating the UMP predictions across a wide range of sleep/wake schedules from different studies and laboratories. We developed the UMP on psychomotor vigilance task (PVT) lapse data from one study encompassing four different CSR conditions (7 d of 3, 5, 7, and 9 h of sleep/night), and predicted performance in five other studies (from four laboratories), including different combinations of TSD (40 to 88 h), CSR (2 to 6 h of sleep/night), control (8 to 10 h of sleep/night), and nap (nocturnal and diurnal) schedules. The UMP accurately predicted PVT performance trends across 14 different sleep/wake conditions, yielding average prediction errors between 7% and 36%, with the predictions lying within 2 standard errors of the measured data 87% of the time. In addition, the UMP accurately predicted performance impairment (average error of 15%) for schedules (TSD and naps) not used in model development. The unified model of performance can be used as a tool to help design sleep/wake schedules to optimize the extent and duration of neurobehavioral performance and to accelerate recovery after sleep loss. © 2016 Associated Professional Sleep Societies, LLC.

  4. Effects of exercise on depressive behavior and striatal levels of norepinephrine, serotonin and their metabolites in sleep-deprived mice.

    PubMed

    Daniele, Thiago Medeiros da Costa; de Bruin, Pedro Felipe Carvalhedo; Rios, Emiliano Ricardo Vasconcelos; de Bruin, Veralice Meireles Sales

    2017-08-14

    Exercise is a promising adjunctive therapy for depressive behavior, sleep/wake abnormalities, cognition and motor dysfunction. Conversely, sleep deprivation impairs mood, cognition and functional performance. The objective of this study is to evaluate the effects of exercise on anxiety and depressive behavior and striatal levels of norepinephrine (NE), serotonin and its metabolites in mice submitted to 6h of total sleep deprivation (6h-TSD) and 72h of Rapid Eye Movement (REM) sleep deprivation (72h-REMSD). Experimental groups were: (1) mice submitted to 6h-TSD by gentle handling; (2) mice submitted to 72h-REMSD by the flower pot method; (3) exercise (treadmill for 8 weeks); (4) exercise followed by 6h-TSD; (5) exercise followed by 72h-REMSD; (6) control (home cage). Behavioral tests included the Elevated Plus Maze and tail-suspension. NE, serotonin and its metabolites were determined in the striatum using high-performance liquid chromatography (HPLC). Sleep deprivation increased depressive behavior (time of immobilization in the tail-suspension test) and previous exercise hindered it. Sleep deprivation increased striatal NE and previous exercise reduced it. Exercise only was associated with higher levels of serotonin. Furthermore, exercise reduced serotonin turnover associated with sleep deprivation. In brief, previous exercise prevented depressive behavior and reduced striatal high NE levels and serotonin turnover. The present findings confirm the effects of exercise on behavior and neurochemical alterations associated with sleep deprivation. These findings provide new avenues for understanding the mechanisms of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. USING A RISK-BASED METHODOLOGY FOR THE TRANSFER OF RADIOACTIVE MATERIAL WITHIN THE SAVANNAH RIVER SITE BOUNDARY

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Loftin, B; Watkins, R; Loibl, M

    2010-06-03

    Shipment of radioactive materials (RAM) is discussed in the Code of Federal Regulations in parts of both 49 CFR and 10 CFR. The regulations provide the requirements and rules necessary for the safe shipment of RAM across public highways, railways, waterways, and through the air. These shipments are sometimes referred to as in-commerce shipments. Shipments of RAM entirely within the boundaries of Department of Energy sites, such as the Savannah River Site (SRS), can be made using methodology allowing provisions to maintain equivalent safety while deviating from the regulations for in-commerce shipments. These onsite shipments are known as transfers atmore » the SRS. These transfers must follow the requirements approved in a site-specific Transportation Safety Document (TSD). The TSD defines how the site will transfer materials so that they have equivalence to the regulations. These equivalences are documented in an Onsite Safety Assessment (OSA). The OSA can show how a particular packaging used onsite is equivalent to that which would be used for an in-commerce shipment. This is known as a deterministic approach. However, when a deterministic approach is not viable, the TSD allows for a risk-based OSA to be written. These risk-based assessments show that if a packaging does not provide the necessary safety to ensure that materials are not released (during normal or accident conditions) then the worst-case release of materials does not result in a dose consequence worse than that defined for the SRS. This paper will discuss recent challenges and successes using this methodology at the SRS.« less

  6. Karyotype analysis and sex determination in Australian Brush-turkeys (Alectura lathami).

    PubMed

    Ortega, Madison T; Foote, Dustin J; Nees, Nicholas; Erdmann, Jason C; Bangs, Charles D; Rosenfeld, Cheryl S

    2017-01-01

    Sexual differentiation across taxa may be due to genetic sex determination (GSD) and/or temperature sex determination (TSD). In many mammals, males are heterogametic (XY); whereas females are homogametic (XX). In most birds, the opposite is the case with females being heterogametic (ZW) and males the homogametic sex (ZZ). Many reptile species lack sex chromosomes, and instead, sexual differentiation is influenced by temperature with specific temperatures promoting males or females varying across species possessing this form of sexual differentiation, although TSD has recently been shown to override GSD in Australian central beaded dragons (Pogona vitticeps). There has been speculation that Australian Brush-turkeys (Alectura lathami) exhibit TSD alone and/or in combination with GSD. Thus, we sought to determine if this species possesses sex chromosomes. Blood was collected from one sexually mature female and two sexually mature males residing at Sylvan Heights Bird Park (SHBP) and shipped for karyotype analysis. Karyotype analysis revealed that contrary to speculation, Australian Brush-turkeys possess the classic avian ZW/ZZ sex chromosomes. It remains a possibility that a biased primary sex ratio of Australian Brush-turkeys might be influenced by maternal condition prior to ovulation that result in her laying predominantly Z- or W-bearing eggs and/or sex-biased mortality due to higher sensitivity of one sex in environmental conditions. A better understanding of how maternal and extrinsic factors might differentially modulate ovulation of Z- or W-bearing eggs and hatching of developing chicks possessing ZW or ZZ sex chromosomes could be essential in conservation strategies used to save endangered members of Megapodiidae.

  7. Sleep deprivation impairs the accurate recognition of human emotions.

    PubMed

    van der Helm, Els; Gujar, Ninad; Walker, Matthew P

    2010-03-01

    Investigate the impact of sleep deprivation on the ability to recognize the intensity of human facial emotions. Randomized total sleep-deprivation or sleep-rested conditions, involving between-group and within-group repeated measures analysis. Experimental laboratory study. Thirty-seven healthy participants, (21 females) aged 18-25 y, were randomly assigned to the sleep control (SC: n = 17) or total sleep deprivation group (TSD: n = 20). Participants performed an emotional face recognition task, in which they evaluated 3 different affective face categories: Sad, Happy, and Angry, each ranging in a gradient from neutral to increasingly emotional. In the TSD group, the task was performed once under conditions of sleep deprivation, and twice under sleep-rested conditions following different durations of sleep recovery. In the SC group, the task was performed twice under sleep-rested conditions, controlling for repeatability. In the TSD group, when sleep-deprived, there was a marked and significant blunting in the recognition of Angry and Happy affective expressions in the moderate (but not extreme) emotional intensity range; differences that were most reliable and significant in female participants. No change in the recognition of Sad expressions was observed. These recognition deficits were, however, ameliorated following one night of recovery sleep. No changes in task performance were observed in the SC group. Sleep deprivation selectively impairs the accurate judgment of human facial emotions, especially threat relevant (Anger) and reward relevant (Happy) categories, an effect observed most significantly in females. Such findings suggest that sleep loss impairs discrete affective neural systems, disrupting the identification of salient affective social cues.

  8. Karyotype analysis and sex determination in Australian Brush-turkeys (Alectura lathami)

    PubMed Central

    Ortega, Madison T.; Foote, Dustin J.; Nees, Nicholas; Erdmann, Jason C.; Bangs, Charles D.

    2017-01-01

    Sexual differentiation across taxa may be due to genetic sex determination (GSD) and/or temperature sex determination (TSD). In many mammals, males are heterogametic (XY); whereas females are homogametic (XX). In most birds, the opposite is the case with females being heterogametic (ZW) and males the homogametic sex (ZZ). Many reptile species lack sex chromosomes, and instead, sexual differentiation is influenced by temperature with specific temperatures promoting males or females varying across species possessing this form of sexual differentiation, although TSD has recently been shown to override GSD in Australian central beaded dragons (Pogona vitticeps). There has been speculation that Australian Brush-turkeys (Alectura lathami) exhibit TSD alone and/or in combination with GSD. Thus, we sought to determine if this species possesses sex chromosomes. Blood was collected from one sexually mature female and two sexually mature males residing at Sylvan Heights Bird Park (SHBP) and shipped for karyotype analysis. Karyotype analysis revealed that contrary to speculation, Australian Brush-turkeys possess the classic avian ZW/ZZ sex chromosomes. It remains a possibility that a biased primary sex ratio of Australian Brush-turkeys might be influenced by maternal condition prior to ovulation that result in her laying predominantly Z- or W-bearing eggs and/or sex-biased mortality due to higher sensitivity of one sex in environmental conditions. A better understanding of how maternal and extrinsic factors might differentially modulate ovulation of Z- or W-bearing eggs and hatching of developing chicks possessing ZW or ZZ sex chromosomes could be essential in conservation strategies used to save endangered members of Megapodiidae. PMID:28910392

  9. 1. Historic American Buildings Survey, August, 1971 SOUTH (FRONT) ELEVATIONS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey, August, 1971 SOUTH (FRONT) ELEVATIONS AT LOVE AND BILGER TIN SHOP (LEFT) AND SACHS BROTHERS STORE (RIGHT). - Love & Bilger Tin Shop, 150 West California Street, Jacksonville, Jackson County, OR

  10. The lesser known challenge of climate change: thermal variance and sex-reversal in vertebrates with temperature-dependent sex determination.

    PubMed

    Neuwald, Jennifer L; Valenzuela, Nicole

    2011-03-23

    Climate change is expected to disrupt biological systems. Particularly susceptible are species with temperature-dependent sex determination (TSD), as in many reptiles. While the potentially devastating effect of rising mean temperatures on sex ratios in TSD species is appreciated, the consequences of increased thermal variance predicted to accompany climate change remain obscure. Surprisingly, no study has tested if the effect of thermal variance around high-temperatures (which are particularly relevant given climate change predictions) has the same or opposite effects as around lower temperatures. Here we show that sex ratios of the painted turtle (Chrysemys picta) were reversed as fluctuations increased around low and high unisexual mean-temperatures. Unexpectedly, the developmental and sexual responses around female-producing temperatures were decoupled in a more complex manner than around male-producing values. Our novel observations are not fully explained by existing ecological models of development and sex determination, and provide strong evidence that thermal fluctuations are critical for shaping the biological outcomes of climate change.

  11. Aerodynamic Modeling of Transonic Aircraft Using Vortex Lattice Coupled with Transonic Small Disturbance for Conceptual Design

    NASA Technical Reports Server (NTRS)

    Chaparro, Daniel; Fujiwara, Gustavo E. C.; Ting, Eric; Nguyen, Nhan

    2016-01-01

    The need to rapidly scan large design spaces during conceptual design calls for computationally inexpensive tools such as the vortex lattice method (VLM). Although some VLM tools, such as Vorview have been extended to model fully-supersonic flow, VLM solutions are typically limited to inviscid, subcritical flow regimes. Many transport aircraft operate at transonic speeds, which limits the applicability of VLM for such applications. This paper presents a novel approach to correct three-dimensional VLM through coupling of two-dimensional transonic small disturbance (TSD) solutions along the span of an aircraft wing in order to accurately predict transonic aerodynamic loading and wave drag for transport aircraft. The approach is extended to predict flow separation and capture the attenuation of aerodynamic forces due to boundary layer viscosity by coupling the TSD solver with an integral boundary layer (IBL) model. The modeling framework is applied to the NASA General Transport Model (GTM) integrated with a novel control surface known as the Variable Camber Continuous Trailing Edge Flap (VCCTEF).

  12. Linear facing target sputtering of the epitaxial Ga-doped ZnO transparent contact layer on GaN-based light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Shin, Hyun-Su; Lee, Ju-Hyun; Kwak, Joon-Seop; Lee, Hyun Hwi; Kim, Han-Ki

    2013-10-01

    In this study, we reported on the plasma damage-free sputtering of epitaxial Ga-doped ZnO (GZO) films on the p-GaN layer for use as a transparent contact layer (TCL) for GaN-based light-emitting diodes (LEDs) using linear facing target sputtering (LFTS). Effective confinement of high-density plasma between faced GZO targets and the substrate position located outside of the plasma region led to the deposition of the epitaxial GZO TCL with a low sheet resistance of 25.7 Ω/s and a high transmittance of 84.6% on a p-GaN layer without severe plasma damage, which was found using the conventional dc sputtering process. The low turn-on voltage of the GaN-based LEDs with an LFTS-grown GZO TCL layer that was grown at a longer target-to-substrate distance (TSD) indicates that the plasma damage of the GaN-LED could be effectively reduced by adjusting the TSD during the LFTS process.

  13. Evaluation of Linear, Inviscid, Viscous, and Reduced-Order Modeling Aeroelastic Solutions of the AGARD 445.6 Wing Using Root Locus Analysis

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Perry, Boyd III; Chwalowski, Pawel

    2014-01-01

    Reduced-order modeling (ROM) methods are applied to the CFD-based aeroelastic analysis of the AGARD 445.6 wing in order to gain insight regarding well-known discrepancies between the aeroelastic analyses and the experimental results. The results presented include aeroelastic solutions using the inviscid CAP-TSD code and the FUN3D code (Euler and Navier-Stokes). Full CFD aeroelastic solutions and ROM aeroelastic solutions, computed at several Mach numbers, are presented in the form of root locus plots in order to better reveal the aeroelastic root migrations with increasing dynamic pressure. Important conclusions are drawn from these results including the ability of the linear CAP-TSD code to accurately predict the entire experimental flutter boundary (repeat of analyses performed in the 1980's), that the Euler solutions at supersonic conditions indicate that the third mode is always unstable, and that the FUN3D Navier-Stokes solutions stabilize the unstable third mode seen in the Euler solutions.

  14. Reflections around 'the cautionary use' of the h-index: response to Teixeira da Silva and Dobránszki.

    PubMed

    Costas, Rodrigo; Franssen, Thomas

    2018-01-01

    In a recent Letter to the Editor Teixeira da Silva and Dobránszki (2018) present a discussion of the issues regarding the h-index as an indicator for the evaluation of individual scholars, particularly in the current landscape of the proliferation of online sources that provide individual level bibliometric indicators. From our point of view, the issues surrounding the h-index go far beyond the problems mentioned by TSD. In this letter we provide some overview of this, mostly by expanding TSD's original argument and discussing more conceptual and global issues related to the indicator, particularly in the outlook of a strong proliferation of online sources providing individual researcher indicators. Our discussion focuses on the h-index and the profusion of sources providing it, but we emphasize that many of our points are of a more general nature, and would be equally relevant for other indicators that reach the same level of popularity as the h-index.

  15. Family-based treatment for transition age youth: parental self-efficacy and caregiver accommodation.

    PubMed

    Dimitropoulos, Gina; Landers, Ashley L; Freeman, Victoria E; Novick, Jason; Cullen, Olivia; Engelberg, Marla; Steinegger, Cathleen; Le Grange, Daniel

    2018-01-01

    Family-Based Treatment (FBT) is the first line of care in paediatric treatment while adult programs focus on individualized models of care. Transition age youth (TAY) with Anorexia Nervosa (AN) are in a unique life stage and between systems of care. As such, they and their caregivers may benefit from specialized, developmentally tailored models of treatment. The primary purpose of this study was to assess if parental self-efficacy and caregiver accommodation changed in caregivers during the course of FBT-TAY for AN. The secondary aim was to determine if changes in parental self-efficacy and caregiver accommodation contributed to improvements in eating disorder behaviour and weight restoration in the transition age youth with AN. Twenty-six participants (ages 16-22) and 39 caregivers were recruited. Caregivers completed the Parents versus Anorexia Scale and Accommodation and Enabling Scale for Eating Disorders at baseline, end-of-treatment (EOT), and 3 months follow-up. Unbalanced repeated measures designs for parental self-efficacy and caregiver accommodation towards illness behaviours were conducted using generalized estimation equations. Parental self-efficacy increased from baseline to EOT, although not significantly ( p =  .398). Parental self-efficacy significantly increased from baseline to 3 months post-treatment ( p  = .002). Caregiver accommodation towards the illness significantly decreased from baseline to EOT ( p  = 0.0001), but not from baseline to 3 months post-treatment ( p  = 1.000). Stepwise ordinary least squares regression estimates of eating disorder behaviour and weight restoration did not show that changes in parental-self efficacy and caregiver accommodation predict eating disorder behaviour or weight restoration at EOT or 3 months post-treatment. Our findings demonstrate, albeit preliminary at this stage, that FBT-TAY promotes positive increases in parental self-efficacy and assists caregivers in decreasing their accommodation

  16. Final Revisions Rule State Budgets and New Unit Set-Asides TSD

    EPA Pesticide Factsheets

    This technical support document shows the underlying data and calculations used to quantify the state budget revisions and new unit set-aside revisions made in the final revisions rule, as well as those revisions included in the direct final revisions rule

  17. CMB in the river frame and gauge invariance at second order

    NASA Astrophysics Data System (ADS)

    Roldan, Omar

    2018-03-01

    Gauge invariance: the Sachs-Wolfe formula describing the Cosmic Microwave Background (CMB) temperature anisotropies is one of the most important relations in cosmology. Despite its importance, the gauge invariance of this formula has only been discussed at first order. Here we discuss the subtle issue of second-order gauge transformations on the CMB. By introducing two rules (needed to handle the subtle issues), we prove the gauge invariance of the second-order Sachs-Wolfe formula and provide several compact expressions which can be useful for the study of gauge transformations on cosmology. Our results go beyond a simple technicality: we discuss from a physical point of view several aspects that improve our understanding of the CMB. We also elucidate how crucial it is to understand gauge transformations on the CMB in order to avoid errors and/or misconceptions as occurred in the past. The river frame: we introduce a cosmological frame which we call the river frame. In this frame, photons and any object can be thought as fishes swimming in the river and relations are easily expressed in either the metric or the covariant formalism then ensuring a transparent geometric meaning. Finally, our results show that the river frame is useful to make perturbative and non-perturbative analysis. In particular, it was already used to obtain the fully nonlinear generalization of the Sachs-Wolfe formula and is used here to describe second-order perturbations.

  18. Seeded hot dark matter models with inflation

    NASA Technical Reports Server (NTRS)

    Gratsias, John; Scherrer, Robert J.; Steigman, Gary; Villumsen, Jens V.

    1993-01-01

    We examine massive neutrino (hot dark matter) models for large-scale structure in which the density perturbations are produced by randomly distributed relic seeds and by inflation. Power spectra, streaming velocities, and the Sachs-Wolfe quadrupole fluctuation are derived for this model. We find that the pure seeded hot dark matter model without inflation produces Sachs-Wolfe fluctuations far smaller than those seen by COBE. With the addition of inflationary perturbations, fluctuations consistent with COBE can be produced. The COBE results set the normalization of the inflationary component, which determines the large-scale (about 50/h Mpc) streaming velocities. The normalization of the seed power spectrum is a free parameter, which can be adjusted to obtain the desired fluctuations on small scales. The power spectra produced are very similar to those seen in mixed hot and cold dark matter models.

  19. Martin Winckler.

    PubMed

    Winckler, Martin

    2004-03-27

    Martin Winckler, born Marc Zaffran in 1955, is a French family doctor, a writer, a translator, and a cultural critic. Since the publication of La Vacation (Paris: POL, 1989), a novel based on his experience in an abortion clinic, he has published more than 20 books (fiction and non-fiction), including a user's manual of contraceptive devices (Contraceptions mode d'emploi. Vauvert: Le Diable Vauvert, 2003). His novel La maladie de Sachs has been translated into English as The Case of Dr Sachs (New York: Seven Stories Press, 2000). Winckler was recently a guest speaker at the Joint Meeting of the American Society of Bioethics and Humanities and the Canadian Society of Bioethics in Montreal, Canada. He will be a guest speaker at the Royal College of General Practitioners' Spring Symposium, in April this year in Bournemouth, UK.

  20. Comparison of three gas chromatography methods for the determination of slip agents in polyethylene films.

    PubMed

    Garrido-López, Alvaro; Esquiu, Vanesa; Tena, María Teresa

    2007-05-25

    Polymers require the use of some slip agents, such as oleamide and erucamide, in order to reduce their friction coefficient and to make films easier to handle. In this communication, three analytical methods consisting in pressurized liquid extraction (PLE) and gas chromatography (GC) are used to determine oleamide and erucamide in polyethylene films. The sample was extracted with pure isopropanol (two times) at 105 degrees C for 16 min. Then, the liquid extract containing oleamide and erucamide was analyzed by GC and three different detection systems: flame ionization detector (FID), thermoionic selective detector (TSD) and ion-trap mass spectrometry detector (MSD). Oleamide and erucamide were separated using a 30 m x 0.25 mm (I.D.) 5% phenyl-95% dimethyl-polysiloxane capillary column in 12 min. The chromatographic methods were characterized and compared in terms of repeatability, linearity and sensitivity. The GC-FID and GC-TSD methods were linear up to about 60 microg ml(-1), whereas the linear range for the GC-MSD method was shorter, from 20.5 to 42 microg ml(-1). LODs identified with GC-MSD were two times higher than those identified with the other two methods. Repeatability values (expressed as relative standard deviation) of less than 2.5% were found for FID and TSD but they were above 10% for MSD. Finally, each method was applied to determine the content of erucamide and oleamide in several polyethylene films and the results obtained were compared with those obtained from the nitrogen content measured by pyrolysis and gas-phase chemiluminescence. No significant differences were observed between the results of the methods.

  1. Entrance dose measurements for in‐vivo diode dosimetry: Comparison of correction factors for two types of commercial silicon diode detectors

    PubMed Central

    Zhu, X. R.

    2000-01-01

    Silicon diode dosimeters have been used routinely for in‐vivo dosimetry. Despite their popularity, an appropriate implementation of an in‐vivo dosimetry program using diode detectors remains a challenge for clinical physicists. One common approach is to relate the diode readout to the entrance dose, that is, dose to the reference depth of maximum dose such as dmax for the 10×10 cm2 field. Various correction factors are needed in order to properly infer the entrance dose from the diode readout, depending on field sizes, target‐to‐surface distances (TSD), and accessories (such as wedges and compensate filters). In some clinical practices, however, no correction factor is used. In this case, a diode‐dosimeter‐based in‐vivo dosimetry program may not serve the purpose effectively; that is, to provide an overall check of the dosimetry procedure. In this paper, we provide a formula to relate the diode readout to the entrance dose. Correction factors for TSD, field size, and wedges used in this formula are also clearly defined. Two types of commercial diode detectors, ISORAD (n‐type) and the newly available QED (p‐type) (Sun Nuclear Corporation), are studied. We compared correction factors for TSDs, field sizes, and wedges. Our results are consistent with the theory of radiation damage of silicon diodes. Radiation damage has been shown to be more serious for n‐type than for p‐type detectors. In general, both types of diode dosimeters require correction factors depending on beam energy, TSD, field size, and wedge. The magnitudes of corrections for QED (p‐type) diodes are smaller than ISORAD detectors. PACS number(s): 87.66.–a, 87.52.–g PMID:11674824

  2. Environmental factor(tm) system: RCRA hazardous waste handler information (on CD-ROM). Data file

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1995-11-01

    Environmental Factor(trademark) RCRA Hazardous Waste Handler Information on CD-ROM unleashes the invaluable information found in two key EPA data sources on hazardous waste handlers and offers cradle-to-grave waste tracking. It`s easy to search and display: (1) Permit status, design capacity, and compliance history for facilities found in the EPA Research Conservation and Recovery Information System (RCRIS) program tracking database; (2) Detailed information on hazardous wastes generation, management, and minimization by companies who are large quantity generators; and (3) Data on the waste management practices of treatment, storage, and disposal (TSD) facilities from the EPA Biennial Reporting System which is collectedmore » every other year. Environmental Factor`s powerful database retrieval system lets you: (1) Search for RCRA facilities by permit type, SIC code, waste codes, corrective action, or violation information, TSD status, generator and transporter status, and more. (2) View compliance information - dates of evaluation, violation, enforcement, and corrective action. (3) Lookup facilities by waste processing categories of marketing, transporting, processing, and energy recovery. (4) Use owner/operator information and names, titles, and telephone numbers of project managers for prospecting. (5) Browse detailed data on TSD facility and large quantity generators` activities such as onsite waste treatment, disposal, or recycling, offsite waste received, and waste generation and management. The product contains databases, search and retrieval software on two CD-ROMs, an installation diskette and User`s Guide. Environmental Factor has online context-sensitive help from any screen and a printed User`s Guide describing installation and step-by-step procedures for searching, retrieving, and exporting.« less

  3. Environmental Factor(tm) system: RCRA hazardous waste handler information (on cd-rom). Database

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1996-04-01

    Environmental Factor(tm) RCRA Hazardous Waste Handler Information on CD-ROM unleashes the invaluable information found in two key EPA data sources on hazardous waste handlers and offers cradle-to-grave waste tracking. It`s easy to search and display: (1) Permit status, design capacity and compliance history for facilities found in the EPA Resource Conservation and Recovery Information System (RCRIS) program tracking database; (2) Detailed information on hazardous wastes generation, management and minimization by companies who are large quantity generators, and (3) Data on the waste management practices of treatment, storage and disposal (TSD) facilities from the EPA Biennial Reporting System which is collectedmore » every other year. Environmental Factor`s powerful database retrieval system lets you: (1) Search for RCRA facilities by permit type, SIC code, waste codes, corrective action or violation information, TSD status, generator and transporter status and more; (2) View compliance information - dates of evaluation, violation, enforcement and corrective action; (3) Lookup facilities by waste processing categories of marketing, transporting, processing and energy recovery; (4) Use owner/operator information and names, titles and telephone numbers of project managers for prospecting; and (5) Browse detailed data on TSD facility and large quantity generators` activities such as onsite waste treatment, disposal, or recycling, offsite waste received, and waste generation and management. The product contains databases, search and retrieval software on two CD-ROMs, an installation diskette and User`s Guide. Environmental Factor has online context-sensitive help from any screen and a printed User`s Guide describing installation and step-by-step procedures for searching, retrieving and exporting. Hotline support is also available for no additional charge.« less

  4. Environmental Factor{trademark} system: RCRA hazardous waste handler information

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1999-03-01

    Environmental Factor{trademark} RCRA Hazardous Waste Handler Information on CD-ROM unleashes the invaluable information found in two key EPA data sources on hazardous waste handlers and offers cradle-to-grave waste tracking. It`s easy to search and display: (1) Permit status, design capacity and compliance history for facilities found in the EPA Resource Conservation and Recovery Information System (RCRIS) program tracking database; (2) Detailed information on hazardous wastes generation, management and minimization by companies who are large quantity generators, and (3) Data on the waste management practices of treatment, storage and disposal (TSD) facilities from the EPA Biennial Reporting System which is collectedmore » every other year. Environmental Factor`s powerful database retrieval system lets you: (1) Search for RCRA facilities by permit type, SIC code, waste codes, corrective action or violation information, TSD status, generator and transporter status and more; (2) View compliance information -- dates of evaluation, violation, enforcement and corrective action; (3) Lookup facilities by waste processing categories of marketing, transporting, processing and energy recovery; (4) Use owner/operator information and names, titles and telephone numbers of project managers for prospecting; and (5) Browse detailed data on TSD facility and large quantity generators` activities such as onsite waste treatment, disposal, or recycling, offsite waste received, and waste generation and management. The product contains databases, search and retrieval software on two CD-ROMs, an installation diskette and User`s Guide. Environmental Factor has online context-sensitive help from any screen and a printed User`s Guide describing installation and step-by-step procedures for searching, retrieving and exporting. Hotline support is also available for no additional charge.« less

  5. Acute Sleep Loss Induces Tissue-Specific Epigenetic and Transcriptional Alterations to Circadian Clock Genes in Men.

    PubMed

    Cedernaes, Jonathan; Osler, Megan E; Voisin, Sarah; Broman, Jan-Erik; Vogel, Heike; Dickson, Suzanne L; Zierath, Juleen R; Schiöth, Helgi B; Benedict, Christian

    2015-09-01

    Shift workers are at increased risk of metabolic morbidities. Clock genes are known to regulate metabolic processes in peripheral tissues, eg, glucose oxidation. This study aimed to investigate how clock genes are affected at the epigenetic and transcriptional level in peripheral human tissues following acute total sleep deprivation (TSD), mimicking shift work with extended wakefulness. In a randomized, two-period, two-condition, crossover clinical study, 15 healthy men underwent two experimental sessions: x sleep (2230-0700 h) and overnight wakefulness. On the subsequent morning, serum cortisol was measured, followed by skeletal muscle and subcutaneous adipose tissue biopsies for DNA methylation and gene expression analyses of core clock genes (BMAL1, CLOCK, CRY1, PER1). Finally, baseline and 2-h post-oral glucose load plasma glucose concentrations were determined. In adipose tissue, acute sleep deprivation vs sleep increased methylation in the promoter of CRY1 (+4%; P = .026) and in two promoter-interacting enhancer regions of PER1 (+15%; P = .036; +9%; P = .026). In skeletal muscle, TSD vs sleep decreased gene expression of BMAL1 (-18%; P = .033) and CRY1 (-22%; P = .047). Concentrations of serum cortisol, which can reset peripheral tissue clocks, were decreased (2449 ± 932 vs 3178 ± 723 nmol/L; P = .039), whereas postprandial plasma glucose concentrations were elevated after TSD (7.77 ± 1.63 vs 6.59 ± 1.32 mmol/L; P = .011). Our findings demonstrate that a single night of wakefulness can alter the epigenetic and transcriptional profile of core circadian clock genes in key metabolic tissues. Tissue-specific clock alterations could explain why shift work may disrupt metabolic integrity as observed herein.

  6. Introduction of the ASP3D Computer Program for Unsteady Aerodynamic and Aeroelastic Analyses

    NASA Technical Reports Server (NTRS)

    Batina, John T.

    2005-01-01

    A new computer program has been developed called ASP3D (Advanced Small Perturbation 3D), which solves the small perturbation potential flow equation in an advanced form including mass-consistent surface and trailing wake boundary conditions, and entropy, vorticity, and viscous effects. The purpose of the program is for unsteady aerodynamic and aeroelastic analyses, especially in the nonlinear transonic flight regime. The program exploits the simplicity of stationary Cartesian meshes with the movement or deformation of the configuration under consideration incorporated into the solution algorithm through a planar surface boundary condition. The new ASP3D code is the result of a decade of developmental work on improvements to the small perturbation formulation, performed while the author was employed as a Senior Research Scientist in the Configuration Aerodynamics Branch at the NASA Langley Research Center. The ASP3D code is a significant improvement to the state-of-the-art for transonic aeroelastic analyses over the CAP-TSD code (Computational Aeroelasticity Program Transonic Small Disturbance), which was developed principally by the author in the mid-1980s. The author is in a unique position as the developer of both computer programs to compare, contrast, and ultimately make conclusions regarding the underlying formulations and utility of each code. The paper describes the salient features of the ASP3D code including the rationale for improvements in comparison with CAP-TSD. Numerous results are presented to demonstrate the ASP3D capability. The general conclusion is that the new ASP3D capability is superior to the older CAP-TSD code because of the myriad improvements developed and incorporated.

  7. Regulation of Pituitary Beta Endorphin Release: Role of Serotonin Neurons

    DTIC Science & Technology

    1983-12-15

    degradable by peptidases , and had a molecular weight of 800-1200. Subsequently, the active factor present in extracts of pig brain was purified...argylene, a drug which prolong’s serotonin’s action at the synapse bv inhibiting enzvmatic degradation of serotonin, also ele- vated circulating...either he re-incorporated into storage granules or degraded enzymatically bv a monoamine oxidase (^tAO)/aldehyde dehydrogenase (ADH) nathvTay to 5

  8. Signal Detection with Criterion Noise: Applications to Recognition Memory

    ERIC Educational Resources Information Center

    Benjamin, Aaron S.; Diaz, Michael; Wee, Serena

    2009-01-01

    A tacit but fundamental assumption of the theory of signal detection is that criterion placement is a noise-free process. This article challenges that assumption on theoretical and empirical grounds and presents the noisy decision theory of signal detection (ND-TSD). Generalized equations for the isosensitivity function and for measures of…

  9. 75 FR 69002 - Revisions to the California State Implementation Plan, Imperial County Air Pollution Control...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-10

    ...: Our proposed action (75 FR 27976) and the associated TSD (pages 2-3) both refer to two ICAPCD analyses... specifically references page 15 of Environ's ``Draft Final Technical Memorandum Regulation VIII BACM Analysis... reference CARB's inventory analysis to support the 50% reduction assumption. \\1\\ Printed in error as III-2...

  10. 75 FR 24542 - Approval and Promulgation of State Implementation Plans: Washington

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... by the State of Washington, Department of Ecology (Ecology). These revisions pertain to the... maintenance plan. On January 17, 2007, EPA received a request from Ecology to approve under section 110 of the... about the SIP revisions Ecology has submitted for approval. The TSD is available for review as part of...

  11. Transient Structured Distance as a Maneuver in Marital Therapy

    ERIC Educational Resources Information Center

    Greene, Bernard L.; And Others

    1973-01-01

    Experience with 73 cases has shown the value of Transient Structured Distance as a maneuver in marriage therapy. While the TSD is a radical form of intervention with risks of anxiety reactions, homosexual panic, or divorce, it has proved effective with difficult forms of acute or chronic marital disharmony. (Author)

  12. 76 FR 54993 - Revisions to the California State Implementation Plan, Placer County Air Pollution Control District

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... nitrogen (NO X ) emissions from biomass fuel-fired boilers. We are proposing action on a local rule that... Submitted PCAPCD 233 Biomass Boilers......... 12/10/09 05/07/10 On June 8, 2010, the submittal for PCAPCD... from biomass boilers and steam generators. EPA's technical support document (TSD) has more information...

  13. The effects of prosthetic foot type and visual alteration on postural steadiness in below-knee amputees

    PubMed Central

    2014-01-01

    Background Achieving independent upright posture has known to be one of the main goals in rehabilitation following lower limb amputation. The purpose of this study was to compare postural steadiness of below knee amputees with visual alterations while wearing three different prosthetic feet. Methods Ten male below-knee amputees were instructed to stand quietly on the Biodex® balance platform while wearing solid ankle cushion heel (SACH), single axis (SA) and energy storage and release (ESAR) prosthetic foot under different visual input conditions (eyes-opened and eyes-closed). The overall stability index (OSI), anterior- posterior stability index (APSI), and medial-lateral stability index (MLSI) were computed. Perceived balance assessment of each foot was evaluated using Activities-specific Balance Confidence (ABC) score. Results The findings highlights that SACH showed lowest overall stability index (indicating less body sway) during eyes-opened (OSI: SACH = 1.09, SA = 1.58, ESAR = 1.59) and SA showed lowest overall stability index during eyes-closed (OSI: SACH = 2.52, SA = 2.30, ESAR = 2.76) condition. However, overall stability indexes between foot types did not differ significantly during eyes-opened or eyes-closed (p = 0.651). There was a trend of instability which occurred more in medial-lateral compared to anterior-posterior direction for all foot types, with significant result in ESAR foot(eyes-opened: MLSI = 1.59, APSI = 0.65, p = 0.034; eyes-closed: MLSI = 2.76, APSI = 1.80, p = 0.017, respectively). When comparing between visual conditions, stability score was significantly higher during eyes-closed compared to eyes-opened situations for SACH and ESAR foot (eyes-closed vs opened; SACH OSI: 3.43 vs 1.71, p = 0.018 and MLSI: 3.43 vs 1.71, p = 0.018; ESAR OSI: 3.58 vs 1.86, p = 0.043 and APSI: 1.80 vs 0.65, p = 0.027). Conclusions The results of this study suggested postural steadiness in

  14. Triangulating Measures of Awareness: A Contribution to the Debate on Learning without Awareness

    ERIC Educational Resources Information Center

    Rebuschat, Patrick; Hamrick, Phillip; Riestenberg, Kate; Sachs, Rebecca; Ziegler, Nicole

    2015-01-01

    Williams's (2005) study on "learning without awareness" and three subsequent extensions (Faretta-Stutenberg & Morgan-Short, 2011; Hama & Leow, 2010; Rebuschat, Hamrick, Sachs, Riestenberg, & Ziegler, 2013) have reported conflicting results, perhaps in part due to differences in how awareness has been measured. The present…

  15. Glenohumeral instability: evaluation with MR arthrography.

    PubMed

    Beltran, J; Rosenberg, Z S; Chandnani, V P; Cuomo, F; Beltran, S; Rokito, A

    1997-01-01

    Magnetic resonance arthrography is superior to other imaging techniques in evaluation of the glenohumeral joint. Normal variants that can be diagnostic pitfalls include the anterosuperior sublabral foramen, the Buford complex, and hyaline cartilage under the labrum. Anteroinferior dislocation is the most frequent cause of anterior glenohumeral instability and produces a constellation of lesions (anteroinferior labral tear, classic and osseous Bankart lesions, Hill-Sachs lesion). Variants of anteroinferior labral tears include anterior labroligamentous periosteal sleeve avulsion and glenoid labral articular disruption. Anterior glenohumeral instability can also involve tears of the anterior or anterosuperior labrum or the glenohumeral ligaments. Posterior glenohumeral instability can involve a posterior labral tear, posterior capsular stripping or laxity; fracture, erosion, or sclerosis and ectopic ossification of the posterior glenoid fossa; reverse Hill-Sachs lesion; McLaughlin fracture; or posterosuperior glenoid impingement. Superior labral anterior and posterior lesions involve the superior labrum with varying degrees of biceps tendon involvement.

  16. Sleep Extension before Sleep Loss: Effects on Performance and Neuromuscular Function.

    PubMed

    Arnal, Pierrick J; Lapole, Thomas; Erblang, Mégane; Guillard, Mathias; Bourrilhon, Cyprien; Léger, Damien; Chennaoui, Mounir; Millet, Guillaume Y

    2016-08-01

    This study aimed to investigate the effects of six nights of sleep extension on motor performance and associated neuromuscular function before and after one night of total sleep deprivation (TSD). Twelve healthy men participated in two experimental conditions (randomized crossover design): extended sleep (EXT, 9.8 ± 0.1 h time in bed) and habitual sleep (HAB, 8.2 ± 0.1 h time in bed). In each condition, subjects performed six nights of either EXT or HAB at home followed by an assessment of motor performance and neuromuscular function at baseline (D0) and after one night of TSD, i.e., 34-37 h of continuous wakefulness (D1). Maximal voluntary contractions with superimposed femoral nerve electrical and transcranial magnetic stimulations and stimulations on relaxed muscles were investigated before and after submaximal isometric knee extensor exercises performed until task failure. Time to exhaustion was longer in EXT compared with HAB (+3.9% ± 7.7% and +8.1% ± 12.3% at D0 and D1, respectively). Performance at D1 decreased from D0 similarly between conditions (-7.2% ± 5.6% and -3.7% ± 7.3% in HAB and EXT, respectively). At D1, the RPE during exercise was lower in EXT compared with HAB (-7.2% ± 7.5%) with no difference at D0. No difference was observed in voluntary activation between the two conditions. Six nights of sleep extension improved sustained contraction time to exhaustion, and this result cannot be explained by smaller reductions in voluntary activation, measured by both nerve and transcranial magnetic stimulation. The beneficial effect on motor performance in the EXT condition was likely due to reduced RPE after TSD.

  17. Soluble TNF-alpha receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight

    NASA Technical Reports Server (NTRS)

    Shearer, W. T.; Reuben, J. M.; Mullington, J. M.; Price, N. J.; Lee, B. N.; Smith, E. O.; Szuba, M. P.; Van Dongen, H. P.; Dinges, D. F.

    2001-01-01

    BACKGROUND: The extent to which sleep loss may predispose astronauts to a state of altered immunity during extended space travel prompts evaluation with ground-based models. OBJECTIVE: We sought to measure plasma levels of selected cytokines and their receptors, including the putative sleep-regulation proteins soluble TNF-alpha receptor (sTNF-alpha R) I and IL-6, in human subjects undergoing 2 types of sleep deprivation during environmental confinement with performance demands. METHODS: Healthy adult men (n = 42) were randomized to schedules that varied in severity of sleep loss: 4 days (88 hours) of partial sleep deprivation (PSD) involving two 2-hour naps per day or 4 days of total sleep deprivation (TSD). Plasma samples were obtained every 6 hours across 5 days and analyzed by using enzyme-linked immunoassays for sTNF-alpha RI, sTNF-alpha RII, IL-6, soluble IL-2 receptor, IL-10, and TNF-alpha. RESULTS: Interactions between the effects of time and sleep deprivation level were detected for sTNF-alpha RI and IL-6 but not for sTNF-alpha RII, soluble IL-2 receptor, IL-10, and TNF-alpha. Relative to the PSD condition, subjects in the TSD condition had elevated plasma levels of sTNF-alpha RI on day 2 (P =.04), day 3 (P =.01), and across days 2 to 4 of sleep loss (P =.01) and elevated levels of IL-6 on day 4 (P =.04). CONCLUSIONS: Total sleep loss produced significant increases in plasma levels of sTNF-alpha RI and IL-6, messengers that connect the nervous, endocrine, and immune systems. These changes appeared to reflect elevations of the homeostatic drive for sleep because they occurred in TSD but not PSD, suggesting that naps may serve as the basis for a countermeasures approach to prolonged spaceflight.

  18. B Plant Complex preclosure work plan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    ADLER, J.G.

    1999-02-02

    This preclosure work plan describes the condition of the dangerous waste treatment storage, and/or disposal (TSD) unit after completion of the B Plant Complex decommissioning Transition Phase preclosure activities. This description includes waste characteristics, waste types, locations, and associated hazards. The goal to be met by the Transition Phase preclosure activities is to place the TSD unit into a safe and environmentally secure condition for the long-term Surveillance and Maintenance (S&M) Phase of the facility decommissioning process. This preclosure work plan has been prepared in accordance with Section 8.0 of the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement)more » (Ecology et al. 1996). The preclosure work plan is one of three critical Transition Phase documents, the other two being: B Plant End Points Document (WHC-SD-WM-TPP-054) and B Plant S&M plan. These documents are prepared by the U.S. Department of Energy, Richland Operations Office (DOE-RL) and its contractors with the involvement of Washington State Department of Ecology (Ecology). The tanks and vessels addressed by this preclosure work plan are limited to those tanks end vessels included on the B Plant Complex Part A, Form 3, Permit Application (DOE/RL-88-21). The criteria for determining which tanks or vessels are in the Part A, Form 3, are discussed in the following. The closure plan for the TSD unit will not be prepared until the Disposition Phase of the facility decommissioning process is initiated, which follows the long-term S&M Phase. Final closure will occur during the Disposition Phase of the facility decommissioning process. The Waste Encapsulation Storage Facility (WESF) is excluded from the scope of this preclosure work plan.« less

  19. Behavioral Sleep-Wake Homeostasis and EEG Delta Power Are Decoupled By Chronic Sleep Restriction in the Rat

    PubMed Central

    Stephenson, Richard; Caron, Aimee M.; Famina, Svetlana

    2015-01-01

    Study Objectives: Chronic sleep restriction (CSR) is prevalent in society and is linked to adverse consequences that might be ameliorated by acclimation of homeostatic drive. This study was designed to test the hypothesis that the sleep-wake homeostat will acclimatize to CSR. DESIGN: A four-parameter model of proportional control was used to quantify sleep homeostasis with and without recourse to a sleep intensity function. Setting: Animal laboratory, rodent walking-wheel apparatus. Subjects: Male Sprague-Dawley rats. Interventions: Acute total sleep deprivation (TSD, 1 day × 18 or 24 h, N = 12), CSR (10 days × 18 h TSD, N = 6, or 5 days × 20 h TSD, N = 5). Measurements and Results: Behavioral rebounds were consistent with model predictions for proportional control of cumulative times in wake, nonrapid eye movement sleep (NREM) and rapid eye movement sleep (REM). Delta (Δ) energy homeostasis was secondary to behavioral homeostasis; a biphasic NREM Δ power rebound contributed to the dynamics (rapid response) but not to the magnitude of the rebound in Δ energy. REM behavioral homeostasis was little affected by CSR. NREM behavioral homeostasis was attenuated in proportion to cumulative NREM deficit, whereas the biphasic NREM Δ power rebound was only slightly suppressed, indicating decoupled regulatory mechanisms following CSR. Conclusions: We conclude that sleep homeostasis is achieved through behavioral regulation, that the nonrapid eye movement sleep behavioral homeostat is susceptible to attenuation during chronic sleep restriction and that the concept of sleep intensity is not essential in a model of sleep-wake regulation. Citation: Stephenson R, Caron AM, Famina S. Behavioral sleep-wake homeostasis and EEG delta power are decoupled by chronic sleep restriction in the rat. SLEEP 2015;38(5):685–697. PMID:25669184

  20. The role of estrogen in turtle sex determination and the effect of PCBs

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Crews, D.; Bergeron, J.M.; McLachlan, J.A.

    1995-10-01

    Gonadal sex is fixed at fertilization by specific chromosomes, a process known as genotypic sex determination (GSD). Only after the gonad is formed do hormones begin to exert an influence that modifies specific structures that eventually will differ between the sexes. Many egg-laying reptiles do not exhibit GSD but rather depend on the temperature of the incubating egg to determine the gonadal sex of the offspring, a process termed temperature-dependent sex determination (TSD). Research on TSD indicates that gonadal sex is not irrevocably set by the genetic composition inherited at fertilization but depends ultimately on which genes encoding for steroidogenicmore » enzymes and hormone receptors are activated during the midtrimester of embryonic development by temperature. Incubation temperature modifies the activity as well as the temporal and spatial sequence of enzymes and hormone receptors to determine gonad type. Estrogen is the physiologic equivalent of incubation temperature and the proximate cue that initiates female sex determination. increasing evidence indicates some polychlorinated biphenyl (PCB) compounds are capable of disrupting reproductive and endocrine function in fish, birds, and mammals, including humans. Reproductive disorders resulting from exposure to these xenobiotic compounds may include reductions in fertility, hatch rate in fish and birds, and viability of offspring, as well as alterations in hormone levels or adult sexual behaviors. Research on the mechanism through which these compounds may be acting to alter reproductive function indicates estrogenic activity, by which the compounds may be altering sexual differentiation. In TSD turtles, the estrogenic effect of some PCBs reverses gonadal sex in individuals incubating at an otherwise male-producing temperature. Furthermore, certain PCBs are synergistic in their effect at very low concentrations. 19 refs., 3 figs., 1 tab.« less

  1. Listed waste determination report. Environmental characterization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1993-06-01

    On September 23, 1988, the US Environmental Protection Agency (EPA) published a notice clarifying interim status requirements for the management of radioactive mixed waste thereby subjecting the Idaho National Engineering Laboratory (INEL) and other applicable Department of Energy (DOE) sites to regulation under the Resource Conservation and Recovery Act (RCRA). Therefore, the DOE was required to submit a Part A Permit application for each treatment, storage, and disposal (TSD) unit within the INEL, defining the waste codes and processes to be regulated under RCRA. The September 1990 revised Part A Permit application, that was approved by the State of Idahomore » identified 101 potential acute and toxic hazardous waste codes (F-, P-, and U- listed wastes according to 40 CFR 261.31 and 40 CFR 261.33) for some TSD units at the Idaho Chemical Processing Plant. Most of these waste were assumed to have been introduced into the High-level Liquid Waste TSD units via laboratory drains connected to the Process Equipment Waste (PEW) evaporator (PEW system). At that time, a detailed and systematic evaluation of hazardous chemical use and disposal practices had not been conducted to determine if F-, P-, or Unlisted waste had been disposed to the PEW system. The purpose of this investigation was to perform a systematic and detailed evaluation of the use and disposal of the 101 F-, P-, and Unlisted chemicals found in the approved September 1990 Part A Permit application. This investigation was aimed at determining which listed wastes, as defined in 40 CFR 261.31 (F-listed) and 261.33 (P & Unlisted) were discharged to the PEW system. Results of this investigation will be used to support revisions to the RCRA Part A Permit application.« less

  2. Characterization and expression profile of the ovarian cytochrome P-450 aromatase (cyp19A1) gene during thermolabile sex determination in Pejerrey, Odontesthes bonariensis

    USGS Publications Warehouse

    Karube, M.; Fernandino, J.I.; Strobl-Mazzulla, P.; Strussmann, C.A.; Yoshizaki, G.; Somoza, G.M.; Patino, R.

    2007-01-01

    Cytochrome P450 aromatase (cyp19) is an enzyme that catalyzes the conversion of androgens to estrogens and may play a role in temperature- dependent sex determination (TSD) of reptiles, amphibians, and fishes. In this study, the ovarian P450 aromatase form (cyp19A1) of pejerrey Odontesthes bonariensis, a teleost with marked TSD, was cloned and its expression profile evaluated during gonadal differentiation at feminizing (17??C, 100% females), mixed-sex producing (24 and 25??C, 73.3 and 26.7% females, respectively), and masculinizing (29??C, 0% females) temperatures. The deduced cyp19A1 amino acid sequence shared high identity (>77.8%) with that from other teleosts but had low identity (<61.8%) with brain forms (cyp19A2), including that of pejerrey itself. The tissue distribution analysis of cyp19A1 mRNA in adult fish revealed high expression in the ovary. Semi-quantitative reverse transcription polymerase chain reaction analysis of the bodies of larvae revealed that cyp19A1 expression increased before the appearance of the first histological signs of ovarian differentiation at the feminizing temperature but remained low at the masculinizing temperature. The expression levels at mixed-sex producing temperatures were bimodal rather than intermediate, showing low and high modal values similar to those at the feminizing and masculinizing temperatures, respectively. The population percentages of high and low expression levels at intermediate temperatures were proportional to the percentage of females and males, respectively, and high levels were first observed at about the time of sex differentiation of females. These results suggest that cyp19A1 is involved in the process of ovarian formation and possibly also in the TSD of pejerrey. ?? 2007 Wiley-Liss, Inc.

  3. A Unified Model of Performance: Validation of its Predictions across Different Sleep/Wake Schedules

    PubMed Central

    Ramakrishnan, Sridhar; Wesensten, Nancy J.; Balkin, Thomas J.; Reifman, Jaques

    2016-01-01

    Study Objectives: Historically, mathematical models of human neurobehavioral performance developed on data from one sleep study were limited to predicting performance in similar studies, restricting their practical utility. We recently developed a unified model of performance (UMP) to predict the effects of the continuum of sleep loss—from chronic sleep restriction (CSR) to total sleep deprivation (TSD) challenges—and validated it using data from two studies of one laboratory. Here, we significantly extended this effort by validating the UMP predictions across a wide range of sleep/wake schedules from different studies and laboratories. Methods: We developed the UMP on psychomotor vigilance task (PVT) lapse data from one study encompassing four different CSR conditions (7 d of 3, 5, 7, and 9 h of sleep/night), and predicted performance in five other studies (from four laboratories), including different combinations of TSD (40 to 88 h), CSR (2 to 6 h of sleep/night), control (8 to 10 h of sleep/night), and nap (nocturnal and diurnal) schedules. Results: The UMP accurately predicted PVT performance trends across 14 different sleep/wake conditions, yielding average prediction errors between 7% and 36%, with the predictions lying within 2 standard errors of the measured data 87% of the time. In addition, the UMP accurately predicted performance impairment (average error of 15%) for schedules (TSD and naps) not used in model development. Conclusions: The unified model of performance can be used as a tool to help design sleep/wake schedules to optimize the extent and duration of neurobehavioral performance and to accelerate recovery after sleep loss. Citation: Ramakrishnan S, Wesensten NJ, Balkin TJ, Reifman J. A unified model of performance: validation of its predictions across different sleep/wake schedules. SLEEP 2016;39(1):249–262. PMID:26518594

  4. 1. Historic American Buildings Survey, August, 1971 STREETSCAPE SHOWING SOUTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey, August, 1971 STREETSCAPE SHOWING SOUTH (FRONT) ELEVATIONS OF LOVE AND BILGER TIN SHOP (FAR LEFT), SACHS BROTHERS STORE, NEUBER'S JEWELRY STORE, KAHLER'S DRUG STORE, BEEKMAN BANK, UNITED STATES HOTEL. - Neuber's Jewelry Store, 130 West California Street, Jacksonville, Jackson County, OR

  5. 78 FR 23963 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-23

    ...''), Citadel Securities LLC (``Citadel''), Citigroup Financial Strategies, Inc. (``Citigroup''), Goldman, Sachs... Agreement) by the Founding Firms to NYSE Market (DE), Inc. (``NYSE Market''), an affiliate of the Exchange... the Founding Firms to NYSE Market as soon as reasonably practicable following April 2, 2013 pursuant...

  6. Constraints on temperature-dependent sex determination in the leopard gecko ( Eublepharis macularius): response to Kratochvil et al.

    NASA Astrophysics Data System (ADS)

    Huang, Victoria; Sakata, Jon T.; Rhen, Turk; Coomber, Patricia; Simmonds, Sarah; Crews, David

    2008-12-01

    Kratochvil et al. (Naturwissenschaften 95:209 215, 2008) reported recently that in the leopard gecko ( Eublepharis macularius) of the family Eublepharidae with temperature-dependent sex determination (TSD), clutches in which eggs were incubated at the same temperature produce only same-sex siblings. Interpreting this result in light of studies of sex steroid hormone involvement in sex determination, they suggested that maternally derived yolk steroid hormones could constrain sex-determining mechanisms in TSD reptiles. We have worked extensively with this species and have routinely incubated clutches at constant temperatures. To test the consistency of high frequency same-sex clutches across different incubation temperatures, we examined our records of clutches at the University of Texas at Austin from 1992 to 2001. We observed that clutches in which eggs were incubated at the same incubation temperature produced mixed-sex clutches as well as same-sex clutches. Furthermore, cases in which eggs within a clutch were separated and incubated at different temperatures produced the expected number of mixed-sex clutches. These results suggest that maternal influences on sex determination are secondary relative to incubation temperature effects.

  7. Hazardous waste crime: a contextual analysis of the offense and the offender

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rebovich, D.J.

    The goal of this study is to analyze hazardous waste offense and offender characteristics. Criminal case data were collected from four sample states (Maine, Maryland, New Jersey, and Pennsylvania). Files of disposed criminal cases charged between 1977 and 1984 were content-analyzed, and interviews were conducted with prominent hazardous waste crime enforcement personnel from the sample states. Areas of analysis include methods of crime commission, skills required for crime commission, patterns of criminal network relationships, and degree of syndicate crime influence. While there has been some previous speculation that hazardous waste criminal behavior is directed through centralized racketeering, the present studymore » of known offenders found little evidence of syndicate crime family infiltration. Crimes occurred within small, informal networks of waste generators, waste transporters, the employees of treatment/storage/disposal (TSD) facilities and certain non-industry peripheral actors. The study concludes that, while attempts have been made by syndicate crime operatives to infiltrate, these attempts have failed largely due to features of criminal commission methods and to the inherent fragmentation of hauling and TSD firm interests.« less

  8. Blended Outreach: Face-to-Face and Remote Programs

    ERIC Educational Resources Information Center

    Poeppelmeyer, Diana

    2011-01-01

    The Texas School for the Deaf (TSD) has two missions. One is to provide educational services to deaf and hard of hearing students and their families on the Austin campus--this is the traditional, face-to-face, center-based service model. The other is to serve as a resource center for the state, providing information, referral, programs, and…

  9. 77 FR 30208 - Approval and Promulgation of Air Quality Implementation Plans; Maryland; Baltimore Nonattainment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... completeness criteria for 2010 is incorrect. As explained in the TSD, the missing data from the primary monitor..., appendix N. Missing data from a primary monitor at a site does not necessarily mean that the data at the monitoring site is incomplete. When data from a collocated monitor is used to substitute for missing data at...

  10. Emptying the Nest: Launching Your Young Adult toward Success and Self-Reliance

    ERIC Educational Resources Information Center

    Sachs, Brad E.

    2010-01-01

    In today's rapidly changing world and challenging economy, young adults increasingly find themselves at a crossroads between financial and emotional dependence and autonomy. Drawing on Dr. Sachs' extensive clinical experience and his illuminating discussion of the latest psychological research, "Emptying the Nest" will support parents in their…

  11. 76 FR 19097 - Ocean Transportation Intermediary License Applicants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-06

    ...: New NVO. Landstar Global Logistics, Inc. (NVO & OFF), 13410 Sutton Park Drive South, Jacksonville, FL... at (202) 523-5843 or by e-mail at [email protected] . Agility Logistics Corp. (OFF), 240 Commerce, Irvine... Sachs, Partner/Logistics Manager (Qualifying Individual), Ali Ismailzada, Partner/CFO, Application Type...

  12. Sign Language and the Learning of Swedish by Deaf Children (Project TSD).

    ERIC Educational Resources Information Center

    Jansson, Karin, Ed.

    1982-01-01

    A project in Sweden focuses on the early linguistic development of preschool deaf children in families where the parents are also deaf. The School for the Deaf in Sweden is involved with describing the Swedish language as it appears to a deaf learner, a description to be used as a basis for teacher training and inservice in the teaching of the…

  13. Microcomputer Processing of LANDSAT Thematic Mapper Data for the Acquisition of Military Tactical Terrain Data.

    DTIC Science & Technology

    1985-04-12

    12 9 5 VPV TiTAY T,%. T , TiRAiU A ~ 6. PERFORMING ORG. REPORT NUMBER 7. AUTHOR(.) 6. CONTRACT OR GRANT NUMBER(a) .-- CPT zi 0 9. PERFORMING ...of period covered, such as the life of a contract covered in a final contractor report. Block 6. Performing Organization Report Number. Only numbers...affiliation of an author if it differs from that of the performing organization. Block 8. Contract or grant Number(s). For a contractor or grantee

  14. Closed Loop Control and Turbulent Flows

    DTIC Science & Technology

    2005-10-01

    10 2.9 A schematic diagram of the PIV setup. The PIV controller synchronizes the firing of the lasers and camera...is 16 ms. Consequently, the frequency scaling factor, f*, is 62 Hz. Twin Nd:YAG PIv Back Laser , measurement tressur I5 area tank Water’SuppIly Laser ...YAG twin 532-nm laser was used to illuminate the flow field, and 8-bit gTay-scale images were captured using a 1360 by 1024-pixel resolution camera

  15. Cultivation of macroscopic marine algae and fresh water aquatic weeds

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ryther, J.H.

    1982-02-01

    The ORCA clone of the red seaweed Gracilaria tikvahiae has been in culture continuously for over two years. Yield for the past year has averaged 12 g ash-free dry wt/m/sup 2/ .day (17.5 t/a.y) in suspended 2600-1 aluminum tank cultures with four exchanges of enriched seawater per day and continuous aeration. Yields from nonintensive pond-bottom culture, similar to commercial Gracilaria culture methods in Taiwan, averaged 3 g afdw/m/sup 2/.day in preliminary experiments. Rope and spray cultures were not successful. Yields of water hyacinths from March 1978 to March 1979 averaged 25 g afdw/m/sup 2/.day (37 t/a.y). Season, nutrient availability (formmore » and quantity) and stand density were found to affect the relative proportions of structural and nonstructural tissue in water hyacinths and thereby significantly affect digestibility of and methane production by the plants. Pennywort (Hydrocotyle) grew poorly in winter and its annual yield averaged only one-third that of water hyacinth. Water lettuce (Pistia) appears more comparable to hyacinths in preliminary studies and its yields will be monitored throughout a complete year. Stable, continuous anaerobic digestion of both water hyacinths and Gracilaria has been maintained with an average gas production from both species of 0.4 1/g volatile solids at 60% methane.« less

  16. Onsite transportation of radioactive materials at the Savannah River Site

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Watkins, R.

    The Savannah River Site (SRS) Transportation Safety Document (TSD) defines the onsite packaging and transportation safety program at SRS and demonstrates its compliance with Department of Energy (DOE) transportation safety requirements, to include DOE Order 460.1C, DOE Order 461.2, Onsite Packaging and Transfer of Materials of National Security Interest, and 10 CFR 830, Nuclear Safety Management (Subpart B).

  17. Engineered Bio-Molecular Nano-Devices/Systems

    DTIC Science & Technology

    2009-03-01

    molecules with proper size will be captured by BCD and produce current blockage events, including, e.g., ibuprofen and thalidomide [37]. However, since...detection of enantiomers ," J. Am. Chem. Soc, vol. 128, pp. 10684-10685, 2006. [38] F. Sachs, J. Neil, and N. Barkakati, "The Automated-Analysis of

  18. 76 FR 71092 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... quoted prices in the respective SPX series at the time of execution, each constituent execution will be... Demeterfi, Emanuel Derman, Michael Kamal and Joseph Zou, Goldman Sachs Quantitative Strategies Research... series. The following table shows the SPX option mid-quote prices prevailing at the time of the S&P 500...

  19. Landscape ecologists have a role in poverty relief. Book review.

    Treesearch

    Louis R. Iverson

    2007-01-01

    The causes, consequences, and solutions to human poverty throughout the world lie squarely in the realm of landscape ecology. I believe the book "The End of Poverty: Economic Possibilities for our Time" by Jeffrey Sachs should motivate additional research and implementation of principles within landscape ecology into this critical arena.

  20. 78 FR 79363 - Petitions for Reconsideration of Action in Rulemaking Proceeding

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ...In this document, Petitions for Reconsideration (Petitions) have been filed in the Commission's Rulemaking proceeding, one by Gerard J. Duffy of Blooston, Modkofsky, Dickens, Duffy & Prendergrast, LLP, on behalf of Blooston Private Microwave Licenses and a second by David L. Nace, of Lukas, Nace, Gutierrez & Sachs, LLP, on behalf of Small Purchasers Coalition.

  1. Human action recognition based on point context tensor shape descriptor

    NASA Astrophysics Data System (ADS)

    Li, Jianjun; Mao, Xia; Chen, Lijiang; Wang, Lan

    2017-07-01

    Motion trajectory recognition is one of the most important means to determine the identity of a moving object. A compact and discriminative feature representation method can improve the trajectory recognition accuracy. This paper presents an efficient framework for action recognition using a three-dimensional skeleton kinematic joint model. First, we put forward a rotation-scale-translation-invariant shape descriptor based on point context (PC) and the normal vector of hypersurface to jointly characterize local motion and shape information. Meanwhile, an algorithm for extracting the key trajectory based on the confidence coefficient is proposed to reduce the randomness and computational complexity. Second, to decrease the eigenvalue decomposition time complexity, a tensor shape descriptor (TSD) based on PC that can globally capture the spatial layout and temporal order to preserve the spatial information of each frame is proposed. Then, a multilinear projection process is achieved by tensor dynamic time warping to map the TSD to a low-dimensional tensor subspace of the same size. Experimental results show that the proposed shape descriptor is effective and feasible, and the proposed approach obtains considerable performance improvement over the state-of-the-art approaches with respect to accuracy on a public action dataset.

  2. Application of Machine-Learning Models to Predict Tacrolimus Stable Dose in Renal Transplant Recipients

    NASA Astrophysics Data System (ADS)

    Tang, Jie; Liu, Rong; Zhang, Yue-Li; Liu, Mou-Ze; Hu, Yong-Fang; Shao, Ming-Jie; Zhu, Li-Jun; Xin, Hua-Wen; Feng, Gui-Wen; Shang, Wen-Jun; Meng, Xiang-Guang; Zhang, Li-Rong; Ming, Ying-Zi; Zhang, Wei

    2017-02-01

    Tacrolimus has a narrow therapeutic window and considerable variability in clinical use. Our goal was to compare the performance of multiple linear regression (MLR) and eight machine learning techniques in pharmacogenetic algorithm-based prediction of tacrolimus stable dose (TSD) in a large Chinese cohort. A total of 1,045 renal transplant patients were recruited, 80% of which were randomly selected as the “derivation cohort” to develop dose-prediction algorithm, while the remaining 20% constituted the “validation cohort” to test the final selected algorithm. MLR, artificial neural network (ANN), regression tree (RT), multivariate adaptive regression splines (MARS), boosted regression tree (BRT), support vector regression (SVR), random forest regression (RFR), lasso regression (LAR) and Bayesian additive regression trees (BART) were applied and their performances were compared in this work. Among all the machine learning models, RT performed best in both derivation [0.71 (0.67-0.76)] and validation cohorts [0.73 (0.63-0.82)]. In addition, the ideal rate of RT was 4% higher than that of MLR. To our knowledge, this is the first study to use machine learning models to predict TSD, which will further facilitate personalized medicine in tacrolimus administration in the future.

  3. Capacitor Test, Evaluation. and Modeling Within NASA Electronic Parts and Packaging (NEPP) Program. "Why Ceramic Capacitors Fracture During Manual Soldering and How to Avoid Failures"

    NASA Technical Reports Server (NTRS)

    Teverovsky, Alexander

    2011-01-01

    Presentation discusses: (1) Why Multi-Layer Ceramic Capacitors(MLCCs) crack during manual soldering? Workmanship and parts issues. (2) Do existing qualification requirements assure crack-free soldering? MIL-spec Thermal Shock (TS) testing. MIL-spec Resistance to Soldering Heat (RSH) test. (3) What test can assure reliable soldering? Mechanical characteristics of ceramics. Comparison of three TS techniques: LND, TSD, and IWT. (4) Simulation of TS conditions.

  4. Aeroelastic modeling of the active flexible wing wind-tunnel model

    NASA Technical Reports Server (NTRS)

    Silva, Walter A.; Heeg, Jennifer; Bennett, Robert M.

    1991-01-01

    The primary issues involved in the generation of linear, state-space equations of motion of a flexible wind tunnel model, the Active Flexible Wing (AFW), are discussed. The codes that were used and their inherent assumptions and limitations are also briefly discussed. The application of the CAP-TSD code to the AFW for determination of the model's transonic flutter boundary is included as well.

  5. Technical Support Document: 50% Energy Savings Design Technology Packages for Highway Lodging Buildings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jiang, Wei; Gowri, Krishnan; Lane, Michael D.

    2009-09-28

    This Technical Support Document (TSD) describes the process, methodology and assumptions for development of the 50% Energy Savings Design Technology Packages for Highway Lodging Buildings, a design guidance document intended to provide recommendations for achieving 50% energy savings in highway lodging properties over the energy-efficiency levels contained in ANSI/ASHRAE/IESNA Standard 90.1-2004, Energy Standard for Buildings Except Low-Rise Residential Buildings.

  6. Harbor Beach Harbor Dredging and Dredged Material Disposal, Huron County, Michigan: The Detroit Edison Company Permit Application and Corps of Engineers’ Maintenance Operations.

    DTIC Science & Technology

    1981-12-01

    Steven W. Congdon Physical Science John Collis Geography Abram J. Nicholson Civil Engineering Franklin L. Snitz Environmental Chemistry 6.02 The data...Isllfeebe tP deil,1t1v -, i .1d IO~ 1 , ’, , o- , ,,r-nS ,,n J. Thi pteId h,11 ’- 1 tr ts.-d o lrrf¢t . withot 5. wrlfan aore’sav of the land Resource

  7. 75 FR 41565 - Reports, Forms, and Record Keeping Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-16

    ...: Docket Management Facility: U.S. Department of Transportation, 1200 New Jersey Avenue, SE., West Building... Floor, Room W12-140, 1200 New Jersey Avenue, SE., between 9 a.m. and 5 p.m. ET, Monday through Friday...--Room W43-481, 1200 New Jersey Avenue, SE., Washington, DC 20590. Mr. Sachs' telephone number is (202...

  8. 78 FR 42436 - Procedures To Establish Appropriate Minimum Block Sizes for Large Notional Off-Facility Swaps and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-16

    ... (ICE). Gold (COMEX and NYSE Liffe).. 2,500 troy oz. Goldman Sachs Commodity Index 5,000 times dollars... (NYMEX) 1,000 troy oz. PG&E Citygate Basis (ICE and 62,500 MMBtu. NYMEX). PJM Western Hub Real Time Off...). Platinum (NYMEX) 500 troy oz. Rainfall Index (CME)......... 10,000 times dollars. index. Rough Rice (CBOT...

  9. Optimization of micro-aeration intensity in acidogenic reactor of a two-phase anaerobic digester treating food waste

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, Suyun; Sino-Forest Applied Research Centre for Pearl River Delta Environment, Department of Biology, Hong Kong Baptist University, Hong Kong Special Administrative Region; Selvam, Ammaiyappan

    Highlights: • Effect of micro-aeration on acidogenesis and hydrolysis of food waste was investigated. • Micro-aeration at 258 L-air/kg TS/d increased the VFAs production 3-fold. • High aeration leads to loss of substrate through microbial biomass and respiration. • Optimum aeration increased methane recovery while high aeration intensity reduced methane yield. - Abstract: Micro-aeration is known to promote the activities of hydrolytic exo-enzymes and used as a strategy to improve the hydrolysis of particulate substrate. The effect of different micro-aeration rates, 0, 129, 258, and 387 L-air/kg TS/d (denoted as LBR-AN, LBR-6h, LBR-3h and LBR-2h, respectively) on the solubilization ofmore » food waste was evaluated at 35 °C in four leach bed reactors (LBR) coupled with methanogenic upflow anaerobic sludge blanket (UASB) reactor. Results indicate that the intensity of micro-aeration influenced the hydrolysis and methane yield. Adequate micro-aeration intensity in LBR-3h and LBR-2h significantly enhanced the carbohydrate and protein hydrolysis by 21–27% and 38–64% respectively. Due to the accelerated acidogenesis, more than 3-fold of acetic acid and butyric acid were produced in LBR-3h as compared to the anaerobic treatment LBR-AN resulting in the maximum methane yield of 0.27 L CH{sub 4}/g VS{sub added} in the UASB. The performance of LBR-6h with inadequate aeration was similar to that of LBR-AN with a comparable hydrolysis degree. Nevertheless, higher aeration intensity in LBR-2h was also unfavorable for methane yield due to significant biomass generation and CO{sub 2} respiration of up to 18.5% and 32.8% of the total soluble hydrolysate, respectively. To conclude, appropriate micro-aeration rate can promote the hydrolysis of solid organic waste and methane yield without undesirable carbon loss and an aeration intensity of 258 L-air/kg TS/d is recommended for acidogenic LBR treating food waste.« less

  10. A proposal for in vitro/GFR molecular erythema action spectrum

    NASA Astrophysics Data System (ADS)

    de Souza, João A. V.; Lorenzini, Fabiane; Rizzatti, Mara R.

    2008-08-01

    We propose an erythema action spectrum based on experimental molecular measurements named molecular erythema action spectrum or in vitro/GFR, where the acronym GFR represents our research group name, Grupo de Física das Radiaçöes. The in vitro methodology was developed by using a derma tissue simulator (TSD), as a radiation protection shield, and monochromatic ultraviolet (UV) sources of 254, 310, 365, 380, and 400 nm. The irradiance from each source was monitored through spectroradiometry in order to obtain the exposure dose over a period of time. Changes in the chemical structure were monitored by Fourier transform infrared spectroscopy (FTIR) and UV and visible spectroscopy (UV-vis). The samples were analyzed by UV-vis at each 200 up to 1000 J/m2 and at each 400 up to 2000 J/m2. FTIR was performed only for samples exposed to a maximum dose of 2000 J/m2. The in vitro action parameters were obtained by considering the redshift revealed through UV-vis analysis, as being the molecular quantification of minimal erythema, and the chemical bond rupture of TSD molecules associated with erythema, revealed through FTIR. The in vitro/GFR action spectrum shows that UV-A and UV-B radiation are equally responsible for the damage observed in TSD. When this proposal was compared to the CIE erythema action spectrum from ISO [ISO17166 CIE S 007/E, Erythema Reference Action Spectrum and Standard Erythema Dose (CIE Central Bureau, Austria, 1998)], similarities could be observed in wavelengths less than 280 nm in UV-B region. However, for wavelengths higher than 300 nm, the efficiency of this radiation to induce damage, mainly in the UV-A part, was much higher than predicted in CIE model. The increasing concern on UV-A radiation, assumed to be as responsible as UV-B for inducing most of the already observed skin injuries, may be better understood when observing the experimental model presented in in vitro/GFR action spectrum.

  11. SU-E-T-191: Commissioning and Dosimetric Characteristics of Elekta Agility for Total Skin Electron Beam (TSEB) Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sayler, E; Charpentier, P; Micaily, B

    2015-06-15

    Purpose The purpose of this work is to publish beam data from Elekta Synergy(R) linear accelerators with Agility(TM) MLC for total skin electron beam (TSEB) therapy using the HDRE1 (High Dose Rate Electron 6MeV) energy. Method & Materials The optimal gantry angles for TSEB were determined using ion chamber measurements along a vertical profile at 450cm SSD. After gantry angles were chosen, field uniformity was measured over the entire treatment area. Uniformity was measured with and without the patient support device, allowing the dosimetric effect of the support device to be determined. Beam output and PDD were measured at themore » calibration point (450cm SSD) for a dual beam using a parallel plate chamber in solid water. These measurements were repeated with the chamber and phantom rotated about the patient isocenter at various angles, in order to measure the contribution from oblique beams. This technique provides a precise measurement of the treatment skin dose (TSD). Lastly, ion chamber measurements were verified by film and diodes. Results The optimal gantry angle for 450 cm SSD was determined to be 90±16°. This achieved uniformity better than 96% on the vertical axis, and 92% along the horizontal axis. HDRE1 was calibrated to deliver 10 cGy/MU at standard geometry (100 cm SSD, 1.2 cm depth). Thus at TSEB geometry (450 cm SSD, 0.1 cm depth) the output of the AP dual field was measured to be 0.35 cGy/MU. The TSD of a 20 cm radius cylinder for six (equally, 60° spaced) dual fields was measured to be 1.19 cGy/MU. Percent Depth Dose data for the AP dual field and TSD are shown in Figure 2. Conclusion This paper provides a modern procedure for commissioning TSEB therapy on a linear accelerator, and clinical beam data for the Elekta Synergy(R) with Agility(TM) MLC.« less

  12. Implementing Capability Based Planning within the Public Safety and Security Sector: Lessons from the Defence Experience

    DTIC Science & Technology

    2011-12-01

    de l’équipement, cela comprend la doctrine et l’instruction. La gestion et la production de capacités sont généralement du ressort...les tendances en matière de gestion et de planification des activités et, en particulier, elle est étayée par l’évolution de la gestion du risque et...National Defence, 2011 © Sa Majesté la Reine (en droit du Canada), telle que représentée par le ministre de

  13. Armor in Vietnam

    DTIC Science & Technology

    1976-05-01

    battles a-Riuot the insurgent enemy, especially with armor. French contingents were present in Tndo Chinh P-w early as 1852, but it was not until 1884...committed to Vietnam were straight infantry. These troons er•A tran -norted in hn4±{ copters and usually airlifted to the battle zone; however, once...0STAINf0 FROM VKTNAM NATIONAL MAP SERVICE (NOS) PHU-YEN OCTOBER 19665 OARLAC ......... KKAN1+ HOA QLWA- DUC TUYEN- DUC PHUOC- NINH_ C;ry OF -10 T CAM RANK TAY

  14. Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships.

    PubMed

    Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu

    2016-01-11

    Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease

  15. Genetically Modified Porcine Skin Grafts for Treatment of Severe Burn Injuries

    DTIC Science & Technology

    2010-07-01

    TITLE: Genetically Modified Porcine Skin Grafts for Treatment of Severe Burn Injuries PRINCIPAL INVESTIGATOR: David H. Sachs, M.D...4. TITLE AND SUBTITLE Genetically Modified Porcine Skin Grafts for Treatment of 5a. CONTRACT NUMBER Severe Burn Injuries 5b. GRANT NUMBER...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release; distribution unlimited 13. SUPPLEMENTARY NOTES Burns, skin grafts , genetic

  16. Stage Structure of Moral Development: A Comparison of Alternative Models.

    ERIC Educational Resources Information Center

    Hau, Kit-Tai

    This study evaluated the stage structure of several quasi-simplex and non-simplex models of moral development in two domains of moral development in a British and a Chinese sample. Analyses were based on data reported by Sachs (1992): the Chinese sample consisted of 1,005 students from grade 9 to post-college, and the British sample consisted of…

  17. Mental Health in Deafness. Experimental Issue 2. Fall 1978.

    ERIC Educational Resources Information Center

    Robinson, Luther D., Ed.

    The publication contains four articles on the subject of mental health as it relates to deaf persons. "Deaf Americans and the President's Commission on Mental Health" discusses the Commission Report as a whole (by L. Robinson), the Report of the Task Subpanel on Special Populations (by B. Sachs), and the section on mental health needs of…

  18. An Integrated Science-based methodology

    EPA Pesticide Factsheets

    The data is secondary in nature. Meaning that no data was generated as part of this review effort. Rather, data that was available in the peer-reviewed literature was used.This dataset is associated with the following publication:Tolaymat , T., A. El Badawy, R. Sequeira, and A. Genaidy. An integrated science-based methodology to assess potential risks and implications of engineered nanomaterials. Diana Aga, Wonyong Choi, Andrew Daugulis, Gianluca Li Puma, Gerasimos Lyberatos, and Joo Hwa Tay JOURNAL OF HAZARDOUS MATERIALS. Elsevier Science Ltd, New York, NY, USA, 298: 270-281, (2015).

  19. Continuous Ultra-Thin MOS2 Films Grown by Low-Temperature Physical Vapor Deposition (Postprint)

    DTIC Science & Technology

    2014-07-01

    MoS2 target of 99.95% purity. The SiO2 and highly oriented pyrolitic graphite (HOPG) substrates were intro- duced via a vacuum load- lock and mounted on...im- mediately prior insertion into a sample vacuum load- lock . In this work, the samples were heated to 350 C and allowed to rotate at approximately...136805 (2010). 6H. Terrones, F. Lopez-Urias, and M. Terrones, Sci. Rep. 3(203), 1549 (2013). 7H. Li, Q. Zhang, C. C. R. Yap, B. K. Tay, T. H. T. Edwin

  20. Estimation and Control of Nonlinear and Hybrid Systems

    DTIC Science & Technology

    1990-10-14

    Boiling AID DC 20332-6449 11. SUPPUMU"TAY NOTES 1a OISTJTIOI /AVAL𔃺U1r STATEMENT L. 015~00 coos Approved for publ to rel ense; distribution unlimited...maneuvering vehicles. 16. Paud C001 [I. S10101" O.ASUUIAMNO It SECURITY CLAS5OIFCON 11I. SECUSIMMOSSMIAtMILU KNIYAN Of ASITtACT OF 41POT OP TMI PAUE OP...of the detector is shown to depend strongly on the region of support of the mark distribution . When false alarms are low, the estimation/detection

  1. National Dam Safety Program. Onondaga Dam (Inventory Number NY 794), Oswego River Basin, Onondaga County, New York. Phase I Inspection Report.

    DTIC Science & Technology

    1981-06-30

    Onondag Darn IC^Tjr 50 DO.GWAO1%Q I /W0 (Inventory Numiber NY 794), Oswego River , Basin , Onondage County, New York.Phs IS.DISR)UTI!4 TAY- I Inspection...Dam: Onondaga Dam ID. No. NY 794 State Located: New York County: Onondaga Watershed: Oswego River Basin Stream: Onondaga Creek Date of Inspection...CL E E C4)S0. 0. w CD 2. > C CD C C I 0 0 PHASE I INSPECTION REPORT ONONDAGA DAM I.D. NO NY 794 OSWEGO RIVER BASIN ONONDAGA COUNTY, NEW YORK SECTION 1

  2. Disease networks. Uncovering disease-disease relationships through the incomplete interactome.

    PubMed

    Menche, Jörg; Sharma, Amitabh; Kitsak, Maksim; Ghiassian, Susan Dina; Vidal, Marc; Loscalzo, Joseph; Barabási, Albert-László

    2015-02-20

    According to the disease module hypothesis, the cellular components associated with a disease segregate in the same neighborhood of the human interactome, the map of biologically relevant molecular interactions. Yet, given the incompleteness of the interactome and the limited knowledge of disease-associated genes, it is not obvious if the available data have sufficient coverage to map out modules associated with each disease. Here we derive mathematical conditions for the identifiability of disease modules and show that the network-based location of each disease module determines its pathobiological relationship to other diseases. For example, diseases with overlapping network modules show significant coexpression patterns, symptom similarity, and comorbidity, whereas diseases residing in separated network neighborhoods are phenotypically distinct. These tools represent an interactome-based platform to predict molecular commonalities between phenotypically related diseases, even if they do not share primary disease genes. Copyright © 2015, American Association for the Advancement of Science.

  3. Spatio-temporal variation in the incubation duration and sex ratio of hawksbill hatchlings: implication for future management.

    PubMed

    dei Marcovaldi, Maria A G; Santos, Armando J B; Santos, Alexsandro S; Soares, Luciano S; Lopez, Gustave G; Godfrey, Matthew H; López-Mendilaharsu, Milagros; Fuentes, Mariana M P B

    2014-08-01

    Climate change poses a unique threat to species with temperature dependent sex determination (TSD), such as marine turtles, where increases in temperature can result in extreme sex ratio biases. Knowledge of the primary sex ratio of populations with TSD is key for providing a baseline to inform management strategies and to accurately predict how future climate changes may affect turtle populations. However, there is a lack of robust data on offspring sex ratio at appropriate temporal and spatial scales to inform management decisions. To address this, we estimate the primary sex ratio of hawksbill hatchlings, Eretmochelys imbricata, from incubation duration of 5514 in situ nests from 10 nesting beaches from two regions in Brazil over the last 27 years. A strong female bias was estimated in all beaches, with 96% and 89% average female sex ratios produced in Bahia (BA) and Rio Grande do Norte (RN). Both inter-annual (BA, 88 to 99%; RN, 75 to 96% female) and inter-beach (BA, 92% to 97%; RN, 81% to 92% female) variability in mean offspring sex ratio was observed. These findings will guide management decisions in Brazil and provide further evidence of highly female-skew sex ratios in hawksbill turtles. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A Blue Spectral Shift of the Hemoglobin Soret Band Correlates with the Age (Time Since Deposition) of Dried Bloodstains

    PubMed Central

    Hanson, Erin K.; Ballantyne, Jack

    2010-01-01

    The ability to determine the time since deposition of a bloodstain found at a crime scene could prove invaluable to law enforcement investigators, defining the time frame in which the individual depositing the evidence was present. Although various methods of accomplishing this have been proposed, none has gained widespread use due to poor time resolution and weak age correlation. We have developed a method for the estimation of the time since deposition (TSD) of dried bloodstains using UV-VIS spectrophotometric analysis of hemoglobin (Hb) that is based upon its characteristic oxidation chemistry. A detailed study of the Hb Soret band (λmax = 412 nm) in aged bloodstains revealed a blue shift (shift to shorter wavelength) as the age of the stain increases. The extent of this shift permits, for the first time, a distinction to be made between bloodstains that were deposited minutes, hours, days and weeks prior to recovery and analysis. The extent of the blue shift was found to be a function of ambient relative humidity and temperature. The method is extremely sensitive, requiring as little as a 1 µl dried bloodstain for analysis. We demonstrate that it might be possible to perform TSD measurements at the crime scene using a portable low-sample-volume spectrophotometer. PMID:20877468

  5. Faces of the Recovery Act: 1366 Technologies

    ScienceCinema

    Sachs, Ely; Mierlo, Frank van; Obama, Barack

    2017-12-09

    LEXINGTON, MA - At 1366 Technologies, Ely Sachs and Frank van Mierlo are using ARPA-E Recovery Act funding to dramatically reduce the costs of solar panel production. To read more about the project: http://arpa-e.energy.gov/FundedProjects.aspx#1366 To see more projects funded by the Recovery Act through ARPA-E: http://arpa-e.energy.gov/FundedProjects.aspx

  6. Faces of the Recovery Act: 1366 Technologies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sachs, Ely; Mierlo, Frank van; Obama, Barack

    2010-01-01

    LEXINGTON, MA - At 1366 Technologies, Ely Sachs and Frank van Mierlo are using ARPA-E Recovery Act funding to dramatically reduce the costs of solar panel production. To read more about the project: http://arpa-e.energy.gov/FundedProjects.aspx#1366 To see more projects funded by the Recovery Act through ARPA-E: http://arpa-e.energy.gov/FundedProjects.aspx

  7. The Electronic Sandtable: An Application of VE-Technology as Tactical Situation Display

    DTIC Science & Technology

    2000-11-01

    plastic stereoscopic intelligibility of a complex tactical situation. The visualization of three-dimensional data. It has been situation scenario is not...generated artificial reality was mentioned first in science ergonomics and human factors is essential for the fiction literature at the middle of the...basically two different types of TSD’s VRML-Browsers and Videogames work like this. used by the strike forces. VE-systems are on their way of becoming

  8. A set of simple cell processes is sufficient to model spiral cleavage.

    PubMed

    Brun-Usan, Miguel; Marín-Riera, Miquel; Grande, Cristina; Truchado-Garcia, Marta; Salazar-Ciudad, Isaac

    2017-01-01

    During cleavage, different cellular processes cause the zygote to become partitioned into a set of cells with a specific spatial arrangement. These processes include the orientation of cell division according to: an animal-vegetal gradient; the main axis (Hertwig's rule) of the cell; and the contact areas between cells or the perpendicularity between consecutive cell divisions (Sachs' rule). Cell adhesion and cortical rotation have also been proposed to be involved in spiral cleavage. We use a computational model of cell and tissue biomechanics to account for the different existing hypotheses about how the specific spatial arrangement of cells in spiral cleavage arises during development. Cell polarization by an animal-vegetal gradient, a bias to perpendicularity between consecutive cell divisions (Sachs' rule), cortical rotation and cell adhesion, when combined, reproduce the spiral cleavage, whereas other combinations of processes cannot. Specifically, cortical rotation is necessary at the 8-cell stage to direct all micromeres in the same direction. By varying the relative strength of these processes, we reproduce the spatial arrangement of cells in the blastulae of seven different invertebrate species. © 2017. Published by The Company of Biologists Ltd.

  9. [Experimental study of dislocations of the scapulohumeral joint].

    PubMed

    Gagey, O; Gagey, N; Boisrenoult, P; Hue, E; Mazas, F

    1993-01-01

    One may produce easily an experimental dislocation (anterior or erecta) of the scapulohumeral joint. The authors discuss, the experimental model then they describe the anatomical lesion produced through the experimental dislocation of 32 shoulders and the correlation observed after RMI assessment of 24 recurrent dislocations. The tear of the inferior glenohumeral ligament is constant, in 20 per cent of the cases the tear lies on the anterior aspect of the glenoid, in the other cases the tear was found on its humeral side. Whatever the situation of the tear of the inferior glenohumeral ligament, the lesion of the labrum was constant. The erecta dislocation was produced with the same movement but with a particular tear of the glenohumeral ligament: the tear was longitudinal. The experimental dislocation needs, in 7 or 8 cases, a desinsertion of the deep aspect of the rotator cuff. The Hill Sachs lesion occurs when the humerus falls along the chest wall after the dislocation. In 50 per cent of the patients, MRI shows modifications of the cuff which are compatible with our results. Hills Sachs lesions appear to be constant after MRI examination.

  10. Microstructure and phase composition characterization in a Co{sub 38}Ni{sub 33}Al{sub 29} ferromagnetic shape memory alloy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lu, J.B.

    2016-08-15

    Transmission electron microscopy was performed to investigate the microstructures of a secondary phase and its surrounding matrix in a Co{sub 38}Ni{sub 33}Al{sub 29} ferromagnetic shape memory alloy. The secondary phase shows a γ′ L1{sub 2} structure exhibiting a dendritic morphology with enclosed B2 austenite regions while the matrix shows the L1{sub 0} martensitic structure. A secondary phase-austenite-martensite sandwich structure with residual austenite ranging from several hundred nanometers to several micrometers wide is observed at the secondary phase-martensite interface due to the depletion of Co and enrichment of Al in the chemical gradient zone and the effect of the strong martensiticmore » start temperature dependency of the element concentrations. The crystallographic orientation relationship of the secondary phase and the B2 austenite fits the Kurdjumov-Sachs relationship. - Highlights: •The secondary phase has a γ′ L1{sub 2} structure exhibiting a dendritic morphology. •A secondary phase-austenite-martensite sandwich structure is observed. •The structural sandwich structure is due to elemental composition variation. •The secondary phase and the B2 austenite fit the Kurdjumov-Sachs relationship.« less

  11. Templated sequence insertion polymorphisms in the human genome

    NASA Astrophysics Data System (ADS)

    Onozawa, Masahiro; Aplan, Peter

    2016-11-01

    Templated Sequence Insertion Polymorphism (TSIP) is a recently described form of polymorphism recognized in the human genome, in which a sequence that is templated from a distant genomic region is inserted into the genome, seemingly at random. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; Class 1 TSIPs show features of insertions that are mediated via the LINE-1 ORF2 protein, including 1) target-site duplication (TSD), 2) polyadenylation 10-30 nucleotides downstream of a “cryptic” polyadenylation signal, and 3) preference for insertion at a 5’-TTTT/A-3’ sequence. In contrast, class 2 TSIPs show features consistent with repair of a DNA double-strand break via insertion of a DNA “patch” that is derived from a distant genomic region. Survey of a large number of normal human volunteers demonstrates that most individuals have 25-30 TSIPs, and that these TSIPs track with specific geographic regions. Similar to other forms of human polymorphism, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases.

  12. An Interactive Map Viewer for the Urban Geology of Ottawa (Canada): an Example of Web Publishing

    NASA Astrophysics Data System (ADS)

    Giroux, D.; Bélanger, R.

    2003-04-01

    Developed by the Terrain Sciences Division (TSD) of the Geological Survey of Canada (GSC), an interactive map viewer, called GEOSERV (www.geoserv.org), is now available on the Internet. The purpose of this viewer is to provide engineers, planners, decision makers, and the general public with the geoscience information required for sound regional planning in densely populated areas, such as Canada's national capital, Ottawa (Ontario). Urban geology studies rely on diverse branches of earth sciences such as hydrology, engineering geology, geochemistry, stratigraphy, and geomorphology in order to build a three-dimensional model of the character of the land and to explain the geological processes involved in the dynamic equilibrium of the local environment. Over the past few years, TSD has compiled geoscientific information derived from various sources such as borehole logs, geological maps, hydrological reports and digital elevation models, compiled it in digital format and stored it in georeferenced databases in the form of point, linear, and polygonal data. This information constitutes the geoscience knowledge base which is then processed by Geographic Information Systems (GIS) to integrate the various sources of information and produce derived graphics, maps and models describing the geological infrastructure and response of the geological environment to human activities. Urban Geology of Canada's National Capital Area is a pilot project aiming at developing approaches, methodologies and standards that can be applied to other major urban centres of the country, while providing the geoscience knowledge required for sound regional planning and environmental protection of the National Capital Area. Based on an application developed by ESRI (Environmental System Research Institute), namely ArcIMS, the TSD has customized this web application to give free access to geoscience information of the Ottawa/Outaouais (Ontario/Québec) area including geological history

  13. Translational Regulation of PTEN/MMAC1 Expression in Prostate Cancer

    DTIC Science & Technology

    2003-05-01

    the transcription of dicistronic RNA encoding Renilla luciferase as the first cistron and firefly luciferase as the second cistron. Translation of the...first cistron ( Renilla luciferase) serves as an indicator of cap-dependent translation while translation of the second cistron (firefly luciferase...cellular IRES (Sachs, 2000). These dicistronic constructs were transfected into HeLa cells and both Renilla and firefly luciferase activities were measured

  14. Auditory Pattern Memory

    DTIC Science & Technology

    1989-10-31

    Psychology Building 410 Gainsvile, L 3611Boi ing AFB, DC 20332-6448 Ia. NAME OF FUNDING/SPONSORING &.OFF ICE SYMBOL 9. PROCUREMENT INSTRUMENT...Observers Robert D. Sorkin Department of Psychology University of Florida Gainesville, Florida 32611 31 October 1989 Annual Technical Report for Period 1...employing single, marked time intervals ( Creelman , 1962; Getty, 1975; Divenyi and Danner, 1977; Divenyi and Sachs, 1978; and Allen, 1979). Sorkin et

  15. Double soft graviton theorems and Bondi-Metzner-Sachs symmetries

    NASA Astrophysics Data System (ADS)

    Anupam, A. H.; Kundu, Arpan; Ray, Krishnendu

    2018-05-01

    It is now well understood that Ward identities associated with the (extended) BMS algebra are equivalent to single soft graviton theorems. In this work, we show that if we consider nested Ward identities constructed out of two BMS charges, a class of double soft factorization theorems can be recovered. By making connections with earlier works in the literature, we argue that at the subleading order, these double soft graviton theorems are the so-called consecutive double soft graviton theorems. We also show how these nested Ward identities can be understood as Ward identities associated with BMS symmetries in scattering states defined around (non-Fock) vacua parametrized by supertranslations or superrotations.

  16. Determination of State Budgets for the Final Ozone Supplemental of the Transport Rule TSD

    EPA Pesticide Factsheets

    In this final rulemaking, EPA finalizes Federal Implementation Plans (FIPs) to address significant contribution to nonattainment and interference with maintenance in Iowa, Michigan, Missouri, Oklahoma, and Wisconsin.

  17. Role of Sleep Deprivation in Fear Conditioning and Extinction: Implications for Treatment of PTSD

    DTIC Science & Technology

    2014-10-01

    The auditory stimulus during the NA trials, a brief (40 ms) pulse of 108 dB is used to induce a startle response, the magnitude of which is the...processing in humans and rodents would aid in mechanistic studies examining SD- induced inattention. We assessed the effects of 36 hours of: 1) Total SD...were required to inhibit from responding. TSD- induced effects on human Psychomotor Vigilance Test (PVT) were also examined. Effects of SD were also

  18. Some Important Diseases of Tree Fruits - Diseases of Vegetable Crops - Diseases of Grapes - Diseases of Tree Nuts.

    ERIC Educational Resources Information Center

    Petersen, Donald H.; And Others

    This agriculture extension service publication from Pennsylvania State University consists of four sections on plant disease recognition and control. The titles of these four sections are: (1) Some Important Diseases of Tree Fruits; (2) Diseases of Vegetable Crops; (3) Diseases of Crops; and (4) Diseases of Tree Nuts. The first section discusses…

  19. Renal disease in patients with celiac disease.

    PubMed

    Boonpheng, Boonphiphop; Cheungpasitporn, Wisit; Wijarnpreecha, Karn

    2018-04-01

    Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.

  20. Inflammatory bowel disease and airway diseases.

    PubMed

    Vutcovici, Maria; Brassard, Paul; Bitton, Alain

    2016-09-14

    Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.